Adiponectin Multimeric Forms but not Total Adiponectin Levels are Associated with Myocardial Infarction in Non-Diabetic Men

Abstract

Multimer complex formation of adiponectin is recognized as an important mechanism modulating the biological functions of this adipokine, but the role of adiponectin isoforms in myocardial infarction (MI) is still unclear. We quantified total adiponectin (TOTAL), high, middle, and low molecular weight adiponectin multimers (HMW, MMW, LMW) in a study of non-diabetic obese (BMI ≥ 30 kg/m(2)) and normal-weight (BMI ≤ 25 kg/m(2)) male subjects with MI and healthy controls (n=180). Subsequently, we designed a prospective nested-case-control study to investigate the association of the adiponectin multimers with fatal and non-fatal MI in n=1236 initially healthy non-diabetic men. Obesity was significantly related to lower levels of TOTAL, HMW, MMW, and LMW in subjects with and without MI (p < 0.01, each). In contrast, MI was strongly related to MMW/TOTAL (p < 0.0001), inversely to HMW/TOTAL (p < 0.0001), but not TOTAL or LMW levels. In particular, the median MMW/HMW ratios were markedly different in men with MI (1.71, interquartile range (1.08-2.40)) and without (0.72 (0.49-1.08), p < 0.0001). In the prospective study, 56 incident fatal and non-fatal MI events occured. The MMW/HMW ratio was associated with fatal and non-fatal MI up to 5 years before the event. The β-estimates for the relationship between MMW/HMW and incident MI decreased with increasing time to the event. Whereas total adiponectin and all isoforms are related to obesity, total adiponectin and LMW levels are not associated with MI in non-diabetic men. In contrast, the MMW/HMW-ratio correlated with incident MI up to 5 years before the event. These data imply that measurement of adiponectin multimers adds significant value in assessing cardiovascular risk compared to total adiponectin alone.