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AimsCardiovascular patients with low socioeconomic status and non-western ethnic background have worse prognostic outcomes. The aim of this nationwide study was first to address whether short-term effects of hospital-based outpatient cardiac rehabilitation (CR) are similar across educational level and ethnic background, and secondly to study whether known disparity in long-term prognosis in patients with cardiovascular disese is diminished by CR participation.MethodsAll patients with myocardial infarction and/or coronary revascularization from August 2015 until March 2018 in the Danish national patient registry or the Danish cardiac rehabilitation database (DHRD) were included. We used descriptive statistics to address disparity in achievement of quality indicators in CR, and Cox proportional hazard regression to examine the association between the disparity measures and MACE (cardiovascular hospitalization and all-cause mortality) with adjustment for age, gender, index-diagnose and co-morbidity.ResultsWe identified 34,511 patients of whom 19,383 had participated in CR and 9,882 provided information on CR outcomes from the DHRD. We demonstrated a socioeconomic gradient in improvements in VO2peak, and non-western patients were less often screened for depression or receive dietary consulting. We found a strong socioeconomic gradient in MACE irrespective of CR participation, medication, and risk factor control (adjusted HR 0.65 (95% CI 0.56–0.77) for high versus low education). Non-western origin was associated with higher risk of MACE (adjusted HR 1.2 (1.1–1.4)).ConclusionWe found only minor socioeconomic and ethnic differences in achievement of CR quality indicators but strong differences in CHD prognosis indication that conventional risk factor control and medical treatment following CR do not diminish the socioeconomic and ethnical disparity in CHD prognosis. Aims Cardiovascular patients with low socioeconomic status and non-western ethnic background have worse prognostic outcomes. The aim of this nationwide study was first to address whether short-term effects of hospital-based outpatient cardiac rehabilitation (CR) are similar across educational level and ethnic background, and secondly to study whether known disparity in long-term prognosis in patients with cardiovascular disese is diminished by CR participation. Methods All patients with myocardial infarction and/or coronary revascularization from August 2015 until March 2018 in the Danish national patient registry or the Danish cardiac rehabilitation database (DHRD) were included. We used descriptive statistics to address disparity in achievement of quality indicators in CR, and Cox proportional hazard regression to examine the association between the disparity measures and MACE (cardiovascular hospitalization and all-cause mortality) with adjustment for age, gender, index-diagnose and co-morbidity. Results We identified 34,511 patients of whom 19,383 had participated in CR and 9,882 provided information on CR outcomes from the DHRD. We demonstrated a socioeconomic gradient in improvements in VO2peak, and non-western patients were less often screened for depression or receive dietary consulting. We found a strong socioeconomic gradient in MACE irrespective of CR participation, medication, and risk factor control (adjusted HR 0.65 (95% CI 0.56–0.77) for high versus low education). Non-western origin was associated with higher risk of MACE (adjusted HR 1.2 (1.1–1.4)). Conclusion We found only minor socioeconomic and ethnic differences in achievement of CR quality indicators but strong differences in CHD prognosis indication that conventional risk factor control and medical treatment following CR do not diminish the socioeconomic and ethnical disparity in CHD prognosis.

