What is the best surveillance for hepatocellular carcinoma in chronic carriers of hepatitis B?

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What is the best surveillance for hepatocellular carcinoma in chronic carriers of hepatitis B?
EVIDENCE-BASED ANSWER

Screening patients with chronic hepatitis B infection (HBsAg+) for hepatocellular carcinoma by alpha-fetoprotein (AFP) or by AFP plus ultrasound (AFP/US) detects hepatocellular carcinoma tumors at earlier stages and increases resection rates (strength of recommendation [SOR]: B, based on a systematic review of fair-quality randomized controlled trials). It is unclear whether screening with AFP or AFP/US improves disease-specific or all-cause mortality (SOR: B).

CLINICAL COMMENTARY

Offer screening to all with chronic hepatitis B infection, but stratify risk for HCC first
Michael Mendoza, MD, MPH
ACCESS Community Health Network and Department of Family Medicine, University of Chicago

Because no mortality benefit to screening for hepatocellular carcinoma has been shown, we should give added consideration to how we counsel our patients before offering screening, particularly since positive screening results can lead to further invasive studies. An important consideration for me is whether a patient has, or is at risk, for cirrhosis, because the incidence of hepatocellular carcinoma is higher if cirrhosis is present. Screening for coinfection with hepatitis C or a history of alcohol abuse becomes especially critical in this situation. Biochemical evidence of chronic active liver inflammation, whatever the cause, should also be an important factor in deciding whether to screen. While I still offer screening to all patients with chronic hepatitis B infection, it helps to have stratified a patient’s underlying risk for hepatocellular carcinoma first and counseling him or her accordingly.

 

Evidence summary

Many serum markers and screening methods have been proposed to detect hepatocellular carcinoma at a treatable stage, but only 2—AFP and US—are in clinical use.1

A Cochrane systematic review on screening for hepatocellular carcinoma in the HBsAg+ population was published in 2003 and updated May 2004.2 Our literature search did not find any subsequent relevant trials. The Cochrane review included 2 randomized control trials. The larger trial was performed in Shanghai, China and included 18,816 HBsAg+ patients aged 35 to 55 years.3 Subjects were recruited from their place of employment and randomized to either AFP/US every 6 months (n=9373) or to no screening (n=9443).

Fifty-one hepatocellular carcinomas were diagnosed in the control group and 86 in screened group. Screened subjects had a significantly higher percentage of tumors that were less than 5 cm at the time of diagnosis and a higher number of patients who underwent resection. While the 5-year survival for those with hepatocellular carcinoma in the screened group was higher, the disease-specific mortality rate was not statistically different between the 2 groups.

Additional data became available in 2002. The original study authors claimed the new data showed a statistically significant disease-specific mortality rate ratio of 0.63, favoring the screened group.4 However, the Cochrane group performed their own analysis on the same data and determined that no statistically significant difference in the disease-specific mortality rates existed between the 2 groups.2 Therefore, it is not clear whether these new data definitively demonstrate that screening provides any benefit.

 

 

 

The other randomized control trial took place in Toronto, and included 1069 patients, 71% of whom were of Asian ancestry. Subjects had AFP testing every 6 months, and half were randomly assigned to have US performed every 6 months.5 Eight of the 11 incident tumors would have been diagnosed based on AFP levels alone, and 3 would have been missed with US alone. The authors conclude that for AFP, sensitivity=64.3% and specificity=91.4%; for US, sensitivity=78.8% and specificity=93.8%. However, their study was too small to determine if AFP/US is superior to AFP for hepatocellular carcinoma screening in a HBsAg+ population. They estimate that detecting such a difference would take a sample size of 10,000 or more.

Both studies have important flaws. Neither study applied a reference standard test (such as a computed tomography scan or magnetic resonance imaging) to both study arms. Carcinomas may have been undetected by either AFP or US. Without knowing the real prevalence of hepatocellular carcinoma, the true sensitivity and specificity for AFP, US, and AFP/US in these studies cannot be determined. Both studies included prevalent tumors (tumors diagnosed during the very first screening cycle) in their analysis. Approximately 20% of detected carcinomas in both studies were present at the start of the studies and did not represent newly incident tumors detected by regular screening.3,5

Both of these trials would be improved if they started with cohorts known to be disease-free at baseline. Additionally, the Shanghai study randomized patients in clusters. The only English-language report of this study did not describe whether adjustments for this were made in analysis;5 failing to do so could overestimate the benefit of screening.

