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What best prevents exercise-induced bronchoconstriction for a child with asthma?
Inhaled short-acting beta-agonists (SABAs) are most effective in preventing exercise-induced bronchoconstriction, followed by inhaled mast cell stabilizers and anticholinergic agents (strength of recommendation [SOR]: A, multiple randomized control trials [RCTs]). Less evidence supports the use of leukotriene antagonists and inhaled corticosteroids, either individually or in combination (SOR: B). Underlying asthma, which commonly contributes to exercise-induced bronchoconstriction, should be diagnosed and controlled first (SOR: C).
Control the asthma and the need for pre-treatment often becomes unnecessary
Because truly isolated exercise-induced bronchoconstriction is uncommon in a nonasthmatic child, and because bronchospasm in a child during exercise more commonly indicates undiagnosed asthma, search for treatable asthma when a child wheezes with exercise. These children have sputum eosinophilia reflecting inflammation, and they are best served by addressing the underlying asthma with inhaled corticosteroids. Once the asthma is under control, their need for “the best pre-treatment” (a SABA) often becomes irrelevant. Ask the child whether he or she is having more shortness of breath and difficulty breathing after exercise than during exercise; this reveals those most likely to benefit from treatment.
Evidence summary
It is difficult to interpret studies on exercise-induced bronchoconstriction (the rather uncommon presence of exercise-induced bronchospasm in a nonasthmatic) and exercise-induced asthma (the more common situation of asthma worsened by exercise). Many studies include both types of patients.
A systematic review of 24 RCTs (of which 13 evaluated children) showed that SABAs, mast cell stabilizers, and anticholinergics provide a significant protective effect against exercise-induced bronchoconstriction with few adverse effects (the child subgroup analyses did not differ significantly from pooled results). Mast cell stabilizers were found less effective at attenuating bronchoconstriction than SABAs, with an average maximum decrease in the forced expiratory volume in 1 second (FEV1) of 11.9% compared with 4.6% for beta-agonists (child subgroup: weighted mean difference=7.3%; 95% confidence interval [CI], 3.9–10.7). Complete protection (defined in this study as maximum % decrease in FEV1 <15% post-exercise) and clinical protection (50% improvement over placebo) measures were included. Fewer children had complete protection (pooled: 66% vs 85%, odds ratio [OR]=0.3; 95% CI, 0.2–0.5) or clinical protection (pooled: 55% vs 77%, OR=0.4; 95% CI, 0.2–0.8).
Mast cell stabilizers were more effective than anticholinergic agents, with average maximum FEV1 decrease of 9.4% compared with 16.0% on anticholinergics (child subgroup: weighted mean difference=6.6%; 95% CI, 1.0–12.2). They also provided more individuals with complete protection (pooled: 73% vs 56%, OR=2.2; 95% CI, 1.3–3.7) and clinical protection (pooled: 73% vs 52%, OR=2.7; 95% CI, 1.1–6.4). Combining mast cell stabilizers with SABAs did not produce significant advantages in pulmonary function over SABAs alone. No significant subgroup differences were seen based on age, severity, or study quality.1
Another systematic review of 20 RCTs (15 studying children and 5 studying adults) with patients aged >6 years showed that 4 mg of nedocromil (Tilade) inhaled 15 to 60 minutes before exercise significantly reduced the severity and duration of exercise-induced bronchoconstriction compared with placebo. It had a greater effect on patients with severe exercise-induced bronchoconstriction (defined as an exercise-induced fall in lung function >30% from baseline).2
Eight RCTs (5 studying children) were included in a systematic review of patients aged >6 years that found no significant difference between nedocromil and cromoglycate with regards to decrease in FEV1, complete protection, clinical protection, or side effects.3
Leukotriene antagonists have been recommended on a trial basis with follow-up to evaluate the treatment response.4 Although there are several long-term studies of leukotriene antagonists for adults, few have studied children. A recent study assessed the effects of montelukast (Singulair) on 64 children with exercise-induced bronchoconstriction. After 8 weeks of treatment, the montelukast group showed significant improvements (compared with placebo) in asthma symptom scores (24.3±8.2 before vs 17.8±6.8 after 8 weeks of montelukast treatment, P<.05; vs 17.7±6.7 8 weeks after stopping treatment, P<.05), maximum percent fall in FEV1 after exercise (36.5±10.2% before vs 27.6±14.4% after 8 wks of treatment, P<.01; vs 26.7±19.4% 8 weeks after stopping treatment, P<.01), and time to recovery (41.8±8.1 min before vs 25.3±23.3 min after 8 weeks of treatment, P<.01; vs 27.7±26.5 min 8 weeks after stopping, P<.05).5
Therapies awaiting further study include a combination of budesonide (Pulmicort) and formoterol (Foradil), which is similar to the currently available preparation of fluticasone and salmeterol (Advair Diskus) but contains a long-acting beta-agonist with quicker onset. The phosphodiesterase-4 inhibitors roflumilast (Daxas) and cilomilast (Ariflo)—neither of which have been FDA-approved—and inhaled low-molecular-weight heparin have potential efficacy.6 Other options suggested for this problem—including inhaled furosemide, vitamin C, antihistamines, calcium channel blockers, and reduced dietary salt intake—need further study.7
Recommendations from others
Review articles on this topic suggest the following to prevent exercise-induced bronchoconstriction: controlling baseline asthma, avoiding known allergens, choosing appropriate sports with short bursts of activity, and selecting warm, humid environments for the activities.6-8 Some authorities recommend warm-up before athletic events to take advantage of a 30- to 90-minute refractory period. This can help prevent exercise-induced bronchoconstriction; however, effects vary considerably from person to person.7,8
The National Asthma Education and Prevention Program recommends prevention of exercise-induced bronchoconstriction by optimally controlling underlying asthma. If a patient remains symptomatic during exercise, you should review medication usage, understanding of dosage instructions, and administration technique before any changes in the treatment regimen.9
1. Spooner CH, Spooner GR, Rowe BH. Mast-cell stabilising agents to prevent exercise-induced bronchoconstriction. Cochrane Database Syst Rev 2003;(4):CD002307.
