Serum caeruloplasmin as a coronary risk factor in the elderly: the Rotterdam Study

Serum Cu and caeruloplasmin levels have been suggested to be independent risk factors for CHD operating through oxidative modification of LDL. However, given its function as an acute-phase protein, the question has been raised whether an elevated caeruloplasmin level is not merely an indicator of inflammation. In the current study, we investigated whether serum caeruloplasmin was associated with subsequent myocardial infarction, taking into account indices of inflammation. The study population consisted of 210 cases of first myocardial infarction and controls, frequency-matched on age (5-year categories) and sex, selected from the population-based cohort of the Rotterdam Study. Serum caeruloplasmin levels were significantly elevated in cases of myocardial infarction compared with controls (510 (SD 110) v. 470 (SD 100) mg/l; P = 0.007). Risk of myocardial infarction for the highest compared with the lowest quartile of caeruloplasmin was 2.46 (95% CI 1.04, 6.00; Ptrend = 0.043) after adjustment for age, sex, BMI, pack-years smoked, serum cholesterol, systolic blood pressure, and income. The relative risk was most evident in current smokers. Adjustment for C-reactive protein and leucocyte count reduced the excess risk by 33%. This suggests that a substantial part of the observed association between serum caeruloplasmin and CHD may be attributed to inflammation processes rather than to the pro-oxidant activity of caeruloplasmin.