Recommendations from others

The American Association for the Study of Liver Disease recommends that carriers of the hepatitis B virus who are at high risk for developing hepatocellular carcinoma—men aged >45 years, those with cirrhosis or a family history of hepatocellular carcinoma—should be screened periodically with AFP/US. Also consider periodic screening for low-risk HBsAg+ patients who are from an area where hepatocellular carcinoma is endemic (SOR: C, based on expert opinion or descriptive epidemiology).6

References

1. Sherman M. Screening for hepatocellular carcinoma. Best Pract Res Clin Gastroenterol 2005;19:101-118.

2. Wun YT, Dickinson JA. Alpha-fetoprotein and/or ultrasonography for liver cancer screening in patients with chronic hepatitis B. Cochrane Database Syst Rev 2003;(2):CD002799.

3. Yang B, Zhang B, Xu Y, et al. Prospective study of early detection for primary liver cancer. J Cancer Res Clin Oncol 1997;123:357-360.

4. Zhang B, Yang B, Tang Z. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol 2004;130:417-422.

5. Sherman M, Peltekian K, Lee C. Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a north American urban population. Hepatology 1995;22:432-438.

6. Lok A, McMahon B. AASLD practice guidelines: chronic Hepatitis B. American Association for the Study of Liver Disease web site. Available at: https://www.aasld.org/eweb/docs/chronichep_B.pdf. Accessed on January 9, 2006.

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EVIDENCE-BASED ANSWER

Screening patients with chronic hepatitis B infection (HBsAg+) for hepatocellular carcinoma by alpha-fetoprotein (AFP) or by AFP plus ultrasound (AFP/US) detects hepatocellular carcinoma tumors at earlier stages and increases resection rates (strength of recommendation [SOR]: B, based on a systematic review of fair-quality randomized controlled trials). It is unclear whether screening with AFP or AFP/US improves disease-specific or all-cause mortality (SOR: B).

CLINICAL COMMENTARY

Offer screening to all with chronic hepatitis B infection, but stratify risk for HCC first
Michael Mendoza, MD, MPH
ACCESS Community Health Network and Department of Family Medicine, University of Chicago

Because no mortality benefit to screening for hepatocellular carcinoma has been shown, we should give added consideration to how we counsel our patients before offering screening, particularly since positive screening results can lead to further invasive studies. An important consideration for me is whether a patient has, or is at risk, for cirrhosis, because the incidence of hepatocellular carcinoma is higher if cirrhosis is present. Screening for coinfection with hepatitis C or a history of alcohol abuse becomes especially critical in this situation. Biochemical evidence of chronic active liver inflammation, whatever the cause, should also be an important factor in deciding whether to screen. While I still offer screening to all patients with chronic hepatitis B infection, it helps to have stratified a patient’s underlying risk for hepatocellular carcinoma first and counseling him or her accordingly.

 

Evidence summary

Many serum markers and screening methods have been proposed to detect hepatocellular carcinoma at a treatable stage, but only 2—AFP and US—are in clinical use.1

A Cochrane systematic review on screening for hepatocellular carcinoma in the HBsAg+ population was published in 2003 and updated May 2004.2 Our literature search did not find any subsequent relevant trials. The Cochrane review included 2 randomized control trials. The larger trial was performed in Shanghai, China and included 18,816 HBsAg+ patients aged 35 to 55 years.3 Subjects were recruited from their place of employment and randomized to either AFP/US every 6 months (n=9373) or to no screening (n=9443).

Fifty-one hepatocellular carcinomas were diagnosed in the control group and 86 in screened group. Screened subjects had a significantly higher percentage of tumors that were less than 5 cm at the time of diagnosis and a higher number of patients who underwent resection. While the 5-year survival for those with hepatocellular carcinoma in the screened group was higher, the disease-specific mortality rate was not statistically different between the 2 groups.

Additional data became available in 2002. The original study authors claimed the new data showed a statistically significant disease-specific mortality rate ratio of 0.63, favoring the screened group.4 However, the Cochrane group performed their own analysis on the same data and determined that no statistically significant difference in the disease-specific mortality rates existed between the 2 groups.2 Therefore, it is not clear whether these new data definitively demonstrate that screening provides any benefit.