The EPIC-CVD project was supported by the European Union Framework 7 (HEALTH-F2-2012-279233), the European Research Council (268834), the UK Medical Research Council (G0800270, MR/L003120/1), the British Heart Foundation (SP/09/002, RG/08/014, RG13/13/30194), and the UK National Institute of Health Research (to EPIC-CVD). The establishment of the subcohort was supported by the EU Sixth Framework Programme (FP6) (grant LSHM_CT_2006_037197 to the InterAct project) and the Medical Research Council Epidemiology Unit (grants MC_ UU_12015/1 and MC_UU_12015/5). The national EPIC cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); Ministry of Health and Social Solidarity, Stavros Niarchos Foundation and Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC) and National Research Council (Italy) and MIUR "Dipartimenti di Eccellenza"(Project D15D18000410001) to the Department of Medical Sciences; Dutch Ministry of Public Health, Welfare and Sports (VWS), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skane and Vasterbotten (Sweden); and Cancer Research UK, Medical Research Council (United Kingdom). LIFE-Heart is funded by the Leipzig Research Center for Civilization Diseases (LIFE). LIFE is an organizational unit affiliated to the Medical Faculty of the University of Leipzig. LIFE is funded by means of the European Union, by the European Regional Development Fund (ERDF), and by funds of the Free State of Saxony within the framework of the excellence initiative. This work is supported by the Dutch Heart Foundation (2013T083 to V.D.), by a UK Medical Research Council Skills Development Fellowship (MR/P014550/1 to S.A.E.P.), and by a Sir Henry Dale Fellowship jointly funded by the Welcome Trust and the Royal Society (204623/Z/16/Z to S.B.). None of the funding sources had a role in the collection, analysis, and interpretation of the data, nor in the decision to submit the article for publication., Background: Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause. Objectives: To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD risk factors in a bidirectional Mendelian randomization (MR) approach, using age at natural menopause (ANM) genetic variants as a measure for genetically determined reproductive aging in women. We also studied the association of these variants with CHD risk (factors) in men. Design: Two-sample MR, using both cohort data as well as summary statistics, with 4 methods: simple and weighted median-based, standard inverse-variance weighted (IVW) regression, and MR-Egger regression. Participants: Data from EPIC-CVD and summary statistics from UK Biobank and publicly available genome-wide association studies were pooled for the different analyses. Main Outcome Measures: CHD, CHD risk factors, and ANM. Results: Across different methods of MR, no association was found between genetically determined reproductive aging and CHD risk in women (relative risk estimateIVW = 0.99; 95% confidence interval (CI), 0.97-1.01), or any of the CHD risk factors. Similarly, no associations were found in men. Neither did the reversed analyses show evidence for an association between CHD (risk factors) and reproductive aging. Conclusion: Genetically determined reproductive aging is not causally associated with CHD risk (factors) in women, nor were the genetic variants associated in men. We found no evidence for a reverse association in a combined sample of women and men., European Commission HEALTH-F2-2012-279233 European Research Council (ERC) European Commission 268834, UK Research & Innovation (UKRI) Medical Research Council UK (MRC) G0800270 MR/L003120/1 British Heart Foundation SP/09/002 RG/08/014 RG13/13/30194, National Institute for Health Research (NIHR), EU Sixth Framework Programme (FP6) LSHM_CT_2006_037197, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) MC_ UU_12015/1 MC_UU_12015/5, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe Federal Ministry of Education & Research (BMBF) Deutsches Krebsforschungszentrum (Germany), Ministry of Health and Social Solidarity (Greece) Stavros Niarchos Foundation (Greece) Hellenic Health Foundation (Greece), Fondazione AIRC per la ricerca sul cancro Consiglio Nazionale delle Ricerche (CNR) MIUR "Dipartimenti di Eccellenza" D15D18000410001, Dutch Ministry of Public Health, Welfare and Sports, LK Research Funds, Dutch Prevention Funds Netherlands Organization for Scientific Research (NWO), World Cancer Research Fund International (WCRF) ERC-2009-AdG 232997, Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Instituto de Salud Carlos III, Junta de Andalucia, Principality of Asturias, Regional Government of Basque Country (Spain) Regional Government of Murcia (Spain) Regional Government of Navarra (Spain), Instituto de Salud Carlos III RD06/0020, Swedish Cancer Society Swedish Scientific Council (Sweden) Regional Government of Skane and Vasterbotten (Sweden), Cancer Research UK UK Research & Innovation (UKRI) Medical Research Council UK (MRC), Leipzig Research Center for Civilization Diseases (LIFE), European Commission, Free State of Saxony, Netherlands Heart Foundation 2013T083, Medical Research Council UK (MRC) MR/P014550/1, Sir Henry Dale Fellowship - Welcome Trust 204623/Z/16/Z, Sir Henry Dale Fellowship - Royal Society 204623/Z/16/Z

Background:Taller people have a lower risk of coronary heart disease but a higher risk of many cancers. Mendelian randomization (MR) studies in unrelated individuals (population MR) have suggested that these relationships are potentially causal. However, population MR studies are sensitive to demography (population stratification, assortative mating) and familial (indirect genetic) effects.Methods:In this study, we performed within-sibship MR analyses using 78,988 siblings, a design robust against demography and indirect genetic effects of parents. For comparison, we also applied population MR and estimated associations with measured height.Results:Within-sibship MR estimated that 1 SD taller height lowers the odds of coronary heart disease by 14% (95% CI: 3–23%) but increases the odds of cancer by 18% (95% CI: 3–34%), highly consistent with population MR and height-disease association estimates. There was some evidence that taller height reduces systolic blood pressure and low-density lipoprotein cholesterol, which may mediate some of the protective effects of taller height on coronary heart disease risk.Conclusions:For the first time, we have demonstrated that the purported effects of height on adulthood disease risk are unlikely to be explained by demographic or familial factors, and so likely reflect an individual-level causal effect. Disentangling the mechanisms via which height affects disease risk may improve the understanding of the etiologies of atherosclerosis and carcinogenesis.Funding:This project was conducted by researchers at the MRC Integrative Epidemiology Unit (MC_UU_00011/1) and also supported by a Norwegian Research Council Grant number 295989.

