W. M. Monique Verschuren

2016 ESC/EAS Guidelines for the Management of Dyslipidaemias

The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS)  Developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR)  ABI : ankle-brachial index

2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS)Developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR).

Authors/Task Force Members:Alberico L. Catapano (Chairperson) (Italy) , Ian Graham (Chairperson) (Ireland) , Guy De Backer (Belgium), Olov Wiklund (Sweden), M. John Chapman (France), Heinz Drexel (Austria), Arno W. Hoes (The Netherlands), Catriona S. Jennings (UK), Ulf Landmesser (Germany), Terje R. Pedersen (Norway), Zeljko Reiner (Croatia), Gabriele Riccardi (Italy), Marja-Riita Taskinen (Finland), Lale Tokgozoglu (Turkey), W.M. Monique Verschuren (The Netherlands), Charalambos Vlachopoulos (Greece), David A. Wood (UK), Jose Luis Zamorano (Spain)

Homocysteine Determinants and the Evidence to What Extent Homocysteine Determines the Risk of Coronary Heart Disease

Cardiovascular diseases (CVD), especially coronary heart disease (CHD), are the most important causes of death in industrialized countries. Increased concentrations of total plasma homocysteine (tHcy) have been associated with an increased risk of CHD. Assuming that this relation is causal, a lower tHcy concentration will reduce the occurrence and recurrence of CHD. Therefore, it is important to know which factors determine the tHcy concentration. In the general population, the most important modifiable determinants of tHcy are folate intake and coffee consumption. Smoking and alcohol consumption are also associated with the tHcy concentration, but more research is necessary to elucidate whether these relations are not originating from residual confounding due to other lifestyle factors. The most important nonmodifiable determinant is the 677 C>T polymorphism in the gene that encodes methylenetetrahydrofolate reductase (MTHFR), a regulating enzyme in homocysteine metabolism. Especially subjects with the homozygous form of this polymorphism (i.e., 677TT genotype) and a low folate status have elevated tHcy concentrations. Specific clinical conditions like the use of antiepileptic drugs or methotrexate, renal failure, cancer, rheumatoid arthritis, and hypothyroidism may lead to elevated tHcy concentrations. The available epidemiological evidence indicates that an increased tHcy concentration is not an important risk factor for CHD in healthy subjects. However, prospective studies, which included subjects at high risk of CHD, and secondary prevention trials with intermediary endpoints consistently show that elevations in the tHcy concentration may be an important risk factor in these subjects for a (recurrent) CHD event. The induction of vascular endothelial dysfunction by homocysteine may underlie this increased risk. Ongoing intervention trials will indicate whether homocysteine-lowering through vitamin supplementation, prevents CHD in the treatment groups.

Mendelian randomization of blood lipids for coronary heart disease.

Aims To investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization. Methods and results We developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, and low-density lipoprotein cholesterol (LDL-C). For each trait, we constructed two scores. The first was unrestricted, including all independent SNPs associated with the lipid trait identified from a prior meta-analysis (threshold P < 2 × 10−6); and the second a restricted score, filtered to remove any SNPs also associated with either of the other two lipid traits at P ≤ 0.01. Mendelian randomization meta-analyses were conducted in 17 studies including 62,199 participants and 12,099 CHD events. Both the unrestricted and restricted allele scores for LDL-C (42 and 19 SNPs, respectively) associated with CHD. For HDL-C, the unrestricted allele score (48 SNPs) was associated with CHD (OR: 0.53; 95% CI: 0.40, 0.70), per 1 mmol/L higher HDL-C, but neither the restricted allele score (19 SNPs; OR: 0.91; 95% CI: 0.42, 1.98) nor the unrestricted HDL-C allele score adjusted for triglycerides, LDL-C, or statin use (OR: 0.81; 95% CI: 0.44, 1.46) showed a robust association. For triglycerides, the unrestricted allele score (67 SNPs) and the restricted allele score (27 SNPs) were both associated with CHD (OR: 1.62; 95% CI: 1.24, 2.11 and 1.61; 95% CI: 1.00, 2.59, respectively) per 1-log unit increment. However, the unrestricted triglyceride score adjusted for HDL-C, LDL-C, and statin use gave an OR for CHD of 1.01 (95% CI: 0.59, 1.75). Conclusion The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain.

European Guidelines on cardiovascular disease prevention in clinical practice (version 2012)

European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) : the Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts).

Migraine and MTHFR C677T genotype in a population-based sample

Migraine with aura is associated with increased risk of stroke. The MTHFR C677T genotype has been associated with increased risk of migraine in selected clinical samples and with elevated homocysteine, a risk factor for stroke. We assessed the association of the MTHFR C677T variant with migraine and the mediating effect of cardiovascular risk factors and metabolic markers of genotype status.

