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The association between dietary patterns (DP) and prevalence of hearing loss in men enrolled in the Caerphilly Prospective Study was investigated. During 1979–1983, the study recruited 2512 men aged 45–59 years. At baseline, dietary data were collected using a semi-quantitative FFQ, and a 7-d weighed food intake (WI) in a 30 % subsample. Five years later, pure-tone unaided audiometric threshold was assessed at 0·5, 1, 2 and 4 kHz. Principal component analysis (PCA) identified three DP and multiple logistic and ordinal logistic regression models examined the association with hearing loss (defined as pure-tone average of frequencies 0·5, 1, 2 and 4 kHz >25 dB). Traditional, healthy and high-sugar/low-alcohol DP were found with both FFQ and WI data. With the FFQ data, fully adjusted models demonstrated significant inverse association between the healthy DP and hearing loss both as a dichotomous variable (OR=0·83; 95 % CI 0·77, 0·90; PPPP=0·02) and as an ordinal variable (OR=1·17; 95 % CI 1·03, 1·33; P=0·02). A healthy DP was significantly and inversely associated with hearing loss in older men. The role of diet in age-related hearing loss warrants further investigation.

Aims Epidemiological evidence suggests that adipokines may be associated with the onset of type 2 diabetes, but the evidence to date is limited and inconclusive. This study examined the association between adiponectin and leptin and the subsequent diagnosis of type 2 diabetes in a UK population based cohort of non-diabetic middle-aged men. Methods Baseline serum levels of leptin and adiponectin were measured in 1839 non-diabetic men aged 50–60 years who were participating in the prospective population-based PRIME study. Over a mean follow-up of 14.7 years, new cases of type 2 diabetes were determined from self-reported clinical information with subsequent validation by general practitioners. Results 151 Participants developed type 2 diabetes during follow-up. In Cox regression models adjusted for age, men in the top third of the leptin distribution were at increased risk (hazard ratio (HR) 4.27, 95% CI 2.67–6.83) and men in the top third of the adiponectin distribution at reduced risk (HR 0.24, 95% CI 0.14–0.42) relative to men in the bottom third. However, significance was lost for leptin after additional adjustment for BMI, waist to hip ratio, lifestyle factors and biological risk factors, including C-reactive protein (CRP). Further adjustment for HOMA-IR also resulted in loss of significance for adiponectin. Conclusions This study provides evidence that adipokines are associated with men’s future type 2 diabetes risk but not independently of other risk factors.

AIMS: Our aims were to evaluate the distribution of troponin I concentrations in population cohorts across Europe, to characterize the association with cardiovascular outcomes, to determine the predictive value beyond the variables used in the ESC SCORE, to test a potentially clinically relevant cut-off value, and to evaluate the improved eligibility for statin therapy based on elevated troponin I concentrations retrospectively.METHODS AND RESULTS: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project, we analysed individual level data from 10 prospective population-based studies including 74 738 participants. We investigated the value of adding troponin I levels to conventional risk factors for prediction of cardiovascular disease by calculating measures of discrimination (C-index) and net reclassification improvement (NRI). We further tested the clinical implication of statin therapy based on troponin concentration in 12 956 individuals free of cardiovascular disease in the JUPITER study. Troponin I remained an independent predictor with a hazard ratio of 1.37 for cardiovascular mortality, 1.23 for cardiovascular disease, and 1.24 for total mortality. The addition of troponin I information to a prognostic model for cardiovascular death constructed of ESC SCORE variables increased the C-index discrimination measure by 0.007 and yielded an NRI of 0.048, whereas the addition to prognostic models for cardiovascular disease and total mortality led to lesser C-index discrimination and NRI increment. In individuals above 6 ng/L of troponin I, a concentration near the upper quintile in BiomarCaRE (5.9 ng/L) and JUPITER (5.8 ng/L), rosuvastatin therapy resulted in higher absolute risk reduction compared with individuals CONCLUSION: In individuals free of cardiovascular disease, the addition of troponin I to variables of established risk score improves prediction of cardiovascular death and cardiovascular disease.

Introduction: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a risk factor for atrial fibrillation and a marker of cardiac function used in detection of heart failure. Few studies evaluated the role of NT-proBNP as risk factor for stroke. Hypothesis: Given the link between cardiac dysfunction and stroke, NT-proBNP is a candidate marker of stroke risk. Our aim was to evaluate the association of NT-proBNP with stroke outcomes and to determine the predictive value beyond a panel of established risk factors for stroke. Methods: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project we analysed data of 43,815 participants (48.3% men; mean age 52 yr) free of cardiovascular disease from 6 prospective population-based cohorts across Europe with a maximum follow-up of 22 years. All NT-proBNP measurements were performed on frozen samples in the central BiomarCaRE laboratory. The endpoints considered were validated fatal and non-fatal stroke. Results: We observed 565 stroke events (78 fatal) in men and 290 (54) in women. Growing quartiles of NT-proBNP were associated with increasing risk of stroke (Table; multivariable cox regression analysis adjusted for the base model: age, centre, smoking, BMI, diabetes, hypertension medication, systolic and diastolic blood pressure, total and HDL cholesterol), both in men (p for trend Conclusions: In European individuals free of cardiovascular disease, levels of NT-proBNP in the top quartile (>87.7 pg/mL) are associated with a doubled risk of stroke. However, the addition of NT-proBNP to variables of established risk score poorly improves prediction of stroke disease.

 Restitution programs are widely used to hold offenders accountable for their actions while providing restoration to victims and community service. However, compliance with restitution requirements is a major problem, as reported by juvenile probation offices across the country. The Firewood Program was developed for juvenile probationers in a rural Pennsylvania county to improve the completion rate of restitution payments to victims and provide community service. This study examines the effectiveness of the restitution program, which was measured as an increase in the offender’s level of empathy and shorter completion times of restitution payments. Â

