Context: Despite established insulin-sensitizing and anti-atherogenic preclinical effects, epidemiological investigations of adiponectin have yielded conflicting findings, and its relationship with coronary heart disease (CHD) remains uncertain.

Objective: To investigate the relationship between adiponectin and CHD in older adults.

Design, Setting, and Participants: Case-control study (N=1,386) nested within the population-based Cardiovascular Health Study from 1992 to 2001. Controls were frequency-matched to cases by age, sex, race, subclinical cardiovascular disease and center.

Main Outcome Measures: Incident CHD was defined as angina pectoris, percutaneous or surgical revascularization, non-fatal myocardial infarction (MI) or CHD death. A more restrictive CHD endpoint was limited to non-fatal MI and CHD death.

Results: Adiponectin exhibited significant negative correlations with baseline adiposity, insulin resistance, dyslipidemia, inflammatory markers, and leptin. After controlling for matching factors, adjustment for waist-hip ratio, hypertension, smoking, alcohol, LDL-cholesterol, creatinine, and leptin revealed a modestly increased risk of incident CHD with adiponectin concentrations at the upper end (OR= 1.37 [Quintile 5 vs. 1–4], 95% CI=1.02–1.84). This association was stronger when the outcome was limited to non-fatal MI and fatal CHD (OR=1.69, 95% CI=1.23–2.32). The findings were not influenced by additional adjustment for weight change, health status, or cystatin C, nor were they abolished by adjustment for potential mediators.

Conclusions: This study shows an association between adiponectin and increased risk of first-ever CHD in older adults. Further research is needed to elucidate the basis for the concurrent beneficial and detrimental aspects of this relationship, and under what circumstances one or the other may predominate.