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.

Background and Purpose-C-reactive protein (CRP) predicts myocardial infarction and stroke. Its role as a predictor of the progression of subclinical atherosclerosis is not yet known. We investigated whether CRP predicts progression of atherosclerosis measured at various sites in the arterial tree. Methods-CRP levels were measured in a random sample of 773 subjects Ն55 years of age who were participating in the Rotterdam Study. Subclinical atherosclerosis was assessed at various sites at 2 points in time, with a mean duration between measurements of 6.5 years. Results-After adjustment for age, sex, and smoking habits, odds ratios (ORs) associated with CRP levels in the highest compared with the lowest quartile were increased for progression of carotid (OR, 1.9; 95% CI, 1.1 to 3.3), aortic (OR, 1.7; 95% CI, 1.0 to 3.0), iliac (OR, 2.0; 95% CI, 1.2 to 3.3), and lower extremity (OR, 1.9; 95% CI, 1.0 to 3.7) atherosclerosis. The OR for generalized progression of atherosclerosis as indicated by a composite progression score was 4.5 (95% CI, 2.3 to 8.5). Except for aortic atherosclerosis, these estimates hardly changed after additional adjustment for multiple cardiovascular risk factors. In addition, ORs for progression of atherosclerosis associated with high CRP levels were as high as those associated with the traditional cardiovascular risk factors high cholesterol, hypertension, and smoking. Geometric mean levels of CRP increased with the total number of sites showing progression of atherosclerosis (Pϭ0.002 for trend). Conclusions-CRP

In a modeling study conducted by Myriam Hunink and colleagues, a population-based cohort from Rotterdam is used to predict the possible lifetime benefits of statin therapy, on a personalized basis.

Background: Congenital coronary-pulmonary fistulas (CPFs) are commonly unilateral, but bilateral and multilateral fistulas may occur. In multilateral CPFs, the value of a multidetector computed tomography (MDCT) imaging technique as an adjuvant to coronary angiography (CAG) is eminent. The purpose of this study was to describe the clinical presentation, diagnostic modalities, and management of coincidentally detected congenital CPFs. Hypothesis: Unilateral and multilateral coronary-pulmonary fistulas are increasingly detected due to the wide speard application of multidetector computed tomography which might be a supplementary or replacing to conventional coronary angiography. Methods: We evaluated 14 adult patients with congenital coronary artery fistulas (CAFs) who were identified from several Dutch cardiology departments. Results: Fourteen adult patients (5 female and 9 male), with a mean age of 57.5 years (range, 24-80 years) had the following abnormal findings: audible systolic cardiac murmur (n = 4), chronic atrial fibrillation (n = 2), nonsustained ventricular tachycardia (n = 1), and cardiomegaly on chest x-ray (n = 2). Echocardiography revealed normal findings with trivial valvular abnormalities (n = 9), depressed left ventricle systolic function (n = 3), and severe mitral regurgitation and atrial dilatation (n = 2). The findings in the rest of the patients were unremarkable. CAG and MDCT were used as a diagnostic imaging techniques either alone (CAG, n = 6; MDCT, n = 1) or in combination (n = 7). Single modality and multimodality diagnostic methods revealed 22 fistulas including CPFs (n = 15), coronary cameral fistulas terminating into the right (n = 2) and the left atrium (n = 1), and systemic-pulmonary fistulas (n = 4). Of all of the fistulas, 10 were unilateral, 6 were bilateral, and 6 was hexalateral.13 N-ammonia positron emission tomography-computed tomography was performed in 3 patients revealing decreased myocardial perfusion reserve. Conclusions: CAG remains the gold standard for detection of CPFs. An adjuvant technique using MDCT provides full anatomical details of the fistulas.The authors have no funding, financial relationships, or conflicts of interest to disclose.

Despite some differences in baseline characteristics, non-enrolled and randomised patients did not differ in one-year outcome, which was favourable for both populations and may be related to the drug-eluting stents used.