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Yes. Sepsis, stroke, chronic kidney disease, pulmonary disease, chemotherapy, heart failure, and stress cardiomyopathy can all raise serum troponin concentrations, and in some cases the elevations are prognostically important. Careful clinical assessment, serial monitoring of troponin levels, and other supportive tests are usually necessary to tell whether troponin elevations are due to acute coronary syndrome or to these other causes.

NOT ONLY A MARKER OF MYOCARDIAL DAMAGE

Troponin, an intracellular protein found in skeletal and cardiac muscle cells, is essential for muscle contraction. Troponin T and troponin I are clinically equivalent, and both are biomarkers of myocardial damage.

A troponin assay is ordered when patients present with sudden onset of symptoms of acute coronary syndrome such as chest pain, dyspnea, diaphoresis, and electrocardiographic abnormalities. The assay is positive when the manufacturer-specified threshold corresponding to a concentration above the 99th percentile is detected.

Serial testing of serum biomarkers of acute myocardial damage is essential to confirm the diagnosis of myocardial infarction. Because of their higher sensitivity and specificity compared with creatine kinase-MB and other markers, troponins are the preferred biomarker in diagnosing acute coronary syndrome.

In 1984, Piper et al¹ reported that free cytosolic pools of cardiac enzymes could be released after reversible myocardial injury as a result of temporary disruption of the cell membrane. This upended the previous assumption that troponin was released only after irreversible myocardial necrosis, and it provided an explanation for troponin elevations observed in conditions with no evidence of epicardial coronary artery disease or permanent myocardial damage.¹

SEPSIS

Studies of patients with sepsis, severe sepsis, and septic shock have shown troponin elevations with no evidence of acute coronary syndrome.² In sepsis, troponin elevations are presumed to be caused by a combination of events. Renal dysfunction leads to decreased clearance of troponin fragments by the kidneys. The massive inflammatory response in septic shock results in cytokine-induced cardiac damage, and increased levels of endogen­ous and exogenous catecholamines damage cardiac myocytes.³

Studies of the prognostic value of these elevations have produced mixed and contradictory results. But a 2013 meta-analysis⁴ showed that patients with a troponin elevation at the time of diagnosis of sepsis had a risk of death almost twice that of patients without a troponin elevation (relative risk 1.91, 95% confidence interval [CI] 1.63–2.24).

STROKE

Acute ischemic stroke can trigger troponin elevations in several ways. Since the risk factors for acute ischemic stroke and coronary stenosis are similar, patients who have an ischemic stroke have a higher risk of coronary atherosclerosis and coronary stenosis than the general population.⁵

Stroke can cause a variety of cardiovascular and respiratory responses (eg, tachyarrhythmia, hypertensive crisis, respiratory failure) that increase the stress on the myocardium. In patients with stroke and concurrent coronary artery stenosis, the increased metabolic demand can exceed the oxygen supply capacity, resulting in myocardial ischemia, which can manifest as increased levels of serum troponin.⁵

Stroke can also cause troponin elevation through neurogenic myocardial damage. Ischemic stroke and intracranial hemorrhage can trigger alterations in autonomic control. Sometimes this results in increased sympathetic activity with concomitant catecholamine surge, leading to contraction band necrosis and other forms of myocardial damage and, as a result, troponin elevation.^5,6 This may explain troponin elevation in patients with acute ischemic stroke in the absence of concomitant coronary artery disease. Recent evidence suggests that patients with acute ischemic stroke and elevated troponin had significantly less angiographic evidence of coronary artery disease than matched patients with non-ST-elevation myocardial infarction.⁷

 

 

CHRONIC KIDNEY DISEASE

Cardiac troponins may be elevated in chronic kidney disease. Explanations for this include the theory that troponin is broken down into fragments that are cleared by the kidney.⁸ Therefore, decreased renal function leads to an increase in troponin fragments measured with troponin assays. Other explanations are chronic volume overload, chronic elevation of proinflammatory cytokines, and associated comorbidities such as hypertension.

Troponin elevations can have prognostic significance in chronic kidney disease. In a meta-analysis of 98 studies of patients with chronic kidney disease and no symptoms of acute coronary syndrome, troponin elevation was associated with 2- to 4-fold higher rates of all-cause mortality, cardiovascular mortality, and major acute coronary events in both dialysis-dependent and nondialysis patients.⁸ Thus, troponin is a unique factor in risk-stratification in patients with chronic kidney disease and could affect how it is managed in the future.

To determine if an acute coronary syndrome is taking place when evaluating patients with chronic kidney disease and elevated troponins, physicians must use other evidence—for example, serial measurements of troponin levels showing continued troponin elevation, elevations in troponin from the patient’s baseline, elevated creatine kinase-MB levels, electrocardiographic changes, and clinical symptoms.

PULMONARY DISEASE

Troponin elevation can signify right heart strain in a variety of pulmonary diseases.

Pulmonary embolism. Troponin elevation is a marker of right ventricular dysfunction in patients with moderate to large pulmonary embolism.

In a study of normotensive patients with acute pulmonary embolism, 52% had elevated serum troponin, and they had a higher risk of an adverse outcome (death, recurrent pulmonary embolism, or major bleeding) within 30 days (odds ratio 4.97, 95% CI 1.71–14.43) and a lower probability of 6-month survival.⁹ Troponin elevation in pulmonary embolism is not helpful in confirming the diagnosis but is primarily useful in prognosis.

Pulmonary arterial hypertension. Cardiac troponin elevations can also indicate severe disease and poor outcomes in patients with pulmonary arterial hypertension. A study by Heresi et al¹⁰ confirmed this, even in patients with only slight elevations in troponin levels. Troponin was detected in 17 (25%) of 68 patients with pulmonary arterial hypertension diagnostic category 1. Further, patients with detectable troponin had more advanced functional class symptoms, a shorter 6-minute walk distance, more pericardial effusions, larger right atrial area, and higher B-type natriuretic peptide and C-reactive protein levels.¹⁰

Measuring troponins in the setting of pulmonary hypertension allows clinicians to identify high-risk patients and may help guide the management of these patients.

Chronic obstructive pulmonary disease. Elevation of serum troponins is also reported in patients with acute exacerbation of chronic obstructive pulmonary disease and has been correlated with increased all-cause mortality rates in these patients.¹¹

CHEMOTHERAPY

Chemotherapy-induced cardiotoxicity may result in troponin elevations. Chemotherapy causes cardiac toxicity by several mechanisms, including production of oxygen free radicals, disturbance of mitochondrial energy metabolism, intracellular calcium overload, and increased lipid peroxidation. Chemotherapeutic agents associated with cardiotoxicity include anthracyclines, trastuzumab, chlormethine, and mitomycin.

Chemotherapy-induced left ventricular deterioration is often irreversible. Monitoring troponin levels can help identify problems before cardiac dysfunction becomes clinically evident during the weeks and months after the start of high-dose chemotherapy.

Cardinale et al¹² found marked myocardial depression 7 months after the start of high-dose chemotherapy. They reported a close relationship between short-term troponin elevation and the greatest reduction in left-ventricular ejection fraction (r = −0.87; P < .0001). Normal troponin values after high-dose chemotherapy also seemed to identify patients at lower risk, with either no cardiac damage or only transient subclinical left-ventricular dysfunction.¹²

HEART FAILURE

Heart failure leads to release of cardiac troponins through myocardial strain and myocardial death. Volume and pressure overload of the ventricles causes excessive wall tension, resulting in myofibrillar damage. Measuring troponins is an effective way to detect cardiac myolysis in heart failure, independent of the presence of coronary artery disease.

In heart failure, elevated troponins correlate with adverse outcome in both hospitalized and stable patients. In addition, elevation of both troponins and B-type natriuretic peptide is associated with worse heart failure outcomes than elevation of either marker alone.

A prospective study¹³ of patients with New York Heart Association class III or IV heart failure showed that an increase in troponin concentration from normal baseline was associated with a risk of death, cardiac transplant, or hospitalization that was 3.4 to 5.09 times higher. Further elevations in B-type natriuretic peptide during the study period were associated with a poor outcome (hazard ratio 5.09; P < .001). Combined elevations of troponin and B-type natriuretic peptide defined the group at highest risk (hazard ratio 8.58; P < .001).

Increased myocardial wall stress may lead to decreased subendocardial perfusion, with resulting troponin elevation and decline in left ventricular systolic function. Further, in vitro experiments with myocytes established a link between myocardial wall stretch and programmed cell death, which may contribute to troponin elevations.¹⁴

 

 

STRESS CARDIOMYOPATHY

Profound reversible myocardial depression and troponin elevation are seen after sudden emotional stress, a condition called stress-induced or takotsubo cardiomyopathy. While the exact mechanism of stress-induced cardiomyopathy remains unclear, it is thought to be due to sudden supraphysiologic elevation of catecholamines and related neuropeptides. Although vasospasm in the epicardial and microvascular circulation has been suggested as the possible mechanism of left ventricular systolic dysfunction and troponin elevation, cardiac myocyte injury from catecholamine- induced cyclic AMP-mediated calcium overload and oxygen-derived free radicals appears to be a more likely mechanism.¹⁵

PSEUDOELEVATIONS OF TROPONIN

In rare cases, endogenous antibodies (eg, heterophilic antibodies) in the blood specimen can interfere with the processing of the troponin immunoassay in the laboratory, causing a false-positive assay. This can occur with samples from patients with a viral infection or autoimmune condition as well as with samples from patients treated with intravenous immunoglobulin (Ig). Heterophilic antibodies can bind to the Fc region of the test antibodies in certain troponin assays, leading to false-positive elevations.¹⁶ Macrotroponin, a molecule found in patients with autoantibodies against troponin I, is composed of troponin I fragments and IgG antibodies and can also cause a false-positive troponin immunoassay.¹⁶

In patients with seropositive rheumatoid arthritis, a false-positive troponin I assay was associated with a high concentration of IgM rheumatoid factor with the use of certain immunoassay techniques.¹⁷ In patients with acute skeletal muscle injury, the first-generation troponin T assay was found to be falsely positive due to the nonspecific binding of skeletal muscle troponin T to the walls of the test tube used for the assay. When the second-generation troponin T assay was used, troponin T levels were found to be slightly more positive than troponin I levels (1.7 vs 1.5 times the upper limit of normal), especially in patients with renal failure.¹⁸

Troponin may also be falsely elevated in hemolyzed blood samples. This has to be taken into consideration in interpreting the results of troponin testing in severely hemolyzed blood samples. However, Puelacher et al¹⁹ suggested that the presence of hemolysis did not appear to interfere with clinical value of the test.

Yes. Sepsis, stroke, chronic kidney disease, pulmonary disease, chemotherapy, heart failure, and stress cardiomyopathy can all raise serum troponin concentrations, and in some cases the elevations are prognostically important. Careful clinical assessment, serial monitoring of troponin levels, and other supportive tests are usually necessary to tell whether troponin elevations are due to acute coronary syndrome or to these other causes.

NOT ONLY A MARKER OF MYOCARDIAL DAMAGE

Troponin, an intracellular protein found in skeletal and cardiac muscle cells, is essential for muscle contraction. Troponin T and troponin I are clinically equivalent, and both are biomarkers of myocardial damage.

A troponin assay is ordered when patients present with sudden onset of symptoms of acute coronary syndrome such as chest pain, dyspnea, diaphoresis, and electrocardiographic abnormalities. The assay is positive when the manufacturer-specified threshold corresponding to a concentration above the 99th percentile is detected.

Serial testing of serum biomarkers of acute myocardial damage is essential to confirm the diagnosis of myocardial infarction. Because of their higher sensitivity and specificity compared with creatine kinase-MB and other markers, troponins are the preferred biomarker in diagnosing acute coronary syndrome.

In 1984, Piper et al¹ reported that free cytosolic pools of cardiac enzymes could be released after reversible myocardial injury as a result of temporary disruption of the cell membrane. This upended the previous assumption that troponin was released only after irreversible myocardial necrosis, and it provided an explanation for troponin elevations observed in conditions with no evidence of epicardial coronary artery disease or permanent myocardial damage.¹

SEPSIS

Studies of patients with sepsis, severe sepsis, and septic shock have shown troponin elevations with no evidence of acute coronary syndrome.² In sepsis, troponin elevations are presumed to be caused by a combination of events. Renal dysfunction leads to decreased clearance of troponin fragments by the kidneys. The massive inflammatory response in septic shock results in cytokine-induced cardiac damage, and increased levels of endogen­ous and exogenous catecholamines damage cardiac myocytes.³

Studies of the prognostic value of these elevations have produced mixed and contradictory results. But a 2013 meta-analysis⁴ showed that patients with a troponin elevation at the time of diagnosis of sepsis had a risk of death almost twice that of patients without a troponin elevation (relative risk 1.91, 95% confidence interval [CI] 1.63–2.24).

STROKE

Acute ischemic stroke can trigger troponin elevations in several ways. Since the risk factors for acute ischemic stroke and coronary stenosis are similar, patients who have an ischemic stroke have a higher risk of coronary atherosclerosis and coronary stenosis than the general population.⁵

Stroke can cause a variety of cardiovascular and respiratory responses (eg, tachyarrhythmia, hypertensive crisis, respiratory failure) that increase the stress on the myocardium. In patients with stroke and concurrent coronary artery stenosis, the increased metabolic demand can exceed the oxygen supply capacity, resulting in myocardial ischemia, which can manifest as increased levels of serum troponin.⁵

Stroke can also cause troponin elevation through neurogenic myocardial damage. Ischemic stroke and intracranial hemorrhage can trigger alterations in autonomic control. Sometimes this results in increased sympathetic activity with concomitant catecholamine surge, leading to contraction band necrosis and other forms of myocardial damage and, as a result, troponin elevation.^5,6 This may explain troponin elevation in patients with acute ischemic stroke in the absence of concomitant coronary artery disease. Recent evidence suggests that patients with acute ischemic stroke and elevated troponin had significantly less angiographic evidence of coronary artery disease than matched patients with non-ST-elevation myocardial infarction.⁷

 

 

CHRONIC KIDNEY DISEASE

Cardiac troponins may be elevated in chronic kidney disease. Explanations for this include the theory that troponin is broken down into fragments that are cleared by the kidney.⁸ Therefore, decreased renal function leads to an increase in troponin fragments measured with troponin assays. Other explanations are chronic volume overload, chronic elevation of proinflammatory cytokines, and associated comorbidities such as hypertension.

Troponin elevations can have prognostic significance in chronic kidney disease. In a meta-analysis of 98 studies of patients with chronic kidney disease and no symptoms of acute coronary syndrome, troponin elevation was associated with 2- to 4-fold higher rates of all-cause mortality, cardiovascular mortality, and major acute coronary events in both dialysis-dependent and nondialysis patients.⁸ Thus, troponin is a unique factor in risk-stratification in patients with chronic kidney disease and could affect how it is managed in the future.

To determine if an acute coronary syndrome is taking place when evaluating patients with chronic kidney disease and elevated troponins, physicians must use other evidence—for example, serial measurements of troponin levels showing continued troponin elevation, elevations in troponin from the patient’s baseline, elevated creatine kinase-MB levels, electrocardiographic changes, and clinical symptoms.

PULMONARY DISEASE

Troponin elevation can signify right heart strain in a variety of pulmonary diseases.

Pulmonary embolism. Troponin elevation is a marker of right ventricular dysfunction in patients with moderate to large pulmonary embolism.

In a study of normotensive patients with acute pulmonary embolism, 52% had elevated serum troponin, and they had a higher risk of an adverse outcome (death, recurrent pulmonary embolism, or major bleeding) within 30 days (odds ratio 4.97, 95% CI 1.71–14.43) and a lower probability of 6-month survival.⁹ Troponin elevation in pulmonary embolism is not helpful in confirming the diagnosis but is primarily useful in prognosis.

