Incidence of obesity-associated cardiovascular disease is related to inflammation-sensitive plasma proteins: a population-based cohort study.

BACKGROUND Although obesity is associated with increased inflammation, it is unclear whether this accounts for the increased cardiovascular risk in obesity. This population-based study explored whether inflammation-sensitive plasma proteins (ISPs) modify the cardiovascular risk in overweight or obese men. METHODS AND RESULTS The ISPs (fibrinogen, orosomucoid, alpha1-antitrypsin, haptoglobin, ceruloplasmin) were measured in 6075 healthy men, aged 28 to 61 years. The incidences of cardiovascular events (myocardial infarction, stroke, cardiovascular deaths), cardiac events (fatal or nonfatal myocardial infarction), and stroke were followed-up over 18+/-4 years. High ISPs were associated with an increased cardiovascular risk in all categories of body mass index (BMI). The age-adjusted relative risks for cardiovascular events in obese men (BMI >30) were 2.1 (95% CI, 1.4 to 3.4), 2.4 (CI, 1.5 to 3.7), 3.7 (CI, 2.3 to 6.0), and 4.5 (CI, 3.0 to 6.6), respectively, for those with 0, 1, 2, and > or =3 ISPs in the top quartile (trend P=0.002) (reference: BMI <25 and no elevated ISP). This trend persisted after adjustments for several potential confounders (P=0.02). Incidence of cardiac events showed similar relations with the number of elevated ISPs in obese men. CONCLUSIONS The cardiovascular risk varies widely between obese or overweight men with high and low ISPs. Relationships with ISPs contribute to, but cannot fully explain, the increased cardiovascular risk in obese men.