C‐Reactive Protein Modifies the Association of Plasma Leptin With Coronary Calcium in Asymptomatic Overweight Individuals

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Abstract
Evidence suggests putative interactions of leptin and C‐reactive protein (CRP) in the pathogenesis of adiposity‐related atherosclerotic cardiovascular disease (CVD). Therefore, we investigated whether CRP levels modify the relationship of leptin levels with coronary artery calcium (CAC). We examined 1,460 asymptomatic individuals from two community‐based cross‐sectional studies coordinated at a single, university‐based research center. We focused on subjects who were overweight or obese (BMI ≥25) given greater biologic plausibility in this setting. In multivariable CAC models, we analyzed the interaction of log‐transformed plasma leptin levels with higher CRP levels as defined by three cut‐points: two clinically based (2 mg/l, 3 mg/l) and one dataset specific (sex‐specific upper quartile). The association of plasma leptin with CAC was modified by higher CRP regardless of cut‐point (interaction term P values all N = 461 vs. 0.94 (0.67–1.31) if CRP levels N = 999) in fully adjusted models. No interaction with CRP was present in control analyses with adiponectin, BMI and waist circumference. In conclusion, in asymptomatic overweight and obese adults, increased leptin levels were independently associated with increased CAC in the presence of high, but not low CRP levels, supporting a leptin‐CRP interface in atherosclerosis risk.

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