Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.

Exercise and Weight Loss in Persons with Pre-existing Coronary Heart Disease

Source: Ades PA, et al. The effect of weight loss and exercise training on flow-mediated dilatation in coronary heart disease: A randomized trial. Chest 2011;140:1420-1427.

There is still some debate about the relationship between being overweight and cardiovascular (CV) health, since among overweight individuals there is great diversity in levels of CV fitness as well as CV risk factors (e.g., hypertension, diabetes, dyslipidemia). Much of the insight we have today about the benefit of cardiac rehabilitation programs was gleaned from trial data in the 1970s and 1980s, at which time many fewer study subjects were obese or morbidly obese. Hence, determining the impact of exercise and weight loss in persons more representative of current coronary heart disease (CHD) demographics is pertinent.

Obese adults (mean baseline BMI = 32.3 kg/m2) with established CHD (n = 38) participated in a regimen of weight loss combined with one of two different intensity exercise programs (walking 45-60 minutes vs 25-40 minutes per session) for 4 months.

Endothelial function, as assessed by flow-mediated dilation, was improved in both groups, but improved more in the group with greater intensity of exercise. The authors also comment that the amount of endothelial functional improvement seen with weight loss was similar in magnitude to that attained with statin treatment. Degree of endothelial functional improvement correlated with amount of weight lost, suggesting a dose-response effect. In an era when more than 80% of persons entering cardiac rehabilitation programs are overweight or obese, it is encouraging that participation in rehabilitation programs that result in weight loss and sustained physical activity improve endothelial function.

Long-Term Effects of Bariatric Surgery: Improved CV Outcomes

Source: Sjostrom L, et al. Bariatric surgery and long-term cardiovascular events. JAMA 2012;307:56-65.

Increases in body mass index (bmi) above normal are linearly associated with cardiovascular (CV) morbidity and mortality. The increased incidence of hypertension and diabetes in overweight and obese individuals explains some of this association. Since the weight reduction subsequent to bariatric surgery (BARS) is usually accompanied by improvements in blood pressure and metabolic profile, one would hope that this would translate into a reduction of CV events.

The Swedish Obese Subjects study provides data from this prospective controlled study of BARS (n = 2010) vs "usual care" (n = 2037) for adult obese subjects. The minimum BMI for inclusion was 34 kg/m2 in men and 38 kg/m2 in women. Subjects were followed for a median of 14.7 years.

The BARS subjects enjoyed a 53% relative-risk reduction in CV deaths (28/2100 vs 49/2037) and a 33% risk reduction in overall fatal and nonfatal CV events (199/2100 vs 234/2037) over the almost 15 years of follow-up.

Although the degree of excess BMI did not correlate with outcomes — i.e., persons who had higher baseline BMI did not enjoy a greater (or lesser) risk reduction than comparators — there was a correlation with insulin resistance. As manifest by baseline plasma insulin concentration, subjects with the highest degree of insulin resistance had the greatest degree of CV risk reduction. This long-term follow-up of a large surgical population is encouraging that BARS reduces CV risk. Demonstration of risk reduction requires both a large population and enduring follow-up, since most of the participants were much younger than are typically enrolled in CV risk reduction trials.

Long-Term Survival in SHEP Trial Participants

Source: Kostis JB, et al. Association between chlorthalidone treatment of systolic hypertension and long-term survival. JAMA 2011;306:2588-2593.

The systolic hypertension in the elderly (SHEP) trial was a prospective, randomized, controlled trial of diuretic (chlorthalidone) vs placebo in 4736 subjects with isolated systolic hypertension over the age of 60. At the conclusion of the trial (4.5 years mean follow-up), chlorthalidone resulted in a statistically significant reduction in cardiovascular (CV) events, but only a favorable trend (NOT statistically significant) in CV mortality. Because of the favorable initial results, at the conclusion of the trial all SHEP participants were advised to use active treatment.

Kostis et al report on 22 years of follow-up of SHEP trial participants. According to their analysis, there was a beneficial difference noted between persons originally assigned to diuretic vs placebo: a statistically significant 11% reduction in CV death, although total mortality was not significantly different between the two groups. Benefits seen years after a clinical trial intervention has ceased are commonly termed "legacy effects," and suggest that a sustained period of blood pressure control with chlorthalidone may extend CV risk reduction over a much longer interval. Because all trial participants were encouraged to receive active treatment post-trial, the favorable between-group differences seen would likely be an underestimate of true attainable benefits.