2. Spooner CH, Saunders LD, Rowe BH. Nedocromil sodium for preventing exercise-induced bronchoconstriction. Cochrane Database Syst Rev 2002;(1):CD001183.
3. Kelly K, Spooner CH, Rowe BH. Nedocromil sodium versus sodium cromoglycate for preventing exercise-induced bronchoconstriction in asthmatics. Cochrane Database Syst Rev 2000;(4):CD002731.
4. Moraes TJ, Selvadurai H. Management of exercise-induced bronchospasm in children: the role of leukotriene antagonists. Treat Respir Med 2004;3:9-15.
5. Kim JH, Lee SY, Kim HB, et al. Prolonged effect of montelukast in asthmatic children with exercise-induced bronchoconstriction. Pediatr Pulmonol 2005;39(2):162-166.
6. Storms WW. Asthma associated with exercise. Immunol Allergy Clin North Am 2005;25:31-43.
7. Sinha T, David AK. Recognition and management of exercise-induced bronchospasm. Am Fam Physician 2003;67(4):769-774, 675.
8. DYNAMED [database online]. Columbia, Mo: Dynamic Medical Information Systems, LLC;1995, continuous daily updating. Updated December 2, 2004.
9. Williams SG, Schmidt DK, Redd SC, Storms W. Key clinical activities for quality asthma care: recommendations of the National Asthma Education and Prevention Program. MMWR Recomm Rep 2003;52(RR-6):1-8.
Inhaled short-acting beta-agonists (SABAs) are most effective in preventing exercise-induced bronchoconstriction, followed by inhaled mast cell stabilizers and anticholinergic agents (strength of recommendation [SOR]: A, multiple randomized control trials [RCTs]). Less evidence supports the use of leukotriene antagonists and inhaled corticosteroids, either individually or in combination (SOR: B). Underlying asthma, which commonly contributes to exercise-induced bronchoconstriction, should be diagnosed and controlled first (SOR: C).
Control the asthma and the need for pre-treatment often becomes unnecessary
Because truly isolated exercise-induced bronchoconstriction is uncommon in a nonasthmatic child, and because bronchospasm in a child during exercise more commonly indicates undiagnosed asthma, search for treatable asthma when a child wheezes with exercise. These children have sputum eosinophilia reflecting inflammation, and they are best served by addressing the underlying asthma with inhaled corticosteroids. Once the asthma is under control, their need for “the best pre-treatment” (a SABA) often becomes irrelevant. Ask the child whether he or she is having more shortness of breath and difficulty breathing after exercise than during exercise; this reveals those most likely to benefit from treatment.
Evidence summary
It is difficult to interpret studies on exercise-induced bronchoconstriction (the rather uncommon presence of exercise-induced bronchospasm in a nonasthmatic) and exercise-induced asthma (the more common situation of asthma worsened by exercise). Many studies include both types of patients.
A systematic review of 24 RCTs (of which 13 evaluated children) showed that SABAs, mast cell stabilizers, and anticholinergics provide a significant protective effect against exercise-induced bronchoconstriction with few adverse effects (the child subgroup analyses did not differ significantly from pooled results). Mast cell stabilizers were found less effective at attenuating bronchoconstriction than SABAs, with an average maximum decrease in the forced expiratory volume in 1 second (FEV1) of 11.9% compared with 4.6% for beta-agonists (child subgroup: weighted mean difference=7.3%; 95% confidence interval [CI], 3.9–10.7). Complete protection (defined in this study as maximum % decrease in FEV1 <15% post-exercise) and clinical protection (50% improvement over placebo) measures were included. Fewer children had complete protection (pooled: 66% vs 85%, odds ratio [OR]=0.3; 95% CI, 0.2–0.5) or clinical protection (pooled: 55% vs 77%, OR=0.4; 95% CI, 0.2–0.8).
