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The article assesses whether the Framingham and PROCAM heart disease risk functions were applicable to men in Belfast and France. External validation study is performed within the PRIME (Prospective Epidemiological Study of Myocardial Infarction) cohort study. Then compared the relative risks of Coronary Heart Disease (CHD), associated with the classic risk factors in PRIME with those in Framingham and PROCAM cohorts and compared the number of predicted and observed 5 year CHD events. There was positive linear relationship between the number of CHD events predicted by the Framingham and PROCAM risk functions and that observed in PRIME.

Aims: The regional and temporal differences in the associations between cardiovascular disease (CVD) and its classic risk factors are unknown. The current study examined these associations in different European regions over a 30-year period., Methods and Results: The study sample comprised 553 818 individuals from 49 cohorts in 11 European countries (baseline: 1982-2012) who were followed up for a maximum of 10 years. Risk factors [sex, smoking, diabetes, non-HDL cholesterol, systolic blood pressure (BP), and body mass index (BMI)] and CVD events (coronary heart disease or stroke) were harmonized across cohorts. Risk factor-outcome associations were analysed using multivariable-adjusted Cox regression models, and differences in associations were assessed using meta-regression. The differences in the risk factor-CVD associations between central Europe, northern Europe, southern Europe, and the UK were generally small. Men had a slightly higher hazard ratio (HR) in southern Europe (P = 0.043 for overall difference), and those with diabetes had a slightly lower HR in central Europe (P = 0.022 for overall difference) compared with the other regions. Of the six CVD risk factors, minor HR decreases per decade were observed for non-HDL cholesterol [7% per mmol/L; 95% confidence interval (CI), 3-10%] and systolic BP (4% per 20 mmHg; 95% CI, 1-8%), while a minor HR increase per decade was observed for BMI (7% per 10 kg/m2; 95% CI, 1-13%)., Conclusion: The results demonstrate that all classic CVD risk factors are still relevant in Europe, irrespective of regional area. Preventive strategies should focus on risk factors with the greatest population attributable risk., Competing Interests: Conflict of interest: M.W. has done consultancy work for Amgen and Freeline in the last 3 years. V.S. has had research collaboration with Bayer Ltd (unrelated to the present study). All other authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Percutaneous coronary intervention reduces mortality in acute coronary syndrome patients but the cost-utility of increasing its use in elderly acute coronary syndrome patients is unknown., Methods: We assessed the efficiency of increased percutaneous coronary intervention use compared to current practice in patients aged ≥75 years admitted for acute coronary syndrome in France, Germany, Greece, Italy, Portugal and Spain with a semi-Markov state transition model. In-hospital mortality reduction estimates by percutaneous coronary intervention use and costs were derived from the EUROpean Treatment & Reduction of Acute Coronary Syndromes cost analysis EU project (n = 28,600). Risk of recurrence and out-of-hospital all-cause mortality were obtained from the Information System for the Development of Research in Primary Care (SIDIAP) database from North-Eastern Spain (n = 55,564). In-hospital mortality was modelled using stratified propensity score analysis. The 8-year acute coronary syndrome recurrence risk and out-of-hospital mortality were estimated with a multistate survival model. The scenarios analysed were to increase percutaneous coronary intervention use among patients with the highest, moderate and lowest probability of receiving percutaneous coronary intervention based on the propensity score analysis., Results: France, Greece and Portugal showed similar total costs/1000 individuals (7.29-11.05 m €); while in Germany, Italy and Spain, costs were higher (13.53-22.57 m €). Incremental cost-utility ratios of providing percutaneous coronary intervention to all patients ranged from 2262.8 €/quality adjusted life year gained for German males to 6324.3 €/quality adjusted life year gained for Italian females. Increasing percutaneous coronary intervention use was cost-effective at a willingness-to-pay threshold of 10,000 €/quality adjusted life year gained for all scenarios in the six countries, in males and females., Conclusion: Compared to current clinical practice, broadening percutaneous coronary intervention use in elderly acute coronary syndrome patients would be cost-effective across different healthcare systems in Europe, regardless of the selected strategy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background Waist circumference and hip circumference are both strongly associated with risk of death; however, their joint association has rarely been investigated. Methods and Results The MONICA Risk, Genetics, Archiving, and Monograph (MORGAM) Project was conducted in 30 cohorts from 11 countries; 90 487 men and women, aged 30 to 74 years, predominantly white, with no history of cardiovascular disease, were recruited in 1986 to 2010 and followed up for up to 24 years. Hazard ratios were estimated using sex-specific Cox models, stratified by cohort, with age as the time scale. Models included baseline categorical obesity measures, age, total and high-density lipoprotein cholesterol, systolic blood pressure , antihypertensive drugs, smoking, and diabetes mellitus. A total of 9105 all-cause deaths were recorded during a median follow-up of 10 years. Hazard ratios for all-cause death presented J- or U-shaped associations with most obesity measures. With waist and hip circumference included in the same model, for all hip sizes, having a smaller waist was strongly associated with lower risk of death, except for men with the smallest hips. In addition, among those with smaller waists, hip size was strongly negatively associated with risk of death, with ≈20% more people identified as being at increased risk compared with waist circumference alone. Conclusions A more complex relationship between hip circumference, waist circumference, and risk of death is revealed when both measures are considered simultaneously. This is particularly true for individuals with smaller waists, where having larger hips was protective. Considering both waist and hip circumference in the clinical setting could help to best identify those at increased risk of death.