BackgroundHistorically, high levels of morbidity and mortality have been associated with cardiovascular disease in the Northern Ireland population. Previously reported associations between single nucleotide polymorphisms (SNPs) and cardiovascular disease within other populations have not always been consistent.ObjectiveTo investigate associations between 33 SNPs with fatal or non-fatal incident coronary heart disease (CHD) events and all-cause mortality in the Northern Irish participants of the Prospective Epidemiological Study of Myocardial Infarction (PRIME).MethodPhase 2 of the PRIME study prospectively evaluated 2,010 men aged 58–74 years in Northern Ireland for more than 10 years for incident CHD events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass, and cardiac death) and more than 15 years for all-cause mortality. SNPs previously reported in association with cardiovascular outcomes were evaluated against incident CHD events and all-cause mortality using Cox’s proportional hazards models adjusted for established cardiovascular disease risk factors.ResultsDuring the follow-up period, 177 incident CHD events were recorded, and 821 men died. BothBCMO1rs6564851 (Hazard ratio [HR] = 0.76; 95% confidence intervals [CI]: 0.60–0.96; P = 0.02) andTGFB1rs1800469 (HR = 1.30; CI: 1.02–1.65; P = 0.04) were significantly associated with incident CHD events in adjusted models. OnlyIL1Brs16944 was significantly associated with all-cause mortality (HR = 1.18; CI: 1.05–1.33; P = 0.005). No associations remained significant following Bonferonni correction for multiple testing.ConclusionWe report a novel association betweenBCMO1rs6564851 and risk of incident CHD events. In addition,TGFB1rs1800469 andIL1Brs16944 were associated with the risk of incident CHD events and all-cause mortality outcomes respectively, supporting previously reported associations.

Background: Scientific studies on cardiovascular disease (CVD) burden and risk factors are predominantly based on short-term risk in Westerner populations, and such information may not be applicable to Asian populations, especially over the longer term. This review aims to estimate the long-term (>10 years) CVD burden, including coronary heart disease (CHD) and stroke, as well as associated risk factors in Asian populations. Methods: PubMed, Embase and Web of Science were systematically searched, and hits screened on: Asian adults, free of CVD at baseline; cohort study design (follow-up >10 years). Primary outcomes were fatal and non-fatal CVD events. Pooled estimates and between-study heterogeneity were calculated using random effects models, Q and I2 statistics. Results: Overall, 32 studies were eligible for inclusion (follow-up: 11–29 years). The average long-term rate of fatal CVD is 3.68 per 1000 person-years (95% CI 2.84–4.53), the long-term cumulative risk 6.35% (95% CI 4.69%–8.01%, mean 20.13 years) and the cumulative fatal stroke/CHD risk ratio 1.5:1. Important risk factors for long-term fatal CVD (RR, 95% CI) were male gender (1.49, 1.36–1.64), age over 60/65 years (7.55, 5.59–10.19) and current smoking (1.68, 1.26–2.24). High non-HDL-c, and β- and γ-tocopherol serum were associated only with CHD (HR 2.46 [95% CI 1.29–4.71] and 2.47 [1.10–5.61] respectively), while stage 1 and 2 hypertensions were associated only with fatal stroke (2.02 [1.19–3.44] and 2.89 [1.68–4.96] respectively). Conclusions: Over a 10 year + follow-up period Asian subjects had a higher risk of stroke than CHD. Contrary to CVD prevention in Western countries, strategies should also consider stroke instead of CHD only.

To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach.MethodsWe undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity.ResultsA 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32-1.68, p = 1.1 × 10 -8). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96-1.30, p = 0.14; p for heterogeneity = 2.6 × 10 -3) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 × 10 -3) when compared with that for CHD.ConclusionsIn contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.

To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach.MethodsWe undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity.ResultsA 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32-1.68, p = 1.1 × 10 -8). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96-1.30, p = 0.14; p for heterogeneity = 2.6 × 10 -3) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 × 10 -3) when compared with that for CHD.ConclusionsIn contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.