Mast cell stabilizers were more effective than anticholinergic agents, with average maximum FEV1 decrease of 9.4% compared with 16.0% on anticholinergics (child subgroup: weighted mean difference=6.6%; 95% CI, 1.0–12.2). They also provided more individuals with complete protection (pooled: 73% vs 56%, OR=2.2; 95% CI, 1.3–3.7) and clinical protection (pooled: 73% vs 52%, OR=2.7; 95% CI, 1.1–6.4). Combining mast cell stabilizers with SABAs did not produce significant advantages in pulmonary function over SABAs alone. No significant subgroup differences were seen based on age, severity, or study quality.1
Another systematic review of 20 RCTs (15 studying children and 5 studying adults) with patients aged >6 years showed that 4 mg of nedocromil (Tilade) inhaled 15 to 60 minutes before exercise significantly reduced the severity and duration of exercise-induced bronchoconstriction compared with placebo. It had a greater effect on patients with severe exercise-induced bronchoconstriction (defined as an exercise-induced fall in lung function >30% from baseline).2
Eight RCTs (5 studying children) were included in a systematic review of patients aged >6 years that found no significant difference between nedocromil and cromoglycate with regards to decrease in FEV1, complete protection, clinical protection, or side effects.3
Leukotriene antagonists have been recommended on a trial basis with follow-up to evaluate the treatment response.4 Although there are several long-term studies of leukotriene antagonists for adults, few have studied children. A recent study assessed the effects of montelukast (Singulair) on 64 children with exercise-induced bronchoconstriction. After 8 weeks of treatment, the montelukast group showed significant improvements (compared with placebo) in asthma symptom scores (24.3±8.2 before vs 17.8±6.8 after 8 weeks of montelukast treatment, P<.05; vs 17.7±6.7 8 weeks after stopping treatment, P<.05), maximum percent fall in FEV1 after exercise (36.5±10.2% before vs 27.6±14.4% after 8 wks of treatment, P<.01; vs 26.7±19.4% 8 weeks after stopping treatment, P<.01), and time to recovery (41.8±8.1 min before vs 25.3±23.3 min after 8 weeks of treatment, P<.01; vs 27.7±26.5 min 8 weeks after stopping, P<.05).5
Therapies awaiting further study include a combination of budesonide (Pulmicort) and formoterol (Foradil), which is similar to the currently available preparation of fluticasone and salmeterol (Advair Diskus) but contains a long-acting beta-agonist with quicker onset. The phosphodiesterase-4 inhibitors roflumilast (Daxas) and cilomilast (Ariflo)—neither of which have been FDA-approved—and inhaled low-molecular-weight heparin have potential efficacy.6 Other options suggested for this problem—including inhaled furosemide, vitamin C, antihistamines, calcium channel blockers, and reduced dietary salt intake—need further study.7
Recommendations from others
Review articles on this topic suggest the following to prevent exercise-induced bronchoconstriction: controlling baseline asthma, avoiding known allergens, choosing appropriate sports with short bursts of activity, and selecting warm, humid environments for the activities.6-8 Some authorities recommend warm-up before athletic events to take advantage of a 30- to 90-minute refractory period. This can help prevent exercise-induced bronchoconstriction; however, effects vary considerably from person to person.7,8
The National Asthma Education and Prevention Program recommends prevention of exercise-induced bronchoconstriction by optimally controlling underlying asthma. If a patient remains symptomatic during exercise, you should review medication usage, understanding of dosage instructions, and administration technique before any changes in the treatment regimen.9
Inhaled short-acting beta-agonists (SABAs) are most effective in preventing exercise-induced bronchoconstriction, followed by inhaled mast cell stabilizers and anticholinergic agents (strength of recommendation [SOR]: A, multiple randomized control trials [RCTs]). Less evidence supports the use of leukotriene antagonists and inhaled corticosteroids, either individually or in combination (SOR: B). Underlying asthma, which commonly contributes to exercise-induced bronchoconstriction, should be diagnosed and controlled first (SOR: C).
Control the asthma and the need for pre-treatment often becomes unnecessary
Because truly isolated exercise-induced bronchoconstriction is uncommon in a nonasthmatic child, and because bronchospasm in a child during exercise more commonly indicates undiagnosed asthma, search for treatable asthma when a child wheezes with exercise. These children have sputum eosinophilia reflecting inflammation, and they are best served by addressing the underlying asthma with inhaled corticosteroids. Once the asthma is under control, their need for “the best pre-treatment” (a SABA) often becomes irrelevant. Ask the child whether he or she is having more shortness of breath and difficulty breathing after exercise than during exercise; this reveals those most likely to benefit from treatment.
Evidence summary
It is difficult to interpret studies on exercise-induced bronchoconstriction (the rather uncommon presence of exercise-induced bronchospasm in a nonasthmatic) and exercise-induced asthma (the more common situation of asthma worsened by exercise). Many studies include both types of patients.
A systematic review of 24 RCTs (of which 13 evaluated children) showed that SABAs, mast cell stabilizers, and anticholinergics provide a significant protective effect against exercise-induced bronchoconstriction with few adverse effects (the child subgroup analyses did not differ significantly from pooled results). Mast cell stabilizers were found less effective at attenuating bronchoconstriction than SABAs, with an average maximum decrease in the forced expiratory volume in 1 second (FEV1) of 11.9% compared with 4.6% for beta-agonists (child subgroup: weighted mean difference=7.3%; 95% confidence interval [CI], 3.9–10.7). Complete protection (defined in this study as maximum % decrease in FEV1 <15% post-exercise) and clinical protection (50% improvement over placebo) measures were included. Fewer children had complete protection (pooled: 66% vs 85%, odds ratio [OR]=0.3; 95% CI, 0.2–0.5) or clinical protection (pooled: 55% vs 77%, OR=0.4; 95% CI, 0.2–0.8).