Pulmonary arterial hypertension. Cardiac troponin elevations can also indicate severe disease and poor outcomes in patients with pulmonary arterial hypertension. A study by Heresi et al¹⁰ confirmed this, even in patients with only slight elevations in troponin levels. Troponin was detected in 17 (25%) of 68 patients with pulmonary arterial hypertension diagnostic category 1. Further, patients with detectable troponin had more advanced functional class symptoms, a shorter 6-minute walk distance, more pericardial effusions, larger right atrial area, and higher B-type natriuretic peptide and C-reactive protein levels.¹⁰

Measuring troponins in the setting of pulmonary hypertension allows clinicians to identify high-risk patients and may help guide the management of these patients.

Chronic obstructive pulmonary disease. Elevation of serum troponins is also reported in patients with acute exacerbation of chronic obstructive pulmonary disease and has been correlated with increased all-cause mortality rates in these patients.¹¹

CHEMOTHERAPY

Chemotherapy-induced cardiotoxicity may result in troponin elevations. Chemotherapy causes cardiac toxicity by several mechanisms, including production of oxygen free radicals, disturbance of mitochondrial energy metabolism, intracellular calcium overload, and increased lipid peroxidation. Chemotherapeutic agents associated with cardiotoxicity include anthracyclines, trastuzumab, chlormethine, and mitomycin.

Chemotherapy-induced left ventricular deterioration is often irreversible. Monitoring troponin levels can help identify problems before cardiac dysfunction becomes clinically evident during the weeks and months after the start of high-dose chemotherapy.

Cardinale et al¹² found marked myocardial depression 7 months after the start of high-dose chemotherapy. They reported a close relationship between short-term troponin elevation and the greatest reduction in left-ventricular ejection fraction (r = −0.87; P < .0001). Normal troponin values after high-dose chemotherapy also seemed to identify patients at lower risk, with either no cardiac damage or only transient subclinical left-ventricular dysfunction.¹²

HEART FAILURE

Heart failure leads to release of cardiac troponins through myocardial strain and myocardial death. Volume and pressure overload of the ventricles causes excessive wall tension, resulting in myofibrillar damage. Measuring troponins is an effective way to detect cardiac myolysis in heart failure, independent of the presence of coronary artery disease.

In heart failure, elevated troponins correlate with adverse outcome in both hospitalized and stable patients. In addition, elevation of both troponins and B-type natriuretic peptide is associated with worse heart failure outcomes than elevation of either marker alone.

A prospective study¹³ of patients with New York Heart Association class III or IV heart failure showed that an increase in troponin concentration from normal baseline was associated with a risk of death, cardiac transplant, or hospitalization that was 3.4 to 5.09 times higher. Further elevations in B-type natriuretic peptide during the study period were associated with a poor outcome (hazard ratio 5.09; P < .001). Combined elevations of troponin and B-type natriuretic peptide defined the group at highest risk (hazard ratio 8.58; P < .001).

Increased myocardial wall stress may lead to decreased subendocardial perfusion, with resulting troponin elevation and decline in left ventricular systolic function. Further, in vitro experiments with myocytes established a link between myocardial wall stretch and programmed cell death, which may contribute to troponin elevations.¹⁴

 

 

STRESS CARDIOMYOPATHY

Profound reversible myocardial depression and troponin elevation are seen after sudden emotional stress, a condition called stress-induced or takotsubo cardiomyopathy. While the exact mechanism of stress-induced cardiomyopathy remains unclear, it is thought to be due to sudden supraphysiologic elevation of catecholamines and related neuropeptides. Although vasospasm in the epicardial and microvascular circulation has been suggested as the possible mechanism of left ventricular systolic dysfunction and troponin elevation, cardiac myocyte injury from catecholamine- induced cyclic AMP-mediated calcium overload and oxygen-derived free radicals appears to be a more likely mechanism.¹⁵

PSEUDOELEVATIONS OF TROPONIN

In rare cases, endogenous antibodies (eg, heterophilic antibodies) in the blood specimen can interfere with the processing of the troponin immunoassay in the laboratory, causing a false-positive assay. This can occur with samples from patients with a viral infection or autoimmune condition as well as with samples from patients treated with intravenous immunoglobulin (Ig). Heterophilic antibodies can bind to the Fc region of the test antibodies in certain troponin assays, leading to false-positive elevations.¹⁶ Macrotroponin, a molecule found in patients with autoantibodies against troponin I, is composed of troponin I fragments and IgG antibodies and can also cause a false-positive troponin immunoassay.¹⁶

In patients with seropositive rheumatoid arthritis, a false-positive troponin I assay was associated with a high concentration of IgM rheumatoid factor with the use of certain immunoassay techniques.¹⁷ In patients with acute skeletal muscle injury, the first-generation troponin T assay was found to be falsely positive due to the nonspecific binding of skeletal muscle troponin T to the walls of the test tube used for the assay. When the second-generation troponin T assay was used, troponin T levels were found to be slightly more positive than troponin I levels (1.7 vs 1.5 times the upper limit of normal), especially in patients with renal failure.¹⁸

Troponin may also be falsely elevated in hemolyzed blood samples. This has to be taken into consideration in interpreting the results of troponin testing in severely hemolyzed blood samples. However, Puelacher et al¹⁹ suggested that the presence of hemolysis did not appear to interfere with clinical value of the test.

Yes. Sepsis, stroke, chronic kidney disease, pulmonary disease, chemotherapy, heart failure, and stress cardiomyopathy can all raise serum troponin concentrations, and in some cases the elevations are prognostically important. Careful clinical assessment, serial monitoring of troponin levels, and other supportive tests are usually necessary to tell whether troponin elevations are due to acute coronary syndrome or to these other causes.

NOT ONLY A MARKER OF MYOCARDIAL DAMAGE

Troponin, an intracellular protein found in skeletal and cardiac muscle cells, is essential for muscle contraction. Troponin T and troponin I are clinically equivalent, and both are biomarkers of myocardial damage.

A troponin assay is ordered when patients present with sudden onset of symptoms of acute coronary syndrome such as chest pain, dyspnea, diaphoresis, and electrocardiographic abnormalities. The assay is positive when the manufacturer-specified threshold corresponding to a concentration above the 99th percentile is detected.

Serial testing of serum biomarkers of acute myocardial damage is essential to confirm the diagnosis of myocardial infarction. Because of their higher sensitivity and specificity compared with creatine kinase-MB and other markers, troponins are the preferred biomarker in diagnosing acute coronary syndrome.

In 1984, Piper et al¹ reported that free cytosolic pools of cardiac enzymes could be released after reversible myocardial injury as a result of temporary disruption of the cell membrane. This upended the previous assumption that troponin was released only after irreversible myocardial necrosis, and it provided an explanation for troponin elevations observed in conditions with no evidence of epicardial coronary artery disease or permanent myocardial damage.¹

SEPSIS

Studies of patients with sepsis, severe sepsis, and septic shock have shown troponin elevations with no evidence of acute coronary syndrome.² In sepsis, troponin elevations are presumed to be caused by a combination of events. Renal dysfunction leads to decreased clearance of troponin fragments by the kidneys. The massive inflammatory response in septic shock results in cytokine-induced cardiac damage, and increased levels of endogen­ous and exogenous catecholamines damage cardiac myocytes.³

Studies of the prognostic value of these elevations have produced mixed and contradictory results. But a 2013 meta-analysis⁴ showed that patients with a troponin elevation at the time of diagnosis of sepsis had a risk of death almost twice that of patients without a troponin elevation (relative risk 1.91, 95% confidence interval [CI] 1.63–2.24).

STROKE

Acute ischemic stroke can trigger troponin elevations in several ways. Since the risk factors for acute ischemic stroke and coronary stenosis are similar, patients who have an ischemic stroke have a higher risk of coronary atherosclerosis and coronary stenosis than the general population.⁵

Stroke can cause a variety of cardiovascular and respiratory responses (eg, tachyarrhythmia, hypertensive crisis, respiratory failure) that increase the stress on the myocardium. In patients with stroke and concurrent coronary artery stenosis, the increased metabolic demand can exceed the oxygen supply capacity, resulting in myocardial ischemia, which can manifest as increased levels of serum troponin.⁵

Stroke can also cause troponin elevation through neurogenic myocardial damage. Ischemic stroke and intracranial hemorrhage can trigger alterations in autonomic control. Sometimes this results in increased sympathetic activity with concomitant catecholamine surge, leading to contraction band necrosis and other forms of myocardial damage and, as a result, troponin elevation.^5,6 This may explain troponin elevation in patients with acute ischemic stroke in the absence of concomitant coronary artery disease. Recent evidence suggests that patients with acute ischemic stroke and elevated troponin had significantly less angiographic evidence of coronary artery disease than matched patients with non-ST-elevation myocardial infarction.⁷

 

 

CHRONIC KIDNEY DISEASE

Cardiac troponins may be elevated in chronic kidney disease. Explanations for this include the theory that troponin is broken down into fragments that are cleared by the kidney.⁸ Therefore, decreased renal function leads to an increase in troponin fragments measured with troponin assays. Other explanations are chronic volume overload, chronic elevation of proinflammatory cytokines, and associated comorbidities such as hypertension.

Troponin elevations can have prognostic significance in chronic kidney disease. In a meta-analysis of 98 studies of patients with chronic kidney disease and no symptoms of acute coronary syndrome, troponin elevation was associated with 2- to 4-fold higher rates of all-cause mortality, cardiovascular mortality, and major acute coronary events in both dialysis-dependent and nondialysis patients.⁸ Thus, troponin is a unique factor in risk-stratification in patients with chronic kidney disease and could affect how it is managed in the future.

To determine if an acute coronary syndrome is taking place when evaluating patients with chronic kidney disease and elevated troponins, physicians must use other evidence—for example, serial measurements of troponin levels showing continued troponin elevation, elevations in troponin from the patient’s baseline, elevated creatine kinase-MB levels, electrocardiographic changes, and clinical symptoms.

PULMONARY DISEASE

Troponin elevation can signify right heart strain in a variety of pulmonary diseases.

Pulmonary embolism. Troponin elevation is a marker of right ventricular dysfunction in patients with moderate to large pulmonary embolism.

In a study of normotensive patients with acute pulmonary embolism, 52% had elevated serum troponin, and they had a higher risk of an adverse outcome (death, recurrent pulmonary embolism, or major bleeding) within 30 days (odds ratio 4.97, 95% CI 1.71–14.43) and a lower probability of 6-month survival.⁹ Troponin elevation in pulmonary embolism is not helpful in confirming the diagnosis but is primarily useful in prognosis.

Pulmonary arterial hypertension. Cardiac troponin elevations can also indicate severe disease and poor outcomes in patients with pulmonary arterial hypertension. A study by Heresi et al¹⁰ confirmed this, even in patients with only slight elevations in troponin levels. Troponin was detected in 17 (25%) of 68 patients with pulmonary arterial hypertension diagnostic category 1. Further, patients with detectable troponin had more advanced functional class symptoms, a shorter 6-minute walk distance, more pericardial effusions, larger right atrial area, and higher B-type natriuretic peptide and C-reactive protein levels.¹⁰

Measuring troponins in the setting of pulmonary hypertension allows clinicians to identify high-risk patients and may help guide the management of these patients.

Chronic obstructive pulmonary disease. Elevation of serum troponins is also reported in patients with acute exacerbation of chronic obstructive pulmonary disease and has been correlated with increased all-cause mortality rates in these patients.¹¹

CHEMOTHERAPY

Chemotherapy-induced cardiotoxicity may result in troponin elevations. Chemotherapy causes cardiac toxicity by several mechanisms, including production of oxygen free radicals, disturbance of mitochondrial energy metabolism, intracellular calcium overload, and increased lipid peroxidation. Chemotherapeutic agents associated with cardiotoxicity include anthracyclines, trastuzumab, chlormethine, and mitomycin.

Chemotherapy-induced left ventricular deterioration is often irreversible. Monitoring troponin levels can help identify problems before cardiac dysfunction becomes clinically evident during the weeks and months after the start of high-dose chemotherapy.

Cardinale et al¹² found marked myocardial depression 7 months after the start of high-dose chemotherapy. They reported a close relationship between short-term troponin elevation and the greatest reduction in left-ventricular ejection fraction (r = −0.87; P < .0001). Normal troponin values after high-dose chemotherapy also seemed to identify patients at lower risk, with either no cardiac damage or only transient subclinical left-ventricular dysfunction.¹²

HEART FAILURE

Heart failure leads to release of cardiac troponins through myocardial strain and myocardial death. Volume and pressure overload of the ventricles causes excessive wall tension, resulting in myofibrillar damage. Measuring troponins is an effective way to detect cardiac myolysis in heart failure, independent of the presence of coronary artery disease.

In heart failure, elevated troponins correlate with adverse outcome in both hospitalized and stable patients. In addition, elevation of both troponins and B-type natriuretic peptide is associated with worse heart failure outcomes than elevation of either marker alone.

A prospective study¹³ of patients with New York Heart Association class III or IV heart failure showed that an increase in troponin concentration from normal baseline was associated with a risk of death, cardiac transplant, or hospitalization that was 3.4 to 5.09 times higher. Further elevations in B-type natriuretic peptide during the study period were associated with a poor outcome (hazard ratio 5.09; P < .001). Combined elevations of troponin and B-type natriuretic peptide defined the group at highest risk (hazard ratio 8.58; P < .001).

Increased myocardial wall stress may lead to decreased subendocardial perfusion, with resulting troponin elevation and decline in left ventricular systolic function. Further, in vitro experiments with myocytes established a link between myocardial wall stretch and programmed cell death, which may contribute to troponin elevations.¹⁴

 

 

STRESS CARDIOMYOPATHY

Profound reversible myocardial depression and troponin elevation are seen after sudden emotional stress, a condition called stress-induced or takotsubo cardiomyopathy. While the exact mechanism of stress-induced cardiomyopathy remains unclear, it is thought to be due to sudden supraphysiologic elevation of catecholamines and related neuropeptides. Although vasospasm in the epicardial and microvascular circulation has been suggested as the possible mechanism of left ventricular systolic dysfunction and troponin elevation, cardiac myocyte injury from catecholamine- induced cyclic AMP-mediated calcium overload and oxygen-derived free radicals appears to be a more likely mechanism.¹⁵

PSEUDOELEVATIONS OF TROPONIN

In rare cases, endogenous antibodies (eg, heterophilic antibodies) in the blood specimen can interfere with the processing of the troponin immunoassay in the laboratory, causing a false-positive assay. This can occur with samples from patients with a viral infection or autoimmune condition as well as with samples from patients treated with intravenous immunoglobulin (Ig). Heterophilic antibodies can bind to the Fc region of the test antibodies in certain troponin assays, leading to false-positive elevations.¹⁶ Macrotroponin, a molecule found in patients with autoantibodies against troponin I, is composed of troponin I fragments and IgG antibodies and can also cause a false-positive troponin immunoassay.¹⁶

In patients with seropositive rheumatoid arthritis, a false-positive troponin I assay was associated with a high concentration of IgM rheumatoid factor with the use of certain immunoassay techniques.¹⁷ In patients with acute skeletal muscle injury, the first-generation troponin T assay was found to be falsely positive due to the nonspecific binding of skeletal muscle troponin T to the walls of the test tube used for the assay. When the second-generation troponin T assay was used, troponin T levels were found to be slightly more positive than troponin I levels (1.7 vs 1.5 times the upper limit of normal), especially in patients with renal failure.¹⁸

Troponin may also be falsely elevated in hemolyzed blood samples. This has to be taken into consideration in interpreting the results of troponin testing in severely hemolyzed blood samples. However, Puelacher et al¹⁹ suggested that the presence of hemolysis did not appear to interfere with clinical value of the test.