Aims: As promising compounds to lower Lipoprotein(a) (Lp(a)) are emerging, the need for a precise characterization and comparability of the Lp(a)-associated cardiovascular risk is increasing. Therefore, we aimed to evaluate the distribution of Lp(a) concentrations across the European population, to characterize the association with cardiovascular outcomes and to provide high comparability of the Lp(a)-associated cardiovascular risk by use of centrally determined Lp(a) concentrations. Methods and results: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project, we analysed data of 56 804 participants from 7 prospective population-based cohorts across Europe with a maximum follow-up of 24 years. All Lp(a) measurements were performed in the central BiomarCaRE laboratory (Biokit Quantia Lp(a)-Test; Abbott Diagnostics). The three endpoints considered were incident major coronary events (MCE), incident cardiovascular disease (CVD) events, and total mortality. We found lower Lp(a) levels in Northern European cohorts (median 4.9 mg/dL) compared to central (median 7.9 mg/dL) and Southern European cohorts (10.9 mg/dL) (Jonckheere-Terpstra test P&thinsp

cardiovascular disease: Emerging opportunities for prevention?☆ Yolande Esquirol ⁎, John Yarnell , Jean Ferrieres , Alun Evans , Jean-Bernard Ruidavets , Aline Wagner , Jean Dallongeville , Dominique Arveiler , Pierre Ducimetiere , Philippe Amouyel , Annie Bingham , Frank Kee d and on behalf of the Prime study a Inserm, UMR1027, Toulouse, F-31073, France b Universite de Toulouse III, UMR1027, Toulouse, F-31073, France c CHU Toulouse, SMPE, F-31059, France d UK Clinical Research Collaboration Centre of Excellence for Public Health, Queen's University Belfast, Belfast, UK e CHU Toulouse, Department of Cardiology B, F-31059, France f Strasbourg MONICA Project, Department of Epidemiology and Public Health, EA 3430, Strasbourg University, 67085 Strasbourg cedex, France g Lille MONICA Project, Inserm UMR744, Lille, France h Institut Pasteur de Lille, Lille, France i Lille Nord de France University, Lille, France j Inserm-Paris XI University, Paul Brousse Hospital, Villejuif, France

Objective To test the applicability of the sex-specific 2008 Framingham general cardiovascular risk equation for coronary heart disease (CHD) and stroke in European middle-aged men from Ireland and France. Methods In the PRIME study, 9638 healthy middle-aged men recruited in France and Ireland were surveyed for 10 years for the occurrence of first CHD and stroke events. The original Framingham equation, the partially calibrated Framingham equation (using the PRIME baseline survival at 10 years), and the completely calibrated Framingham equation (additionally using risk factor means calculated in PRIME) were assessed. Model fit (expected versus observed events) and discrimination ability were assessed using a modified Hosmer–Lemeshow Chi-square statistic and Harrell's c-index respectively. Results The original (uncalibrated) Framingham equation overestimated by 1.94-fold the risk of CHD and stroke combined in PRIME, and by 2.23 and 1.42-fold in PRIME-France and PRIME-Ireland respectively. Adequate fit was found after complete calibration. However, discrimination ability of the Framingham equation was poor as shown by Harrell's c-index lower than 0.70. Conclusion The (completely) calibrated 2008 Framingham equation predicted accurate number of CHD and stroke events but discriminated poorly individuals at higher from those at lower event risk in a European population of middle-aged men.

To investigate the association between periodontitis and mortality from all causes in a prospective study in a homogenous group of 60- to 70-year-old West European men.A representative sample of 1400 dentate men, (mean age 63.8, SD 3.0 years), drawn from the population of Northern Ireland, had a comprehensive periodontal examination between 2001 and 2003. Men were divided into thirds on the basis of their mean periodontal attachment loss (PAL). The primary endpoint, death from any cause, was analysed using Kaplan-Meier survival plots and Cox's proportional hazards model.In total, 152 (10.9%) of the men died during a mean follow-up of 8.9 (SD 0.7) years; 37 (7.9%) men in the third with the lowest PAL (1.8 mm) died compared with 73 (15.7%) in the third with the highest PAL (2.6 mm). The unadjusted hazard ratio (HR) for death in the men with the highest level of PAL compared with those with the lowest PAL was 2.11 (95% CI 1.42-3.14), p 0.0001. After adjustment for confounding variables (age, smoking, hypertension, BMI, diabetes, cholesterol, education, marital status and previous history of a cardiovascular event) the HR was 1.57 (1.04-2.36), p = 0.03.The European men in this prospective cohort study with the most severe loss of periodontal attachment were at an increased risk of death compared with those with the lowest loss of periodontal attachment.

Activated partial thromboplastin time (aPTT) and prothrombin time (PT) are clinical tests commonly used to screen for coagulation-factor deficiencies. One genome-wide association study (GWAS) has been reported previously for aPTT, but no GWAS has been reported for PT. We conducted a GWAS and meta-analysis to identify genetic loci for aPTT and PT. The GWAS for aPTT was conducted in 9,240 individuals of European ancestry from the Atherosclerosis Risk in Communities (ARIC) study, and the GWAS for PT was conducted in 2,583 participants from the Genetic Study of Three Population Microisolates in South Tyrol (MICROS) and the Lothian Birth Cohorts (LBC) of 1921 and 1936. Replication was assessed in 1,041 to 3,467 individuals. For aPTT, previously reported associations with KNG1, HRG, F11, F12, and ABO were confirmed. A second independent association in ABO was identified and replicated (rs8176704, p = 4.26 × 10(-24)). Pooling the ARIC and replication data yielded two additional loci in F5 (rs6028, p = 3.22 × 10(-9)) and AGBL1 (rs2469184, p = 3.61 × 10(-8)). For PT, significant associations were identified and confirmed in F7 (rs561241, p = 3.71 × 10(-56)) and PROCR/EDEM2 (rs2295888, p = 5.25 × 10(-13)). Assessment of existing gene expression and coronary artery disease (CAD) databases identified associations of five of the GWAS loci with altered gene expression and two with CAD. In summary, eight genetic loci that account for ∼29% of the variance in aPTT and two loci that account for ∼14% of the variance in PT were detected and supported by functional data.

