Clinical research study
Obesity Paradox in Patients with Hypertension and Coronary Artery Disease

This work was presented in part at the 2005 Scientific Session of the American Society of Hypertension, San Francisco, Calif.
https://doi.org/10.1016/j.amjmed.2007.05.011Get rights and content

Abstract

Purpose

An obesity paradox, a “paradoxical” decrease in morbidity and mortality with increasing body mass index (BMI), has been shown in patients with heart failure and those undergoing percutaneous coronary intervention. However, whether this phenomenon exists in patients with hypertension and coronary artery disease is not known.

Methods

A total of 22,576 hypertensive patients with coronary artery disease (follow-up 61,835 patient years, mean age 66 ± 9.8 years) were randomized to a verapamil-SR or atenolol strategy. Dose titration and additional drugs (trandolapril and/or hydrochlorothiazide) were added to achieve target blood pressure control according to the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure targets. Patients were classified into 5 groups according to baseline BMI: less than 20 kg/m2 (thin), 20 to 25 kg/m2 (normal weight), 25 to 30 kg/m2 (overweight), 30 to 35 kg/m2 (class I obesity), and 35 kg/m2 or more (class II-III obesity). The primary outcome was first occurrence of death, nonfatal myocardial infarction, or nonfatal stroke.

Results

With patients of normal weight (BMI 20 to <25 kg/m2) as the reference group, the risk of primary outcome was lower in the overweight patients (adjusted hazard ratio [HR] 0.77, 95% confidence interval [CI], 0.70-0.86, P <.001), class I obese patients (adjusted HR 0.68, 95% CI, 0.59-0.78, P <.001), and class II to III obese patients (adjusted HR 0.76, 95% CI, 0.65-0.88, P <.001). Class I obese patients had the lowest rate of primary outcome and death despite having smaller blood pressure reduction compared with patients of normal weight at 24 months (−17.5 ± 21.9 mm Hg/−9.8 ± 12.4 mm Hg vs −20.7 ± 23.1 mm Hg /−10.6 ± 12.5 mm Hg, P <.001).

Conclusion

In a population with hypertension and coronary artery disease, overweight and obese patients had a decreased risk of primary outcome compared with patients of normal weight, which was driven primarily by a decreased risk of all-cause mortality. Our results further suggest a protective effect of obesity in patients with known cardiovascular disease in concordance with data in patients with heart failure and those undergoing percutaneous coronary intervention.

Section snippets

Study Design

INVEST was a prospective, randomized, international study of 22,576 patients with hypertension and coronary artery disease. The inclusion and exclusion criteria, study design, and results have been published elsewhere.19 In brief, eligible patients were randomized to a verapamil-SR–based or an atenolol-based treatment strategy to achieve the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure targets (<140/90 mm Hg or <130/85 mm Hg in those

Baseline Characteristics

The mean age was 66 ± 9.8 years, and the mean follow-up was 2.7 years (range, 1 day to 5.4 years) with 61,835 patient years accumulated. Of the 22,572 patients included in this analysis, 2.2% were thin, 20.0% were normal weight, 39.9% were overweight, 24.6% had class I obesity, and 13.2% had class II to III obesity. Pertinent baseline characteristics by BMI class are summarized in Table 1. Compared with normal-weight patients, overweight and class I to III obese patients were younger, had a

Discussion

This study addressed the effect of BMI on cardiovascular outcomes in a cohort of patients with hypertension and coronary artery disease. Our study is in agreement with previous studies that observed an obesity paradox in patients with previous cardiovascular disease.

Conclusion

In this well-treated hypertensive cohort with coronary artery disease, increasing BMI was associated with decreased morbidity and mortality when compared with normal-weight patients, consistent with an “obesity paradox.” Whether this relationship is the result of the shortcomings of BMI as a risk factor needs to be further elucidated.

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