Objective: Cardiovascular diseases (CVD) are the main cause of death worldwide and despite a higher prevalence in men, mortality from CVD is higher among women. Few studies have assessed sex differences in chest pain management in ambulatory care. The objective of this post hoc analysis of data from a prospective cohort study was to assess sex differences in the management of chest pain in ambulatory care. Setting: We used data from the Thoracic Pain in Community cohort study that was realized in 58 primary care practices and one university ambulatory clinic in Switzerland. Participants: In total, 672 consecutive patients aged over 16 years attending a primary care practice or ambulatory care clinic with a complaint of chest pain were included between February and June 2001. Their mean age was 55.2 years and 52.5% were women. Main outcome measures: The main outcome was the proportion of patients referred to a cardiologist at 12 months follow-up. A panel of primary care physicians assessed the final diagnosis retained for chest pain at 12 months. Results: The prevalence of chest pain of cardiovascular origin (n = 108, 16.1%) was similar for men and women (17.5% vs 14.8%, respectively, p = 0.4). Men with chest pain were 2.5 times more likely to be referred to a cardiologist than women (16.6% vs 7.4%, odds ratio: 2.49, 95% confidence interval: 1.52–4.09). After adjustment for the patients’ age and cardiovascular disease risk factors, the estimates did not significantly change (odds ratio: 2.30, 95% confidence interval: 1.30–3.78). Conclusion: Although the same proportion of women and men present with a chest pain of cardiovascular origin in ambulatory care, there is a strong sex bias in their management. These data suggest that effort must be made to assure equity between men and women in medical care.

ObjectivesWe investigate the independent and interacting long-term associations of occupational physical activity (OPA) and sport physical activity (SpPA) with the incidence of coronary heart disease (CHD) and cardiovascular diseases (CVD; CHD plus ischaemic stroke) in North Italian male workers.Methods3574 employed men aged 25–64 years, free of CVD at baseline, recruited in three population-based and one factory-based cohorts, were included in the analysis. The Baecke Questionnaire was used to assess OPA and SpPA in ‘minutes per week’ of moderate or vigorous PA. We estimated the associations between different domains of PA and the endpoints, adjusting for major CVD risk factors, using Cox models.ResultsDuring a median follow-up of 14 years, 135 and 174 first CHD and CVD events, fatal and non-fatal, occurred. Compared with the intermediate OPA tertile, the HRs for CHD among low and high OPA workers were 1.66 (95% CI 1.06 to 2.59) and 1.18 (0.72 to 1.94), respectively (P value=0.07). Decreasing trends in CHD and CVD rates across increasing levels of SpPA were also found, with an HR for CVD of 0.68 (0.46 to 0.98) for intermediate/recommended SpPA compared with poor SpPA. We also found a statistically significant SpPA-OPA interaction, and the protective effect of SpPA was only found among sedentary workers, for both endpoints. Conversely, high OPA workers with intermediate/recommended SpPA levels had increased CHD and CVD rates compared with the poor SpPA category.ConclusionsOur results provide further evidence on the health paradox of OPA, with higher CVD rates among workers with intense PA at work. Moreover, the protective effect on CVDs of SpPA is prominent in sedentary workers, but it attenuates and even reverses in moderate and strenuous OPA workers.

Background: The EUROASPIRE (European Action on Secondary and Primary Prevention by Intervention to Reduce Events) cross-sectional surveys describe time trends in lifestyle and risk factor control among coronary patients between 1999 and 2013 in Belgium, Czech Republic, Finland, France, Ireland, the Netherlands, Poland, Slovenia, and the United Kingdom as part of the EuroObservational Research Programme under the auspices of European Society of Cardiology.Objectives: This study sought to describe time trends in lifestyle, risk factor control, and the use of evidencebased medication in coronary patients across Europe.Methods: The EUROASPIRE II (1999 to 2000), III (2006 to 2007), and IV (2012 to 13) surveys were conducted in the same geographical areas and selected hospitals in each country. Consecutive patients (≤70 years) after coronary artery bypass graft, percutaneous coronary intervention, or an acute coronary syndrome identified from hospital records were interviewed and examined ≥6 months later with standardized methods.Results: Of 12,775 identified coronary patients, 8,456 (66.2%) were interviewed. Proportion of current smokers was similar across the 3 surveys. Prevalence of obesity increased by 7%. The prevalence of raised blood pressure (≥140/90 mm Hg or ≥140/80 mm Hg with diabetes) dropped by 8% from EUROASPIRE III to IV, and therapeutic control of blood pressure improved with 55% of patients below target in IV. The prevalence of low-density lipoprotein cholesterol ≥2.5 mmol/l decreased by 44%. In EUROASPIRE IV, 75% were above the target low-density lipoprotein cholesterol