We should aim for a standard office systolic pressure lower than 130 mm Hg in most adults age 65 and older if the patient can take multiple antihypertensive medications and be followed closely for adverse effects.

This recommendation is part of the 2017 hypertension guideline from the American College of Cardiology and American Heart Association.¹ This new guideline advocates drug treatment of hypertension to a target less than 130/80 mm Hg for patients of all ages for secondary prevention of cardiovascular disease, and for primary prevention in those at high risk (ie, an estimated 10-year risk of atherosclerotic cardiovascular disease of 10% or higher). The target blood pressure for those at lower risk is less than 140/90 mm Hg.

There are multiple tools to estimate the 10-year risk. All tools incorporate major predictors such as age, blood pressure, cholesterol profile, and other markers, depending on the tool. Although risk increases with age, the tools are inaccurate once the patient is approximately 80 years of age.

The recommendation for older adults omits a target diastolic pressure, since treating elevated systolic pressure has more data supporting it than treating elevated diastolic blood pressure in older people. These recommendations apply only to older adults who can walk and are living in the community, not in an institution, and includes the subset of older adults who have mild cognitive impairment and frailty. The goals of treatment should be patient-centered.

DATA BEHIND THE GUIDELINE: THE SPRINT TRIAL

The Systolic Blood Pressure Intervention Trial (SPRINT)² enrolled 9,361 patients who, to enter, had to be at least 50 years old (the mean age was 67.9), have a systolic blood pressure of 130 to 180 mm Hg (the mean was 139.7 mm Hg), and be at risk of cardiovascular disease due to chronic kidney disease, clinical or subclinical cardiovascular disease, a 10-year Framingham risk score of at least 15%, or age 75 or older. They had few comorbidities, and patients with diabetes mellitus or prior stroke were excluded. The objective was to see if intensive blood pressure treatment reduced the incidence of adverse cardiovascular outcomes compared with standard control.

The participants were randomized to either an intensive treatment goal of systolic pressure less than 120 mm Hg or a standard treatment goal of less than 140 mm Hg. Investigators chose drugs and doses according to their clinical judgment. The study protocol called for blood pressure measurement using an untended automated cuff, which probably resulted in systolic pressure readings 5 to 10 mm Hg lower than with typical methods used in the office.³

The intensive treatment group achieved a mean systolic pressure of 121.5 mm Hg, which required an average of 3 drugs. In contrast, the standard treatment group achieved a systolic pressure of 136.2 mm Hg, which required an average of 1.9 drugs.

Due to an absolute risk reduction in cardiovascular events and mortality, SPRINT was discontinued early after a median follow-up of 3.3 years. In the entire cohort, 61 patients needed to be treated intensively to prevent 1 cardiovascular event, and 90 needed to be treated intensively to prevent 1 death.²

Favorable outcomes in the oldest subgroup

The oldest patients in the SPRINT trial tolerated the intensive treatment as well as the youngest.^2,4

Exploratory analysis of the subgroup of patients age 75 and older, who constituted 28% of the patients in the trial, demonstrated significant benefit from intensive treatment. In this subgroup, 27 patients needed to be treated aggressively (compared with standard treatment) to prevent 1 cardiovascular event,  and 41 needed to be treated intensively to prevent 1 death.⁴ The lower numbers needing to be treated in the older subgroup than in the overall trial reflect the higher absolute risk in this older population.

Serious adverse events were more common with intensive treatment than with standard treatment in the subgroup of older patients who were frail.⁴ Emergency department visits or serious adverse events were more likely when gait speed (a measure of frailty) was missing from the medical record in the intensive treatment group compared with the standard treatment group. Hyponatremia (serum sodium level < 130 mmol/L) was more likely in the intensively treated group than in the standard treatment group. Although the rate of falls was higher in the oldest subgroup than in the overall SPRINT population, within this subgroup the rate of injurious falls resulting in an emergency department visit was lower with intensive treatment than with standard treatment (11.6% vs 14.1%, P = .04).⁴

Most of the oldest patients scored below the nominal cutoff for normal (26 points)⁵ on the 30-point Montreal Cognitive Assessment, and about one-quarter scored below 19, which may be consistent with a major neurocognitive disorder.⁶

The SPRINT investigators validated a frailty scale in the study patients and found that the most frail benefited from intensive blood pressure control, as did the slowest walkers.

SPRINT results do not apply to very frail, sick patients

For older patients with hypertension, a high burden of comorbidity, and a limited life expectancy, the 2017 guidelines defer treatment decisions to clinical judgment and patient preference.

There have been no randomized trials of blood pressure management for older adults with substantial comorbidities or dementia. The “frail” older adults in the SPRINT trial were still living in the community, without dementia. The intensively treated frail older adults had more serious adverse events than with standard treatment. Those who were documented as being unable to walk at the time of enrollment also had more serious adverse events. Institutionalized older adults and nonambulatory adults in the community would likely have even higher rates of serious adverse events with intensive treatment than the SPRINT patients, and there is concern for excessive adverse effects from intensive blood pressure control in more debilitated older patients.

 

 

DOES TREATING HIGH BLOOD PRESSURE PREVENT FRAILTY OR DEMENTIA?

Aging without frailty is an important goal of geriatric care and is likely related to cardiovascular health.⁷ An older adult who becomes slower physically or mentally, with diminished strength and energy, is less likely to be able to live independently.

Would treating systolic blood pressure to a target of 120 to 130 mm Hg reduce the risk of prefrailty or frailty? Unfortunately, the 3-year SPRINT follow-up of the adults age 75 and older did not show any effect of intensive treatment on gait speed or mobility limitation.⁸ It is possible that the early termination of the study limited outcomes.

Regarding cognition, the new guidelines say that lowering blood pressure in adults with hypertension to prevent cognitive decline and dementia is reasonable, giving it a class IIa (moderate) recommendation, but they do not offer a particular blood pressure target.

Two systematic reviews of randomized placebo-controlled trials^9,10 suggested that pharmacologic treatment of hypertension reduces the progression of cognitive impairment. The trials did not use an intensive treatment goal.

The impact of intensive treatment of hypertension (to a target of 120–130 mm Hg) on the development or progression of cognitive impairment is not known at this time. The SPRINT Memory and Cognition in Decreased Hypertension analysis may shed light on the effect of intensive treatment of blood pressure on the incidence of dementia, although the early termination of SPRINT may limit its conclusions as well.

GOALS SHOULD BE PATIENT-CENTERED

The new hypertension guideline gives clinicians 2 things to think about when treating hypertensive, ambulatory, noninstitutionalized, nondemented older adults, including those age 75 and older:

• Older adults tolerate intensive blood pressure treatment as well as standard treatment. In particular, the fall rate is not increased and may even be less with intensive treatment.
• Older adults have better cardiovascular outcomes with blood pressure less than 130 mm Hg than with higher levels.

Adherence to the new guidelines would require many older adults without significant multimorbidity to take 3 drugs and undergo more frequent monitoring. This burden may align with the goals of care for many older adults. However, data do not exist to prove a benefit from intensive blood pressure control in debilitated elderly patients, and there may be harm. Lowering the medication burden may be a more important goal than lowering the pressure for this population. Blood pressure targets and hypertension management should reflect patient-centered goals of care.

We should aim for a standard office systolic pressure lower than 130 mm Hg in most adults age 65 and older if the patient can take multiple antihypertensive medications and be followed closely for adverse effects.

This recommendation is part of the 2017 hypertension guideline from the American College of Cardiology and American Heart Association.¹ This new guideline advocates drug treatment of hypertension to a target less than 130/80 mm Hg for patients of all ages for secondary prevention of cardiovascular disease, and for primary prevention in those at high risk (ie, an estimated 10-year risk of atherosclerotic cardiovascular disease of 10% or higher). The target blood pressure for those at lower risk is less than 140/90 mm Hg.

There are multiple tools to estimate the 10-year risk. All tools incorporate major predictors such as age, blood pressure, cholesterol profile, and other markers, depending on the tool. Although risk increases with age, the tools are inaccurate once the patient is approximately 80 years of age.

The recommendation for older adults omits a target diastolic pressure, since treating elevated systolic pressure has more data supporting it than treating elevated diastolic blood pressure in older people. These recommendations apply only to older adults who can walk and are living in the community, not in an institution, and includes the subset of older adults who have mild cognitive impairment and frailty. The goals of treatment should be patient-centered.

DATA BEHIND THE GUIDELINE: THE SPRINT TRIAL

The Systolic Blood Pressure Intervention Trial (SPRINT)² enrolled 9,361 patients who, to enter, had to be at least 50 years old (the mean age was 67.9), have a systolic blood pressure of 130 to 180 mm Hg (the mean was 139.7 mm Hg), and be at risk of cardiovascular disease due to chronic kidney disease, clinical or subclinical cardiovascular disease, a 10-year Framingham risk score of at least 15%, or age 75 or older. They had few comorbidities, and patients with diabetes mellitus or prior stroke were excluded. The objective was to see if intensive blood pressure treatment reduced the incidence of adverse cardiovascular outcomes compared with standard control.

The participants were randomized to either an intensive treatment goal of systolic pressure less than 120 mm Hg or a standard treatment goal of less than 140 mm Hg. Investigators chose drugs and doses according to their clinical judgment. The study protocol called for blood pressure measurement using an untended automated cuff, which probably resulted in systolic pressure readings 5 to 10 mm Hg lower than with typical methods used in the office.³

The intensive treatment group achieved a mean systolic pressure of 121.5 mm Hg, which required an average of 3 drugs. In contrast, the standard treatment group achieved a systolic pressure of 136.2 mm Hg, which required an average of 1.9 drugs.

Due to an absolute risk reduction in cardiovascular events and mortality, SPRINT was discontinued early after a median follow-up of 3.3 years. In the entire cohort, 61 patients needed to be treated intensively to prevent 1 cardiovascular event, and 90 needed to be treated intensively to prevent 1 death.²

Favorable outcomes in the oldest subgroup

The oldest patients in the SPRINT trial tolerated the intensive treatment as well as the youngest.^2,4

Exploratory analysis of the subgroup of patients age 75 and older, who constituted 28% of the patients in the trial, demonstrated significant benefit from intensive treatment. In this subgroup, 27 patients needed to be treated aggressively (compared with standard treatment) to prevent 1 cardiovascular event,  and 41 needed to be treated intensively to prevent 1 death.⁴ The lower numbers needing to be treated in the older subgroup than in the overall trial reflect the higher absolute risk in this older population.

Serious adverse events were more common with intensive treatment than with standard treatment in the subgroup of older patients who were frail.⁴ Emergency department visits or serious adverse events were more likely when gait speed (a measure of frailty) was missing from the medical record in the intensive treatment group compared with the standard treatment group. Hyponatremia (serum sodium level < 130 mmol/L) was more likely in the intensively treated group than in the standard treatment group. Although the rate of falls was higher in the oldest subgroup than in the overall SPRINT population, within this subgroup the rate of injurious falls resulting in an emergency department visit was lower with intensive treatment than with standard treatment (11.6% vs 14.1%, P = .04).⁴

Most of the oldest patients scored below the nominal cutoff for normal (26 points)⁵ on the 30-point Montreal Cognitive Assessment, and about one-quarter scored below 19, which may be consistent with a major neurocognitive disorder.⁶

The SPRINT investigators validated a frailty scale in the study patients and found that the most frail benefited from intensive blood pressure control, as did the slowest walkers.

SPRINT results do not apply to very frail, sick patients

For older patients with hypertension, a high burden of comorbidity, and a limited life expectancy, the 2017 guidelines defer treatment decisions to clinical judgment and patient preference.

There have been no randomized trials of blood pressure management for older adults with substantial comorbidities or dementia. The “frail” older adults in the SPRINT trial were still living in the community, without dementia. The intensively treated frail older adults had more serious adverse events than with standard treatment. Those who were documented as being unable to walk at the time of enrollment also had more serious adverse events. Institutionalized older adults and nonambulatory adults in the community would likely have even higher rates of serious adverse events with intensive treatment than the SPRINT patients, and there is concern for excessive adverse effects from intensive blood pressure control in more debilitated older patients.

 

 

DOES TREATING HIGH BLOOD PRESSURE PREVENT FRAILTY OR DEMENTIA?

Aging without frailty is an important goal of geriatric care and is likely related to cardiovascular health.⁷ An older adult who becomes slower physically or mentally, with diminished strength and energy, is less likely to be able to live independently.

Would treating systolic blood pressure to a target of 120 to 130 mm Hg reduce the risk of prefrailty or frailty? Unfortunately, the 3-year SPRINT follow-up of the adults age 75 and older did not show any effect of intensive treatment on gait speed or mobility limitation.⁸ It is possible that the early termination of the study limited outcomes.

Regarding cognition, the new guidelines say that lowering blood pressure in adults with hypertension to prevent cognitive decline and dementia is reasonable, giving it a class IIa (moderate) recommendation, but they do not offer a particular blood pressure target.

Two systematic reviews of randomized placebo-controlled trials^9,10 suggested that pharmacologic treatment of hypertension reduces the progression of cognitive impairment. The trials did not use an intensive treatment goal.

The impact of intensive treatment of hypertension (to a target of 120–130 mm Hg) on the development or progression of cognitive impairment is not known at this time. The SPRINT Memory and Cognition in Decreased Hypertension analysis may shed light on the effect of intensive treatment of blood pressure on the incidence of dementia, although the early termination of SPRINT may limit its conclusions as well.

GOALS SHOULD BE PATIENT-CENTERED

The new hypertension guideline gives clinicians 2 things to think about when treating hypertensive, ambulatory, noninstitutionalized, nondemented older adults, including those age 75 and older:

• Older adults tolerate intensive blood pressure treatment as well as standard treatment. In particular, the fall rate is not increased and may even be less with intensive treatment.
• Older adults have better cardiovascular outcomes with blood pressure less than 130 mm Hg than with higher levels.

Adherence to the new guidelines would require many older adults without significant multimorbidity to take 3 drugs and undergo more frequent monitoring. This burden may align with the goals of care for many older adults. However, data do not exist to prove a benefit from intensive blood pressure control in debilitated elderly patients, and there may be harm. Lowering the medication burden may be a more important goal than lowering the pressure for this population. Blood pressure targets and hypertension management should reflect patient-centered goals of care.

We should aim for a standard office systolic pressure lower than 130 mm Hg in most adults age 65 and older if the patient can take multiple antihypertensive medications and be followed closely for adverse effects.

This recommendation is part of the 2017 hypertension guideline from the American College of Cardiology and American Heart Association.¹ This new guideline advocates drug treatment of hypertension to a target less than 130/80 mm Hg for patients of all ages for secondary prevention of cardiovascular disease, and for primary prevention in those at high risk (ie, an estimated 10-year risk of atherosclerotic cardiovascular disease of 10% or higher). The target blood pressure for those at lower risk is less than 140/90 mm Hg.

There are multiple tools to estimate the 10-year risk. All tools incorporate major predictors such as age, blood pressure, cholesterol profile, and other markers, depending on the tool. Although risk increases with age, the tools are inaccurate once the patient is approximately 80 years of age.

The recommendation for older adults omits a target diastolic pressure, since treating elevated systolic pressure has more data supporting it than treating elevated diastolic blood pressure in older people. These recommendations apply only to older adults who can walk and are living in the community, not in an institution, and includes the subset of older adults who have mild cognitive impairment and frailty. The goals of treatment should be patient-centered.

DATA BEHIND THE GUIDELINE: THE SPRINT TRIAL

The Systolic Blood Pressure Intervention Trial (SPRINT)² enrolled 9,361 patients who, to enter, had to be at least 50 years old (the mean age was 67.9), have a systolic blood pressure of 130 to 180 mm Hg (the mean was 139.7 mm Hg), and be at risk of cardiovascular disease due to chronic kidney disease, clinical or subclinical cardiovascular disease, a 10-year Framingham risk score of at least 15%, or age 75 or older. They had few comorbidities, and patients with diabetes mellitus or prior stroke were excluded. The objective was to see if intensive blood pressure treatment reduced the incidence of adverse cardiovascular outcomes compared with standard control.

