Impact of overweight and obesity on cardiac benefit of antihypertensive treatment

https://doi.org/10.1016/j.numecd.2011.03.008Get rights and content

Abstract

Background and aims

Increased body mass index (BMI) has been associated with increased cardiovascular morbidity and mortality in hypertension. Less is known about the impact of BMI on improvement in left ventricular (LV) structure and function during antihypertensive treatment.

Methods and results

Annual BMI, echocardiograms and cardiovascular events were recorded in 875 hypertensive patients with LV hypertrophy during 4.8 years randomized treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography substudy. Patients were grouped by baseline BMI into normal (n = 282), overweight (n = 405), obese (n = 150) and severely obese groups (n = 38) (BMI ≤24.9, 25.0–29.9, 30.0–34.9, and ≥35.0 kg/m2, respectively). At study end, residual LV hypertrophy was present in 54% of obese and 79% of severely obese patients compared to 31% of normal weight patients (both p < 0.01). In regression analyses, adjusting for initial LV mass/height2.7, higher BMI predicted less LV hypertrophy reduction and more reduction in LV ejection fraction (both p < 0.05), independent of blood pressure reduction, diabetes and in-study weight change. During follow-up, 91 patients suffered cardiovascular death, myocardial infarction or stroke. In Cox regression analysis 1 kg/m2 higher baseline BMI predicted a 5% higher rate of cardiovascular events and 10% higher cardiovascular mortality over 4.8 years (both p < 0.05).

Conclusions

In hypertensive patients in the LIFE study, increased BMI was associated with less reduction of LV hypertrophy and less improvement in LV systolic function which may contribute to the observed higher cardiovascular event rate of treated hypertensive patients.

Introduction

The increased prevalence of hypertension and diabetes in obese subjects has been suggested to at least partly explain the increased cardiovascular risk observed in obesity [1], [2]. In hypertensive populations obesity has been associated with higher prevalence of left ventricular (LV) hypertrophy as well as lower LV systolic function [3], [4], [5]. It is well known that systematic antihypertensive treatment induces regression of hypertensive LV hypertrophy [6]. However, as documented from the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study that randomized 9193 hypertensive patients with signs of LV hypertrophy on the electrocardiogram to 4.8 years blinded losartan- or atenolol-based antihypertensive treatment, concomitant obesity predicted increased cardiovascular mortality during follow-up independent of other individual cardiovascular risk factors and type of antihypertensive treatment [7]. Furthermore, clustering of metabolic abnormalities has been associated with blunted reduction in hypertensive LV hypertrophy assessed by electrocardiography [8].

Less is known about the impact of obesity on cardiac benefit, including regression of LV hypertrophy and improvement of LV systolic function measured by serial echocardiograms during systematic long-term antihypertensive treatment. Thus, the aim of the present analysis was to assess whether obesity itself attenuates the known beneficial effects of aggressive antihypertensive treatment on LV structure and systolic function.

Section snippets

Patient population

The present analysis was added to the LIFE echocardiography analysis plan before unblinding of data. The LIFE echocardiography study, a prospectively planned substudy of the main LIFE study, enrolled 960 of the 9193 participants in the parent trial for annual echocardiographic follow-up [9]. Results from the main LIFE study that randomized patients aged 55–80 years with essential hypertension (baseline blood pressure 160–200/95–115 mm Hg) and electrocardiographic (ECG) LV hypertrophy (according

Results

At baseline, obese patients groups were younger, and included more women and patients with diabetes and of African American ethnicity (all p < 0.01), while blood pressure was comparable between groups (Table 1). Baseline LV dimensions and wall thicknesses increased progressively with increasing BMI class, and prevalence of LV hypertrophy was significantly higher in overweight and obese groups than in the normal weight group (Table 2, Fig. 1).

During antihypertensive treatment, BMI and body

Discussion

The purpose of this study was to evaluate the impact of obesity on cardiac benefit including regression of LV hypertrophy and improvement of LV systolic function, during systematic long-term antihypertensive treatment. As expected from previous publications, obese patient groups had higher prevalence of LV hypertrophy before starting antihypertensive treatment [3], [4], [5]. However, our findings add to previous knowledge by demonstrating that regression of LV hypertrophy and improvement in LV

Conclusions

In hypertensive patients, obesity is associated with less regression of echocardiographic LV hypertrophy as well as less improvement of LV systolic function during antihypertensive treatment independent of concomitant diabetes. These findings may help explain the increased rate of cardiovascular events observed among obese hypertensive patients participating in the LIFE study despite a beneficial shift from concentric to eccentric LV hypertrophy pattern.

Disclosures

E.G., K.W., K.B. and M.S.N. have all received grant support from Merck & Co, the sponsor of the LIFE study. R.B.D. and B.D. have received grant support and served as consultants for Merck & Co. B.P.L. and G.d.S. have no disclosures relating to this manuscript.

Acknowledgment

The LIFE echocardiography substudy was supported in part by grant COZ-368 from Merck & Co, Inc., West Point, PA, USA (the sponsor of the parent LIFE study).

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