Mast cell stabilizers were more effective than anticholinergic agents, with average maximum FEV1 decrease of 9.4% compared with 16.0% on anticholinergics (child subgroup: weighted mean difference=6.6%; 95% CI, 1.0–12.2). They also provided more individuals with complete protection (pooled: 73% vs 56%, OR=2.2; 95% CI, 1.3–3.7) and clinical protection (pooled: 73% vs 52%, OR=2.7; 95% CI, 1.1–6.4). Combining mast cell stabilizers with SABAs did not produce significant advantages in pulmonary function over SABAs alone. No significant subgroup differences were seen based on age, severity, or study quality.1
Another systematic review of 20 RCTs (15 studying children and 5 studying adults) with patients aged >6 years showed that 4 mg of nedocromil (Tilade) inhaled 15 to 60 minutes before exercise significantly reduced the severity and duration of exercise-induced bronchoconstriction compared with placebo. It had a greater effect on patients with severe exercise-induced bronchoconstriction (defined as an exercise-induced fall in lung function >30% from baseline).2
Eight RCTs (5 studying children) were included in a systematic review of patients aged >6 years that found no significant difference between nedocromil and cromoglycate with regards to decrease in FEV1, complete protection, clinical protection, or side effects.3
Leukotriene antagonists have been recommended on a trial basis with follow-up to evaluate the treatment response.4 Although there are several long-term studies of leukotriene antagonists for adults, few have studied children. A recent study assessed the effects of montelukast (Singulair) on 64 children with exercise-induced bronchoconstriction. After 8 weeks of treatment, the montelukast group showed significant improvements (compared with placebo) in asthma symptom scores (24.3±8.2 before vs 17.8±6.8 after 8 weeks of montelukast treatment, P<.05; vs 17.7±6.7 8 weeks after stopping treatment, P<.05), maximum percent fall in FEV1 after exercise (36.5±10.2% before vs 27.6±14.4% after 8 wks of treatment, P<.01; vs 26.7±19.4% 8 weeks after stopping treatment, P<.01), and time to recovery (41.8±8.1 min before vs 25.3±23.3 min after 8 weeks of treatment, P<.01; vs 27.7±26.5 min 8 weeks after stopping, P<.05).5
Therapies awaiting further study include a combination of budesonide (Pulmicort) and formoterol (Foradil), which is similar to the currently available preparation of fluticasone and salmeterol (Advair Diskus) but contains a long-acting beta-agonist with quicker onset. The phosphodiesterase-4 inhibitors roflumilast (Daxas) and cilomilast (Ariflo)—neither of which have been FDA-approved—and inhaled low-molecular-weight heparin have potential efficacy.6 Other options suggested for this problem—including inhaled furosemide, vitamin C, antihistamines, calcium channel blockers, and reduced dietary salt intake—need further study.7
Recommendations from others
Review articles on this topic suggest the following to prevent exercise-induced bronchoconstriction: controlling baseline asthma, avoiding known allergens, choosing appropriate sports with short bursts of activity, and selecting warm, humid environments for the activities.6-8 Some authorities recommend warm-up before athletic events to take advantage of a 30- to 90-minute refractory period. This can help prevent exercise-induced bronchoconstriction; however, effects vary considerably from person to person.7,8
The National Asthma Education and Prevention Program recommends prevention of exercise-induced bronchoconstriction by optimally controlling underlying asthma. If a patient remains symptomatic during exercise, you should review medication usage, understanding of dosage instructions, and administration technique before any changes in the treatment regimen.9
1. Spooner CH, Spooner GR, Rowe BH. Mast-cell stabilising agents to prevent exercise-induced bronchoconstriction. Cochrane Database Syst Rev 2003;(4):CD002307.
2. Spooner CH, Saunders LD, Rowe BH. Nedocromil sodium for preventing exercise-induced bronchoconstriction. Cochrane Database Syst Rev 2002;(1):CD001183.
3. Kelly K, Spooner CH, Rowe BH. Nedocromil sodium versus sodium cromoglycate for preventing exercise-induced bronchoconstriction in asthmatics. Cochrane Database Syst Rev 2000;(4):CD002731.
4. Moraes TJ, Selvadurai H. Management of exercise-induced bronchospasm in children: the role of leukotriene antagonists. Treat Respir Med 2004;3:9-15.
5. Kim JH, Lee SY, Kim HB, et al. Prolonged effect of montelukast in asthmatic children with exercise-induced bronchoconstriction. Pediatr Pulmonol 2005;39(2):162-166.
6. Storms WW. Asthma associated with exercise. Immunol Allergy Clin North Am 2005;25:31-43.
7. Sinha T, David AK. Recognition and management of exercise-induced bronchospasm. Am Fam Physician 2003;67(4):769-774, 675.