Objective: Adipocytokines are hormones secreted from adipose tissue that possibly link adiposity and the risk of cardiovascular disease, but limited prospective data exist on plasma adipocytokines and ischemic stroke risk. We investigated associations and predictive properties of 4 plasma adipocytokines, namely resistin, adipsin, leptin, and total adiponectin, with regard to incident ischemic stroke in the PRIME Study. Methods: A cohort of 9,771 healthy men 50 to 59 years of age at baseline was followed up over a period of 10 years. In a nested case–control study, 95 ischemic stroke cases were matched with 190 controls on age, study center, and date of examination. Hazard ratios (HRs) per standard deviation increase in plasma adipocytokine levels were estimated using conditional logistic regression analysis. The additive value of adipocytokines in stroke risk prediction was evaluated by discrimination and reclassification metrics. Results: Resistin (HR, 1.88; 95% confidence interval [CI], 1.16–3.03), adipsin (HR, 2.01; 95% CI, 1.33–3.04), and total adiponectin (HR, 1.53; 95% CI, 1.01–2.34), but not leptin, were independent predictors of ischemic stroke. The performance of a traditional risk factor model predicting ischemic stroke was significantly improved by the simultaneous inclusion of resistin, adipsin, and total adiponectin (c-statistic: 0.673 [95% CI, 0.631–0.766] vs 0.826 [95% CI, 0.792–0.892], p < 0.001; net reclassification improvement: 38.1%, p < 0.001). Interpretation: Higher plasma levels of resistin, adipsin, and total adiponectin were associated with an increased 10-year risk of ischemic stroke among healthy middle-aged men. Resistin, adipsin, and total adiponectin provided incremental value over traditional risk factors for the prediction of ischemic stroke risk. ANN NEUROL 2012

Objective To examine the contribution of lifestyle behaviours to the socioeconomic gradient in all-cause mortality, and fatal and non-fatal cardiovascular events. Method 10,600 men aged 50–59 years examined in 1991–1994 in Northern Ireland (NI) and France and followed annually for deaths and cardiovascular events for 10 years. Baseline smoking habit, physical activity, and fruit, vegetable, and alcohol consumption were assessed. Results All lifestyle behaviours showed marked socioeconomic gradients for most indicators in NI and France, with the exception of percentage of alcohol consumers in NI and frequency of alcohol consumption in NI and France. At 10 years, there were 544 deaths from any cause and 440 fatal and non-fatal cardiovascular events. After adjustment for country and age, socioeconomic gradients were further adjusted for lifestyle behaviours. For total mortality, the median residual contribution of lifestyle behaviours was 28% and for cardiovascular incidence, 41%. When cardiovascular risk factors were considered in conjunction with lifestyle behaviours these percentages increased to 38% and 67% respectively. Conclusion Lifestyle behaviours contribute to the gradient in mortality and cardiovascular incidence between socioeconomic groups, particularly for cardiovascular incidence, but a substantial proportion of these differentials was not explained by lifestyle behaviours and cardiovascular risk factors.

Background: The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain. Methods: We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies. Results: For people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators. Conclusion: Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2012; all rights reserved.

Background This study examines the contribution of lifetime smoking habit to the socioeconomic gradient in all-cause and smoking-related mortality and in cardiovascular incidence in two countries. Methods 10 600 men aged 50–59 years were examined in 1991–4 in centres in Northern Ireland and France and followed annually for 10 years. Deaths and cardiovascular events were documented. Current smoking habit, lifetime smoking (pack-years) and other health behaviours were evaluated at baseline. As socio-occupational coding schemes differ between the countries seven proxy socioeconomic indicators were used. Results Lifetime smoking habit showed marked associations with most socioeconomic indicators in both countries, but lifetime smoking was more than 10 pack-years greater overall in Northern Ireland and smoking patterns differed. Total mortality was 49% higher in Northern Ireland than in France, and smoking-related mortality and cardiovascular incidence were 93% and 92% higher, respectively. Both lifetime smoking and fibrinogen contributed independently to these differentials, but together explained only 42% of the difference in total mortality between countries, adjusted for both biological and lifestyle confounders. Socioeconomic gradients were steeper for total and smoking-related mortality than for cardiovascular incidence. Residual contributions of lifetime smoking habit ranged from 6% to 34% for the seven proxy indicators of socioeconomic position for total and smoking-related mortality. Socioeconomic gradients in cardiovascular incidence were minimal following adjustment for confounders. Conclusion In Northern Ireland and France lifetime smoking appeared to explain a significant part of the gradients in total and smoking-related mortality between socioeconomic groups, but the contribution of smoking was generally small for cardiovascular incidence.

Objective— Hemostasis and inflammation have been implicated in dementia. This study investigates the role of specific hemostatic and inflammatory pathways with incident vascular and nonvascular dementia. Methods and Results— This was a prospective study of a population sample of men aged 65 to 84 years, with baseline assessment of hemostatic and inflammatory factors and cognition measured 17 years later. The sample included 865 men (59 had dementia and 112 had cognitive impairment, not dementia), free of vascular disease at baseline and for whom hemostatic and inflammatory marker data were available and cognitive status was known. A total of 15 hemostatic and 6 inflammatory markers were assessed. Factor analysis was used to identify hemostatic subsystems. The National Institute of Neurological Disorders and Stroke–Association Internationale pour la Recherche et l’Enseignement en Neurologie criteria were used to identify vascular dementia. By using standardized ( z ) scores for hemostatic and inflammatory markers, and after adjustment for age and risk factors, vascular dementia was associated with fibrinogen (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.02–2.76), factor VIII (HR, 1.79; 95% CI, 1.09–3.00), and plasminogen activator inhibitor 1 (HR, 3.13; 95% CI, 1.73–5.70). For vascular dementia, the HR risk from high levels of all three hemostatic variables (fibrinogen, factor VIII, and plasminogen activator inhibitor 1) was 2.97 ( P Conclusion— The associations of these hemostatic markers with vascular dementia may implicate clot formation as the primary mechanism and are consistent with a microinfarct model of vascular dementia.

Aim: To compare within the same cohort the association of a large panel of lipids with the risk of incident coronary heart disease (CHD) and ischemic stroke events in participants of the Prospective Epidemiological Study of Myocardial Infarction. Methods: In this binational (Northern Ireland and France) prospective cohort, we considered 9,711 men aged 50–59 years free of CHD and stroke at baseline (1991–1993). The hazard ratios of each lipid marker for CHD and ischemic stroke events were estimated in separate Cox proportional hazard models adjusted for age, study center, systolic blood pressure, antihypertensive treatment, current smoking status, body mass index and diabetes. Results: After 10 years of follow-up, 635 men had a first CHD and 98 a first ischemic stroke event. Total cholesterol (total-C), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-HDL-C, triglycerides, apolipoprotein (Apo) A1 and Apo B100, their ratios and lipoprotein (a) [Lp(a)] were all significantly predictive of future CHD. Associations with ischemic stroke followed the same trend as for CHD, but with lower strength, and none were statistically significant. However, none of the differences between the hazard ratios for CHD and for ischemic stroke were statistically significant. Conclusions: In healthy, middle-aged men, total-C, HDL-C, LDL-C, non-HDL-C, triglycerides, Apo A1 and Apo B100, their ratios and Lp(a) are, if anything, weak predictors of ischemic stroke events over a 10-year period.