 

 

 

The other randomized control trial took place in Toronto, and included 1069 patients, 71% of whom were of Asian ancestry. Subjects had AFP testing every 6 months, and half were randomly assigned to have US performed every 6 months.5 Eight of the 11 incident tumors would have been diagnosed based on AFP levels alone, and 3 would have been missed with US alone. The authors conclude that for AFP, sensitivity=64.3% and specificity=91.4%; for US, sensitivity=78.8% and specificity=93.8%. However, their study was too small to determine if AFP/US is superior to AFP for hepatocellular carcinoma screening in a HBsAg+ population. They estimate that detecting such a difference would take a sample size of 10,000 or more.

Both studies have important flaws. Neither study applied a reference standard test (such as a computed tomography scan or magnetic resonance imaging) to both study arms. Carcinomas may have been undetected by either AFP or US. Without knowing the real prevalence of hepatocellular carcinoma, the true sensitivity and specificity for AFP, US, and AFP/US in these studies cannot be determined. Both studies included prevalent tumors (tumors diagnosed during the very first screening cycle) in their analysis. Approximately 20% of detected carcinomas in both studies were present at the start of the studies and did not represent newly incident tumors detected by regular screening.3,5

Both of these trials would be improved if they started with cohorts known to be disease-free at baseline. Additionally, the Shanghai study randomized patients in clusters. The only English-language report of this study did not describe whether adjustments for this were made in analysis;5 failing to do so could overestimate the benefit of screening.

Recommendations from others

The American Association for the Study of Liver Disease recommends that carriers of the hepatitis B virus who are at high risk for developing hepatocellular carcinoma—men aged >45 years, those with cirrhosis or a family history of hepatocellular carcinoma—should be screened periodically with AFP/US. Also consider periodic screening for low-risk HBsAg+ patients who are from an area where hepatocellular carcinoma is endemic (SOR: C, based on expert opinion or descriptive epidemiology).6

EVIDENCE-BASED ANSWER

Screening patients with chronic hepatitis B infection (HBsAg+) for hepatocellular carcinoma by alpha-fetoprotein (AFP) or by AFP plus ultrasound (AFP/US) detects hepatocellular carcinoma tumors at earlier stages and increases resection rates (strength of recommendation [SOR]: B, based on a systematic review of fair-quality randomized controlled trials). It is unclear whether screening with AFP or AFP/US improves disease-specific or all-cause mortality (SOR: B).

CLINICAL COMMENTARY

Offer screening to all with chronic hepatitis B infection, but stratify risk for HCC first
Michael Mendoza, MD, MPH
ACCESS Community Health Network and Department of Family Medicine, University of Chicago

Because no mortality benefit to screening for hepatocellular carcinoma has been shown, we should give added consideration to how we counsel our patients before offering screening, particularly since positive screening results can lead to further invasive studies. An important consideration for me is whether a patient has, or is at risk, for cirrhosis, because the incidence of hepatocellular carcinoma is higher if cirrhosis is present. Screening for coinfection with hepatitis C or a history of alcohol abuse becomes especially critical in this situation. Biochemical evidence of chronic active liver inflammation, whatever the cause, should also be an important factor in deciding whether to screen. While I still offer screening to all patients with chronic hepatitis B infection, it helps to have stratified a patient’s underlying risk for hepatocellular carcinoma first and counseling him or her accordingly.

 

Evidence summary

Many serum markers and screening methods have been proposed to detect hepatocellular carcinoma at a treatable stage, but only 2—AFP and US—are in clinical use.1

A Cochrane systematic review on screening for hepatocellular carcinoma in the HBsAg+ population was published in 2003 and updated May 2004.2 Our literature search did not find any subsequent relevant trials. The Cochrane review included 2 randomized control trials. The larger trial was performed in Shanghai, China and included 18,816 HBsAg+ patients aged 35 to 55 years.3 Subjects were recruited from their place of employment and randomized to either AFP/US every 6 months (n=9373) or to no screening (n=9443).

Fifty-one hepatocellular carcinomas were diagnosed in the control group and 86 in screened group. Screened subjects had a significantly higher percentage of tumors that were less than 5 cm at the time of diagnosis and a higher number of patients who underwent resection. While the 5-year survival for those with hepatocellular carcinoma in the screened group was higher, the disease-specific mortality rate was not statistically different between the 2 groups.