The participants were randomized to either an intensive treatment goal of systolic pressure less than 120 mm Hg or a standard treatment goal of less than 140 mm Hg. Investigators chose drugs and doses according to their clinical judgment. The study protocol called for blood pressure measurement using an untended automated cuff, which probably resulted in systolic pressure readings 5 to 10 mm Hg lower than with typical methods used in the office.³

The intensive treatment group achieved a mean systolic pressure of 121.5 mm Hg, which required an average of 3 drugs. In contrast, the standard treatment group achieved a systolic pressure of 136.2 mm Hg, which required an average of 1.9 drugs.

Due to an absolute risk reduction in cardiovascular events and mortality, SPRINT was discontinued early after a median follow-up of 3.3 years. In the entire cohort, 61 patients needed to be treated intensively to prevent 1 cardiovascular event, and 90 needed to be treated intensively to prevent 1 death.²

Favorable outcomes in the oldest subgroup

The oldest patients in the SPRINT trial tolerated the intensive treatment as well as the youngest.^2,4

Exploratory analysis of the subgroup of patients age 75 and older, who constituted 28% of the patients in the trial, demonstrated significant benefit from intensive treatment. In this subgroup, 27 patients needed to be treated aggressively (compared with standard treatment) to prevent 1 cardiovascular event,  and 41 needed to be treated intensively to prevent 1 death.⁴ The lower numbers needing to be treated in the older subgroup than in the overall trial reflect the higher absolute risk in this older population.

Serious adverse events were more common with intensive treatment than with standard treatment in the subgroup of older patients who were frail.⁴ Emergency department visits or serious adverse events were more likely when gait speed (a measure of frailty) was missing from the medical record in the intensive treatment group compared with the standard treatment group. Hyponatremia (serum sodium level < 130 mmol/L) was more likely in the intensively treated group than in the standard treatment group. Although the rate of falls was higher in the oldest subgroup than in the overall SPRINT population, within this subgroup the rate of injurious falls resulting in an emergency department visit was lower with intensive treatment than with standard treatment (11.6% vs 14.1%, P = .04).⁴

Most of the oldest patients scored below the nominal cutoff for normal (26 points)⁵ on the 30-point Montreal Cognitive Assessment, and about one-quarter scored below 19, which may be consistent with a major neurocognitive disorder.⁶

The SPRINT investigators validated a frailty scale in the study patients and found that the most frail benefited from intensive blood pressure control, as did the slowest walkers.

SPRINT results do not apply to very frail, sick patients

For older patients with hypertension, a high burden of comorbidity, and a limited life expectancy, the 2017 guidelines defer treatment decisions to clinical judgment and patient preference.

There have been no randomized trials of blood pressure management for older adults with substantial comorbidities or dementia. The “frail” older adults in the SPRINT trial were still living in the community, without dementia. The intensively treated frail older adults had more serious adverse events than with standard treatment. Those who were documented as being unable to walk at the time of enrollment also had more serious adverse events. Institutionalized older adults and nonambulatory adults in the community would likely have even higher rates of serious adverse events with intensive treatment than the SPRINT patients, and there is concern for excessive adverse effects from intensive blood pressure control in more debilitated older patients.

 

 

DOES TREATING HIGH BLOOD PRESSURE PREVENT FRAILTY OR DEMENTIA?

Aging without frailty is an important goal of geriatric care and is likely related to cardiovascular health.⁷ An older adult who becomes slower physically or mentally, with diminished strength and energy, is less likely to be able to live independently.

Would treating systolic blood pressure to a target of 120 to 130 mm Hg reduce the risk of prefrailty or frailty? Unfortunately, the 3-year SPRINT follow-up of the adults age 75 and older did not show any effect of intensive treatment on gait speed or mobility limitation.⁸ It is possible that the early termination of the study limited outcomes.

Regarding cognition, the new guidelines say that lowering blood pressure in adults with hypertension to prevent cognitive decline and dementia is reasonable, giving it a class IIa (moderate) recommendation, but they do not offer a particular blood pressure target.

Two systematic reviews of randomized placebo-controlled trials^9,10 suggested that pharmacologic treatment of hypertension reduces the progression of cognitive impairment. The trials did not use an intensive treatment goal.

The impact of intensive treatment of hypertension (to a target of 120–130 mm Hg) on the development or progression of cognitive impairment is not known at this time. The SPRINT Memory and Cognition in Decreased Hypertension analysis may shed light on the effect of intensive treatment of blood pressure on the incidence of dementia, although the early termination of SPRINT may limit its conclusions as well.

GOALS SHOULD BE PATIENT-CENTERED

The new hypertension guideline gives clinicians 2 things to think about when treating hypertensive, ambulatory, noninstitutionalized, nondemented older adults, including those age 75 and older:

• Older adults tolerate intensive blood pressure treatment as well as standard treatment. In particular, the fall rate is not increased and may even be less with intensive treatment.
• Older adults have better cardiovascular outcomes with blood pressure less than 130 mm Hg than with higher levels.

Adherence to the new guidelines would require many older adults without significant multimorbidity to take 3 drugs and undergo more frequent monitoring. This burden may align with the goals of care for many older adults. However, data do not exist to prove a benefit from intensive blood pressure control in debilitated elderly patients, and there may be harm. Lowering the medication burden may be a more important goal than lowering the pressure for this population. Blood pressure targets and hypertension management should reflect patient-centered goals of care.

Neither of the two cardiac risk assessment indexes most commonly used (Table 1)^1,2 is completely accurate, nor is one superior to the other. To provide the most accurate assessment of cardiac risk, practitioners need to select the index most applicable to the circumstances of the individual patient.

CARDIAC COMPLICATIONS ARE INCREASING

About 5% of patients undergoing noncardiac surgery have a major cardiac complication within the first 30 postoperative days.^3,4 This rate has been rising, primarily due to an increasing prevalence of cardiac comorbidities. Thus, accurate preoperative cardiac risk stratification is needed to assess the risk of perioperative major cardiac complications in all patients scheduled for noncardiac surgery. This information helps the perioperative team and patient to better weigh the benefits and risks of surgery and to optimize its timing and location (eg, inpatient vs outpatient surgery center).

CARDIAC RISK ASSESSMENT INDEXES

The 2 risk assessment indexes most often used are:

• The Revised Cardiac Risk Index (RCRI)¹
• The National Surgical Quality Improvement Program (NSQIP) risk index, also known as the Gupta index.²

Both are endorsed by the American College of Cardiology (ACC) and the American Heart Association (AHA).⁵ The RCRI, introduced in 1999, is more commonly used, but the NSQIP, introduced in 2011, is based on a larger sample size.

Both indexes consider various factors in estimating the risk, with some overlap. The main outcome assessed in both indexes is the risk of a major cardiac event, ie, myocardial infarction or cardiac arrest. The RCRI outcome also includes ventricular fibrillation, complete heart block, and pulmonary edema, which may be sequelae to cardiac arrest and myocardial infarction. This difference in defined outcomes between the indexes is not likely to account for a significant variation in the prediction of risk; however, this is difficult to prove.

Each index defines myocardial infarction differently. The current clinical definition⁶ includes detection of a rise or fall of cardiac biomarker values (preferably cardiac troponins) with at least 1 value above the 99th percentile upper reference limit and at least 1 of the following:

• Symptoms of ischemia
• New ST-T wave changes or new left bundle branch block
• New pathologic Q waves
• Imaging evidence of new loss of viable myocardium tissue or new regional wall- motion abnormality
• Finding of an intracoronary thrombus.

As seen in Table 1, the definition of myocardial infarction in NSQIP was one of the following: ST-segment elevation, new left bundle branch block, Q waves, or a troponin level greater than 3 times normal. Patients may have mild troponin leak of unknown significance without chest pain after surgery. This suggests that NSQIP may have overdiagnosed myocardial infarction.

USE IN CLINICAL PRACTICE

In clinical practice, which risk index is more accurate? Should clinicians become familiar with one index and keep using it? The 2014 ACC/AHA guidelines⁵ do not recommend one over the other, nor do they define the clinical situations that could lead to significant underestimation of risk.

The following are cases in which the indexes provide contradictory risk assessments.

Case 1. A 60-year-old man scheduled for surgery has diabetes mellitus, for which he takes insulin, and stable heart failure (left ventricular ejection fraction 40%). His RCRI score is 2, indicating an elevated 7% risk of cardiac complications; however, his NSQIP index is 0.31%. In this case, the NSQIP index probably underestimates the risk, as insulin-dependent diabetes and heart failure are not variables in the NSQIP index.

Case 2. A 60-year-old man who is partially functionally dependent and is on oxygen for severe chronic obstructive pulmonary disease is scheduled for craniotomy. His RCRI score is 0 (low risk), but his NSQIP index score (4.87%) indicates an elevated risk of cardiac complications based on his functional status, symptomatic chronic obstructive pulmonary disease, and high-risk surgery. In this case, the RCRI probably underestimates the risk.

These cases show that practitioners should not rely on just one index, but should rather decide which index to apply case by case. This avoids underestimating the risk. In patients with poor functional status and higher American Society of Anesthesiology class, the NSQIP index may provide a more accurate risk estimation than the RCRI. Patients with cardiomyopathy as well as those with insulin-dependent diabetes may be well assessed by the RCRI.

The following situations require additional caution when using these indexes, to avoid over- and underestimating cardiac risk.

 

 

PATIENTS WITH SEVERE AORTIC STENOSIS

Neither index lists severe aortic stenosis as a risk factor. The RCRI derivation and validation studies had only 5 patients with severe aortic stenosis, and the NSQIP validation study did not include any patients with aortic stenosis. Nevertheless, severe aortic stenosis increases the risk of cardiac complications in the perioperative period,⁷ making it important to consider in these patients.

Although patients with severe symptomatic aortic stenosis need valvular intervention before the surgery, patients who have asymptomatic severe aortic stenosis without associated cardiac dysfunction do not. Close hemodynamic monitoring during surgery is reasonable in the latter group.^5,7

PATIENTS WITH RECENT STROKE

What would be the cardiac risk for a patient scheduled for elective hip surgery who has had a stroke within the last 3 months? If one applies both indexes, the cardiac risk comes to less than 1% (low risk) in both cases. However, this could be deceiving. A large study⁸ published in 2014 showed an elevated risk of cardiac complications in patients undergoing noncardiac surgery who had had an ischemic stroke within the previous 6 months; in the first 3 months, the odds ratio of developing a major adverse cardiovascular event was 14.23.This clearly overrides the traditional expert opinion-based evidence, which is that a time lapse of only 1 month after an ischemic stroke is safe for surgery.

PATIENTS WITH DIASTOLIC DYSFUNCTION

A 2016 meta-analysis and systematic review found that preoperative diastolic dysfunction was associated with higher rates of postoperative mortality and major adverse cardiac events, regardless of the left ventricular ejection fraction.⁹ However, the studies investigated included mostly patients undergoing cardiovascular surgeries. This raises the question of whether asymptomatic patients need echocardiography before surgery.

In a patient who has diastolic dysfunction, one should maintain adequate blood pressure control and euvolemia before the surgery and avoid hypertensive spikes in the immediate perioperative period, as hypertension is the worst enemy of those with diastolic dysfunction. Patients with atrial fibrillation may need more stringent heart rate control.

In a prospective study involving 1,005 consecutive vascular surgery patients, the 30-day cardiovascular event rate was highest in patients with symptomatic heart failure (49%), followed by those with asymptomatic systolic left ventricular dysfunction (23%), asymptomatic diastolic left ventricular dysfunction (18%), and normal left ventricular function (10%).¹⁰

Further studies are needed to determine whether the data obtained from the assessment of ventricular function in patients without signs or symptoms are significant enough to require updates to the criteria.

WHAT ABOUT THE ROLE OF BNP?

In a meta-analysis of 15 noncardiac surgery studies in 850 patients, preoperative B-type natriuretic peptide (BNP) levels independently predicted major adverse cardiac events, with levels greater than 372 pg/mL having a 36.7% incidence of major adverse cardiac events.¹¹

A recent publication by the Canadian Cardiovascular Society¹² strongly recommended measuring N-terminal-proBNP or BNP before noncardiac surgery to enhance perioperative cardiac risk estimation in patients who are age 65 or older, patients who are age 45 to 64 with significant cardiovascular disease, or patients who have an RCRI score of 1 or higher.

Further prospective randomized studies are needed to assess the utility of measuring BNP for preoperative cardiac risk evaluation.

PATIENTS WITH OBSTRUCTIVE SLEEP APNEA

Patients with obstructive sleep apnea scheduled for surgery under anesthesia have a higher risk of perioperative complications than patients without the disease, including higher rates of cardiac complications and atrial fibrillation. However, the evidence is insufficient to support canceling or delaying surgery in patients with suspected obstructive sleep apnea.

After comorbid conditions are optimally treated, patients with obstructive sleep apnea can proceed to surgery, provided strategies for mitigating complications are implemented.¹³

 

 

TO STRESS OR NOT TO STRESS?

A common question is whether to perform a stress test before surgery. Based on the ACC/AHA guidelines,⁵ preoperative stress testing is not indicated solely to assess surgical risk if there is no other indication for it.

Stress testing can be used to determine whether the patient needs coronary revascularization. However, routine coronary revascularization is not recommended before noncardiac surgery exclusively to reduce perioperative cardiac events.

This conclusion is based on a landmark trial in which revascularization had no significant effect on outcomes.¹⁴ That trial included high-risk patients undergoing major vascular surgery who had greater than 70% stenosis of 1 or more major coronary arteries on angiography, randomized to either revascularization or no revascularization. It excluded patients with severe left main artery disease, ejection fraction less than 20%, and severe aortic stenosis. Results showed no differences in the rates of postoperative death, myocardial infarction, and stroke between the 2 groups. Furthermore, there was no postoperative survival difference during 5 years of follow-up.

Stress testing may be considered for patients with elevated risk and whose functional capacity is poor (< 4 metabolic equivalents) or unknown if it will change the management strategy. Another consideration affecting whether to perform stress testing is whether the surgery can be deferred for a month if the stress test is positive and a bare-metal coronary stent is placed, to allow for completion of dual antiplatelet therapy.

SHOULD WE ROUTINELY MONITOR TROPONIN AFTER SURGERY IN ASYMPTOMATIC PATIENTS?

Currently, the role of routine monitoring of troponin postoperatively in asymptomatic patients is unclear. The Canadian Cardiovascular Society¹² recommends monitoring troponin in selected group of patients, eg, those with an RCRI score of 1 or higher, age 65 or older, a significant cardiac history, or elevated BNP preoperatively. However, at this point we do not have strong evidence regarding the implications of mild asymptomatic troponin elevation postoperatively and how to manage it. Two currently ongoing randomized controlled trials will answer those questions:

• The Management of Myocardial Injury After Noncardiac Surgery (MANAGE) trial, comparing the use of dabigatran and omeprazole vs placebo in myocardial injury postoperatively
• The Study of Ticagrelor Versus Aspirin Treatment in Patients With Myocardial Injury Post Major Non-cardiac Surgery (INTREPID).

Neither of the two cardiac risk assessment indexes most commonly used (Table 1)^1,2 is completely accurate, nor is one superior to the other. To provide the most accurate assessment of cardiac risk, practitioners need to select the index most applicable to the circumstances of the individual patient.