The association between cognitive function and mortality is of increasing interest. We followed 1870 men aged 55–69 years at cognitive assessment for 16 years to establish associations with all case and cause specific mortality. Cognitive assessment included AH4, 4 choice reaction time (used as estimates of mid-life cognition) and the National Adult Reading Test (used as an estimate of early-life cognition). Causal models were tested for the effects of a) early-life cognition, b) confounding through mid-life disease, and c) the effects of sociodemographic and lifestyle factors. A fully adjusted model was also tested. Age adjusted associations with mid-life cognitive function were found with mortality from circulatory, coronary, respiratory and digestive disease but not from cancer mortality. Age adjusted associations were attenuated and in some cases nullified by further adjustment for each of early-life cognition, mid-life disease risk and sociodemographic and lifestyle factors. These associations cannot be assumed to be unbiased estimates of effect due to the complex confounding structures that exist in these data. Future studies should explore natural experiments, use different populations where the confounding structures may be different and evaluate more complex methods that may be able to deal with the inherent complexities of a life course perspective.

Although pharmacological treatments of hypertension and dyslipidaemia are both associated with a reduction in cardiovascular risk, little is known about the degree of cardiovascular risk remaining in treated individuals, by assessing the levels of their risk factors achieved, that is their 'residual cardiovascular risk'. We then used the data from the Prospective Epidemiological Study of Myocardial Infarction (PRIME), which involved 9649 men aged 50-59 years, from France and Northern Ireland with a 10-year follow-up, to test the presence of specific residual cardiovascular risks of coronary heart disease, stroke, total of fatal and non-fatal cardiovascular events and cardiovascular mortality, in patients treated with antihypertensive agents or lipid-lowering agents. In the whole cohort, a total of 796 patients developed a fatal or non-fatal cardiovascular event. Antihypertensive drug use at baseline was significantly associated (RR=1.50, 95% CI: 1.25-1.80) with total cardiovascular event risk, but not lipid-lowering drug use, after adjusting for classic risk factors (age, smoking, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure and diabetes). Similar results were obtained for coronary heart disease (RR=1.46, 95% CI: 1.18-1.80), stroke (RR=1.75, 95% CI: 1.14-2.70) and cardiovascular death (RR=1.62, 95% CI: 1.02-2.58), but neither for total death (RR=1.15, 95% CI: 0.89-1.48) nor for non-cardiovascular death (RR=1.00, 95% CI: 0.74-1.36). For any cardiovascular end point, residual risks did not globally differ according to the antihypertensive drug class prescribed at baseline. In conclusion, treatment with antihypertensive agents, but not with lipid-lowering agents, was associated with a sizeable residual cardiovascular risk, suggesting that more efficient risk reduction strategies in hypertension should be developed as a priority.

We investigated the associations of circulating C-reactive protein (CRP) and interleukin-6 (IL-6) with cancer risk. We examined the associations of CRP and IL-6 with incident cancer in two prospective cohorts, the British Women’s Heart and Health Study (4,286 women aged 60–80) and the Caerphilly Cohort (2,398 men aged 45–59) using Cox regression and pooled our findings with previous prospective studies’ in fixed and random effects meta-analyses. CRP and IL-6 were associated with some incident cancers in our cohorts, but the numbers of cancer cases were small. In our meta-analyses elevated CRP was associated with an increased overall risk of cancer (random effects estimate (RE): 1.10, 95% CI: 1.02, 1.18) and lung cancer (RE: 1.32, 95% CI: 1.08, 1.61). Its associations with colorectal (RE: 1.09, 95% CI: 0.98, 1.21) and breast cancer risks (RE: 1.10, 95% CI: 0.97, 1.26) were weaker. CRP appeared unrelated to prostate cancer risk (RE: 1.00 0.88, 1.13). IL-6 was associated with increased lung and breast cancer risks and decreased prostate cancer risk, and was unrelated to colorectal cancer risk. Our findings suggest an etiological role for CRP and IL-6 in some cancers. Further large prospective and genetic studies would help to better understand this role.

Other experts who contributed to parts of the guidelines: Edmond Walma, Schoonhoven (The Netherlands), Tony Fitzgerald, Dublin (Ireland), Marie Therese Cooney, Dublin (Ireland), Alexandra Dudina, Dublin (Ireland) European Society of Cardiology (ESC) Committee for Practice Guidelines (CPG):, Alec Vahanian (Chairperson) (France), John Camm (UK), Raffaele De Caterina (Italy), Veronica Dean (France), Kenneth Dickstein (Norway), Christian Funck-Brentano (France), Gerasimos Filippatos (Greece), Irene Hellemans (The Netherlands), Steen Dalby Kristensen (Denmark), Keith McGregor (France), Udo Sechtem (Germany), Sigmund Silber (Germany), Michal Tendera (Poland), Petr Widimsky (Czech Republic), José Luis Zamorano (Spain) Document reviewers: Irene Hellemans (CPG Review Coordinator) (The Netherlands), Attila Altiner (Germany), Enzo Bonora (Italy), Paul N. Durrington (UK), Robert Fagard (Belgium), Simona Giampaoli(Italy), Harry Hemingway (UK), Jan Hakansson (Sweden), Sverre Erik Kjeldsen (Norway), Mogens Lytken Larsen (Denmark), Giuseppe Mancia (Italy), Athanasios J. Manolis (Greece), Kristina Orth-Gomer (Sweden), Terje Pedersen (Norway), Mike Rayner (UK), Lars Ryden (Sweden), Mario Sammut (Malta), Neil Schneiderman (USA), Anton F. Stalenhoef (The Netherlands), Lale Tokgözoglu (Turkey), Olov Wiklund (Sweden), Antonis Zampelas (Greece)