Background: Patients with coronary heart disease (CHD) and survivors of acute coronary syndrome (ACS) are at very high risk for adverse cardiovascular events. Lowering low-density lipoprotein cholesterol (LDL-C) can reduce the risk, with effective lipid-lowering therapy (LLT) readily available; however, dyslipidemia remains prevalent throughout Europe., Design: The observational Dyslipidemia International Study II (DYSIS II) aimed to identify unmet treatment needs in adult ACS and CHD patients. Data for the seven participating European countries are presented herein., Methods: The study was carried out from December 2012 to November 2014. Use of LLT and attainment of European-guideline-recommended LDL-C targets were assessed. For ACS patients, changes in lipid levels and LLT were evaluated 4 months post-hospitalization., Results: Of the 4344 patients enrolled, 2946 were attending a physician visit for the assessment of stable CHD, while 1398 had been hospitalized for an ACS event. In both patient sets, mean LDL-C levels were high (89.5 and 112.5 mg/dl, respectively) and <70 mg/dl target attainment extremely poor. The mean daily statin dosage (normalized to atorvastatin potency) was 27 ± 20 mg for CHD and 22 ± 17 mg for ACS patients. Treatment was intensified slightly for ACS subjects after hospitalization, with the dosage reaching 35 ± 24 mg/day. LDL-C target attainment was higher by the end of the 4-month follow up (30.9% and 41.5% for patients on LLT and without LLT at baseline, respectively; p < 0.05)., Conclusion: Elevated blood cholesterol levels are highly prevalent across Europe, with low numbers of coronary patients reaching their recommended LDL-C target. While use of LLT is widespread, there is significant scope for intensifying treatment.

Background and Purpose: The aim was to investigate prospectively the all-cause mortality risk up to and after coronary heart disease (CHD) and stroke events in European middle-aged men., Methods: The study population comprised 10 424 men 50 to 59 years of age recruited between 1991 and 1994 in France (N=7855) and Northern Ireland (N=2747) within the Prospective Epidemiological Study of Myocardial Infarction. Incident CHD and stroke events and deaths from all causes were prospectively registered during the 10-year follow-up. In Cox's proportional hazards regression analysis, CHD and stroke events during follow-up were used as time-dependent covariates., Results: A total of 769 CHD and 132 stroke events were adjudicated, and 569 deaths up to and 66 after CHD or stroke occurred during follow-up. After adjustment for study country and cardiovascular risk factors, the hazard ratios of all-cause mortality were 1.58 (95% confidence interval 1.18-2.12) after CHD and 3.13 (95% confidence interval 1.98-4.92) after stroke., Conclusions: These findings support continuous efforts to promote both primary and secondary prevention of cardiovascular disease., (© 2015 American Heart Association, Inc.)