CARDIAC COMPLICATIONS ARE INCREASING

About 5% of patients undergoing noncardiac surgery have a major cardiac complication within the first 30 postoperative days.^3,4 This rate has been rising, primarily due to an increasing prevalence of cardiac comorbidities. Thus, accurate preoperative cardiac risk stratification is needed to assess the risk of perioperative major cardiac complications in all patients scheduled for noncardiac surgery. This information helps the perioperative team and patient to better weigh the benefits and risks of surgery and to optimize its timing and location (eg, inpatient vs outpatient surgery center).

CARDIAC RISK ASSESSMENT INDEXES

The 2 risk assessment indexes most often used are:

• The Revised Cardiac Risk Index (RCRI)¹
• The National Surgical Quality Improvement Program (NSQIP) risk index, also known as the Gupta index.²

Both are endorsed by the American College of Cardiology (ACC) and the American Heart Association (AHA).⁵ The RCRI, introduced in 1999, is more commonly used, but the NSQIP, introduced in 2011, is based on a larger sample size.

Both indexes consider various factors in estimating the risk, with some overlap. The main outcome assessed in both indexes is the risk of a major cardiac event, ie, myocardial infarction or cardiac arrest. The RCRI outcome also includes ventricular fibrillation, complete heart block, and pulmonary edema, which may be sequelae to cardiac arrest and myocardial infarction. This difference in defined outcomes between the indexes is not likely to account for a significant variation in the prediction of risk; however, this is difficult to prove.

Each index defines myocardial infarction differently. The current clinical definition⁶ includes detection of a rise or fall of cardiac biomarker values (preferably cardiac troponins) with at least 1 value above the 99th percentile upper reference limit and at least 1 of the following:

• Symptoms of ischemia
• New ST-T wave changes or new left bundle branch block
• New pathologic Q waves
• Imaging evidence of new loss of viable myocardium tissue or new regional wall- motion abnormality
• Finding of an intracoronary thrombus.

As seen in Table 1, the definition of myocardial infarction in NSQIP was one of the following: ST-segment elevation, new left bundle branch block, Q waves, or a troponin level greater than 3 times normal. Patients may have mild troponin leak of unknown significance without chest pain after surgery. This suggests that NSQIP may have overdiagnosed myocardial infarction.

USE IN CLINICAL PRACTICE

In clinical practice, which risk index is more accurate? Should clinicians become familiar with one index and keep using it? The 2014 ACC/AHA guidelines⁵ do not recommend one over the other, nor do they define the clinical situations that could lead to significant underestimation of risk.

The following are cases in which the indexes provide contradictory risk assessments.

Case 1. A 60-year-old man scheduled for surgery has diabetes mellitus, for which he takes insulin, and stable heart failure (left ventricular ejection fraction 40%). His RCRI score is 2, indicating an elevated 7% risk of cardiac complications; however, his NSQIP index is 0.31%. In this case, the NSQIP index probably underestimates the risk, as insulin-dependent diabetes and heart failure are not variables in the NSQIP index.

Case 2. A 60-year-old man who is partially functionally dependent and is on oxygen for severe chronic obstructive pulmonary disease is scheduled for craniotomy. His RCRI score is 0 (low risk), but his NSQIP index score (4.87%) indicates an elevated risk of cardiac complications based on his functional status, symptomatic chronic obstructive pulmonary disease, and high-risk surgery. In this case, the RCRI probably underestimates the risk.

These cases show that practitioners should not rely on just one index, but should rather decide which index to apply case by case. This avoids underestimating the risk. In patients with poor functional status and higher American Society of Anesthesiology class, the NSQIP index may provide a more accurate risk estimation than the RCRI. Patients with cardiomyopathy as well as those with insulin-dependent diabetes may be well assessed by the RCRI.

The following situations require additional caution when using these indexes, to avoid over- and underestimating cardiac risk.

 

 

PATIENTS WITH SEVERE AORTIC STENOSIS

Neither index lists severe aortic stenosis as a risk factor. The RCRI derivation and validation studies had only 5 patients with severe aortic stenosis, and the NSQIP validation study did not include any patients with aortic stenosis. Nevertheless, severe aortic stenosis increases the risk of cardiac complications in the perioperative period,⁷ making it important to consider in these patients.

Although patients with severe symptomatic aortic stenosis need valvular intervention before the surgery, patients who have asymptomatic severe aortic stenosis without associated cardiac dysfunction do not. Close hemodynamic monitoring during surgery is reasonable in the latter group.^5,7

PATIENTS WITH RECENT STROKE

What would be the cardiac risk for a patient scheduled for elective hip surgery who has had a stroke within the last 3 months? If one applies both indexes, the cardiac risk comes to less than 1% (low risk) in both cases. However, this could be deceiving. A large study⁸ published in 2014 showed an elevated risk of cardiac complications in patients undergoing noncardiac surgery who had had an ischemic stroke within the previous 6 months; in the first 3 months, the odds ratio of developing a major adverse cardiovascular event was 14.23.This clearly overrides the traditional expert opinion-based evidence, which is that a time lapse of only 1 month after an ischemic stroke is safe for surgery.

PATIENTS WITH DIASTOLIC DYSFUNCTION

A 2016 meta-analysis and systematic review found that preoperative diastolic dysfunction was associated with higher rates of postoperative mortality and major adverse cardiac events, regardless of the left ventricular ejection fraction.⁹ However, the studies investigated included mostly patients undergoing cardiovascular surgeries. This raises the question of whether asymptomatic patients need echocardiography before surgery.

In a patient who has diastolic dysfunction, one should maintain adequate blood pressure control and euvolemia before the surgery and avoid hypertensive spikes in the immediate perioperative period, as hypertension is the worst enemy of those with diastolic dysfunction. Patients with atrial fibrillation may need more stringent heart rate control.

In a prospective study involving 1,005 consecutive vascular surgery patients, the 30-day cardiovascular event rate was highest in patients with symptomatic heart failure (49%), followed by those with asymptomatic systolic left ventricular dysfunction (23%), asymptomatic diastolic left ventricular dysfunction (18%), and normal left ventricular function (10%).¹⁰

Further studies are needed to determine whether the data obtained from the assessment of ventricular function in patients without signs or symptoms are significant enough to require updates to the criteria.

WHAT ABOUT THE ROLE OF BNP?

In a meta-analysis of 15 noncardiac surgery studies in 850 patients, preoperative B-type natriuretic peptide (BNP) levels independently predicted major adverse cardiac events, with levels greater than 372 pg/mL having a 36.7% incidence of major adverse cardiac events.¹¹

A recent publication by the Canadian Cardiovascular Society¹² strongly recommended measuring N-terminal-proBNP or BNP before noncardiac surgery to enhance perioperative cardiac risk estimation in patients who are age 65 or older, patients who are age 45 to 64 with significant cardiovascular disease, or patients who have an RCRI score of 1 or higher.

Further prospective randomized studies are needed to assess the utility of measuring BNP for preoperative cardiac risk evaluation.

PATIENTS WITH OBSTRUCTIVE SLEEP APNEA

Patients with obstructive sleep apnea scheduled for surgery under anesthesia have a higher risk of perioperative complications than patients without the disease, including higher rates of cardiac complications and atrial fibrillation. However, the evidence is insufficient to support canceling or delaying surgery in patients with suspected obstructive sleep apnea.

After comorbid conditions are optimally treated, patients with obstructive sleep apnea can proceed to surgery, provided strategies for mitigating complications are implemented.¹³

 

 

TO STRESS OR NOT TO STRESS?

A common question is whether to perform a stress test before surgery. Based on the ACC/AHA guidelines,⁵ preoperative stress testing is not indicated solely to assess surgical risk if there is no other indication for it.

Stress testing can be used to determine whether the patient needs coronary revascularization. However, routine coronary revascularization is not recommended before noncardiac surgery exclusively to reduce perioperative cardiac events.

This conclusion is based on a landmark trial in which revascularization had no significant effect on outcomes.¹⁴ That trial included high-risk patients undergoing major vascular surgery who had greater than 70% stenosis of 1 or more major coronary arteries on angiography, randomized to either revascularization or no revascularization. It excluded patients with severe left main artery disease, ejection fraction less than 20%, and severe aortic stenosis. Results showed no differences in the rates of postoperative death, myocardial infarction, and stroke between the 2 groups. Furthermore, there was no postoperative survival difference during 5 years of follow-up.

Stress testing may be considered for patients with elevated risk and whose functional capacity is poor (< 4 metabolic equivalents) or unknown if it will change the management strategy. Another consideration affecting whether to perform stress testing is whether the surgery can be deferred for a month if the stress test is positive and a bare-metal coronary stent is placed, to allow for completion of dual antiplatelet therapy.

SHOULD WE ROUTINELY MONITOR TROPONIN AFTER SURGERY IN ASYMPTOMATIC PATIENTS?

Currently, the role of routine monitoring of troponin postoperatively in asymptomatic patients is unclear. The Canadian Cardiovascular Society¹² recommends monitoring troponin in selected group of patients, eg, those with an RCRI score of 1 or higher, age 65 or older, a significant cardiac history, or elevated BNP preoperatively. However, at this point we do not have strong evidence regarding the implications of mild asymptomatic troponin elevation postoperatively and how to manage it. Two currently ongoing randomized controlled trials will answer those questions:

• The Management of Myocardial Injury After Noncardiac Surgery (MANAGE) trial, comparing the use of dabigatran and omeprazole vs placebo in myocardial injury postoperatively
• The Study of Ticagrelor Versus Aspirin Treatment in Patients With Myocardial Injury Post Major Non-cardiac Surgery (INTREPID).

Neither of the two cardiac risk assessment indexes most commonly used (Table 1)^1,2 is completely accurate, nor is one superior to the other. To provide the most accurate assessment of cardiac risk, practitioners need to select the index most applicable to the circumstances of the individual patient.

CARDIAC COMPLICATIONS ARE INCREASING

About 5% of patients undergoing noncardiac surgery have a major cardiac complication within the first 30 postoperative days.^3,4 This rate has been rising, primarily due to an increasing prevalence of cardiac comorbidities. Thus, accurate preoperative cardiac risk stratification is needed to assess the risk of perioperative major cardiac complications in all patients scheduled for noncardiac surgery. This information helps the perioperative team and patient to better weigh the benefits and risks of surgery and to optimize its timing and location (eg, inpatient vs outpatient surgery center).

CARDIAC RISK ASSESSMENT INDEXES

The 2 risk assessment indexes most often used are:

• The Revised Cardiac Risk Index (RCRI)¹
• The National Surgical Quality Improvement Program (NSQIP) risk index, also known as the Gupta index.²

Both are endorsed by the American College of Cardiology (ACC) and the American Heart Association (AHA).⁵ The RCRI, introduced in 1999, is more commonly used, but the NSQIP, introduced in 2011, is based on a larger sample size.

Both indexes consider various factors in estimating the risk, with some overlap. The main outcome assessed in both indexes is the risk of a major cardiac event, ie, myocardial infarction or cardiac arrest. The RCRI outcome also includes ventricular fibrillation, complete heart block, and pulmonary edema, which may be sequelae to cardiac arrest and myocardial infarction. This difference in defined outcomes between the indexes is not likely to account for a significant variation in the prediction of risk; however, this is difficult to prove.

Each index defines myocardial infarction differently. The current clinical definition⁶ includes detection of a rise or fall of cardiac biomarker values (preferably cardiac troponins) with at least 1 value above the 99th percentile upper reference limit and at least 1 of the following:

• Symptoms of ischemia
• New ST-T wave changes or new left bundle branch block
• New pathologic Q waves
• Imaging evidence of new loss of viable myocardium tissue or new regional wall- motion abnormality
• Finding of an intracoronary thrombus.

As seen in Table 1, the definition of myocardial infarction in NSQIP was one of the following: ST-segment elevation, new left bundle branch block, Q waves, or a troponin level greater than 3 times normal. Patients may have mild troponin leak of unknown significance without chest pain after surgery. This suggests that NSQIP may have overdiagnosed myocardial infarction.

USE IN CLINICAL PRACTICE

In clinical practice, which risk index is more accurate? Should clinicians become familiar with one index and keep using it? The 2014 ACC/AHA guidelines⁵ do not recommend one over the other, nor do they define the clinical situations that could lead to significant underestimation of risk.

The following are cases in which the indexes provide contradictory risk assessments.

Case 1. A 60-year-old man scheduled for surgery has diabetes mellitus, for which he takes insulin, and stable heart failure (left ventricular ejection fraction 40%). His RCRI score is 2, indicating an elevated 7% risk of cardiac complications; however, his NSQIP index is 0.31%. In this case, the NSQIP index probably underestimates the risk, as insulin-dependent diabetes and heart failure are not variables in the NSQIP index.

Case 2. A 60-year-old man who is partially functionally dependent and is on oxygen for severe chronic obstructive pulmonary disease is scheduled for craniotomy. His RCRI score is 0 (low risk), but his NSQIP index score (4.87%) indicates an elevated risk of cardiac complications based on his functional status, symptomatic chronic obstructive pulmonary disease, and high-risk surgery. In this case, the RCRI probably underestimates the risk.

These cases show that practitioners should not rely on just one index, but should rather decide which index to apply case by case. This avoids underestimating the risk. In patients with poor functional status and higher American Society of Anesthesiology class, the NSQIP index may provide a more accurate risk estimation than the RCRI. Patients with cardiomyopathy as well as those with insulin-dependent diabetes may be well assessed by the RCRI.

The following situations require additional caution when using these indexes, to avoid over- and underestimating cardiac risk.

 

 

PATIENTS WITH SEVERE AORTIC STENOSIS

Neither index lists severe aortic stenosis as a risk factor. The RCRI derivation and validation studies had only 5 patients with severe aortic stenosis, and the NSQIP validation study did not include any patients with aortic stenosis. Nevertheless, severe aortic stenosis increases the risk of cardiac complications in the perioperative period,⁷ making it important to consider in these patients.

Although patients with severe symptomatic aortic stenosis need valvular intervention before the surgery, patients who have asymptomatic severe aortic stenosis without associated cardiac dysfunction do not. Close hemodynamic monitoring during surgery is reasonable in the latter group.^5,7

PATIENTS WITH RECENT STROKE

What would be the cardiac risk for a patient scheduled for elective hip surgery who has had a stroke within the last 3 months? If one applies both indexes, the cardiac risk comes to less than 1% (low risk) in both cases. However, this could be deceiving. A large study⁸ published in 2014 showed an elevated risk of cardiac complications in patients undergoing noncardiac surgery who had had an ischemic stroke within the previous 6 months; in the first 3 months, the odds ratio of developing a major adverse cardiovascular event was 14.23.This clearly overrides the traditional expert opinion-based evidence, which is that a time lapse of only 1 month after an ischemic stroke is safe for surgery.

PATIENTS WITH DIASTOLIC DYSFUNCTION

A 2016 meta-analysis and systematic review found that preoperative diastolic dysfunction was associated with higher rates of postoperative mortality and major adverse cardiac events, regardless of the left ventricular ejection fraction.⁹ However, the studies investigated included mostly patients undergoing cardiovascular surgeries. This raises the question of whether asymptomatic patients need echocardiography before surgery.

In a patient who has diastolic dysfunction, one should maintain adequate blood pressure control and euvolemia before the surgery and avoid hypertensive spikes in the immediate perioperative period, as hypertension is the worst enemy of those with diastolic dysfunction. Patients with atrial fibrillation may need more stringent heart rate control.

In a prospective study involving 1,005 consecutive vascular surgery patients, the 30-day cardiovascular event rate was highest in patients with symptomatic heart failure (49%), followed by those with asymptomatic systolic left ventricular dysfunction (23%), asymptomatic diastolic left ventricular dysfunction (18%), and normal left ventricular function (10%).¹⁰

Further studies are needed to determine whether the data obtained from the assessment of ventricular function in patients without signs or symptoms are significant enough to require updates to the criteria.