Additional data became available in 2002. The original study authors claimed the new data showed a statistically significant disease-specific mortality rate ratio of 0.63, favoring the screened group.4 However, the Cochrane group performed their own analysis on the same data and determined that no statistically significant difference in the disease-specific mortality rates existed between the 2 groups.2 Therefore, it is not clear whether these new data definitively demonstrate that screening provides any benefit.

 

 

 

The other randomized control trial took place in Toronto, and included 1069 patients, 71% of whom were of Asian ancestry. Subjects had AFP testing every 6 months, and half were randomly assigned to have US performed every 6 months.5 Eight of the 11 incident tumors would have been diagnosed based on AFP levels alone, and 3 would have been missed with US alone. The authors conclude that for AFP, sensitivity=64.3% and specificity=91.4%; for US, sensitivity=78.8% and specificity=93.8%. However, their study was too small to determine if AFP/US is superior to AFP for hepatocellular carcinoma screening in a HBsAg+ population. They estimate that detecting such a difference would take a sample size of 10,000 or more.

Both studies have important flaws. Neither study applied a reference standard test (such as a computed tomography scan or magnetic resonance imaging) to both study arms. Carcinomas may have been undetected by either AFP or US. Without knowing the real prevalence of hepatocellular carcinoma, the true sensitivity and specificity for AFP, US, and AFP/US in these studies cannot be determined. Both studies included prevalent tumors (tumors diagnosed during the very first screening cycle) in their analysis. Approximately 20% of detected carcinomas in both studies were present at the start of the studies and did not represent newly incident tumors detected by regular screening.3,5

Both of these trials would be improved if they started with cohorts known to be disease-free at baseline. Additionally, the Shanghai study randomized patients in clusters. The only English-language report of this study did not describe whether adjustments for this were made in analysis;5 failing to do so could overestimate the benefit of screening.

Recommendations from others

The American Association for the Study of Liver Disease recommends that carriers of the hepatitis B virus who are at high risk for developing hepatocellular carcinoma—men aged >45 years, those with cirrhosis or a family history of hepatocellular carcinoma—should be screened periodically with AFP/US. Also consider periodic screening for low-risk HBsAg+ patients who are from an area where hepatocellular carcinoma is endemic (SOR: C, based on expert opinion or descriptive epidemiology).6

References

1. Sherman M. Screening for hepatocellular carcinoma. Best Pract Res Clin Gastroenterol 2005;19:101-118.

2. Wun YT, Dickinson JA. Alpha-fetoprotein and/or ultrasonography for liver cancer screening in patients with chronic hepatitis B. Cochrane Database Syst Rev 2003;(2):CD002799.

3. Yang B, Zhang B, Xu Y, et al. Prospective study of early detection for primary liver cancer. J Cancer Res Clin Oncol 1997;123:357-360.

4. Zhang B, Yang B, Tang Z. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol 2004;130:417-422.

5. Sherman M, Peltekian K, Lee C. Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a north American urban population. Hepatology 1995;22:432-438.

6. Lok A, McMahon B. AASLD practice guidelines: chronic Hepatitis B. American Association for the Study of Liver Disease web site. Available at: https://www.aasld.org/eweb/docs/chronichep_B.pdf. Accessed on January 9, 2006.

References

1. Sherman M. Screening for hepatocellular carcinoma. Best Pract Res Clin Gastroenterol 2005;19:101-118.

2. Wun YT, Dickinson JA. Alpha-fetoprotein and/or ultrasonography for liver cancer screening in patients with chronic hepatitis B. Cochrane Database Syst Rev 2003;(2):CD002799.

3. Yang B, Zhang B, Xu Y, et al. Prospective study of early detection for primary liver cancer. J Cancer Res Clin Oncol 1997;123:357-360.

4. Zhang B, Yang B, Tang Z. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol 2004;130:417-422.

5. Sherman M, Peltekian K, Lee C. Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a north American urban population. Hepatology 1995;22:432-438.

6. Lok A, McMahon B. AASLD practice guidelines: chronic Hepatitis B. American Association for the Study of Liver Disease web site. Available at: https://www.aasld.org/eweb/docs/chronichep_B.pdf. Accessed on January 9, 2006.