Objectives To display and discuss the reasons and consequences of length and time-dependent bias. They might occur in presence of a time-dependent study entry or a time-dependent exposure which might change from unexposed to exposed. Study Design and Setting Recalling the popular study of Oscar nominees and using a real-data example from hospital epidemiology, we give innovative and easy-to-understand graphical presentations of how these biases corrupt the analyses via distorted time-at-risk. Cumulative hazard plots and Cox proportional hazards models were used. We are building bridges to medical disciplines such as critical care medicine, hepatology, pharmaco-epidemiology, transplantation medicine, neurology, gynecology and cardiology. Results In presence of time-dependent bias, the hazard ratio (comparing exposed with unexposed) is artificially underestimated. The length bias leads to an artificial underestimation of the overall hazard. When both biases coexist it can lead to different directions of biased hazard ratios. Conclusion Since length and time-dependent bias might occur in several medical disciplines, we conclude that understanding and awareness are the best prevention of survival bias.

To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach.MethodsWe undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity.ResultsA 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32-1.68, p = 1.1 × 10 -8). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96-1.30, p = 0.14; p for heterogeneity = 2.6 × 10 -3) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 × 10 -3) when compared with that for CHD.ConclusionsIn contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.

BACKGROUND: Past and recent research suggests that psychological and biological factors may increase women's risk of coronary heart disease (CHD). This study examined the prevalence and correlates of self-reported heart disease among Jewish women from the Negev, a socio-economically and culturally unique region in south of Israel. METHOD: A cross-sectional design was used. We interviewed over the phone 526 randomly-selected women (mean age: 44.3+/-14.2 years) about background variables (e.g., education), biomedical risk factors (e.g., body mass index or BMI), self-reported inflammatory diseases (rheumatoid arthritis or RA, urinary infections), psychosocial factors (depression, hopelessness, self-esteem, social-support) and self-rated health and heart disease. RESULTS: Prior physician diagnosis of heart disease was reported by 8.2% of women. Age, economic difficulties, diabetes, hypertension, BMI, physical exercise, RA and urinary infections were significantly associated with reported heart disease. Of all psychosocial factors considered, hopelessness and self-esteem significantly distinguished heart disease cases from non-cases. In a multiple logistic regression, poor self-esteem, RA and hypertension were significant independent correlates of self-reported heart disease. CONCLUSIONS: Pending replication with objective measures of heart disease and a prospective design, poor self-esteem and RA may prove to be new CHD risk factors in women.

Objectives Systemic lupus erythematosus (SLE) is associated with considerable cardiovascular morbidity that has not yet been directly compared with other diseases with known cardiovascular risk. Methods Two hundred and forty-one patients of the multicentre Swiss SLE cohort study (SSCS) were cross-sectionally assessed for coronary heart disease (CHD), cerebrovascular disease (CVD) and peripheral artery disease (PAD). SLE patients were compared with a cohort of 193 patients with type-1 diabetes mellitus being followed at the University Hospital Basel. A subgroup analysis of 50 age- and sex-matched patients from the University Hospital Basel was performed. Results Of patients within the SSCS 13.3% had one or more vascular events: 8.3% CHD, 5% CVD and 1.2% PAD. In type-1 diabetes mellitus patients, 15% had vascular events: 9.3% CHD, 3.1% CVD and 5.6% PAD. In the matched subgroup, 26% of SLE patients had vascular events (14% CHD) compared with 12% in type-1 DM patients (2% CHD). Cardiovascular risk factors were similar in both groups. Vascular events in SLE patients were associated with age, longer disease duration, dyslipidaemia, and hypertension. Conclusion Cardiovascular morbidity in SLE is at least as frequent as in age- and sex-matched type-1 diabetes mellitus patients. Therefore, aggressive screening and management of cardiovascular risk factors should be performed.