8. DYNAMED [database online]. Columbia, Mo: Dynamic Medical Information Systems, LLC;1995, continuous daily updating. Updated December 2, 2004.
9. Williams SG, Schmidt DK, Redd SC, Storms W. Key clinical activities for quality asthma care: recommendations of the National Asthma Education and Prevention Program. MMWR Recomm Rep 2003;52(RR-6):1-8.
1. Spooner CH, Spooner GR, Rowe BH. Mast-cell stabilising agents to prevent exercise-induced bronchoconstriction. Cochrane Database Syst Rev 2003;(4):CD002307.
2. Spooner CH, Saunders LD, Rowe BH. Nedocromil sodium for preventing exercise-induced bronchoconstriction. Cochrane Database Syst Rev 2002;(1):CD001183.
3. Kelly K, Spooner CH, Rowe BH. Nedocromil sodium versus sodium cromoglycate for preventing exercise-induced bronchoconstriction in asthmatics. Cochrane Database Syst Rev 2000;(4):CD002731.
4. Moraes TJ, Selvadurai H. Management of exercise-induced bronchospasm in children: the role of leukotriene antagonists. Treat Respir Med 2004;3:9-15.
5. Kim JH, Lee SY, Kim HB, et al. Prolonged effect of montelukast in asthmatic children with exercise-induced bronchoconstriction. Pediatr Pulmonol 2005;39(2):162-166.
6. Storms WW. Asthma associated with exercise. Immunol Allergy Clin North Am 2005;25:31-43.
7. Sinha T, David AK. Recognition and management of exercise-induced bronchospasm. Am Fam Physician 2003;67(4):769-774, 675.
8. DYNAMED [database online]. Columbia, Mo: Dynamic Medical Information Systems, LLC;1995, continuous daily updating. Updated December 2, 2004.
9. Williams SG, Schmidt DK, Redd SC, Storms W. Key clinical activities for quality asthma care: recommendations of the National Asthma Education and Prevention Program. MMWR Recomm Rep 2003;52(RR-6):1-8.
Evidence-based answers from the Family Physicians Inquiries Network
When should we treat isolated high triglycerides?
No evidence exists that treating isolated high triglyceride levels in the absence of other risk factors prevents coronary events. Although elevated triglycerides in some studies correlates with coronary events, the association weakens when controlled for factors such as diabetes, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, body mass index, and other cardiac risk factors.
Coincident lowering of triglycerides, while treating other dyslipidemias (such as high LDL and low HDL), can contribute to decreasing coronary events (strength of recommendation [SOR]: A, based randomized controlled trials). Treating triglyceride levels over 500 to 1000 mg/dL may reduce the risk of pancreatitis (SOR: C, expert opinion).
Evidence summary
Truly isolated hypertriglyceridemia is rare. To date, no good trials directly address the effect of reducing truly isolated hypertriglyceridemia on cardiovascular morbidity or mortality. High triglycerides are usually accompanied by other features of the “metabolic syndrome” (low HDL, high LDL, insulin resistance, diabetes, hypertension, and obesity), making it almost impossible to look at these in isolation or attribute risk to a specific component.1
Whether high triglyceride levels pose risk in the true absence of these other metabolic factors is controversial. One meta-analysis of 17 population-based prospective studies of triglycerides and cardiovascular disease (including 57,000 patients) showed high triglyceride levels to be predictive of cardiac events, even when adjusted for HDL and other risk factors (age, total and LDL cholesterol, smoking, body mass index, and blood pressure).2 After adjusting for these other risk factors, the authors found an increased risk for all cardiac endpoints (myocardial infarction, death, etc) of 14% for men and 32% for women (Men: relative risk [RR]=1.14; 95% confidence interval [CI], 1.05–1.28; Women: RR=1.37; 95% CI, 1.13–1.66).
Another meta-analysis of 3 prospective intervention trials with 15,880 enrolled subjects found that triglyceride levels did not provide any clinically meaningful information about risk beyond that provided by other cholesterol subfractions.3
In treatment trials, the most impressive risk reductions come from the groups who fit the lipid triad of low HDL, high LDL, and high triglycerides. Low levels of HDL appear to interact with hypertriglyceridemia to increase coronary risk, and all studies showing improved outcomes have simultaneously increased HDL while lowering triglycerides.4-6 In 3 large-scale prospective, placebo-controlled trials (the Helsinki Heart Study, a primary prevention study, and the VA-HIT and Bezafibrate Infarction Prevention trials, both secondary prevention studies), lowering triglycerides and raising HDL concurrently improved outcomes.5 Successful dietary and medical interventions, especially with statins and fibrates, improved overall lipid profiles—not just triglyceride levels.
Accordingly, elevated triglycerides should prompt providers to rigorously identify these other risk factors for cardiovascular morbidity and mortality, which may not be immediately obvious. In the absence of such other factors, no evidence exists to guide therapy. Expert opinion7,8 supported by epidemiologic evidence9 suggests that patients with triglyceride levels of 500 to 1000 mg/dL may have an increased risk of pancreatitis. Accordingly, providers should consider therapy to lower triglycerides to less than 500 in these patients, regardless of accompanying risk factors.