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How effective are lifestyle changes for controlling hypertension?

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How effective are lifestyle changes for controlling hypertension?
EVIDENCE-BASED ANSWER

Regular aerobic exercise, weight loss of 3% to 9% of body weight, reduced dietary salt, the DASH diet, and moderation of alcohol intake are all lifestyle interventions that lower blood pressure. Average blood pressure decreases range from 3 to 11 mm Hg systolic and 2.5 to 5.5 mm Hg diastolic, depending on the particular intervention (strength of recommendation [SOR]: A, based on systematic reviews of randomized controlled trials [RCTs]). Studies of community-based interventions advocating combinations of the above have had mixed results with less reduction in blood pressure noted than for the individual interventions described above (SOR: B, RCTs with inconsistent results).

CLINICAL COMMENTARY

Lifestyle modifications plus drug therapy is the best treatment for patients with hypertension
Joseph Saseen, PharmD, FCCP, BCPS
Departments of Clinical Pharmacy and Family Medicine, University of Colorado Health Sciences Center

Most Americans with hypertension are not at their goal blood pressure, so the value of lifestyle modifications cannot be ignored. While some clinicians argue that these modifications are unreliable, this review should serve to reinforce the substantial impact of lifestyle modifications. Clinicians should remember that drug therapy is the only treatment modality proven to lower blood pressure and cardiovascular morbidity and mortality due to hypertension, based on evidence from outcome-based studies. Reducing cardiovascular morbidity and mortality is the ultimate goal of treating hypertension. Therefore, lifestyle modifications with antihypertensive drug therapy are the best treatments to reduce cardiovascular risk and attain goal blood pressure values for patients with hypertension.

 

Evidence summary

Lifestyle changes are advocated as first-line therapy for hypertension. This review examines the evidence on exercise, dietary interventions, weight loss, alcohol moderation, and smoking cessation. Average systolic blood pressure (SBP) and diastolic blood pressure (DBP) changes are reported in the TABLE.

Exercise. A well-done systematic review and meta-analysis from 2002 (including 15 studies with 770 participants) concluded that for hypertensive patients, aerobic exercise with at least one 40-minute session of moderate intensity per week is associated with a drop in SBP of about 5 mm Hg and a drop in DBP of about 4 mm Hg.1

DASH diet. The Dietary Approaches to Stop Hypertension (DASH) diet is a diet rich in fish, chicken, lean meat, low-fat dairy, fruits, vegetables, whole grains, legumes, nuts, and seeds. In a high-quality RCT, the DASH diet lowered SBP for hypertensive patients by an average of 11 mm Hg and DBP by an average of 5.5 mm Hg compared with the control group.2 Participants were provided with all food during the entire 8-week length of the trial.

Weight loss. A Cochrane review of 18 trials with 2611 participants concluded that for overweight hypertensive patients, weight loss of 3% to 9% of body weight is associated with 3 mm Hg decreases in both SBP and DBP.3

Salt reduction. A Cochrane review of 17 trials with 734 participants concluded that for individuals with hypertension, a reduced-salt diet results in a mean SBP and DBP reductions of 5 mm Hg and 3 mm Hg, respectively.4

Alcohol moderation. A well-done meta-analysis of alcohol reduction and blood pressure included 7 studies with 415 hypertensive patients.5 Mean baseline alcohol consumption was 3 to 6 alcoholic drinks per day, and the mean reduction in consumption was 67%. For this patient population, the average improvement was almost 4 mm Hg for SBP and nearly 2.5 mm Hg for DBP.

Smoking cessation. No high-quality studies show a long-term effect of smoking cessation on blood pressure. Smoking cessation has other well-documented health benefits and should still be recommended for patients with hypertension.

Multifactorial interventions. Thirteen randomized controlled trials of community-based interventions involving various combinations of lifestyle change advice show mixed results. In general, studies of interventions that were more intensive (ie, longer in duration, larger number of sessions, small group or one-on-one as opposed to large group lectures) and studies with shorter follow-up periods showed more positive results. The magnitude of the blood pressure improvements tended to be lower than for each individual intervention described above. (References are located in the APPENDIX on our web site at www.jfponline.com.

