Associations of Total and High-Molecular-Weight Adiponectin With All-Cause and Cardiovascular Mortality in Older Persons: The Cardiovascular Health Study

Study Questions:

What is the association of adiponectin profiles with mortality in an elderly population?

Methods:

The relationship of total and high-molecular-weight adiponectin with mortality was analyzed in 4,685 subjects >65 years of age grouped by baseline cardiovascular (CV) status: group 1 = no CV disease, heart failure, or atrial fibrillation; group 2 = CV disease, but no heart failure or atrial fibrillation; group 3 = heart failure and atrial fibrillation.

Results:

The association in group 1 was U-shaped, with increasing levels of total adiponectin up to 12.4 mg/L associated with lower mortality after adjustment for confounders (hazard ratio [HR] = 0.81 per 1 standard deviation), but above this cut point, higher levels conferred greater risk (HR = 1.19). There was no significant association in group 2, but in group 3, total adiponectin showed a direct adjusted association. Additional adjustment for putative metabolic/inflammatory intermediates suggested a direct association for group 2, and magnified the one for group 3 (HR = 1.31; 95% confidence interval, 1.15-1.50). Results were similar for high-molecular-weight adiponectin and for CV mortality.

Conclusions:

Adiponectin exhibits distinct associations with mortality in elderly persons, which shift from U-shaped to flat to direct with greater baseline cardiovascular dysfunction, but become more consistently adverse after accounting for metabolic/inflammatory factors presumed to be favorably regulated by the adipokine.

Perspective:

Adiponectin is the most abundant circulating adipokine. Interestingly, its concentration is inversely related to adiposity, and it has been shown to exhibit insulin sensitizing and cardioprotective effects in some studies. Thus, reduced levels of adiponectin in states of obesity could be causally related to increased insulin resistance and CV disease. However, some epidemiologic studies have linked higher levels of adiponectin with adverse CV outcomes. This study may shed light on this adiponectin paradox by demonstrating effects of baseline CV and metabolic status on associations between adiponectin and outcomes. Further study is needed to explain the basis for these complex associations.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Adipokines, Risk Factors, Insulin Resistance, Hyperinsulinism, Biological Markers, Adiponectin, Heart Failure, Epidemiologic Studies, Adiposity, Cardiovascular Diseases, Obesity, Atrial Fibrillation, Confidence Intervals


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