Recommendations from others
The American College of Physicians, the European Society of Cardiology, and the US Preventive Services Task Force do not recommend screening for hypertriglyceridemia. Clinical guidelines of the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III), American Heart Association/American College of Cardiology, and the American Diabetes Association all support LDL lowering as the primary target of therapy based on the patients risk profile.10 NCEP/ATP III has identified triglyceride levels of <150 as normal, 150–199 as borderline high, 200–499 as high, and 500 as very high.7
A patient with high triglycerides should prompt a search for components of the “meta-bolic syndrome” and secondary causes, including high dietary fat, high alcohol intake, drugs (steroids, beta-blockers, high-estrogen oral contraceptives), medical conditions (hypothyroidism, nephrosis, renal failure, liver disease, Cushing disease, and lupus), and rare familial dyslipidemias.7,10,11
Elevated triglyceride level? First look at the big picture
Donald C. Spencer, MD, MBA
University of North Carolina at Chapel Hill
Observing the pendulum swings of medical knowledge over time is one of the hallmarks of the experienced family physician. As a student, I was warned of the evils of high triglycerides, only to enter a period in the 1970s and 1980s of therapeutic nihilism when triglycerides were not thought to be an independent coronary risk factor.
As outlined here, the pendulum is moving toward a more complex consideration of the effect of triglycerides on heart disease—and what we should do about it. Our patients are better served when we focus on total coronary risk rather than a specific level of triglycerides. An elevated triglyceride level leads me first to look at the glucose. I have found several poorly controlled or even new diabetic patients this way. By then following the adage to “major on the majors and minor on the minors,” I have focused on glucose and LDL control to the benefit of my patients.
1. Forrester JS. Triglycerides: risk factor or fellow traveler? Curr Opin Cardiol 2001;16:261-264.
2. Austin MA, Hokanson JE, Edwards KL. Hypertriglyceridemia as a cardiovascular risk factor. Am J Cardiol 1998;81(4A):7B-12B.
3. Avins AL, Neuhaus JM. Do triglycerides provide meaningful information about heart disease risk? Arch Intern Med 2000;160:1937-1944.
4. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999;341:410-418.
5. Secondary prevention by raising HDL cholesterol and reducing triglyceride in patients with coronary disease: the Bezafibrate Infarction Prevention (BIP) Study. Circulation 2000;102:21-27.
6. Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study a randomised study. Lancet 2001;357:905-910.
7. Expert Panel on Detection. Evaluation and. Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP). Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.
8. Chait A, Brunzell JD. Chylomicronemia syndrome. Adv Intern Med 1992;37:249-273.
9. Athyros VG, Giouleme OI, Nikolaidis NL, et al. Long-term follow-up of patients with acute hypertriglyceridemia-induced pancreatitis. J Clin Gastroenterol 2002;34:472-475.
10. Breuer HW. Hypertriglyceridemia: a review of clinical relevance and treatment options: focus on cerivastatin. Curr Med Res Opin 2001;17:60-73.
11. Malloy MJ, Kane JP. A risk factor for atherosclerosis: triglyceride-rich lipoproteins. Adv Intern Med 2001;47:111-136.
No evidence exists that treating isolated high triglyceride levels in the absence of other risk factors prevents coronary events. Although elevated triglycerides in some studies correlates with coronary events, the association weakens when controlled for factors such as diabetes, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, body mass index, and other cardiac risk factors.
Coincident lowering of triglycerides, while treating other dyslipidemias (such as high LDL and low HDL), can contribute to decreasing coronary events (strength of recommendation [SOR]: A, based randomized controlled trials). Treating triglyceride levels over 500 to 1000 mg/dL may reduce the risk of pancreatitis (SOR: C, expert opinion).
Evidence summary
Truly isolated hypertriglyceridemia is rare. To date, no good trials directly address the effect of reducing truly isolated hypertriglyceridemia on cardiovascular morbidity or mortality. High triglycerides are usually accompanied by other features of the “metabolic syndrome” (low HDL, high LDL, insulin resistance, diabetes, hypertension, and obesity), making it almost impossible to look at these in isolation or attribute risk to a specific component.1
Whether high triglyceride levels pose risk in the true absence of these other metabolic factors is controversial. One meta-analysis of 17 population-based prospective studies of triglycerides and cardiovascular disease (including 57,000 patients) showed high triglyceride levels to be predictive of cardiac events, even when adjusted for HDL and other risk factors (age, total and LDL cholesterol, smoking, body mass index, and blood pressure).2 After adjusting for these other risk factors, the authors found an increased risk for all cardiac endpoints (myocardial infarction, death, etc) of 14% for men and 32% for women (Men: relative risk [RR]=1.14; 95% confidence interval [CI], 1.05–1.28; Women: RR=1.37; 95% CI, 1.13–1.66).