TABLE
Average effect on blood pressure from lifestyle interventions

LIFESTYLE INTERVENTIONAVERAGE EFFECT ON SBP (MM HG)AVERAGE EFFECT ON DBP (MM HG)
Regular aerobic exercise–5–4
DASH diet–11–5.5
Weight loss of 3% to 9% of body weight in overweight patients–3–3
Reduced salt diet–5–3
Alcohol moderation–4–2.5
SBP, systolic blood pressure; DBP, diastolic blood pressure

Recommendations from others

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends lifestyle modifications for all patients with hypertension.6 They point out that DASH diet plan with 1600 mg sodium had average blood pressure effects similar to single-drug therapy.

References

1. Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: A meta-analysis of randomized, controlled trials. Ann Intern Med 2002;136:493-503.

2. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH collaborative research group. N Engl J Med 1997;336:1117-1124.

3. Mulrow CD, Chiquette E, Angel L, et al. Dieting to reduce body weight for controlling hypertension in adults. Cochrane Database Syst Rev 2000;(2):000484.-

4. He FJ, MacGregor GA. Effect of longer-term modest salt reduction on blood pressure. Cochrane Database Syst Rev 2004;(3):004937.-

5. Xin X, He J, Frontini MG, Ogden LG, Motsamai OI, Whelton PK. Effects of alcohol reduction on blood pressure: A meta-analysis of randomized controlled trials. Hypertension 2001;38:1112-1117.

6. Chobanian AV, Bakris GL, Black HR, et al. National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National High Blood Pressure Education Program Coordinating Committee. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: The JNC 7 report. JAMA 2003;289:2560-2572.

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EVIDENCE-BASED ANSWER

Regular aerobic exercise, weight loss of 3% to 9% of body weight, reduced dietary salt, the DASH diet, and moderation of alcohol intake are all lifestyle interventions that lower blood pressure. Average blood pressure decreases range from 3 to 11 mm Hg systolic and 2.5 to 5.5 mm Hg diastolic, depending on the particular intervention (strength of recommendation [SOR]: A, based on systematic reviews of randomized controlled trials [RCTs]). Studies of community-based interventions advocating combinations of the above have had mixed results with less reduction in blood pressure noted than for the individual interventions described above (SOR: B, RCTs with inconsistent results).

CLINICAL COMMENTARY

Lifestyle modifications plus drug therapy is the best treatment for patients with hypertension
Joseph Saseen, PharmD, FCCP, BCPS
Departments of Clinical Pharmacy and Family Medicine, University of Colorado Health Sciences Center

Most Americans with hypertension are not at their goal blood pressure, so the value of lifestyle modifications cannot be ignored. While some clinicians argue that these modifications are unreliable, this review should serve to reinforce the substantial impact of lifestyle modifications. Clinicians should remember that drug therapy is the only treatment modality proven to lower blood pressure and cardiovascular morbidity and mortality due to hypertension, based on evidence from outcome-based studies. Reducing cardiovascular morbidity and mortality is the ultimate goal of treating hypertension. Therefore, lifestyle modifications with antihypertensive drug therapy are the best treatments to reduce cardiovascular risk and attain goal blood pressure values for patients with hypertension.

 

Evidence summary

Lifestyle changes are advocated as first-line therapy for hypertension. This review examines the evidence on exercise, dietary interventions, weight loss, alcohol moderation, and smoking cessation. Average systolic blood pressure (SBP) and diastolic blood pressure (DBP) changes are reported in the TABLE.

Exercise. A well-done systematic review and meta-analysis from 2002 (including 15 studies with 770 participants) concluded that for hypertensive patients, aerobic exercise with at least one 40-minute session of moderate intensity per week is associated with a drop in SBP of about 5 mm Hg and a drop in DBP of about 4 mm Hg.1

DASH diet. The Dietary Approaches to Stop Hypertension (DASH) diet is a diet rich in fish, chicken, lean meat, low-fat dairy, fruits, vegetables, whole grains, legumes, nuts, and seeds. In a high-quality RCT, the DASH diet lowered SBP for hypertensive patients by an average of 11 mm Hg and DBP by an average of 5.5 mm Hg compared with the control group.2 Participants were provided with all food during the entire 8-week length of the trial.