WHAT ABOUT THE ROLE OF BNP?

In a meta-analysis of 15 noncardiac surgery studies in 850 patients, preoperative B-type natriuretic peptide (BNP) levels independently predicted major adverse cardiac events, with levels greater than 372 pg/mL having a 36.7% incidence of major adverse cardiac events.¹¹

A recent publication by the Canadian Cardiovascular Society¹² strongly recommended measuring N-terminal-proBNP or BNP before noncardiac surgery to enhance perioperative cardiac risk estimation in patients who are age 65 or older, patients who are age 45 to 64 with significant cardiovascular disease, or patients who have an RCRI score of 1 or higher.

Further prospective randomized studies are needed to assess the utility of measuring BNP for preoperative cardiac risk evaluation.

PATIENTS WITH OBSTRUCTIVE SLEEP APNEA

Patients with obstructive sleep apnea scheduled for surgery under anesthesia have a higher risk of perioperative complications than patients without the disease, including higher rates of cardiac complications and atrial fibrillation. However, the evidence is insufficient to support canceling or delaying surgery in patients with suspected obstructive sleep apnea.

After comorbid conditions are optimally treated, patients with obstructive sleep apnea can proceed to surgery, provided strategies for mitigating complications are implemented.¹³

 

 

TO STRESS OR NOT TO STRESS?

A common question is whether to perform a stress test before surgery. Based on the ACC/AHA guidelines,⁵ preoperative stress testing is not indicated solely to assess surgical risk if there is no other indication for it.

Stress testing can be used to determine whether the patient needs coronary revascularization. However, routine coronary revascularization is not recommended before noncardiac surgery exclusively to reduce perioperative cardiac events.

This conclusion is based on a landmark trial in which revascularization had no significant effect on outcomes.¹⁴ That trial included high-risk patients undergoing major vascular surgery who had greater than 70% stenosis of 1 or more major coronary arteries on angiography, randomized to either revascularization or no revascularization. It excluded patients with severe left main artery disease, ejection fraction less than 20%, and severe aortic stenosis. Results showed no differences in the rates of postoperative death, myocardial infarction, and stroke between the 2 groups. Furthermore, there was no postoperative survival difference during 5 years of follow-up.

Stress testing may be considered for patients with elevated risk and whose functional capacity is poor (< 4 metabolic equivalents) or unknown if it will change the management strategy. Another consideration affecting whether to perform stress testing is whether the surgery can be deferred for a month if the stress test is positive and a bare-metal coronary stent is placed, to allow for completion of dual antiplatelet therapy.

SHOULD WE ROUTINELY MONITOR TROPONIN AFTER SURGERY IN ASYMPTOMATIC PATIENTS?

Currently, the role of routine monitoring of troponin postoperatively in asymptomatic patients is unclear. The Canadian Cardiovascular Society¹² recommends monitoring troponin in selected group of patients, eg, those with an RCRI score of 1 or higher, age 65 or older, a significant cardiac history, or elevated BNP preoperatively. However, at this point we do not have strong evidence regarding the implications of mild asymptomatic troponin elevation postoperatively and how to manage it. Two currently ongoing randomized controlled trials will answer those questions:

• The Management of Myocardial Injury After Noncardiac Surgery (MANAGE) trial, comparing the use of dabigatran and omeprazole vs placebo in myocardial injury postoperatively
• The Study of Ticagrelor Versus Aspirin Treatment in Patients With Myocardial Injury Post Major Non-cardiac Surgery (INTREPID).

For patients age 16 and older with advanced chronic kidney disease (CKD), including those undergoing hemodialysis, we recommend a higher dose of hepatitis B virus (HBV) vaccine, more doses, or both. Vaccination with a higher dose may improve the immune response. The hepatitis B surface antibody (anti-HBs) titer should be monitored 1 to 2 months after completion of the vaccination schedule and annually thereafter, with a target titer of 10 IU/mL or greater. For patients who do not develop a protective antibody titer after completing the initial vaccination schedule, the vaccination schedule should be repeated.

RECOMMENDED DOSES AND SCHEDULES

Recommendation 1

Give higher vaccine doses, increase the number of doses, or both.

Rationale. Patients with CKD, especially those on hemodialysis, are in an immunocompromised state and thus are less likely to achieve protective anti-HBs levels after vaccination with standard dosages.^1–3 Two main vaccine formulations are available (Table 1). Recombivax-HB contains 40 µg/mL and is given in a 3-dose schedule at 0, 1, and 6 months. Engerix-B contains a standard dose of 20 µg/mL and should be given in a 4-dose schedule at double the standard dose (ie, a total of 40 µg/mL). Both regimens are recommended in the 2017 update of the United States Advisory Committee on Immunization Practices (ACIP) recommendations for adult immunization schedule.⁴

Recommendation 2

A 4-dose regimen may provide a better antibody response than a 3-dose regimen. (Note: This recommendation applies only to Engerix-B; 4 doses of Recombivax-HB would be an off-label use.)

Rationale. The US Centers for Disease Control and Prevention reported that after completion of a 3-dose vaccination schedule, the median proportion of patients developing a protective antibody response was 64% (range 34%–88%) vs a median of 86% (range 40%–98%) after a 4-dose schedule.³

Lacson et al⁵ compared antibody response rates after 3 doses of Recombivax-HB and after 4 doses of Engerix-B and found a better response rate with the 4-dose schedule. The rate of persistent protective anti-HBs titer after 1 year was 77% for Engerix-B vs 53% for Recombivax-HB.

Agarwal et al⁶ evaluated response rates in patients who had mild CKD (serum creatinine levels 1.5–3.0 mg/dL), moderate CKD (creatinine 3.0–6.0 mg/dL), and severe CKD (creatinine > 6.0 mg/dL). The seroconversion rates after 3 doses of 40-μg HBV vaccine were 87.5% in those with mild CKD, 66.6% in those with moderate CKD, and 35.7% in those with severe disease. After a fourth dose, rates improved significantly to 100%, 77%, and 36.4%, respectively.

Recommendation 3

In patients with CKD, vaccination should be done early, before they become dependent on hemodialysis.

Rationale. Patients with advanced CKD may have a lower seroconversion rate. Fraser et al⁷ found that after a 4-dose series, the seroprotection rate in adult prehemodialysis patients with serum creatinine levels of 4 mg/dL or less was 86%, compared with 37% in patients with serum creatinine levels above 4 mg/dL, of whom 88% were on hemodialysis.⁷

In a 2003 prospective cohort study by DaRoza et al,⁸ patients with higher levels of kidney function were more likely to respond to HBV vaccination, and the level of kidney function was found to be an independent predictor of seroconversion.⁸

A 2012 prospective study by Ghadiani et al⁹ compared seroconversion rates in patients with stage 3 or 4 CKD vs patients on hemodialysis, with medical staff as controls. The authors reported seroprotection rates of 26.1% in patients on hemodialysis, 55.2% in patients with stage 3 or 4 CKD, and 96.2% in controls. They concluded that vaccination is more likely to induce seroconversion in earlier stages of kidney disease.⁹

 

 

MONITORING THE RESPONSE TO VACCINATION AND REVACCINATION

Testing after vaccination is recommended to determine response. Testing should be done 1 to 2 months after the last dose of the vaccination schedule.^1–3 Anti-HBs levels 10 IU/mL and greater are considered protective.¹⁰

Revaccination with a full vaccination series is recommended for patients who do not develop adequate levels of protective antibodies after completion of the vaccination schedule.² Reported response rates to revaccination have varied from 40% to 50% after 2 or 3 additional intramuscular  doses of 40 µg, to 64% after 4 additional intramuscular doses of 10 µg.³ Serologic testing should be repeated after the last dose of the vaccination series, as serologic testing after only 1 or 2 additional doses appears to be no more cost-effective.^2,3

To the best of our knowledge, no data exist to indicate that in nonresponders, further doses given after completion of 2 full vaccination schedules would induce an antibody response.

ANTIBODY PERSISTENCE AND BOOSTER DOSES

Antibody levels fall with time in patients on hemodialysis. Limited data suggest that in patients who respond to the primary vaccination series, antibodies remain detectable for 6 months in 80% to 100% (median 100%) of patients and for 12 months in 58% to 100% (median 70%) of patients.³ The need for booster doses should be assessed by annual monitoring.^2,11 Booster doses should be given when the anti-HBs titer declines to below 10 IU/mL. Limited data indicate that nearly all such patients would respond to a booster dose.³

OTHER WAYS TO IMPROVE VACCINE RESPONSE

Other strategies to improve vaccine response, such as the addition of adjuvants or immunostimulants, have shown variable success.¹² Intradermal HBV vaccination in patients on chronic hemodialysis has also been proposed. The efficacy of intradermal vaccination may be related to the dense network of immunologic dendritic cells within the dermis. After intradermal administration, the antigen is taken up by dendritic cells residing in the dermis, which mature and travel to the regional lymph node where further immunostimulation takes place.¹³

In a systematic review of four prospective trials with a total of 204 hemodialysis patients,¹³ a significantly higher proportion of patients achieved seroconversion with intradermal HBV vaccine administration than with intramuscular administration. The authors concluded that the intradermal route in primary nonresponders undergoing hemodialysis provides an effective alternative to the intramuscular route to protect against HBV infection in this highly susceptible population.

Additional well-designed, double-blinded, randomized trials are needed to establish clear guidelines on intradermal HBV vaccine dosing and vaccination schedules.

For patients age 16 and older with advanced chronic kidney disease (CKD), including those undergoing hemodialysis, we recommend a higher dose of hepatitis B virus (HBV) vaccine, more doses, or both. Vaccination with a higher dose may improve the immune response. The hepatitis B surface antibody (anti-HBs) titer should be monitored 1 to 2 months after completion of the vaccination schedule and annually thereafter, with a target titer of 10 IU/mL or greater. For patients who do not develop a protective antibody titer after completing the initial vaccination schedule, the vaccination schedule should be repeated.

RECOMMENDED DOSES AND SCHEDULES

Recommendation 1

Give higher vaccine doses, increase the number of doses, or both.

Rationale. Patients with CKD, especially those on hemodialysis, are in an immunocompromised state and thus are less likely to achieve protective anti-HBs levels after vaccination with standard dosages.^1–3 Two main vaccine formulations are available (Table 1). Recombivax-HB contains 40 µg/mL and is given in a 3-dose schedule at 0, 1, and 6 months. Engerix-B contains a standard dose of 20 µg/mL and should be given in a 4-dose schedule at double the standard dose (ie, a total of 40 µg/mL). Both regimens are recommended in the 2017 update of the United States Advisory Committee on Immunization Practices (ACIP) recommendations for adult immunization schedule.⁴

Recommendation 2

A 4-dose regimen may provide a better antibody response than a 3-dose regimen. (Note: This recommendation applies only to Engerix-B; 4 doses of Recombivax-HB would be an off-label use.)

Rationale. The US Centers for Disease Control and Prevention reported that after completion of a 3-dose vaccination schedule, the median proportion of patients developing a protective antibody response was 64% (range 34%–88%) vs a median of 86% (range 40%–98%) after a 4-dose schedule.³

Lacson et al⁵ compared antibody response rates after 3 doses of Recombivax-HB and after 4 doses of Engerix-B and found a better response rate with the 4-dose schedule. The rate of persistent protective anti-HBs titer after 1 year was 77% for Engerix-B vs 53% for Recombivax-HB.

Agarwal et al⁶ evaluated response rates in patients who had mild CKD (serum creatinine levels 1.5–3.0 mg/dL), moderate CKD (creatinine 3.0–6.0 mg/dL), and severe CKD (creatinine > 6.0 mg/dL). The seroconversion rates after 3 doses of 40-μg HBV vaccine were 87.5% in those with mild CKD, 66.6% in those with moderate CKD, and 35.7% in those with severe disease. After a fourth dose, rates improved significantly to 100%, 77%, and 36.4%, respectively.

Recommendation 3

In patients with CKD, vaccination should be done early, before they become dependent on hemodialysis.

Rationale. Patients with advanced CKD may have a lower seroconversion rate. Fraser et al⁷ found that after a 4-dose series, the seroprotection rate in adult prehemodialysis patients with serum creatinine levels of 4 mg/dL or less was 86%, compared with 37% in patients with serum creatinine levels above 4 mg/dL, of whom 88% were on hemodialysis.⁷

In a 2003 prospective cohort study by DaRoza et al,⁸ patients with higher levels of kidney function were more likely to respond to HBV vaccination, and the level of kidney function was found to be an independent predictor of seroconversion.⁸

A 2012 prospective study by Ghadiani et al⁹ compared seroconversion rates in patients with stage 3 or 4 CKD vs patients on hemodialysis, with medical staff as controls. The authors reported seroprotection rates of 26.1% in patients on hemodialysis, 55.2% in patients with stage 3 or 4 CKD, and 96.2% in controls. They concluded that vaccination is more likely to induce seroconversion in earlier stages of kidney disease.⁹

 

 

MONITORING THE RESPONSE TO VACCINATION AND REVACCINATION

Testing after vaccination is recommended to determine response. Testing should be done 1 to 2 months after the last dose of the vaccination schedule.^1–3 Anti-HBs levels 10 IU/mL and greater are considered protective.¹⁰

Revaccination with a full vaccination series is recommended for patients who do not develop adequate levels of protective antibodies after completion of the vaccination schedule.² Reported response rates to revaccination have varied from 40% to 50% after 2 or 3 additional intramuscular  doses of 40 µg, to 64% after 4 additional intramuscular doses of 10 µg.³ Serologic testing should be repeated after the last dose of the vaccination series, as serologic testing after only 1 or 2 additional doses appears to be no more cost-effective.^2,3

To the best of our knowledge, no data exist to indicate that in nonresponders, further doses given after completion of 2 full vaccination schedules would induce an antibody response.

ANTIBODY PERSISTENCE AND BOOSTER DOSES

Antibody levels fall with time in patients on hemodialysis. Limited data suggest that in patients who respond to the primary vaccination series, antibodies remain detectable for 6 months in 80% to 100% (median 100%) of patients and for 12 months in 58% to 100% (median 70%) of patients.³ The need for booster doses should be assessed by annual monitoring.^2,11 Booster doses should be given when the anti-HBs titer declines to below 10 IU/mL. Limited data indicate that nearly all such patients would respond to a booster dose.³

OTHER WAYS TO IMPROVE VACCINE RESPONSE

Other strategies to improve vaccine response, such as the addition of adjuvants or immunostimulants, have shown variable success.¹² Intradermal HBV vaccination in patients on chronic hemodialysis has also been proposed. The efficacy of intradermal vaccination may be related to the dense network of immunologic dendritic cells within the dermis. After intradermal administration, the antigen is taken up by dendritic cells residing in the dermis, which mature and travel to the regional lymph node where further immunostimulation takes place.¹³

In a systematic review of four prospective trials with a total of 204 hemodialysis patients,¹³ a significantly higher proportion of patients achieved seroconversion with intradermal HBV vaccine administration than with intramuscular administration. The authors concluded that the intradermal route in primary nonresponders undergoing hemodialysis provides an effective alternative to the intramuscular route to protect against HBV infection in this highly susceptible population.

Additional well-designed, double-blinded, randomized trials are needed to establish clear guidelines on intradermal HBV vaccine dosing and vaccination schedules.

For patients age 16 and older with advanced chronic kidney disease (CKD), including those undergoing hemodialysis, we recommend a higher dose of hepatitis B virus (HBV) vaccine, more doses, or both. Vaccination with a higher dose may improve the immune response. The hepatitis B surface antibody (anti-HBs) titer should be monitored 1 to 2 months after completion of the vaccination schedule and annually thereafter, with a target titer of 10 IU/mL or greater. For patients who do not develop a protective antibody titer after completing the initial vaccination schedule, the vaccination schedule should be repeated.

