Elsevier

Atherosclerosis

Volume 220, Issue 2, February 2012, Pages 587-592
Atherosclerosis

Adiponectin is associated with increased mortality and heart failure in patients with stable ischemic heart disease: Data from the Heart and Soul Study

https://doi.org/10.1016/j.atherosclerosis.2011.11.038Get rights and content

Abstract

Objective

Serum adiponectin protects against incident ischemic heart disease (IHD). However, in patients with existing IHD, higher adiponectin levels are paradoxically associated with worse outcomes. We investigated this paradox by evaluating the relationship between adiponectin and cardiovascular events in patients with existing IHD.

Methods

We measured total serum adiponectin and cardiac disease severity by stress echocardiography in 981 outpatients with stable IHD who were recruited for the Heart and Soul Study between September 2000 and December 2002. Subsequent heart failure hospitalizations, myocardial infarction, and death were recorded.

Results

During an average of 7.1 years of follow-up, patients with adiponectin levels in the highest quartile were more likely than those in the lowest quartile to be hospitalized for heart failure (23% vs. 13%; demographics-adjusted hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.04–2.56, p = 0.03) or die (49% vs. 31%; HR 1.67, 95% CI 1.24–2.26, p < 0.008), but not more likely to have a myocardial infarction (12% vs. 17%; HR 0.64, 95% CI 0.38–1.06, p = 0.08). The combined outcome of myocardial infarction, heart failure, or death occurred in 56% (136/245) of participants in the highest quartile of adiponectin vs. 38% (94/246) of participants in the lowest quartile (HR 1.54, 95% CI 1.31–2.21, p < 0.002). Adjustment for left ventricular ejection fraction, diastolic dysfunction, inducible ischemia, C-reactive protein, and NT-proBNP attenuated the association between higher adiponectin and increased risk of subsequent events (HR 1.43, 95% CI 0.98–2.09, p = 0.06).

Conclusions

Higher concentrations of adiponectin were associated with heart failure and mortality among patients with existing IHD.

Introduction

Adiponectin is an abundant serum protein that is secreted primarily from adipose tissue [1], with concentrations that are inversely associated with obesity [2]. In animal and in vitro models, adiponectin exerts insulin-sensitizing, anti-inflammatory and anti-atherosclerotic effects [1]. Likewise, in humans low adiponectin levels, such as those seen in obesity, are associated with low HDL [3], hypertension [4], insulin resistance [2], [3], and diabetes [2]. Given its connections with cardiovascular disease risk factors, recent population studies have investigated the association of adiponectin with incident cardiovascular events. In patients without previously diagnosed cardiovascular disease, higher levels of adiponectin are thought to be protective against disease [5], [6], [7], although this relationship is not consistently present in women [6], [8], minorities [9], or the elderly [10].

Despite adiponectin being associated with a favorable cardiovascular risk profile, higher levels of adiponectin have paradoxically been associated with inducible ischemia [11], worse outcomes among patients with acute coronary syndrome [12], and worse outcomes among patients with existing heart failure [10]. The underlying mechanisms of the association between adiponectin and severity of disease in individuals with existing cardiovascular disease are not well understood. In the present study, we further investigated this apparent paradox by evaluating the association between adiponectin and cardiovascular disease outcomes in a cohort of patients with stable ischemic heart disease (IHD).

Section snippets

Participants

The Heart and Soul Study is a prospective cohort study designed to investigate the effects of psychosocial factors on health outcomes in patients with stable IHD. Methods have been previously described [13]. Patients were eligible if they had at least 1 of the following: history of myocardial infarction, angiographic evidence of ≥50% stenosis in ≥1 coronary vessels, evidence of exercise-induced ischemia by treadmill ECG or stress nuclear perfusion imaging, or a history of coronary

Results

Among 981 participants, the median adiponectin level was 21.3 μg/mL (interquartile range 12.6–35.6 μg/mL). Compared to those participants in the lowest quartile, participants in the highest quartile were older, less likely to be male, and more likely to be white (Table 1). While no significant difference was noted with regard to prevalence of hypertension, myocardial infarction, or heart failure, participants with higher adiponectin were less likely to have diabetes mellitus. With regard to

Discussion

In a cohort of patients with stable IHD, we found that higher adiponectin concentrations were associated with lower BMI, lower non-HDL cholesterol, higher HDL cholesterol, and less diabetes. Despite this favorable metabolic profile, higher adiponectin concentrations were also associated with worse cardiovascular outcomes, particularly heart failure and death. Remarkably, nearly half of participants with adiponectin levels in the highest quartile died during the 7 years of follow-up. After

Acknowledgments

Alexis Beatty is supported by Award Number F32HL110518 from the National Heart, Lung, and Blood Institute. Mary Zhang was supported by a fellowship from the University of California, San Francisco (Medical Student Research Training Program). The Heart and Soul Study was supported by grants from the Department of Veterans Affairs (Epidemiology Merit Review Program), the National Heart, Lung and Blood Institute (R01 HL079235), the Robert Wood Johnson Foundation (Generalist Physician Faculty

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