Weight loss. A Cochrane review of 18 trials with 2611 participants concluded that for overweight hypertensive patients, weight loss of 3% to 9% of body weight is associated with 3 mm Hg decreases in both SBP and DBP.3

Salt reduction. A Cochrane review of 17 trials with 734 participants concluded that for individuals with hypertension, a reduced-salt diet results in a mean SBP and DBP reductions of 5 mm Hg and 3 mm Hg, respectively.4

Alcohol moderation. A well-done meta-analysis of alcohol reduction and blood pressure included 7 studies with 415 hypertensive patients.5 Mean baseline alcohol consumption was 3 to 6 alcoholic drinks per day, and the mean reduction in consumption was 67%. For this patient population, the average improvement was almost 4 mm Hg for SBP and nearly 2.5 mm Hg for DBP.

Smoking cessation. No high-quality studies show a long-term effect of smoking cessation on blood pressure. Smoking cessation has other well-documented health benefits and should still be recommended for patients with hypertension.

Multifactorial interventions. Thirteen randomized controlled trials of community-based interventions involving various combinations of lifestyle change advice show mixed results. In general, studies of interventions that were more intensive (ie, longer in duration, larger number of sessions, small group or one-on-one as opposed to large group lectures) and studies with shorter follow-up periods showed more positive results. The magnitude of the blood pressure improvements tended to be lower than for each individual intervention described above. (References are located in the APPENDIX on our web site at www.jfponline.com.

TABLE
Average effect on blood pressure from lifestyle interventions

LIFESTYLE INTERVENTIONAVERAGE EFFECT ON SBP (MM HG)AVERAGE EFFECT ON DBP (MM HG)
Regular aerobic exercise–5–4
DASH diet–11–5.5
Weight loss of 3% to 9% of body weight in overweight patients–3–3
Reduced salt diet–5–3
Alcohol moderation–4–2.5
SBP, systolic blood pressure; DBP, diastolic blood pressure

Recommendations from others

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends lifestyle modifications for all patients with hypertension.6 They point out that DASH diet plan with 1600 mg sodium had average blood pressure effects similar to single-drug therapy.

EVIDENCE-BASED ANSWER

Regular aerobic exercise, weight loss of 3% to 9% of body weight, reduced dietary salt, the DASH diet, and moderation of alcohol intake are all lifestyle interventions that lower blood pressure. Average blood pressure decreases range from 3 to 11 mm Hg systolic and 2.5 to 5.5 mm Hg diastolic, depending on the particular intervention (strength of recommendation [SOR]: A, based on systematic reviews of randomized controlled trials [RCTs]). Studies of community-based interventions advocating combinations of the above have had mixed results with less reduction in blood pressure noted than for the individual interventions described above (SOR: B, RCTs with inconsistent results).

CLINICAL COMMENTARY

Lifestyle modifications plus drug therapy is the best treatment for patients with hypertension
Joseph Saseen, PharmD, FCCP, BCPS
Departments of Clinical Pharmacy and Family Medicine, University of Colorado Health Sciences Center

Most Americans with hypertension are not at their goal blood pressure, so the value of lifestyle modifications cannot be ignored. While some clinicians argue that these modifications are unreliable, this review should serve to reinforce the substantial impact of lifestyle modifications. Clinicians should remember that drug therapy is the only treatment modality proven to lower blood pressure and cardiovascular morbidity and mortality due to hypertension, based on evidence from outcome-based studies. Reducing cardiovascular morbidity and mortality is the ultimate goal of treating hypertension. Therefore, lifestyle modifications with antihypertensive drug therapy are the best treatments to reduce cardiovascular risk and attain goal blood pressure values for patients with hypertension.

 

Evidence summary

Lifestyle changes are advocated as first-line therapy for hypertension. This review examines the evidence on exercise, dietary interventions, weight loss, alcohol moderation, and smoking cessation. Average systolic blood pressure (SBP) and diastolic blood pressure (DBP) changes are reported in the TABLE.

Exercise. A well-done systematic review and meta-analysis from 2002 (including 15 studies with 770 participants) concluded that for hypertensive patients, aerobic exercise with at least one 40-minute session of moderate intensity per week is associated with a drop in SBP of about 5 mm Hg and a drop in DBP of about 4 mm Hg.1

DASH diet. The Dietary Approaches to Stop Hypertension (DASH) diet is a diet rich in fish, chicken, lean meat, low-fat dairy, fruits, vegetables, whole grains, legumes, nuts, and seeds. In a high-quality RCT, the DASH diet lowered SBP for hypertensive patients by an average of 11 mm Hg and DBP by an average of 5.5 mm Hg compared with the control group.2 Participants were provided with all food during the entire 8-week length of the trial.