Another meta-analysis of 3 prospective intervention trials with 15,880 enrolled subjects found that triglyceride levels did not provide any clinically meaningful information about risk beyond that provided by other cholesterol subfractions.3
In treatment trials, the most impressive risk reductions come from the groups who fit the lipid triad of low HDL, high LDL, and high triglycerides. Low levels of HDL appear to interact with hypertriglyceridemia to increase coronary risk, and all studies showing improved outcomes have simultaneously increased HDL while lowering triglycerides.4-6 In 3 large-scale prospective, placebo-controlled trials (the Helsinki Heart Study, a primary prevention study, and the VA-HIT and Bezafibrate Infarction Prevention trials, both secondary prevention studies), lowering triglycerides and raising HDL concurrently improved outcomes.5 Successful dietary and medical interventions, especially with statins and fibrates, improved overall lipid profiles—not just triglyceride levels.
Accordingly, elevated triglycerides should prompt providers to rigorously identify these other risk factors for cardiovascular morbidity and mortality, which may not be immediately obvious. In the absence of such other factors, no evidence exists to guide therapy. Expert opinion7,8 supported by epidemiologic evidence9 suggests that patients with triglyceride levels of 500 to 1000 mg/dL may have an increased risk of pancreatitis. Accordingly, providers should consider therapy to lower triglycerides to less than 500 in these patients, regardless of accompanying risk factors.
Recommendations from others
The American College of Physicians, the European Society of Cardiology, and the US Preventive Services Task Force do not recommend screening for hypertriglyceridemia. Clinical guidelines of the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III), American Heart Association/American College of Cardiology, and the American Diabetes Association all support LDL lowering as the primary target of therapy based on the patients risk profile.10 NCEP/ATP III has identified triglyceride levels of <150 as normal, 150–199 as borderline high, 200–499 as high, and 500 as very high.7
A patient with high triglycerides should prompt a search for components of the “meta-bolic syndrome” and secondary causes, including high dietary fat, high alcohol intake, drugs (steroids, beta-blockers, high-estrogen oral contraceptives), medical conditions (hypothyroidism, nephrosis, renal failure, liver disease, Cushing disease, and lupus), and rare familial dyslipidemias.7,10,11
Elevated triglyceride level? First look at the big picture
Donald C. Spencer, MD, MBA
University of North Carolina at Chapel Hill
Observing the pendulum swings of medical knowledge over time is one of the hallmarks of the experienced family physician. As a student, I was warned of the evils of high triglycerides, only to enter a period in the 1970s and 1980s of therapeutic nihilism when triglycerides were not thought to be an independent coronary risk factor.
As outlined here, the pendulum is moving toward a more complex consideration of the effect of triglycerides on heart disease—and what we should do about it. Our patients are better served when we focus on total coronary risk rather than a specific level of triglycerides. An elevated triglyceride level leads me first to look at the glucose. I have found several poorly controlled or even new diabetic patients this way. By then following the adage to “major on the majors and minor on the minors,” I have focused on glucose and LDL control to the benefit of my patients.
No evidence exists that treating isolated high triglyceride levels in the absence of other risk factors prevents coronary events. Although elevated triglycerides in some studies correlates with coronary events, the association weakens when controlled for factors such as diabetes, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, body mass index, and other cardiac risk factors.
Coincident lowering of triglycerides, while treating other dyslipidemias (such as high LDL and low HDL), can contribute to decreasing coronary events (strength of recommendation [SOR]: A, based randomized controlled trials). Treating triglyceride levels over 500 to 1000 mg/dL may reduce the risk of pancreatitis (SOR: C, expert opinion).
Evidence summary
Truly isolated hypertriglyceridemia is rare. To date, no good trials directly address the effect of reducing truly isolated hypertriglyceridemia on cardiovascular morbidity or mortality. High triglycerides are usually accompanied by other features of the “metabolic syndrome” (low HDL, high LDL, insulin resistance, diabetes, hypertension, and obesity), making it almost impossible to look at these in isolation or attribute risk to a specific component.1
Whether high triglyceride levels pose risk in the true absence of these other metabolic factors is controversial. One meta-analysis of 17 population-based prospective studies of triglycerides and cardiovascular disease (including 57,000 patients) showed high triglyceride levels to be predictive of cardiac events, even when adjusted for HDL and other risk factors (age, total and LDL cholesterol, smoking, body mass index, and blood pressure).2 After adjusting for these other risk factors, the authors found an increased risk for all cardiac endpoints (myocardial infarction, death, etc) of 14% for men and 32% for women (Men: relative risk [RR]=1.14; 95% confidence interval [CI], 1.05–1.28; Women: RR=1.37; 95% CI, 1.13–1.66).
Another meta-analysis of 3 prospective intervention trials with 15,880 enrolled subjects found that triglyceride levels did not provide any clinically meaningful information about risk beyond that provided by other cholesterol subfractions.3
In treatment trials, the most impressive risk reductions come from the groups who fit the lipid triad of low HDL, high LDL, and high triglycerides. Low levels of HDL appear to interact with hypertriglyceridemia to increase coronary risk, and all studies showing improved outcomes have simultaneously increased HDL while lowering triglycerides.4-6 In 3 large-scale prospective, placebo-controlled trials (the Helsinki Heart Study, a primary prevention study, and the VA-HIT and Bezafibrate Infarction Prevention trials, both secondary prevention studies), lowering triglycerides and raising HDL concurrently improved outcomes.5 Successful dietary and medical interventions, especially with statins and fibrates, improved overall lipid profiles—not just triglyceride levels.