Background Unless effective preventive strategies are implemented, aging of the population will result in a significant worsening of the heart failure (HF) epidemic. Few data exist on whether baseline electrocardiographic (ECG) abnormalities can refine risk prediction for HF. Methods We examined a prospective cohort of 2,915 participants aged 70 to 79 years without preexisting HF, enrolled between April 1997 and June 1998 in the Health, Aging, and Body Composition (Health ABC) study. Minnesota Code was used to define major and minor ECG abnormalities at baseline and at year 4 follow-up. Using Cox models, we assessed (1) the association between ECG abnormalities and incident HF and (2) the incremental value of adding ECG to the Health ABC HF Risk Score using the net reclassification index. Results At baseline, 380 participants (13.0%) had minor, and 620 (21.3%) had major ECG abnormalities. During a median follow-up of 11.4 years, 485 participants (16.6%) developed incident HF. After adjusting for the Health ABC HF Risk Score variables, the hazard ratio (HR) was 1.27 (95% CI 0.96-1.68) for minor and 1.99 (95% CI 1.61-2.44) for major ECG abnormalities. At year 4, 263 participants developed new and 549 had persistent abnormalities; both were associated with increased subsequent HF risk (HR 1.94, 95% CI 1.38-2.72 for new and HR 2.35, 95% CI 1.82-3.02 for persistent ECG abnormalities). Baseline ECG correctly reclassified 10.5% of patients with HF events, 0.8% of those without HF events, and 1.4% of the overall population. The net reclassification index across the Health ABC HF risk categories was 0.11 (95% CI 0.03-0.19). Conclusions Among older adults, baseline and new ECG abnormalities are independently associated with increased risk of HF. The contribution of ECG screening for targeted prevention of HF should be evaluated in clinical trials.

CONTEXT: In populations of older adults, prediction of coronary heart disease (CHD) events through traditional risk factors is less accurate than in middle-aged adults. Electrocardiographic (ECG) abnormalities are common in older adults and might be of value for CHD prediction. OBJECTIVE: To determine whether baseline ECG abnormalities or development of new and persistent ECG abnormalities are associated with increased CHD events. DESIGN, SETTING, AND PARTICIPANTS: A population-based study of 2192 white and black older adults aged 70 to 79 years from the Health, Aging, and Body Composition Study (Health ABC Study) without known cardiovascular disease. Adjudicated CHD events were collected over 8 years between 1997-1998 and 2006-2007. Baseline and 4-year ECG abnormalities were classified according to the Minnesota Code as major and minor. Using Cox proportional hazards regression models, the addition of ECG abnormalities to traditional risk factors were examined to predict CHD events. MAIN OUTCOME MEASURE: Adjudicated CHD events (acute myocardial infarction [MI], CHD death, and hospitalization for angina or coronary revascularization). RESULTS: At baseline, 276 participants (13%) had minor and 506 (23%) had major ECG abnormalities. During follow-up, 351 participants had CHD events (96 CHD deaths, 101 acute MIs, and 154 hospitalizations for angina or coronary revascularizations). Both baseline minor and major ECG abnormalities were associated with an increased risk of CHD after adjustment for traditional risk factors (17.2 per 1000 person-years among those with no abnormalities; 29.3 per 1000 person-years; hazard ratio [HR], 1.35; 95% CI, 1.02-1.81; for minor abnormalities; and 31.6 per 1000 person-years; HR, 1.51; 95% CI, 1.20-1.90; for major abnormalities). When ECG abnormalities were added to a model containing traditional risk factors alone, 13.6% of intermediate-risk participants with both major and minor ECG abnormalities were correctly reclassified (overall net reclassification improvement [NRI], 7.4%; 95% CI, 3.1%-19.0%; integrated discrimination improvement, 0.99%; 95% CI, 0.32%-2.15%). After 4 years, 208 participants had new and 416 had persistent abnormalities. Both new and persistent ECG abnormalities were associated with an increased risk of subsequent CHD events (HR, 2.01; 95% CI, 1.33-3.02; and HR, 1.66; 95% CI, 1.18-2.34; respectively). When added to the Framingham Risk Score, the NRI was not significant (5.7%; 95% CI, -0.4% to 11.8%). CONCLUSIONS: Major and minor ECG abnormalities among older adults were associated with an increased risk of CHD events. Depending on the model, adding ECG abnormalities was associated with improved risk prediction beyond traditional risk factors.

Chronic hemodialysis (CHD) patients have a high incidence and prevalence of atherosclerotic disease which may be related to numerous atherosclerotic risk factors. Among them dyslipidemia plays a significant role. Elevated Lp(a) levels, which are strongly associated with atherosclerosis, have been reported recently in uremic patients. The aim of our study was the determination of the levels of lipid parameters including Lp(a) in 151 CHD patients (76 male) aged 57 (12-81) years, who were on hemodialysis for a mean of 44.3 (range 1 to 189) months. Eighty-four normal individuals age and sex matched were used as controls. The median serum Lp(a) concentration in hemodialysis patients was 13 mg/dL compared with 6.5 mg/dL in healthy controls, p < 0.001 by distribution-free Mann-Whitney test. The prevalence of subjects with Lp(a) levels above 25 mg/dL was significantly higher in CHD patients compared to normal subjects (30% vs. 8%, p < 0.001). Even if CHD patients were matched for fasting lipid levels, they showed Lp(a) levels significantly higher than controls. No significant correlation was found between Lp(a) levels and either the age of the patients or the duration of hemodialysis. The etiology of primary renal disease did not influence the Lp(a) levels. Ren Fail