RECOMMENDED DOSES AND SCHEDULES

Recommendation 1

Give higher vaccine doses, increase the number of doses, or both.

Rationale. Patients with CKD, especially those on hemodialysis, are in an immunocompromised state and thus are less likely to achieve protective anti-HBs levels after vaccination with standard dosages.^1–3 Two main vaccine formulations are available (Table 1). Recombivax-HB contains 40 µg/mL and is given in a 3-dose schedule at 0, 1, and 6 months. Engerix-B contains a standard dose of 20 µg/mL and should be given in a 4-dose schedule at double the standard dose (ie, a total of 40 µg/mL). Both regimens are recommended in the 2017 update of the United States Advisory Committee on Immunization Practices (ACIP) recommendations for adult immunization schedule.⁴

Recommendation 2

A 4-dose regimen may provide a better antibody response than a 3-dose regimen. (Note: This recommendation applies only to Engerix-B; 4 doses of Recombivax-HB would be an off-label use.)

Rationale. The US Centers for Disease Control and Prevention reported that after completion of a 3-dose vaccination schedule, the median proportion of patients developing a protective antibody response was 64% (range 34%–88%) vs a median of 86% (range 40%–98%) after a 4-dose schedule.³

Lacson et al⁵ compared antibody response rates after 3 doses of Recombivax-HB and after 4 doses of Engerix-B and found a better response rate with the 4-dose schedule. The rate of persistent protective anti-HBs titer after 1 year was 77% for Engerix-B vs 53% for Recombivax-HB.

Agarwal et al⁶ evaluated response rates in patients who had mild CKD (serum creatinine levels 1.5–3.0 mg/dL), moderate CKD (creatinine 3.0–6.0 mg/dL), and severe CKD (creatinine > 6.0 mg/dL). The seroconversion rates after 3 doses of 40-μg HBV vaccine were 87.5% in those with mild CKD, 66.6% in those with moderate CKD, and 35.7% in those with severe disease. After a fourth dose, rates improved significantly to 100%, 77%, and 36.4%, respectively.

Recommendation 3

In patients with CKD, vaccination should be done early, before they become dependent on hemodialysis.

Rationale. Patients with advanced CKD may have a lower seroconversion rate. Fraser et al⁷ found that after a 4-dose series, the seroprotection rate in adult prehemodialysis patients with serum creatinine levels of 4 mg/dL or less was 86%, compared with 37% in patients with serum creatinine levels above 4 mg/dL, of whom 88% were on hemodialysis.⁷

In a 2003 prospective cohort study by DaRoza et al,⁸ patients with higher levels of kidney function were more likely to respond to HBV vaccination, and the level of kidney function was found to be an independent predictor of seroconversion.⁸

A 2012 prospective study by Ghadiani et al⁹ compared seroconversion rates in patients with stage 3 or 4 CKD vs patients on hemodialysis, with medical staff as controls. The authors reported seroprotection rates of 26.1% in patients on hemodialysis, 55.2% in patients with stage 3 or 4 CKD, and 96.2% in controls. They concluded that vaccination is more likely to induce seroconversion in earlier stages of kidney disease.⁹

 

 

MONITORING THE RESPONSE TO VACCINATION AND REVACCINATION

Testing after vaccination is recommended to determine response. Testing should be done 1 to 2 months after the last dose of the vaccination schedule.^1–3 Anti-HBs levels 10 IU/mL and greater are considered protective.¹⁰

Revaccination with a full vaccination series is recommended for patients who do not develop adequate levels of protective antibodies after completion of the vaccination schedule.² Reported response rates to revaccination have varied from 40% to 50% after 2 or 3 additional intramuscular  doses of 40 µg, to 64% after 4 additional intramuscular doses of 10 µg.³ Serologic testing should be repeated after the last dose of the vaccination series, as serologic testing after only 1 or 2 additional doses appears to be no more cost-effective.^2,3

To the best of our knowledge, no data exist to indicate that in nonresponders, further doses given after completion of 2 full vaccination schedules would induce an antibody response.

ANTIBODY PERSISTENCE AND BOOSTER DOSES

Antibody levels fall with time in patients on hemodialysis. Limited data suggest that in patients who respond to the primary vaccination series, antibodies remain detectable for 6 months in 80% to 100% (median 100%) of patients and for 12 months in 58% to 100% (median 70%) of patients.³ The need for booster doses should be assessed by annual monitoring.^2,11 Booster doses should be given when the anti-HBs titer declines to below 10 IU/mL. Limited data indicate that nearly all such patients would respond to a booster dose.³

OTHER WAYS TO IMPROVE VACCINE RESPONSE

Other strategies to improve vaccine response, such as the addition of adjuvants or immunostimulants, have shown variable success.¹² Intradermal HBV vaccination in patients on chronic hemodialysis has also been proposed. The efficacy of intradermal vaccination may be related to the dense network of immunologic dendritic cells within the dermis. After intradermal administration, the antigen is taken up by dendritic cells residing in the dermis, which mature and travel to the regional lymph node where further immunostimulation takes place.¹³

In a systematic review of four prospective trials with a total of 204 hemodialysis patients,¹³ a significantly higher proportion of patients achieved seroconversion with intradermal HBV vaccine administration than with intramuscular administration. The authors concluded that the intradermal route in primary nonresponders undergoing hemodialysis provides an effective alternative to the intramuscular route to protect against HBV infection in this highly susceptible population.

Additional well-designed, double-blinded, randomized trials are needed to establish clear guidelines on intradermal HBV vaccine dosing and vaccination schedules.

Yes. The time has come to change the way we think about fasting before routine lipid testing. We now have robust evidence supporting the routine use of nonfasting lipid testing. Fasting lipid testing is rarely needed, but may be considered for patients with very high triglycerides or before starting treatment in patients with genetic lipid disorders. For most patients, nonfasting lipid testing is appropriate: it is evidence-based, safe, valid, and convenient. More widespread adoption of this strategy by US healthcare providers would improve quality of care and patient and clinician satisfaction.

GUIDELINES HAVE CHANGED

In 2014, the US Department of Veterans Affairs practice guidelines recommended nonfasting lipid testing for cardiovascular risk assessment.¹ Other recent clinical guidelines and expert consensus statements from Europe and Canada now also recommend nonfasting lipid testing for most routine clinical evaluations.

Physiologically, we spend most of our lives in the nonfasting state, yet fasting lipid testing was standard practice advocated by earlier clinical guidelines. The rationale for fasting before measuring lipids was to reduce variability and to allow for a more accurate derivation of the low-density lipoprotein cholesterol (LDL-C) concentration using the Friedewald formula. There was also concern that an increase in triglyceride concentrations after consuming a fatty meal would reduce the validity of the results. However, numerous studies have found that the increase in plasma triglycerides after normal food intake is much less than that during a fat-tolerance test, making this less of a concern for most patients.^2,3

In addition, recent studies suggest that postprandial effects do not diminish and may even strengthen the risk associations of lipids with cardiovascular disease, in particular for triglycerides.⁴ Moreover, in certain patients, such as those with metabolic syndrome, diabetes mellitus, or certain genetic abnormalities, fasting can mask abnormalities in triglyceride-rich lipid metabolism, which may only be detected when triglycerides are measured in a nonfasting state. Nonfasting measurements may identify patients with elevated residual risk despite optimal guideline-based treatment.

In 2016, a joint consensus statement of the European Atherosclerosis Society and the European Federation of Clinical Chemistry and Laboratory Medicine⁵ recommended nonfasting lipid testing as the new standard for lipid measurement, with fasting lipid testing considered for patients with triglyceride levels over 400 mg/dL (5 mmol/L). The statement also recommends that nonfasting triglyceride levels greater than or equal to 175 mg/dL (2 mmol/L) should be considered elevated as compared with the 150 mg/dL (1.7 mmol/L) traditionally used for fasting panels.

Recently published recommendations for nonfasting lipid testing for routine assessments are summarized in Table 1.^1,5–11

EFFECTS OF THE POSTPRANDIAL STATE ON LIPID LEVELS AND RISK ASSESSMENT

A common concern for clinicians who do not routinely order nonfasting lipid testing is the potential variability in lipid levels and interpretation of these values for treatment decisions. But in most circumstances the differences between fasting and nonfasting measurements are small and are not clinically relevant. Differences in high-density lipoprotein  cholesterol (HDL-C) are negligible; slightly lower levels are seen (up to −8 mg/dL) for nonfasting total cholesterol, LDL-C, and non-HDL-C compared with fasting levels; and differences are modest (up to 25 mg/dL higher) for triglycerides.⁵ These data should reassure clinicians who rely on lipid levels to guide management decisions.⁹

Cardiovascular risk assessment

Current algorithms for assessing risk of cardiovascular disease use total cholesterol and HDL-C, not triglycerides or LDL-C. Hence, eating has no effect on the risk estimates.

For clinicians who prefer an absolute lipid target for managing risk in patients on lipid-modifying therapy, a nonfasting LDL-C or non-HDL-C (or apolipoprotein B) may be used. The non-HDL-C level is a better risk marker than LDL-C, particularly in patients with low LDL-C or with triglyceride levels of 200 mg/dL or higher.¹² Treatment goals for non-HDL-C are 30 mg/dL higher than for LDL-C (fasting or nonfasting). In addition, for these patients with low LDL-C or high triglycerides, a new LDL-C calculation method has more consistent results for fasting and nonfasting values than the commonly used Friedewald calculation.¹²

 

 

EVIDENCE SUPPORTING NONFASTING LIPID TESTING

The adequacy of nonfasting lipid testing for general screening for cardiovascular disease has been verified in large prospective studies over the past several decades.^2,13,14 These studies evaluated cardiovascular event and mortality rates and found consistent associations of nonfasting lipid levels with cardiovascular disease. Studies that included both fasting and nonfasting patient populations found similar or occasionally even greater cardiovascular risk associations for nonfasting lipid measurements (including for LDL-C and triglycerides) compared with fasting lipid measurements.

The Emerging Risk Factors Collaboration¹⁴ reviewed the data from 68 studies in more than 300,000 people and found that the relationship between lipid levels and incident cardiovascular events was just as strong when nonfasting lipid values were used. In fact, at least 3 large statin trials reviewed (a total of 43,000 people) used nonfasting lipids.¹⁴

Genetic studies using mendelian randomization have also linked nonfasting triglyceride levels (and remnant cholesterol) to an increased risk of cardiovascular events and of death from any cause.^15,16

Therefore, the evidence overall suggests that nonfasting lipid measurements are acceptable with respect to risk assessment, and indeed may be preferred in most instances, especially in patients with an atherogenic metabolic milieu that may otherwise be masked by the fasting state.

OTHER BENEFITS OF NONFASTING LIPID TESTING

Nonfasting lipid panels are more economical and safer for certain groups, such as elderly or diabetic patients. A pilot study¹⁷ found that up to 27.1% of patients with diabetes reported experiencing a fasting-evoked hypoglycemic event en route to testing because of fasting for blood work. These events are vastly underreported and add to patient morbidity that can easily be avoided by adopting nonfasting lipid testing.

No study has assessed the cost-effectiveness of fasting vs nonfasting lipid testing. It is common for patients to present for their office appointment without having obtained a fasting lipid panel simply because they forgot to fast and were turned away by the laboratory. Thus, management decisions during the visit are often deferred, and patients must return to the laboratory and reschedule follow-up visits. This is inefficient, increases outpatient waiting times, and also potentially deprives others of access to needed care. Laboratory workflow can also suffer from an influx of early morning visits for fasting tests, decreasing system efficiency. Decreased efficiency in multiple levels of the healthcare system leads to increased costs, burden on healthcare providers, and decreased patient and physician satisfaction.

GETTING WITH THE GUIDELINES

The 2002 National Cholesterol Education Program expert panel report¹⁸ and the 2013 joint cholesterol guidelines of the American College of Cardiology and the American Heart Association⁹ both recommended that initial screening should involve fasting lipid testing, but they also allowed measuring nonfasting total cholesterol, HDL-C, and non-HDL-C.¹⁸ And internationally, there has been a shift in practice recommendations toward nonfasting lipids over the past 10 years (Table 1).

In 2014, the US Department of Veterans Affairs, the UK National Clinical Guideline Centre, and the Joint British Societies said that fasting is no longer needed for routine testing.¹⁰ In 2016, the European Atherosclerosis Society and the European Federation of Clinical Chemistry and Laboratory Medicine recommended nonfasting lipid testing as the standard of care and provided clinically useful cut points for both fasting and nonfasting lipid measurements.⁵

In most guidelines, the threshold for elevated nonfasting triglycerides was defined as 175 mg/dL (≥ 2 mmol/L) or greater, and this level has been validated prospectively in a large study of US women.^5,19 Repeat measurement of fasting triglycerides may be considered when nonfasting levels are greater than  400 mg/dL,⁵ although there is no consensus in the guidelines regarding when or if fasting triglycerides should be remeasured. (In the Danish experience,⁵ only 10% of patients have required repeat fasting values). In addition, the 2016 Canadian Hypertension Education Program guidelines⁶ removed fasting as a requirement. The 2016 Canadian Cardiovascular Society dyslipidemia guidelines⁷ reported that nonfasting lipid testing is a suitable alternative to fasting. Furthermore, the most recent revision of the European Society of Cardiology dyslipidemia guidelines⁸ acknowledged that nonfasting lipid panels are acceptable for screening and management of patients without severe hypertriglyceridemia or those with extremely low LDL-C levels.

LIMITATIONS OF THE EVIDENCE

To date, no study has assessed the predictive value of fasting vs nonfasting lipid measurements in the same individuals, and there have been no randomized outcomes trials or cost-effectiveness analyses. Ethnic variations in lipoproteins and nonfasting status also need to be investigated as nonfasting lipid testing becomes more universally accepted.

TAKE-HOME POINTS

• Robust evidence supports the routine use of nonfasting lipid testing, with fasting panels reserved potentially for patients with very high triglycerides and before starting treatment in those with genetic lipid disorders.
• For most patients, nonfasting tests are evidence-based, safe, valid, and convenient.
• More widespread adoption of this strategy by US healthcare providers would improve both quality of care and patient-clinician satisfaction.

Yes. The time has come to change the way we think about fasting before routine lipid testing. We now have robust evidence supporting the routine use of nonfasting lipid testing. Fasting lipid testing is rarely needed, but may be considered for patients with very high triglycerides or before starting treatment in patients with genetic lipid disorders. For most patients, nonfasting lipid testing is appropriate: it is evidence-based, safe, valid, and convenient. More widespread adoption of this strategy by US healthcare providers would improve quality of care and patient and clinician satisfaction.

GUIDELINES HAVE CHANGED

In 2014, the US Department of Veterans Affairs practice guidelines recommended nonfasting lipid testing for cardiovascular risk assessment.¹ Other recent clinical guidelines and expert consensus statements from Europe and Canada now also recommend nonfasting lipid testing for most routine clinical evaluations.

Physiologically, we spend most of our lives in the nonfasting state, yet fasting lipid testing was standard practice advocated by earlier clinical guidelines. The rationale for fasting before measuring lipids was to reduce variability and to allow for a more accurate derivation of the low-density lipoprotein cholesterol (LDL-C) concentration using the Friedewald formula. There was also concern that an increase in triglyceride concentrations after consuming a fatty meal would reduce the validity of the results. However, numerous studies have found that the increase in plasma triglycerides after normal food intake is much less than that during a fat-tolerance test, making this less of a concern for most patients.^2,3

In addition, recent studies suggest that postprandial effects do not diminish and may even strengthen the risk associations of lipids with cardiovascular disease, in particular for triglycerides.⁴ Moreover, in certain patients, such as those with metabolic syndrome, diabetes mellitus, or certain genetic abnormalities, fasting can mask abnormalities in triglyceride-rich lipid metabolism, which may only be detected when triglycerides are measured in a nonfasting state. Nonfasting measurements may identify patients with elevated residual risk despite optimal guideline-based treatment.

