Abstract 1188: Adiponectin Multimeric Forms But Not Total Adiponectin Levels Predict Myocardial Infarction In Non-diabetic Men
Introduction: While a number of studies reported hypoadiponectinemia as a risk factor for coronary disease (CAD), others provided opposite results challenging the accumulated experimental and epidemiological data that support adiponectins’ role as a protective cardiovascular molecule. Special attention should be addressed to the problems related to the analytical determination of this adipokine, present in the human circulation in predominantly three multimeric forms, low-molecular-weight trimeric form (LMW), mid-molecular-hexameric-weight form (MMW), and high-molecular-weight multimers (HMW).
Methods: We used a novel multimeric ELISA kit to quantify total adiponectin (TOTAL), HMW-, MMW-, and LMW multimers in a cross-sectional study of non-diabetic obese (BMI≥30 kg/m2) and normal weight (BMI≤25) male subjects with and without myocardial infarction (MI, n=180). Subsequently, we designed a prospective matched nested case-control study to explore the predicitve capability of the adiponectin multimers on fatal and non-fatal MI in 1158 healthy non-diabetic men.
Results: In the cross-sectional study TOTAL, HMW, MMW, and LMW levels were significantly lower in obese than normal weight subjects with and without MI (all p>0.0001). In contrast, MI was strongly related to MMW/TOTAL (1.86±0.09 vs. 0.80±0.09, p=1×10−14), HMW/TOTAL (0.26±0.01 vs. 0.38±0.01, p=2×10−11), and MMW/HMW ratios (0.38±0.1 vs. 0.27±0.1, p=5×10−17), but not TOTAL. These effects could be identified in obese and normal weight subjects. In the prospective study, 53 incident fatal and non-fatal MI events occured. The MMW/HMW ratio predicted fatal and non-fatal MI up to 5 years before the event, with β-estimates decreasing with increasing time to event (≤2 years: 1.0±0.4, p=0.008; ≤ 3 years: 0.9±0.3, p=0.003; ≤4 years: 0.7±0.2, p=0.003; ≤5 years: 0.5±0.2, p=0.01).
Conclusion: Whereas total adiponectin and all isoforms are related to obesity, total adiponectin levels are not associated with MI in non-diabetic men. In contrast, the MMW/HMW ratio was revealed as a strong independent predictor for incident MI up to 5 years before the event. These data imply that the multimeric isoforms should be determined to evaluate their incremental values with respect to CAD.