Findings from short-term randomized trials indicate that dietary supplements of omega-3 polyunsaturated fatty acids (PFA) lower blood pressure of hypertensive persons, but effect size in nonhypertensive individuals is small and nonsignificant. Data are lacking on food omega-3 PFA and blood pressure in general populations. The International Study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP) is an international cross-sectional epidemio- logic study of 4680 men and women ages 40 to 59 from 17 population-based samples in China, Japan, United Kingdom, and United States. We report associations of food omega-3 PFA intake (total, linolenic acid, long-chain) of individuals with blood pressure. Systolic and diastolic blood pressure were measured 8 times at 4 visits. With several models to control for possible confounders (dietary, other), linear regression analyses showed inverse relationship of total omega-3 PFA from food (percent kilocalories, from four 24-hour dietary recalls) to systolic and diastolic blood pressures. With adjustment for 17 variables, estimated systolic blood pressure/diastolic blood pressure differences with 2 standard deviation higher (0.67% kcal) omega-3 PFA were 0.55/0.57 mm Hg (Z-score 1.33, 2.00); for 2238 persons without medical or dietary intervention, 1.01/0.98 mm Hg (Z 1.63, 2.25); for 2038 nonhypertensive persons from this sub-cohort, 0.91/0.92 mm Hg (Z 1.80, 2.38). For linolenic acid (largely from vegetable foods), blood pressure differences were similar, eg, for the 2238 "nonintervened" individuals, 0.97/0.87 mm Hg (Z 1.52, 1.95); blood pressure differences were 0.32/0.45 mm Hg for long-chain omega-3 PFA (largely from fish). In summary, food omega-3 PFA intake related inversely to blood pressure, including in nonhypertensive persons, with small estimated effect size. Food omega-3 PFA may contribute to prevention and control of adverse blood pressure levels. (Hypertension. 2007;50:313-319.)

Objective: The aim of this study was to assess the relationship between lycopene and insulin-like growth factor-1 levels in a healthy male population. Design: Insulin-like growth factor-1 status was assessed in healthy men aged 30–49 years (n = 104) with either high or low lycopene concentrations. Results: There was no significant difference between insulin-like growth factor-1 levels in the high- and low-lycopene groups; high lycopene group; 8.21 (2.73) nmol/L; low lycopene group; 7.65 (2.14) nmol/L, p = 0.46 (Mean (SD)). Conclusions: In this small observational study, no association was found between lycopene concentration and insulin-like growth factor-1 concentration.

Isolated negative T waves (INTW) are considered a common and minor electrocardiographic (ECG) abnormality. However, few recent studies have associated the presence of INTW with an increased risk of all-causes and cardiovascular mortalities. The aim was to evaluate the predictive value of INTW for coronary heart disease (CHD) and all-cause mortality.Between 1991 and 1994, 12-lead ECGs were recorded in a sample of 10,600 men (PRIME Study). Among them, 1284 (12.1%) were excluded because of major ECG abnormalities at entry according to Minnesota code, a history of CHD or likely ischemic chest pain on the Rose Questionnaire. INTW were found in 256 subjects (2.74%). The primary outcome was myocardial infarction and angina pectoris after a 10 year follow-up (9.6 ± 1.4). Secondary outcome was all causes of death.After multivariate adjustment, INTW1 mm in anterior or inferior leads was associated with a higher risk of angina pectoris [HR 3.04 95% CI (1.13-8.22) and HR 3.67 95% CI (1.35-9.96) respectively] and INTW ≥ 1 mm in lateral or anterior leads were associated with a higher incidence of myocardial infarction [HR 2.75, 95% CI (1.29-5.88) and HR 3.20 95% CI (1.68-6.09) respectively]. The association of INTW ≥ 1 mm in leads V1 to V5 with mortality remained highly significant [HR 3.17 95% CI (1.77-5.65)] after multivariate adjustment.In middle-age men, INTW is associated with a 2 to 3-fold higher risk of death, myocardial infarction and angina pectoris.

Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10−107) and stratified analyses (all P < 3.3 × 10−30). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the

Summary Metabolic Syndrome (MetS) was found associated with an increased CHD risk in several studies but data about this relationship in Southern Europe are lacking. We studied the association of MetS according to three different indexes (the National Cholesterol Education Program's definition (NCEP), a modified World Health Organization's definition (WHO) and the recent International Diabetes Federation's definition (IDF)) with CHD risk in a case-control study nested within the PRIME cohort, composed of subjects from France (Southern Europe) and Belfast (Northern Europe). The PRIME prospective study is composed of 10 592 men, aged 50-59 at baseline and followed for 5 years. Subjects included in this nested case-control study were 296 cases of incident CHD and 540 controls, who remained free of CHD during the 5 years of follow-up of the PRIME cohort and matched for age, recruitment centre and recruitment date. All subjects had questionnaires and a medical examination at baseline, and a blood sample was taken. Using the IDF's, the WHO's and the NCEP's definitions respectively, the frequency of MetS was 38.9%, 35.5% and 29.7% in cases and 32.4%, 28.7% and 22.6% in controls. After adjustment for physical activity, smoking and drinking habits, MetS was associated with CHD risk whichever the definition used (OR IDF =1.41 [1.02-1.95], P WHO =1.40 [1.01-1.94], P NCEP= 1.46[1.04-2.04], P Our results add further evidence that MetS is predictive of CHD risk in middle-aged men from Northern and Southern Europe, and highlight differences between the three definitions studied.

Summary Global assays, such as resonance-thrombography (RTG), which measure the interaction between platelets, coagulation and fibrinolysis have been used as summary measures of risk for over two decades but have not been evaluated in epidemiological studies. We examined whether RTG indices are risk indicators for incident coronary heart disease (CHD). RTG indices, related haematological variables and other risk factors were measured between 1984 and 1988 in a cohort of 2398 British men. Reaction time (r) and amplitude of fibrin leg (AF) were associated with lifestyle risk factors. During 9 years of follow-up, 282 (12%) men developed a major new CHD event, as classified by World Health Organization criteria. On adjustment for age, only r and AF measured at baseline were related to risk of incident CHD. On multivariate adjustment in a multiple logistic regression model that included age, diastolic blood pressure, body mass index, total and high-density lipoprotein cholesterol, lifestyle risk factors and use of prescribed medicine, these associations weakened but remained significant. Additional adjustment for fibrinogen, viscosity, white cell count and fibrin d-dimer either reduced these associations to non-significance (AF) or to borderline significance (r).

Aims We compare the predictive values of plasma lipids (total and HDL-cholesterol, triglycerides) and three haemostatic/inflammatory risk markers for subsequent ischaemic heart disease (IHD). Methods and results Two UK populations totalling 4860 men were screened for evidence of IHD between 1979 and 1983. Men were followed over 10 years and validated coronary events were recorded. Risk estimates were made using relative odds, receiver operating characteristic (ROC) curves and deciles of risk. Regression dilution effects were also examined. By 10 years, 525 men had a coronary event (fatal, non-fatal or silent myocardial infarction, MI). Two alternative multivariate models were compared – a lipid model (total, HDL-cholesterol, triglyceride) and a haemostatic/inflammatory model (fibrinogen, viscosity and white cell count). `Correction' for regression dilution increased relative odds for most risk factors. In the distribution of predicted risk, using established risk factors in conjunction with either lipid or haemostatic/inflammatory factors, the deciles of risk analysis showed that the observed 10-year risk of IHD was 34–35% in men in the top tenth, compared to 2–3% in the lowest tenth of the distribution. Conclusion At the 10 years' follow-up, major, haemostatic/inflammatory risk factors showed a graded relationship to incident IHD that was at least as strong as that given by plasma lipids. Haemostatic/inflammatory factors provide possible additional targets for intervention.