Accordingly, elevated triglycerides should prompt providers to rigorously identify these other risk factors for cardiovascular morbidity and mortality, which may not be immediately obvious. In the absence of such other factors, no evidence exists to guide therapy. Expert opinion7,8 supported by epidemiologic evidence9 suggests that patients with triglyceride levels of 500 to 1000 mg/dL may have an increased risk of pancreatitis. Accordingly, providers should consider therapy to lower triglycerides to less than 500 in these patients, regardless of accompanying risk factors.
Recommendations from others
The American College of Physicians, the European Society of Cardiology, and the US Preventive Services Task Force do not recommend screening for hypertriglyceridemia. Clinical guidelines of the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III), American Heart Association/American College of Cardiology, and the American Diabetes Association all support LDL lowering as the primary target of therapy based on the patients risk profile.10 NCEP/ATP III has identified triglyceride levels of <150 as normal, 150–199 as borderline high, 200–499 as high, and 500 as very high.7
A patient with high triglycerides should prompt a search for components of the “meta-bolic syndrome” and secondary causes, including high dietary fat, high alcohol intake, drugs (steroids, beta-blockers, high-estrogen oral contraceptives), medical conditions (hypothyroidism, nephrosis, renal failure, liver disease, Cushing disease, and lupus), and rare familial dyslipidemias.7,10,11
Elevated triglyceride level? First look at the big picture
Donald C. Spencer, MD, MBA
University of North Carolina at Chapel Hill
Observing the pendulum swings of medical knowledge over time is one of the hallmarks of the experienced family physician. As a student, I was warned of the evils of high triglycerides, only to enter a period in the 1970s and 1980s of therapeutic nihilism when triglycerides were not thought to be an independent coronary risk factor.
As outlined here, the pendulum is moving toward a more complex consideration of the effect of triglycerides on heart disease—and what we should do about it. Our patients are better served when we focus on total coronary risk rather than a specific level of triglycerides. An elevated triglyceride level leads me first to look at the glucose. I have found several poorly controlled or even new diabetic patients this way. By then following the adage to “major on the majors and minor on the minors,” I have focused on glucose and LDL control to the benefit of my patients.
1. Forrester JS. Triglycerides: risk factor or fellow traveler? Curr Opin Cardiol 2001;16:261-264.
2. Austin MA, Hokanson JE, Edwards KL. Hypertriglyceridemia as a cardiovascular risk factor. Am J Cardiol 1998;81(4A):7B-12B.
3. Avins AL, Neuhaus JM. Do triglycerides provide meaningful information about heart disease risk? Arch Intern Med 2000;160:1937-1944.
4. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999;341:410-418.
5. Secondary prevention by raising HDL cholesterol and reducing triglyceride in patients with coronary disease: the Bezafibrate Infarction Prevention (BIP) Study. Circulation 2000;102:21-27.
6. Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study a randomised study. Lancet 2001;357:905-910.
7. Expert Panel on Detection. Evaluation and. Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP). Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.
8. Chait A, Brunzell JD. Chylomicronemia syndrome. Adv Intern Med 1992;37:249-273.
9. Athyros VG, Giouleme OI, Nikolaidis NL, et al. Long-term follow-up of patients with acute hypertriglyceridemia-induced pancreatitis. J Clin Gastroenterol 2002;34:472-475.
10. Breuer HW. Hypertriglyceridemia: a review of clinical relevance and treatment options: focus on cerivastatin. Curr Med Res Opin 2001;17:60-73.
11. Malloy MJ, Kane JP. A risk factor for atherosclerosis: triglyceride-rich lipoproteins. Adv Intern Med 2001;47:111-136.
1. Forrester JS. Triglycerides: risk factor or fellow traveler? Curr Opin Cardiol 2001;16:261-264.
2. Austin MA, Hokanson JE, Edwards KL. Hypertriglyceridemia as a cardiovascular risk factor. Am J Cardiol 1998;81(4A):7B-12B.
3. Avins AL, Neuhaus JM. Do triglycerides provide meaningful information about heart disease risk? Arch Intern Med 2000;160:1937-1944.
4. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999;341:410-418.
5. Secondary prevention by raising HDL cholesterol and reducing triglyceride in patients with coronary disease: the Bezafibrate Infarction Prevention (BIP) Study. Circulation 2000;102:21-27.
6. Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study a randomised study. Lancet 2001;357:905-910.
7. Expert Panel on Detection. Evaluation and. Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP). Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.
8. Chait A, Brunzell JD. Chylomicronemia syndrome. Adv Intern Med 1992;37:249-273.
9. Athyros VG, Giouleme OI, Nikolaidis NL, et al. Long-term follow-up of patients with acute hypertriglyceridemia-induced pancreatitis. J Clin Gastroenterol 2002;34:472-475.
10. Breuer HW. Hypertriglyceridemia: a review of clinical relevance and treatment options: focus on cerivastatin. Curr Med Res Opin 2001;17:60-73.
11. Malloy MJ, Kane JP. A risk factor for atherosclerosis: triglyceride-rich lipoproteins. Adv Intern Med 2001;47:111-136.
Evidence-based answers from the Family Physicians Inquiries Network