Personalized prediction of lifetime benefits with statin therapy for asymptomatic individuals: a modeling study.

BACKGROUND: Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing risk of death due to other causes. We aimed to predict the potential lifetime benefits with statin therapy, taking into account competing risks. METHODS AND FINDINGS: A microsimulation model based on 5-y follow-up data from the Rotterdam Study, a population-based cohort of individuals aged 55 y and older living in the Ommoord district of Rotterdam, the Netherlands, was used to estimate lifetime outcomes with and without statin therapy. The model was validated in-sample using 10-y follow-up data. We used baseline variables and model output to construct (1) a web-based calculator for gains in total and CVD-free life expectancy and (2) color charts for comparing these gains to the Systematic Coronary Risk Evaluation (SCORE) charts. In 2,428 participants (mean age 67.7 y, 35.5% men), statin therapy increased total life expectancy by 0.3 y (SD 0.2) and CVD-free life expectancy by 0.7 y (SD 0.4). Age, sex, smoking, blood pressure, hypertension, lipids, diabetes, glucose, body mass index, waist-to-hip ratio, and creatinine were included in the calculator. Gains in total and CVD-free life expectancy increased with blood pressure, unfavorable lipid levels, and body mass index after multivariable adjustment. Gains decreased considerably with advancing age, while SCORE 10-y CVD mortality risk increased with age. Twenty-five percent of participants with a low SCORE risk achieved equal or larger gains in CVD-free life expectancy than the median gain in participants with a high SCORE risk. CONCLUSIONS: We developed tools to predict personalized increases in total and CVD-free life expectancy with statin therapy. The predicted gains we found are small. If the underlying model is validated in an independent cohort, the tools may be useful in discussing with patients their individual outcomes with statin therapy.

Blood Culture-negative Endocarditis Caused by Tropheryma whipplei: Whipple's endocarditis.

CASE DESCRIPTION: A 67-year-old man was admitted with progressive heart failure due to blood culture-negative endocarditis of the aortic valve. Urgent aortic valve replacement was needed. Polymerase chain reaction (PCR) testing of samples of the explanted aortic valve revealed Tropheryma whipplei. The patient received ceftriaxone, followed by long-term co-trimoxazole. Recent arthralgia may have been a diagnostic clue. CONCLUSION: Whipple's endocarditis should be considered in patients with arthralgia and blood culture-negative endocarditis (BCNIE). LEARNING POINTS: Whipple's endocarditis should be considered in patients with symptoms of arthralgia and blood culture-negative endocarditis (BCNIE).Serum polymerase chain reaction is the main diagnostic test.Both physician awareness and multidisciplinary management by regional endocarditis teams are recommended strategies to provide optimal patient care.

Apparent and internal validity of a Monte Carlo-Markov model for cardiovascular disease in a cohort follow-up study.

OBJECTIVE: To determine the apparent and internal validity of the Rotterdam Ischemic heart disease & Stroke Computer (RISC) model, a Monte Carlo-Markov model, designed to evaluate the impact of cardiovascular disease (CVD) risk factors and their modification on life expectancy (LE) and cardiovascular disease-free LE (DFLE) in a general population (hereinafter, these will be referred to together as (DF)LE). METHODS: The model is based on data from the Rotterdam Study, a cohort follow-up study of 6871 subjects aged 55 years and older who visited the research center for risk factor assessment at baseline (1990-1993) and completed a follow-up visit 7 years later (original cohort). The transition probabilities and risk factor trends used in the RISC model were based on data from 3501 subjects (the study cohort). To validate the RISC model, the number of simulated CVD events during 7 years' follow-up were compared with the observed number of events in the study cohort and the original cohort, respectively, and simulated (DF)LEs were compared with the (DF)LEs calculated from multistate life tables. RESULTS: Both in the study cohort and in the original cohort, the simulated distribution of CVD events was consistent with the observed number of events (CVD deaths: 7.1% v. 6.6% and 7.4% v. 7.6%, respectively; non-CVD deaths: 11.2% v. 11.5% and 12.9% v. 13.0%, respectively). The distribution of (DF)LEs estimated with the RISC model consistently encompassed the (DF)LEs calculated with multistate life tables. CONCLUSIONS: The simulated events and (DF)LE estimates from the RISC model are consistent with observed data from a cohort follow-up study.

C-reactive protein predicts progression of atherosclerosis measured at various sites in the arterial tree: the Rotterdam Study.

UNLABELLED: 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 >/=55 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 (P=0.002 for trend). CONCLUSIONS: CRP predicts progression of atherosclerosis measured at various sites in the arterial tree.

Estrogen receptor alpha gene polymorphisms and risk of myocardial infarction.

CONTEXT: The role of estrogens in ischemic heart disease (IHD) is uncertain. Evidence suggests that genetic variations in the estrogen receptor alpha (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.454-397T>C (PvuII) and c.454-351A>G (XbaI) polymorphisms is associated with myocardial infarction (MI) and IHD risk. DESIGN, SETTING, AND PARTICIPANTS: In 2617 men and 3791 postmenopausal women from The Rotterdam Study (enrollment between 1989-1993 and follow-up to January 2000), a population-based, prospective cohort study of participants aged 55 years and older, ESR1 c.454-397T>C and c.454-351A>G 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. CONCLUSIONS: In 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.

Unilateral and multilateral congenital coronary-pulmonary fistulas in adults: clinical presentation, diagnostic modalities, and management with a brief review of the literature.

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.