Contains fulltext : 59288.pdf (Publisher’s version ) (Closed access) Thymidylate synthase (TYMS) and 5,10-methylenetetrahydrofolate reductase (MTHFR) may compete for their common cofactor 5,10-methylenetetrahyhdrofolate (5,10-meTHF). Limiting 5,10-meTHF results in elevated homocysteine, especially in individuals homozygous for the T allele of the MTHFR C677T polymorphism. The TYMS gene has a tandem repeat polymorphism (two repeats or three repeats, designated 2R or 3R, respectively), which may also affect homocysteine concentrations. The 3R allele is subject to increased translational efficiency in vitro and the 3R3R genotype is associated with both decreased serum folate and elevated plasma homocysteine (tHcy) in a population of Singapore Chinese. We assessed the relationship between TYMS genotype and key biochemical and genetic variables in a random sample of 392 healthy young Northwestern European men and women. The tHcy concentrations for 3R3R homozygotes (median 8.5 micromol/l) did not differ significantly from those for 2R2R homozygotes (median 8.7 micromol/l) or 2R3R heterozygotes (median 9.3 micromol/l) in the population as a whole (P=0.43), or in subsets of subjects with low serum folate (P=0.60) or the MTHFR 677TT genotype (P=0.90). Furthermore, there was no trend toward elevated tHcy in 3R3R homozygotes. Similarly, the TYMS tandem repeat polymorphism was not associated with serum folate concentrations. Our findings indicate that the TYMS 3R3R genotype is not a determinant of homocysteine in this sample of healthy young Caucasian adults from Northern Ireland.

Background Sedentary behaviour in leisure time or at home increases cardiovascular risk, but it is uncertain whether this is also the case for occupational activity. Purpose To investigate the qualitative and quantitative effects of different types of occupational tasks and how they interacted together on incidence of cardiovascular disease (CVD). Methods The study included 7796 active middle aged European men from the PRIME cohort. Using Cox proportional hazards analysis, and taking account of anthropometric and biomedical factors, energy expenditure during leisure time and commuting related physical activity, lifestyle habits and social factors, the effects of time spent sitting or standing still, carrying objects and walking at work were investigated to assess how they influenced the incidence of CVD over 10 years’ of follow-up. Results The incidence of CVD from time spent sitting or standing still at work showed a U-shape relationship. >300-1200 and 1200-1800mins/week spent sitting or standing at work halved the risk of CVD HR: 0.63[0.42-0.94]; 0.48[0.31-0.76], respectively. The risk was higher for men who routinely carried heavy objects when their jobs involved little or no time spent sitting or standing still at work, although this risk was decreased for men who spent >300-1200mins/week sitting or standing still at work. Conclusion The effects of occupational activities on CVD depend not only on the types of occupational tasks but also on the balance of activities at work and the potential compensatory effects of other activities. Cardiovascular prevention strategies should include a range of occupational physical activities.

Guidelines aim to present all the relevant evidence on a particular issue in order to help physicians to weigh the benefits and risks of a particular diagnostic or therapeutic procedure. They should be helpful in everyday clinical decision-making. A great number of guidelines have been issued in recent years by different organizations-European Society of Cardiology (ESC), American Heart Association (AHA), American College of Cardiology (ACC), and other related societies. By means of links to web sites of National Societies several hundred guidelines are available. This profusion can put at stake the authority and validity of guidelines, which can only be guaranteed if they have been developed by an unquestionable decision-making process. This is one of the reasons why the ESC and others have issued recommendations for formulating and issuing guidelines. In spite of the fact that standards for issuing good quality guidelines are well defined, recent surveys of guidelines published in peer-reviewed journals between 1985 and 1998 have shown that methodological standards were not complied with in the vast majority of cases. It is therefore of great importance that guidelines and recommendations are presented in formats that are easily interpreted. Subsequently, their implementation programmes must also be well conducted. Attempts have been made to determine whether guidelines improve the quality of clinical practice and the utilization of health resources. In addition, the legal implications of medical guidelines have been discussed and examined, resulting in position documents, which have been published by a specific Task Force. The ESC Committee for Practice Guidelines (CPG) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces, expert groups or consensus panels. The Committee is also responsible for the endorsement of these guidelines or statements. The rationale for an active approach to the prevention of cardiovascular diseases (CVD) is …

Background— Fish consumption decreases risk of sudden death. The goal of the present study was to assess the relationship between fish consumption and heart rate. Methods and Results— A cross-sectional analysis was conducted of 9758 men, age 50 to 59 years, without coronary heart disease (CHD) who were recruited in France and Belfast, Ireland, from 1991 to 1993. Heart rate and CHD risk factors were compared among 4 categories of fish consumption, as follows: (1) less than once per week (n=2662), (2) once per week (n=4576), (3) twice per week (n=1964), and (4) more than twice per week (n=556). Fatty acid profiles of erythrocyte phospholipids were determined in a random subsample of 407 subjects. In erythrocyte phospholipids, eicosapentaenoic acid ( P P P P P P P P P for trend P Conclusions— Fish consumption is associated with decreased heart rate in men. Because heart rate is positively associated with risk of sudden death, this association may explain, at least in part, the lower risk of sudden death among fish consumers.

Background— The hypothesis that paraoxonase (PON1) has a role in preventing atherosclerosis is based on experimental, transgenic, and case-control studies but has not previously been tested prospectively. Methods and Results— The Caerphilly Prospective Study is a cohort study of men aged 49 to 65 years observed for coronary heart disease (CHD) events (fatal and nonfatal myocardial infarction) over a mean period of 15 years. Serum PON1 activity toward paraoxon was measured in 1353 participants. PON1 activity was 20% lower in the 163 men who had a coronary event ( P =0.039). Men in the highest quintile of PON1 activity had a decreased risk compared with those in the lowest quintile (OR 0.57 [95% CI, 0.33 to 0.96]). The inverse relationship between quintiles of serum PON1 activity and CHD risk was graded, the median change in OR across each quintile being 0.87 (0.77 to 0.98). After adjustment for all other CHD risk factors, including HDL cholesterol, this median value became 0.90 (0.78 to 1.02). PON1 was most predictive of a new CHD event in patients at highest risk by virtue of preexisting CHD (adjusted median OR for each quintile, 0.74 [0.59 to 0.93]; n=313) or the presence of other risk factors. For the highest tertile of CHD risk (n=390) calculated by the Framingham equation, adjusted median OR for each quintile was 0.84 (0.66 to 1.05); n=390. Conclusions— Low serum PON1 activity toward paraoxon is an independent risk factor for coronary events in men at high risk because of preexisting disease or other CHD risk factors.

