Background-Coronary calcification detected by electron beam tomography may improve cardiovascular risk prediction.The technique is particularly promising in the elderly because the predictive power of cardiovascular risk factors weakens with age. We investigated the prognostic value of coronary calcification for cardiovascular events and mortality in a general, asymptomatic population of elderly subjects. Methods and Results-From 1997 to 2000, electron beam tomography scanning to assess coronary calcification was performed in subjects of the population-based Rotterdam Study. Risk factors were measured by standardized procedures. Coronary calcium scores were available for 1795 asymptomatic participants (mean age, 71 years; range, 62 to 85 years). During a mean follow-up of 3.3 years, 88 cardiovascular events, including 50 coronary events, occurred. The risk of coronary heart disease increased with increasing calcium score. The multivariate-adjusted relative risk of coronary events was 3.1 (95% CI, 1.2 to 7.9) for calcium scores of 101 to 400, 4.6 (95% CI, 1.8 to 11.8) for calcium scores of 401 to 1000, and 8.3 (95% CI, 3.3 to 21.1) for calcium scores Ͼ1000 compared with calcium scores of 0 to 100. The predictive value in subjects Ͼ70 years of age was similar. Risk prediction based on the cardiovascular risk factors improved when coronary calcification was added. Conclusions-Coronary calcification is a strong and independent predictor of coronary heart disease, also in the elderly.Coronary calcification improves prediction of coronary events based on cardiovascular risk factors. Risk stratification by assessment of coronary calcification may have an important role in the primary prevention of coronary heart disease events in the elderly. (Circulation. 2005;112:572-577.)

ContextThe role of estrogens in ischemic heart disease (IHD) is uncertain. Evidence suggests that genetic variations in the estrogen receptor ␣ (ESR1) gene may influence IHD risk, but the role of common sequence variations in the ESR1 gene is unclear.Objective To determine whether the ESR1 haplotype created by the c.454-397TϾC (PvuII) and c.454-351AϾG (XbaI) polymorphisms is associated with myocardial infarction (MI) and IHD risk. Design, Setting, and ParticipantsIn 2617 men and 3791 postmenopausal women from The Rotterdam Study (enrollment between 1989(enrollment between -1993(enrollment between and follow-up to January 2000, a population-based, prospective cohort study of participants aged 55 years and older, ESR1 c.454-397TϾC and c.454-351AϾG haplotypes were determined. Detailed interviews and physical examinations were performed, blood samples were obtained, and cardiovascular risk factors were assessed.Main Outcome Measure The primary outcome was MI and IHD defined as MIs, revascularization procedures, and IHD mortality.Results Approximately 29% of women and 28.2% of men were homozygous carriers of the ESR1 haplotype 1 (−397 T and −351 A) allele, 49% of women and 50% of men were heterozygous carriers, and 22% of women and 21.4% of men were noncarriers. During a mean follow-up of 7.0 years, 285 participants (115 women; 170 men) had MI, and 440 (168 women; 272 men) had an IHD event, of which 97 were fatal. After adjustment for known cardiovascular risk factors, female heterozygous carriers of haplotype 1 had an increased risk of MI (event rate, 2.8%; relative risk [RR], 2.23; 95% confidence interval [CI], 1.13-4.43) compared with noncarriers (event rate, 1.3%), whereas homozygous carriers had an increased risk (event rate, 3.2%; RR, 2.48; 95% CI, 1.22-5.03). For IHD events, we observed a similar association. In women, the effect of haplotype 1 on fatal IHD was larger than on nonfatal IHD. In men, the ESR1 haplotypes were not associated with an increased risk of MI (event rate, 5.7%; RR, 0.93; 95% CI, 0.59-1.46 for heterozygous carriers; and event rate, 5.1%; RR, 0.82; 95% CI, 0.49-1.38 for homozygous carriers) compared with noncarriers (event rate, 5.8%) and were not associated with an increased risk of IHD. ConclusionsIn this population-based, prospective cohort study, postmenopausal women who carry ESR1 haplotype 1 (c.454-397 T allele and c.454-351 A allele) have an increased risk of MI and IHD, independent of known cardiovascular risk factors. In men, no association was observed.

In this population-based study, graded associations were found between coronary calcification and common carotid IMT, carotid plaques and aortic calcification. A nonlinear association was found between coronary calcification and the AAI.

Background-Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been proposed as an inflammatory marker of cardiovascular disease. In the present study, we investigated whether Lp-PLA2 is an independent predictor of coronary heart disease and ischemic stroke. Methods and Results-The Rotterdam Study is a population-based follow-up study in 7983 subjects Ն55 years of age. We performed a case-cohort study, including 308 coronary heart disease cases, 110 ischemic stroke cases, and a random sample of 1820 subjects. We used Cox proportional-hazard models with modification of the standard errors based on robust variance estimates to compute hazard ratios adjusted for age, sex, body mass index, systolic blood pressure, non-HDL cholesterol, HDL cholesterol, diabetes, smoking, alcohol consumption, cholesterol-lowering medication, white blood cell count, and C-reactive protein.Compared with the first quartile of Lp-PLA2 activity, multivariateadjusted hazard ratios for coronary heart disease for the second, third, and fourth quartiles were 1.39 (95% CI, 0.92 to 2.10), 1.99 (95% CI, 1.32 to 3.00), and 1.97 (95% CI, 1.28 to 3.02), respectively (P for trendϭ0.01). Corresponding multivariate-adjusted hazard ratios for ischemic stroke were 1.08 (95% CI, 0.55 to 2.11), 1.58 (95% CI, 0.82 to 3.04), and 1.97 (95% CI, 1.03 to 3.79) (P for trendϭ0.03). The relation between Lp-PLA2 and coronary heart disease was present in both subjects with non-HDL cholesterol levels below the median and those with non-HDL cholesterol levels above the median. Conclusions-This study shows that Lp-PLA2 activity is an independent predictor of coronary heart disease and ischemic stroke in the general population. (Circulation. 2005;111:570-575.)