Objective: To assess the seasonality of cardiovascular risk factors (CVRF) in a large set of population-based studies., Methods: Cross-sectional data from 24 population-based studies from 15 countries, with a total sample size of 237 979 subjects. CVRFs included Body Mass Index (BMI) and waist circumference; systolic (SBP) and diastolic (DBP) blood pressure; total, high (HDL) and low (LDL) density lipoprotein cholesterol; triglycerides and glucose levels. Within each study, all data were adjusted for age, gender and current smoking. For blood pressure, lipids and glucose levels, further adjustments on BMI and drug treatment were performed., Results: In the Northern and Southern Hemispheres, CVRFs levels tended to be higher in winter and lower in summer months. These patterns were observed for most studies. In the Northern Hemisphere, the estimated seasonal variations were 0.26 kg/m(2) for BMI, 0.6 cm for waist circumference, 2.9 mm Hg for SBP, 1.4 mm Hg for DBP, 0.02 mmol/L for triglycerides, 0.10 mmol/L for total cholesterol, 0.01 mmol/L for HDL cholesterol, 0.11 mmol/L for LDL cholesterol, and 0.07 mmol/L for glycaemia. Similar results were obtained when the analysis was restricted to studies collecting fasting blood samples. Similar seasonal variations were found for most CVRFs in the Southern Hemisphere, with the exception of waist circumference, HDL, and LDL cholesterol., Conclusions: CVRFs show a seasonal pattern characterised by higher levels in winter, and lower levels in summer. This pattern could contribute to the seasonality of CV mortality., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Aims: Despite common European Society of Cardiology recommendations, adherence to guideline therapy varies, both temporally and geographically. We sought to examine current differences in the use of guideline-recommended therapies among 14 European countries in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI)., Methods and Results: Data were obtained from the Antiplatelet Therapy Observational Registry (APTOR), a non-interventional, prospective observational cohort study enrolling patients with ACS undergoing PCI. Medication data were captured through 1 year. The large majority of patients in the APTOR registry received statins at hospital discharge (89%) and remained on statins at 1 year (87%), a finding that was consistent across countries. Likewise, beta-blocker use was similar at discharge and 1 year (83 and 81%, respectively). There was large disparity in aspirin loading dose between countries, but the discharge maintenance dose was more consistent, with most receiving ≤ 100 mg (87%). While 95% of patients were discharged on dual antiplatelet therapy, 71% remained on both treatments by 1 year, with wide variation by country in 1-year use., Conclusions: These data from the APTOR study provide key information on current European ACS patient care management from hospitalization through 1 year. Even with European Society of Cardiology (ESC) guidelines, variations in practice patterns exist among ACS patients treated with PCI between the 14 European countries studied, including the use of proven therapies, as well as appropriate duration and dosing of antiplatelet regimens. Efforts are needed to further explain why such variation exists and to continue to improve adherence to ESC guidelines to improve patient care.

Objective: End-stage coagulation and the structure/function of fibrin are implicated in the pathogenesis of ischemic stroke. We explored whether genetic variants associated with end-stage coagulation in healthy volunteers account for the genetic predisposition to ischemic stroke and examined their influence on stroke subtype., Methods: Common genetic variants identified through genome-wide association studies of coagulation factors and fibrin structure/function in healthy twins (n = 2,100, Stage 1) were examined in ischemic stroke (n = 4,200 cases) using 2 independent samples of European ancestry (Stage 2). A third clinical collection having stroke subtyping (total 8,900 cases, 55,000 controls) was used for replication (Stage 3)., Results: Stage 1 identified 524 single nucleotide polymorphisms (SNPs) from 23 linkage disequilibrium blocks having significant association (p < 5 × 10(-8)) with 1 or more coagulation/fibrin phenotypes. The most striking associations included SNP rs5985 with factor XIII activity (p = 2.6 × 10(-186)), rs10665 with FVII (p = 2.4 × 10(-47)), and rs505922 in the ABO gene with both von Willebrand factor (p = 4.7 × 10(-57)) and factor VIII (p = 1.2 × 10(-36)). In Stage 2, the 23 independent SNPs were examined in stroke cases/noncases using MOnica Risk, Genetics, Archiving and Monograph (MORGAM) and Wellcome Trust Case Control Consortium 2 collections. SNP rs505922 was nominally associated with ischemic stroke (odds ratio = 0.94, 95% confidence interval = 0.88-0.99, p = 0.023). Independent replication in Meta-Stroke confirmed the rs505922 association with stroke, beta (standard error, SE) = 0.066 (0.02), p = 0.001, a finding specific to large-vessel and cardioembolic stroke (p = 0.001 and p = < 0.001, respectively) but not seen with small-vessel stroke (p = 0.811)., Interpretation: ABO gene variants are associated with large-vessel and cardioembolic stroke but not small-vessel disease. This work sheds light on the different pathogenic mechanisms underpinning stroke subtype., (Copyright © 2012 American Neurological Association.)