Objective: To examine the optimal intensity of leisure time physical activity (LTPA) to decrease the risk of all cause, cardiovascular disease (CVD), and coronary heart disease (CHD) mortality in a population sample of middle aged British men. Design: Prospective study of middle aged men with an 11 year follow up. Setting: A whole population sample of men from Caerphilly, South Wales, UK. Subjects: 1975 men aged 49–64 years without historical or clinical evidence of CHD at baseline examination. Main outcome measures: All cause, CVD, and CHD mortality. Results: Total (cumulative) LTPA had a graded, significant relation with all cause, CVD, and CHD mortality but no trend with cancer deaths. When different intensities of activity were considered, light and moderate intensity LTPA had inconsistent and non-significant relations with all cause, CVD, or CHD mortality whether adjusted only for age or for other cardiovascular risk factors. In contrast a significant dose–response relation was found for heavy intensity LTPA for all cause, CVD, and CHD mortality fully adjusted for other risk factors. Conclusions: These data suggest that, in a population of men without evidence of CHD at baseline, only leisure exercise classified as heavy or vigorous was independently associated with reduced risk of premature death from CVD.

The aim of the present study was to assess the joint contribution of hypertension and body mass index to coronary heart disease risk. DESIGN Prospective study on men aged 50-59 years free of coronary heart disease at entry recruited in three regions of France (n = 7359) and in Northern Ireland (n = 2399).The recruitment frame was based on industry and various employment groups, on health screening centers and general practice.Incident cases of effort angina, unstable angina, myocardial infarction and coronary death were recorded over a 5-year follow-up.Compared with the reference group [body mass index (BMI) 25 kg/m2], the relative risk of coronary event was higher in the second (25or =BMI 27.6) and third BMI tertiles: 1.27 (95% confidence interval 0.94-1.70) and 1.14 (0.84-1.56) after adjustment for confounders and covariates, including diabetes, hypertension and lipoprotein levels. Further analyses revealed a significant interaction between hypertension and BMI on coronary disease risk (P0.05), suggesting that hypertension modifies coronary heart disease (CHD) risk attributable to BMI. Among hypertensive men, the relative risk of coronary heart disease was 1.34 (0.85-2.11) and 1.61 (1.04-2.50) in the second and third BMI tertiles, respectively. In normotensive men, BMI was not associated with CHD risk; relative risk 1.25 (0.85-1.85) and 0.66 (0.40-1.09) in the second and third BMI, respectively.These results indicate that hypertension and overweight jointly increase coronary heart disease risk.

Whether the protective effect of high density lipoprotein (HDL) on incident coronary heart disease (CHD) can be attributed to one or both HDL subfractions remains controversial. The associations of HDL(2) and HDL(3) cholesterol with the incidence of CHD in the 9-year follow-up of the Caerphilly study are described. A total of 2398 middle-aged British men were recruited from the general population between 1984 and 1988 and were followed, on average, for 9 years. Total and HDL(3) cholesterol were measured by a two-step precipitation technique on fresh, fasting samples from 2225 men. HDL(2) cholesterol was calculated by subtracting HDL(3) from total HDL cholesterol. Relative odds and 95% confidence intervals (CI) for incident CHD were obtained by use of a logistic regression model. During follow-up, 282 (12%) men developed a major new CHD event. Total HDL and HDL(3) cholesterol were significantly and inversely associated with the risk of incident CHD. When divided into fifths of the distributions of total HDL and HDL(3) cholesterol, multivariate-adjusted relative odds were 1.00, 0.95, 0.72, 0.85, 0.38 and 1.00, 1.05, 0.92, 0.67, 0.39, respectively graded from the least to the most quintile, with the lowest quintile group as referent. Tests for trend were significant (P for trend 0.003 and 0.001, respectively). In a multivariate model, the contribution of HDL(3) was significant (standardized relative odds, 0.76; 95% CI, 0.64-0.91), whereas HDL(2) was not significant. No linear combination of the two subfractions was a better predictor of CHD than total HDL cholesterol alone. HDL(3) cholesterol was an independent predictor of incident CHD and may be more closely related to the development of CHD than HDL(2) cholesterol. The prediction of the risk of CHD from total HDL cholesterol alone could not be improved upon by measurement of the two HDL subfractions. In our view, the only way to improve our understanding of this situation is to measure both subfractions independently of each other and not to calculate one by subtraction.

Objective To evaluate the level of understanding and the practice of community development among Health and Social Service professionals in Northern Ireland and to assess the potential need for formal training in community development. Design A survey using questionnaires among a representative sample of health and social service professionals in Northern Ireland. Qualitative data was obtained from separate focus groups. Setting Questionnaires were self-completed by subjects contacted at their place of work. Focus groups were carried out by experienced interviewers in workplace settings. Method Ten Health and Social Services Community Trusts were selected to be representative of Trusts in Northern Ireland. Questionnaires were distributed to all 502 Health and Social Service professionals working in these Trusts. A focus group session was carried out in each of four Health and Social Services Community Trusts across the Province. Results The overall response rate was 57 per cent. Two hundred and eighty-seven questionnaires were returned from a total of 502. High response rates were obtained among health visitors, community psychiatric nurses, and social workers for disability, but groups such as community midwives may have been less well represented in our study sample (response rate 21 per cent). Over 28 per cent of subjects, particularly social workers, said they were unfamiliar with the concept of community development. Thirty- nine per cent described their knowledge as adequate and 4 per cent as good. Almost 40 per cent of the subjects said that they never used a document which had been widely distributed in Northern Ireland on a strategy for community development. Seventy-two per cent of subjects had not used the Voluntary Activity Unit's Handbook for Practitioners which had also been widely distributed in the Province. Questions on training required by professionals suggested that the majority of professionals required training in methods and techniques, values and principles, definition and clarification of professional roles, and knowledge of practice elsewhere. Focus groups reported that a high level of commitment and out- of-hours involvement was required to further enhance community development. Conclusions The majority of professional groups were positive about community development, but were unable to find or provide examples. Training needs were identified among all professional groups in this study.