Weight loss. A Cochrane review of 18 trials with 2611 participants concluded that for overweight hypertensive patients, weight loss of 3% to 9% of body weight is associated with 3 mm Hg decreases in both SBP and DBP.3

Salt reduction. A Cochrane review of 17 trials with 734 participants concluded that for individuals with hypertension, a reduced-salt diet results in a mean SBP and DBP reductions of 5 mm Hg and 3 mm Hg, respectively.4

Alcohol moderation. A well-done meta-analysis of alcohol reduction and blood pressure included 7 studies with 415 hypertensive patients.5 Mean baseline alcohol consumption was 3 to 6 alcoholic drinks per day, and the mean reduction in consumption was 67%. For this patient population, the average improvement was almost 4 mm Hg for SBP and nearly 2.5 mm Hg for DBP.

Smoking cessation. No high-quality studies show a long-term effect of smoking cessation on blood pressure. Smoking cessation has other well-documented health benefits and should still be recommended for patients with hypertension.

Multifactorial interventions. Thirteen randomized controlled trials of community-based interventions involving various combinations of lifestyle change advice show mixed results. In general, studies of interventions that were more intensive (ie, longer in duration, larger number of sessions, small group or one-on-one as opposed to large group lectures) and studies with shorter follow-up periods showed more positive results. The magnitude of the blood pressure improvements tended to be lower than for each individual intervention described above. (References are located in the APPENDIX on our web site at www.jfponline.com.

TABLE
Average effect on blood pressure from lifestyle interventions

LIFESTYLE INTERVENTIONAVERAGE EFFECT ON SBP (MM HG)AVERAGE EFFECT ON DBP (MM HG)
Regular aerobic exercise–5–4
DASH diet–11–5.5
Weight loss of 3% to 9% of body weight in overweight patients–3–3
Reduced salt diet–5–3
Alcohol moderation–4–2.5
SBP, systolic blood pressure; DBP, diastolic blood pressure

Recommendations from others

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends lifestyle modifications for all patients with hypertension.6 They point out that DASH diet plan with 1600 mg sodium had average blood pressure effects similar to single-drug therapy.

References

1. Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: A meta-analysis of randomized, controlled trials. Ann Intern Med 2002;136:493-503.

2. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH collaborative research group. N Engl J Med 1997;336:1117-1124.

3. Mulrow CD, Chiquette E, Angel L, et al. Dieting to reduce body weight for controlling hypertension in adults. Cochrane Database Syst Rev 2000;(2):000484.-

4. He FJ, MacGregor GA. Effect of longer-term modest salt reduction on blood pressure. Cochrane Database Syst Rev 2004;(3):004937.-

5. Xin X, He J, Frontini MG, Ogden LG, Motsamai OI, Whelton PK. Effects of alcohol reduction on blood pressure: A meta-analysis of randomized controlled trials. Hypertension 2001;38:1112-1117.

6. Chobanian AV, Bakris GL, Black HR, et al. National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National High Blood Pressure Education Program Coordinating Committee. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: The JNC 7 report. JAMA 2003;289:2560-2572.

References

1. Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: A meta-analysis of randomized, controlled trials. Ann Intern Med 2002;136:493-503.

2. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH collaborative research group. N Engl J Med 1997;336:1117-1124.

3. Mulrow CD, Chiquette E, Angel L, et al. Dieting to reduce body weight for controlling hypertension in adults. Cochrane Database Syst Rev 2000;(2):000484.-

4. He FJ, MacGregor GA. Effect of longer-term modest salt reduction on blood pressure. Cochrane Database Syst Rev 2004;(3):004937.-

5. Xin X, He J, Frontini MG, Ogden LG, Motsamai OI, Whelton PK. Effects of alcohol reduction on blood pressure: A meta-analysis of randomized controlled trials. Hypertension 2001;38:1112-1117.

6. Chobanian AV, Bakris GL, Black HR, et al. National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National High Blood Pressure Education Program Coordinating Committee. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: The JNC 7 report. JAMA 2003;289:2560-2572.

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The Journal of Family Practice - 55(1)
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