Background Wartime stress has been associated with increased late-life mortality of all causes of death. We evaluated whether wounded Finnish World War II veterans who were alive at the age of 55 have increased long-term coronary heart disease (CHD) mortality. Methods Health survey data were recorded in 1980 from 667 men, aged 55 years. Of them 102 had been wounded or injured in action during 1939-1945. The remaining participants served as the comparison group. The death certificates during a 28-year follow-up were obtained from the national statistics centre. Statistical comparisons were done by Cox proportional hazard regression model. Results There were altogether 140 deaths from CHD. In men who had been wounded or injured in action the crude CHD mortality rate per 10,000 population was 2843, while in the comparison group the corresponding figure was 1961. Men who had been wounded or injured in action were 1.7 times (95% CI 1.1-2.5; p = 0.01) more likely to die from CHD than the comparison group. Conclusions Physical trauma at young adulthood may extend to lifelong effects on health. This study suggests that being physically wounded or injured in war may lead to increased CHD mortality in late adulthood in a Finnish population.

CONTEXT: Plasma levels of C-reactive protein (CRP) are independently associated with risk of coronary heart disease, but whether CRP is causally associated with coronary heart disease or merely a marker of underlying atherosclerosis is uncertain. OBJECTIVE: To investigate association of genetic loci with CRP levels and risk of coronary heart disease. DESIGN, SETTING, AND PARTICIPANTS: We first carried out a genome-wide association (n = 17,967) and replication study (n = 13,615) to identify genetic loci associated with plasma CRP concentrations. Data collection took place between 1989 and 2008 and genotyping between 2003 and 2008. We carried out a mendelian randomization study of the most closely associated single-nucleotide polymorphism (SNP) in the CRP locus and published data on other CRP variants involving a total of 28,112 cases and 100,823 controls, to investigate the association of CRP variants with coronary heart disease. We compared our finding with that predicted from meta-analysis of observational studies of CRP levels and risk of coronary heart disease. For the other loci associated with CRP levels, we selected the most closely associated SNP for testing against coronary heart disease among 14,365 cases and 32,069 controls. MAIN OUTCOME MEASURE: Risk of coronary heart disease. RESULTS: Polymorphisms in 5 genetic loci were strongly associated with CRP levels (% difference per minor allele): SNP rs6700896 in LEPR (-14.8%; 95% confidence interval [CI], -17.6% to -12.0%; P = 6.2 x 10(-22)), rs4537545 in IL6R (-11.5%; 95% CI, -14.4% to -8.5%; P = 1.3 x 10(-12)), rs7553007 in the CRP locus (-20.7%; 95% CI, -23.4% to -17.9%; P = 1.3 x 10(-38)), rs1183910 in HNF1A (-13.8%; 95% CI, -16.6% to -10.9%; P = 1.9 x 10(-18)), and rs4420638 in APOE-CI-CII (-21.8%; 95% CI, -25.3% to -18.1%; P = 8.1 x 10(-26)). Association of SNP rs7553007 in the CRP locus with coronary heart disease gave an odds ratio (OR) of 0.98 (95% CI, 0.94 to 1.01) per 20% lower CRP level. Our mendelian randomization study of variants in the CRP locus showed no association with coronary heart disease: OR, 1.00; 95% CI, 0.97 to 1.02; per 20% lower CRP level, compared with OR, 0.94; 95% CI, 0.94 to 0.95; predicted from meta-analysis of the observational studies of CRP levels and coronary heart disease (z score, -3.45; P < .001). SNPs rs6700896 in LEPR (OR, 1.06; 95% CI, 1.02 to 1.09; per minor allele), rs4537545 in IL6R (OR, 0.94; 95% CI, 0.91 to 0.97), and rs4420638 in the APOE-CI-CII cluster (OR, 1.16; 95% CI, 1.12 to 1.21) were all associated with risk of coronary heart disease. CONCLUSION: The lack of concordance between the effect on coronary heart disease risk of CRP genotypes and CRP levels argues against a causal association of CRP with coronary heart disease. JAMA