Association of Cardiometabolic Multimorbidity With Mortality The Emerging Risk Factors Collaboration

IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy. RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

Validity of coronary heart diseases and heart failure based on hospital discharge and mortality data in the Netherlands using the cardiovascular registry Maastricht cohort study

Incidence rates of cardiovascular diseases are often estimated by linkage to hospital discharge and mortality registries. The validity depends on the quality of the registries and the linkage. Therefore, we validated incidence rates of coronary heart disease (CHD), acute myocardial infarction, unstable angina pectoris, and heart failure, estimated by this method, against the disease registry of the cardiovascular registry Maastricht cohort study. The cohort consists of 21,148 persons, born between 1927 and 1977, who were randomly sampled from Maastricht and surrounding communities in 1987–1997. Incident cases were identified by linkage to the Netherlands causes of death registry and either the hospital discharge registry (HDR) or the cardiology information system (CIS) of the University Hospital Maastricht. Sensitivities and positive predictive values were calculated using the CIS-based registry as gold standard. Relatively high sensitivities and positive predictive values were found for CHD (72 and 91%, respectively) and acute myocardial infarction (84 and 97%, respectively). These values were considerably lower for unstable angina pectoris (53 and 78%, respectively) and heart failure (43 and 80%, respectively). A substantial number of cases (14–47%) were found only in the CIS-based registry, because they were missed or miscoded in the HDR-based registry. As a consequence, the incidence rates in the HDR-based registry were considerably lower than in the CIS-based registry, especially for unstable angina pectoris and heart failure. Incidence rates based on hospital discharge and mortality data may underestimate the true incidence rates, especially for unstable angina pectoris and heart failure.

Tea and Coffee Consumption and Cardiovascular Morbidity and Mortality

Objective—To examine the associations of coffee and tea consumption with risk of morbidity and mortality of stroke and coronary heart disease (CHD) and with all-cause mortality. Methods and Results—Coffee and tea consumption were assessed with a validated food-frequency questionnaire, and 37 514 participants were observed for 13 years for the occurrence of cardiovascular morbidity and mortality. A U-shaped association between coffee and CHD was found, with the lowest hazard ratio (HR [95% CI]) for 2.1 to 3.0 cups per day (0.79 [0.65 to 0.96]; Ptrend=0.01). Tea was inversely associated with CHD, with the lowest HR (95% CI) for more than 6.0 cups per day (0.64 [0.46 to 0.90]; Ptrend=0.02). No associations between tea or coffee and stroke were found (Ptrend=0.63 and Ptrend=0.32, respectively). Although not significant, coffee slightly reduced the risk for CHD mortality (HR, 0.64; 95% CI, 0.37 to 1.11; Ptrend=0.12) for 3.1 to 6.0 cups per day. A U-shaped association between tea and CHD mortality was observed, with an HR of 0.55 (95% CI, 0.31 to 0.97; Ptrend=0.03) for 3.1 to 6.0 cups per day. Neither coffee nor tea was associated with stroke (Ptrend=0.22 and Ptrend=0.74, respectively) and all-cause mortality (Ptrend=0.33 and Ptrend=0.43, respectively). Conclusion—High tea consumption is associated with a reduced risk of CHD mortality. Our results suggest a slight risk reduction for CHD mortality with moderate coffee consumption and strengthen the evidence on the lower risk of CHD with coffee and tea consumption.

Effects of retirement on lifestyle in relation to changes in weight and waist circumference in Dutch men: a prospective study.

OBJECTIVE To study changes in lifestyle in relation to changes in body weight and waist circumference associated with occupational retirement in men. DESIGN A prospective cohort study with 5 years of follow-up. At baseline and at follow-up, questionnaires were completed and body weight and waist circumference were measured. SETTING The Doetinchem Cohort Study, consisting of inhabitants of Doetinchem, a town in a rural area of The Netherlands. SUBJECTS In total 288 healthy men aged 50-65 years at baseline, who either remained employed or retired over follow-up. RESULTS The effect of retirement on changes in weight and waist circumference was dependent on type of former occupation. Increase in body weight and waist circumference was higher among men who retired from active jobs (0.42 kg year(-1) and 0.77 cm year(-1), respectively) than among men who retired from sedentary jobs (0.08 kg year(-1) and 0.23 cm year(-1), respectively). Weight gain and increase in waist circumference were associated with a decrease in fruit consumption and fibre density of the diet, with an increase in frequency of eating breakfast, and with a decrease in several physical activities, such as household activities, bicycling, walking and doing odd jobs. CONCLUSION Retirement was associated with an increase in weight and waist circumference among those with former active jobs, but not among those with former sedentary jobs. Retirement may bring opportunities for healthy changes in diet and physical activity, which could be used in health promotion programmes.