Objective: This study evaluated the success in attaining non-HDL-cholesterol (non-HDL-C) goals in the multinational L-TAP 2 study., Methods: 9955 patients ≥20 years of age with dyslipidemia on stable lipid-lowering therapy were enrolled from nine countries., Results: Success rates for non-HDL-C goals were 86% in low, 70% in moderate, and 52% in high-risk patients (63% overall). In patients with triglycerides of >200 mg/dL success rates for non-HDL-C goals were 35% vs. 69% in those with ≤200 mg/dL (p < 0.0001). Among patients attaining their LDL-C goal, 18% did not attain their non-HDL-C goal. In those with coronary disease and at least two risk factors, only 34% and 30% attained respectively their non-HDL-C and LDL-C goals. Rates of failure in attaining both LDL-C and non-HDL-C goals were highest in Latin America., Conclusions: Non-HDL-C goal attainment lagged behind LDL-C goal attainment; this gap was greatest in higher-risk patients., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: To examine prospectively the association of high-sensitivity C-reactive protein, interleukin 6, and fibrinogen with sudden death in asymptomatic European men., Methods and Results: Among the 9771 men from the Etude PRospective de l'Infarctus du Myocarde (PRIME) Study, 664 had a first coronary heart disease over 10 years, including 50 sudden deaths, 34 nonsudden coronary deaths, and 580 nonfatal coronary heart disease events. For each outcome, 2 matched controls, who were free of coronary heart disease at the index date, were randomly selected from the initial cohort (nested case control study design). There was a 3-fold increased risk (95% CI, 1.20 to 7.81) of sudden death between the upper and the lower third of interleukin 6 after adjustment for baseline confounders in conditional logistic regression analysis. Neither high-sensitivity C-reactive protein (hazard ratio(third versus first tertile)=1.27; 95% CI, 0.51 to 3.17) nor fibrinogen (hazard ratio(third versus first tertile)=1.90; 95% CI, 0.76 to 4.75) was associated with sudden death. For comparison, there was a 6-fold increased risk of nonsudden coronary death from the highest compared with the lowest tertile of fibrinogen and a trend toward an association with higher C-reactive protein and higher interleukin 6. All 3 inflammatory biomarkers were moderately, but significantly, associated with nonfatal coronary heart disease., Conclusions: Interleukin 6, but not high-sensitivity C-reactive protein or fibrinogen, is an independent predictor of sudden death in asymptomatic European men.

Background: Data on the possible association between depressive disorders and inflammatory markers are scarce and inconsistent. We investigated whether subjects with depressive mood had higher levels of a wide range of inflammatory markers involved in coronary heart disease (CHD) incidence and examined the contribution of these inflammatory markers and depressive mood to CHD outcome., Methods and Results: We built a nested case-referent study within the Prospective Epidemiological Study of Myocardial Infarction (PRIME) study of healthy middle-aged men from Belfast and France. We considered the baseline plasma sample from 335 future cases (angina pectoris, nonfatal myocardial infarction, coronary death) and 670 matched controls (2 controls per case). Depressive mood characterized men whose baseline depression score (13-item modification of the Welsh depression subscale) was in the fourth quartile (mean score, 5.75; range, 4 to 12). On average, men with depressive mood had 46%, 16%, and 10% higher C-reactive protein, interleukin-6, and intercellular adhesion molecule-1 levels, respectively, independently of case-control status, social characteristics, and classic cardiovascular risk factors; no statistical difference was found for fibrinogen. The odds ratios of depressive mood for CHD were 1.35 (95% CI, 1.05 to 1.73) in univariate analysis and 1.50 (95% CI, 1.04 to 2.15) after adjustment for social characteristics and classic cardiovascular risk factors. The latter odds ratio remained unchanged when each inflammatory marker was added separately, and in this analysis, each inflammatory marker contributed significantly to CHD event risk., Conclusions: These data support an association of depressive mood with inflammatory markers and suggest that depressive mood is related to CHD even after adjustment for these inflammatory markers.