OBJECTIVE: To compare the predictive accuracy of the original and recalibrated Framingham risk function on current morbidity from coronary heart disease (CHD) and mortality data from the Swiss population. METHODS: Data from the CoLaus study, a cross-sectional, population-based study conducted between 2003 and 2006 on 5,773 participants aged 35-74 without CHD were used to recalibrate the Framingham risk function. The predicted number of events from each risk function were compared with those issued from local MONICA incidence rates and official mortality data from Switzerland. RESULTS: With the original risk function, 57.3%, 21.2%, 16.4% and 5.1% of men and 94.9%, 3.8%, 1.2% and 0.1% of women were at very low (20%) risk, respectively. With the recalibrated risk function, the corresponding values were 84.7%, 10.3%, 4.3% and 0.6% in men and 99.5%, 0.4%, 0.0% and 0.1% in women, respectively. The number of CHD events over 10 years predicted by the original Framingham risk function was 2-3 fold higher than predicted by mortality+case fatality or by MONICA incidence rates (men: 191 vs. 92 and 51 events, respectively). The recalibrated risk function provided more reasonable estimates, albeit slightly overestimated (92 events, 5-95th percentile: 26-223 events); sensitivity analyses showed that the magnitude of the overestimation was between 0.4 and 2.2 in men, and 0.7 and 3.3 in women. CONCLUSION: The recalibrated Framingham risk function provides a reasonable alternative to assess CHD risk in men, but not in women.

Amaç: Aile gelirinin sigara içiciliği, metabolik sendrom (MS) ve bileşenleri, hiperapo B, yüksek C-reaktif protein (CRP) ile yeni gelişen koroner kalp hastalığı (KKH) bakımlarından öngördürücülüğü, cinsiyet farkları da gözetilerek araştırıldı. Çalışma planı: TEKHARF çalışması 1997/98 ve 2002/03 taramalarında yer alan ve 2004/05 taramasına kadar izlenen, 28 yaş veya üzerindeki 3273 katılımcı (1610 erkek, 1630 kadın; ort. yaş 48.3±12; ortalama izlem 5.9 yıl) prospektif biçimde incelendi. Aylık aile geliri, katılımcıların bildirimine göre, dört dilimde gruplandırıldı. Yüksek apo B için 120 mg/dl, yüksek CRP için 3.0 mg/l sınır olarak alındı; MS için TEKHARF modifikasyonlu ATP III tanısına uyuldu; KKH tanısı, öykü, kardiyovasküler sistem fizik muayenesi ve istirahat EKG’lerinin Minnesota kodlamasına dayandırıldı. Bulgular: Lojistik regresyon analiziyle yaş ayarlamasından sonra, erkeklerde gelir dilimi artışıyla diyabet, hipertansiyon ve hiperapo B’de artış öngörüldü. Kadınlarda ise, sigara içiciliği ile hiperapo B gelirle doğrusal; obezite, abdominal obezite ve - anlamlılığa erişmese de - trigliserid/HDL dislipidemi gelişmesi ters ilişki içindeydi; diyabet ve hipertansiyon gelirle öngörülemedi. Her iki cinsiyette de, yüksek CRP düzeyi riski gelir azlığında (dilim 1-3

Background and PurposeCoronary heart disease (CHD) is one of the most pressing health problems of our time and a major cause of preventable death. CHD results from complex interactions between genetic and environmental factors. Using multiplex serological testing for persistent or frequently recurring infections and genome-wide analysis in a prospective population study, we delineate the respective and combined influences of genetic variation, infections, and low-grade inflammation on the risk of incident CHD.Participants and MethodsStudy participants are enrolled in the CoLaus|PsyCoLaus study, a longitudinal, population-based cohort with baseline assessments from 2003 through 2008 and follow-up visits every five years. We analyzed a subgroup of 3’459 individuals with available genome-wide genotyping data and immunoglobulin G levels for 22 persistent or frequently recurring pathogens. All reported CHD events were evaluated by a panel of specialists. We identified independent associations with incident CHD using univariable and multivariable stepwise Cox proportional hazards regression analyses.ResultsOf the 3’459 study participants, 210 (6.07%) had at least one CHD event during the 12 years of follow-up. Multivariable stepwise Cox regression analysis, adjusted for known cardiovascular risk factors, socioeconomic status and statin intake, revealed that high polygenic risk (hazard ratio (HR) 1.31, 95% CI 1.10–156, P = 2.64e-03) and infection with Fusobacterium nucleatum (HR 1.63, 95% CI 1.08–2.45, P = 1.99e-02) were independently associated with incident CHD.ConclusionIn a prospective, population-based cohort, high polygenic risk and infection with Fusobacterium nucleatum have a small, yet independent impact on CHD risk.