In 2016, a joint consensus statement of the European Atherosclerosis Society and the European Federation of Clinical Chemistry and Laboratory Medicine⁵ recommended nonfasting lipid testing as the new standard for lipid measurement, with fasting lipid testing considered for patients with triglyceride levels over 400 mg/dL (5 mmol/L). The statement also recommends that nonfasting triglyceride levels greater than or equal to 175 mg/dL (2 mmol/L) should be considered elevated as compared with the 150 mg/dL (1.7 mmol/L) traditionally used for fasting panels.

Recently published recommendations for nonfasting lipid testing for routine assessments are summarized in Table 1.^1,5–11

EFFECTS OF THE POSTPRANDIAL STATE ON LIPID LEVELS AND RISK ASSESSMENT

A common concern for clinicians who do not routinely order nonfasting lipid testing is the potential variability in lipid levels and interpretation of these values for treatment decisions. But in most circumstances the differences between fasting and nonfasting measurements are small and are not clinically relevant. Differences in high-density lipoprotein  cholesterol (HDL-C) are negligible; slightly lower levels are seen (up to −8 mg/dL) for nonfasting total cholesterol, LDL-C, and non-HDL-C compared with fasting levels; and differences are modest (up to 25 mg/dL higher) for triglycerides.⁵ These data should reassure clinicians who rely on lipid levels to guide management decisions.⁹

Cardiovascular risk assessment

Current algorithms for assessing risk of cardiovascular disease use total cholesterol and HDL-C, not triglycerides or LDL-C. Hence, eating has no effect on the risk estimates.

For clinicians who prefer an absolute lipid target for managing risk in patients on lipid-modifying therapy, a nonfasting LDL-C or non-HDL-C (or apolipoprotein B) may be used. The non-HDL-C level is a better risk marker than LDL-C, particularly in patients with low LDL-C or with triglyceride levels of 200 mg/dL or higher.¹² Treatment goals for non-HDL-C are 30 mg/dL higher than for LDL-C (fasting or nonfasting). In addition, for these patients with low LDL-C or high triglycerides, a new LDL-C calculation method has more consistent results for fasting and nonfasting values than the commonly used Friedewald calculation.¹²

 

 

EVIDENCE SUPPORTING NONFASTING LIPID TESTING

The adequacy of nonfasting lipid testing for general screening for cardiovascular disease has been verified in large prospective studies over the past several decades.^2,13,14 These studies evaluated cardiovascular event and mortality rates and found consistent associations of nonfasting lipid levels with cardiovascular disease. Studies that included both fasting and nonfasting patient populations found similar or occasionally even greater cardiovascular risk associations for nonfasting lipid measurements (including for LDL-C and triglycerides) compared with fasting lipid measurements.

The Emerging Risk Factors Collaboration¹⁴ reviewed the data from 68 studies in more than 300,000 people and found that the relationship between lipid levels and incident cardiovascular events was just as strong when nonfasting lipid values were used. In fact, at least 3 large statin trials reviewed (a total of 43,000 people) used nonfasting lipids.¹⁴

Genetic studies using mendelian randomization have also linked nonfasting triglyceride levels (and remnant cholesterol) to an increased risk of cardiovascular events and of death from any cause.^15,16

Therefore, the evidence overall suggests that nonfasting lipid measurements are acceptable with respect to risk assessment, and indeed may be preferred in most instances, especially in patients with an atherogenic metabolic milieu that may otherwise be masked by the fasting state.

OTHER BENEFITS OF NONFASTING LIPID TESTING

Nonfasting lipid panels are more economical and safer for certain groups, such as elderly or diabetic patients. A pilot study¹⁷ found that up to 27.1% of patients with diabetes reported experiencing a fasting-evoked hypoglycemic event en route to testing because of fasting for blood work. These events are vastly underreported and add to patient morbidity that can easily be avoided by adopting nonfasting lipid testing.

No study has assessed the cost-effectiveness of fasting vs nonfasting lipid testing. It is common for patients to present for their office appointment without having obtained a fasting lipid panel simply because they forgot to fast and were turned away by the laboratory. Thus, management decisions during the visit are often deferred, and patients must return to the laboratory and reschedule follow-up visits. This is inefficient, increases outpatient waiting times, and also potentially deprives others of access to needed care. Laboratory workflow can also suffer from an influx of early morning visits for fasting tests, decreasing system efficiency. Decreased efficiency in multiple levels of the healthcare system leads to increased costs, burden on healthcare providers, and decreased patient and physician satisfaction.

GETTING WITH THE GUIDELINES

The 2002 National Cholesterol Education Program expert panel report¹⁸ and the 2013 joint cholesterol guidelines of the American College of Cardiology and the American Heart Association⁹ both recommended that initial screening should involve fasting lipid testing, but they also allowed measuring nonfasting total cholesterol, HDL-C, and non-HDL-C.¹⁸ And internationally, there has been a shift in practice recommendations toward nonfasting lipids over the past 10 years (Table 1).

In 2014, the US Department of Veterans Affairs, the UK National Clinical Guideline Centre, and the Joint British Societies said that fasting is no longer needed for routine testing.¹⁰ In 2016, the European Atherosclerosis Society and the European Federation of Clinical Chemistry and Laboratory Medicine recommended nonfasting lipid testing as the standard of care and provided clinically useful cut points for both fasting and nonfasting lipid measurements.⁵

In most guidelines, the threshold for elevated nonfasting triglycerides was defined as 175 mg/dL (≥ 2 mmol/L) or greater, and this level has been validated prospectively in a large study of US women.^5,19 Repeat measurement of fasting triglycerides may be considered when nonfasting levels are greater than  400 mg/dL,⁵ although there is no consensus in the guidelines regarding when or if fasting triglycerides should be remeasured. (In the Danish experience,⁵ only 10% of patients have required repeat fasting values). In addition, the 2016 Canadian Hypertension Education Program guidelines⁶ removed fasting as a requirement. The 2016 Canadian Cardiovascular Society dyslipidemia guidelines⁷ reported that nonfasting lipid testing is a suitable alternative to fasting. Furthermore, the most recent revision of the European Society of Cardiology dyslipidemia guidelines⁸ acknowledged that nonfasting lipid panels are acceptable for screening and management of patients without severe hypertriglyceridemia or those with extremely low LDL-C levels.

LIMITATIONS OF THE EVIDENCE

To date, no study has assessed the predictive value of fasting vs nonfasting lipid measurements in the same individuals, and there have been no randomized outcomes trials or cost-effectiveness analyses. Ethnic variations in lipoproteins and nonfasting status also need to be investigated as nonfasting lipid testing becomes more universally accepted.

TAKE-HOME POINTS

• Robust evidence supports the routine use of nonfasting lipid testing, with fasting panels reserved potentially for patients with very high triglycerides and before starting treatment in those with genetic lipid disorders.
• For most patients, nonfasting tests are evidence-based, safe, valid, and convenient.
• More widespread adoption of this strategy by US healthcare providers would improve both quality of care and patient-clinician satisfaction.

Yes. The time has come to change the way we think about fasting before routine lipid testing. We now have robust evidence supporting the routine use of nonfasting lipid testing. Fasting lipid testing is rarely needed, but may be considered for patients with very high triglycerides or before starting treatment in patients with genetic lipid disorders. For most patients, nonfasting lipid testing is appropriate: it is evidence-based, safe, valid, and convenient. More widespread adoption of this strategy by US healthcare providers would improve quality of care and patient and clinician satisfaction.

GUIDELINES HAVE CHANGED

In 2014, the US Department of Veterans Affairs practice guidelines recommended nonfasting lipid testing for cardiovascular risk assessment.¹ Other recent clinical guidelines and expert consensus statements from Europe and Canada now also recommend nonfasting lipid testing for most routine clinical evaluations.

Physiologically, we spend most of our lives in the nonfasting state, yet fasting lipid testing was standard practice advocated by earlier clinical guidelines. The rationale for fasting before measuring lipids was to reduce variability and to allow for a more accurate derivation of the low-density lipoprotein cholesterol (LDL-C) concentration using the Friedewald formula. There was also concern that an increase in triglyceride concentrations after consuming a fatty meal would reduce the validity of the results. However, numerous studies have found that the increase in plasma triglycerides after normal food intake is much less than that during a fat-tolerance test, making this less of a concern for most patients.^2,3

In addition, recent studies suggest that postprandial effects do not diminish and may even strengthen the risk associations of lipids with cardiovascular disease, in particular for triglycerides.⁴ Moreover, in certain patients, such as those with metabolic syndrome, diabetes mellitus, or certain genetic abnormalities, fasting can mask abnormalities in triglyceride-rich lipid metabolism, which may only be detected when triglycerides are measured in a nonfasting state. Nonfasting measurements may identify patients with elevated residual risk despite optimal guideline-based treatment.

In 2016, a joint consensus statement of the European Atherosclerosis Society and the European Federation of Clinical Chemistry and Laboratory Medicine⁵ recommended nonfasting lipid testing as the new standard for lipid measurement, with fasting lipid testing considered for patients with triglyceride levels over 400 mg/dL (5 mmol/L). The statement also recommends that nonfasting triglyceride levels greater than or equal to 175 mg/dL (2 mmol/L) should be considered elevated as compared with the 150 mg/dL (1.7 mmol/L) traditionally used for fasting panels.

Recently published recommendations for nonfasting lipid testing for routine assessments are summarized in Table 1.^1,5–11

EFFECTS OF THE POSTPRANDIAL STATE ON LIPID LEVELS AND RISK ASSESSMENT

A common concern for clinicians who do not routinely order nonfasting lipid testing is the potential variability in lipid levels and interpretation of these values for treatment decisions. But in most circumstances the differences between fasting and nonfasting measurements are small and are not clinically relevant. Differences in high-density lipoprotein  cholesterol (HDL-C) are negligible; slightly lower levels are seen (up to −8 mg/dL) for nonfasting total cholesterol, LDL-C, and non-HDL-C compared with fasting levels; and differences are modest (up to 25 mg/dL higher) for triglycerides.⁵ These data should reassure clinicians who rely on lipid levels to guide management decisions.⁹

Cardiovascular risk assessment

Current algorithms for assessing risk of cardiovascular disease use total cholesterol and HDL-C, not triglycerides or LDL-C. Hence, eating has no effect on the risk estimates.

For clinicians who prefer an absolute lipid target for managing risk in patients on lipid-modifying therapy, a nonfasting LDL-C or non-HDL-C (or apolipoprotein B) may be used. The non-HDL-C level is a better risk marker than LDL-C, particularly in patients with low LDL-C or with triglyceride levels of 200 mg/dL or higher.¹² Treatment goals for non-HDL-C are 30 mg/dL higher than for LDL-C (fasting or nonfasting). In addition, for these patients with low LDL-C or high triglycerides, a new LDL-C calculation method has more consistent results for fasting and nonfasting values than the commonly used Friedewald calculation.¹²

 

 

EVIDENCE SUPPORTING NONFASTING LIPID TESTING

The adequacy of nonfasting lipid testing for general screening for cardiovascular disease has been verified in large prospective studies over the past several decades.^2,13,14 These studies evaluated cardiovascular event and mortality rates and found consistent associations of nonfasting lipid levels with cardiovascular disease. Studies that included both fasting and nonfasting patient populations found similar or occasionally even greater cardiovascular risk associations for nonfasting lipid measurements (including for LDL-C and triglycerides) compared with fasting lipid measurements.

The Emerging Risk Factors Collaboration¹⁴ reviewed the data from 68 studies in more than 300,000 people and found that the relationship between lipid levels and incident cardiovascular events was just as strong when nonfasting lipid values were used. In fact, at least 3 large statin trials reviewed (a total of 43,000 people) used nonfasting lipids.¹⁴

Genetic studies using mendelian randomization have also linked nonfasting triglyceride levels (and remnant cholesterol) to an increased risk of cardiovascular events and of death from any cause.^15,16

Therefore, the evidence overall suggests that nonfasting lipid measurements are acceptable with respect to risk assessment, and indeed may be preferred in most instances, especially in patients with an atherogenic metabolic milieu that may otherwise be masked by the fasting state.

OTHER BENEFITS OF NONFASTING LIPID TESTING

Nonfasting lipid panels are more economical and safer for certain groups, such as elderly or diabetic patients. A pilot study¹⁷ found that up to 27.1% of patients with diabetes reported experiencing a fasting-evoked hypoglycemic event en route to testing because of fasting for blood work. These events are vastly underreported and add to patient morbidity that can easily be avoided by adopting nonfasting lipid testing.

No study has assessed the cost-effectiveness of fasting vs nonfasting lipid testing. It is common for patients to present for their office appointment without having obtained a fasting lipid panel simply because they forgot to fast and were turned away by the laboratory. Thus, management decisions during the visit are often deferred, and patients must return to the laboratory and reschedule follow-up visits. This is inefficient, increases outpatient waiting times, and also potentially deprives others of access to needed care. Laboratory workflow can also suffer from an influx of early morning visits for fasting tests, decreasing system efficiency. Decreased efficiency in multiple levels of the healthcare system leads to increased costs, burden on healthcare providers, and decreased patient and physician satisfaction.

GETTING WITH THE GUIDELINES

The 2002 National Cholesterol Education Program expert panel report¹⁸ and the 2013 joint cholesterol guidelines of the American College of Cardiology and the American Heart Association⁹ both recommended that initial screening should involve fasting lipid testing, but they also allowed measuring nonfasting total cholesterol, HDL-C, and non-HDL-C.¹⁸ And internationally, there has been a shift in practice recommendations toward nonfasting lipids over the past 10 years (Table 1).

In 2014, the US Department of Veterans Affairs, the UK National Clinical Guideline Centre, and the Joint British Societies said that fasting is no longer needed for routine testing.¹⁰ In 2016, the European Atherosclerosis Society and the European Federation of Clinical Chemistry and Laboratory Medicine recommended nonfasting lipid testing as the standard of care and provided clinically useful cut points for both fasting and nonfasting lipid measurements.⁵

In most guidelines, the threshold for elevated nonfasting triglycerides was defined as 175 mg/dL (≥ 2 mmol/L) or greater, and this level has been validated prospectively in a large study of US women.^5,19 Repeat measurement of fasting triglycerides may be considered when nonfasting levels are greater than  400 mg/dL,⁵ although there is no consensus in the guidelines regarding when or if fasting triglycerides should be remeasured. (In the Danish experience,⁵ only 10% of patients have required repeat fasting values). In addition, the 2016 Canadian Hypertension Education Program guidelines⁶ removed fasting as a requirement. The 2016 Canadian Cardiovascular Society dyslipidemia guidelines⁷ reported that nonfasting lipid testing is a suitable alternative to fasting. Furthermore, the most recent revision of the European Society of Cardiology dyslipidemia guidelines⁸ acknowledged that nonfasting lipid panels are acceptable for screening and management of patients without severe hypertriglyceridemia or those with extremely low LDL-C levels.

LIMITATIONS OF THE EVIDENCE

To date, no study has assessed the predictive value of fasting vs nonfasting lipid measurements in the same individuals, and there have been no randomized outcomes trials or cost-effectiveness analyses. Ethnic variations in lipoproteins and nonfasting status also need to be investigated as nonfasting lipid testing becomes more universally accepted.

TAKE-HOME POINTS

• Robust evidence supports the routine use of nonfasting lipid testing, with fasting panels reserved potentially for patients with very high triglycerides and before starting treatment in those with genetic lipid disorders.
• For most patients, nonfasting tests are evidence-based, safe, valid, and convenient.
• More widespread adoption of this strategy by US healthcare providers would improve both quality of care and patient-clinician satisfaction.