To assess the predictive value of central obesity for risk of ischaemic heart disease (IHD) in a long-term follow-up, measured by skinfold thickness in comparison to general measures of overweight and obesity such as Quetelet's index.A total of 2512 men aged 45-59 y from the general population first examined in 1979-1982. Men were re-examined at approximately 5 y intervals. All fatal and non-fatal cases of IHD during a 14 y follow-up were recorded.Skinfold thickness was measured at four sites. Height (m) and weight (kg) were also measured and Quetelet's index (weight/height(2)) was used as the reference body mass index (BMI).Data were available for 2512 men among whom 411 new cases of IHD (fatal and non-fatal) occurred during 14 y of follow-up. Increasing values of BMI showed a statistically significant trend with increasing risk of new IHD that contributed independently to risk of IHD when adjusted for age, smoking habit and social class. Skinfold thickness measures were entered singly and in combination into this model with and without the additional inclusion of BMI. All individual skinfolds were significantly associated with risk of new IHD when BMI was excluded from the regression model, as was the sum of four skinfolds and the sum of subscapular and abdominal skinfolds. Only the subscapular skinfold measure contributed independently to risk of subsequent IHD when BMI was included in the model although biceps, biceps plus triceps and total sum of skinfolds were close to achieving statistical significance. The relative odds of IHD in the upper quintile of subscapular skinfold compared to the lowest was 1.9 (95% CI 1.3-2.8) when adjusted for age, smoking habit and social class.In general skinfold measurements contribute only marginally to improved prediction of risk of IHD as measured by BMI, but central obesity, as measured by the subscapular skinfold, is predictive of IHD independently of BMI.

OBJECTIVE: To examine the influence of physical activity on body mass index (BMI), waist circumference (W) and body mass changes (ΔBMI) in middle-aged men, with special regard to moderate-intensity activities. DESIGN: Longitudinal study of adults who participated in the PRIME Study. SUBJECTS: A cohort of 8865 men aged 50–59 y, free of coronary heart disease. MEASUREMENTS: BMI and W at baseline, body mass changes over a 5 y period. Detailed baseline assessment of net energy expenditure due to physical activity (PAE) in the preceding year, according to category of activity, by means of the MOSPA Questionnaire. PAE was expressed in weekly metabolic equivalent scores (MET h/week). RESULTS: After adjustment for confounders, the multiple regression analyses indicated that BMI, W and ΔBMI were inversely associated with PAE spent in getting to work (P

SummaryWe have previously reported that plasma fibrin D-dimer (a marker of turnover of cross-linked fibrin) showed a strong and independent association with incident ischaemic heart disease (IHD) in the Caerphilly Study cohort of 1,998 men aged 49-65. To establish the specificity of this finding, we assayed plasma samples from this cohort with a more specific assay for fibrin D-dimer: this showed an association with incident IHD which was at least as strong and independent as that for the original assay (odds ratio, OR for top fifth compared to bottom fifth 3.79; 95% CI 1.77-8.10; p < 0.0001). To establish potential causes of the increased fibrin turnover, we also assayed several potential markers of coagulation activation or thrombotic tendency (prothrombin fragment F1+2, thrombin-antithrombin complexes, factor VIIc, activated partial thromboplastin time [APTT] and activated protein C resistance): none of these variables were associated with incident IHD in this cohort. We suggest that further studies are required to establish the causes of increased cross-linked fibrin turnover, which is associated with incident IHD in the general population when measured by a specific assay.

Item does not contain fulltext Epidemiological evidence has revealed that an elevated plasma homocysteine level (hyperhomocysteinemia) confers an increased risk of cardiovascular disease and neural tube defects. Hyperhomocysteinemia is caused by both nutritional (e.g. folate, vitamins B(6) and B(12)) and genetic factors, including functional polymorphisms of key enzymes involved in homocysteine metabolism. One such enzyme, methionine synthase reductase (MTRR), maintains adequate levels of methylcob(III)alamin, the activated cofactor for methionine synthase, which catalyzes the remethylation of homocysteine to methionine. A common MTRR polymorphism, i.e. a 66 A-->G substitution specifying an isoleucine to methionine substitution (I22M), was recently identified. To assess the influence of this polymorphism on total plasma homocysteine (tHcy), we undertook a genotype/phenotype analysis in a study population of 601 Northern-Irish men, aged 30--49, for which biochemical and genetic data relevant to folate/homocysteine metabolism had already been acquired. The 66AA genotype has a frequency of 29% in this population. We established that there was a significant influence of MTRR genotype on tHcy ranking (P=0.004) and that the 66AA genotype contributes to a moderate increase in tHcy levels across the distribution [OR 1.59 (95% CI: 1.10--2.25) for the 66AA genotype to be in the upper half of the tHcy distribution, P=0.03]. The homocysteine-elevating effect of the 66AA genotype is independent of serum folate, vitamin B(12) and vitamin B(6) levels. Based on published estimates of the enhanced cardiovascular disease risk conferred by defined increments of plasma tHcy, we estimate that 66AA homozygotes have, on average, an approximately 4% increase in cardiovascular disease risk compared to 66GG homozygotes. This study provides the first evidence that the MTRR A66G polymorphism significantly influences the circulating tHcy concentration.

OBJECTIVE—The prevalence of obesity is increasing in many European countries and in the United States. This report examines the mortality and morbidity associated with being overweight and obese in the Caerphilly Prospective Study and the relative effects of weight in middle age and self reported weight at 18 years. DESIGN—All men aged 45 to 59 years from the town of Caerphilly, South Wales and outlying villages were identified and 2512 men were examined for the first time between 1979 and 1983. Men were asked to recall their weight at 18 years of age (when the majority had been examined for National Service) so that weight then, weight at screening, and the difference could be related to their 14 year follow up from screening. A total of 2335 men could recall their weight at 18 years. By 14 years of follow up from screening 465 men had died and 382 had had coronary events. RESULTS—Mean body mass index in men who reported their weight at 18 years was 22.3 (SD 2.8) kg/m2 and only 41 of these men (1.8%) were classified as obese (index ⩾ 30 kg/m2). The index did not predict all cause mortality when examined by quintile. For major ischaemic heart disease (non-fatal or fatal ischaemic heart disease) the relative odds was 1.73 (95% CI 1.21, 2.48) in the top fifth of the distribution (body mass index ⩾ 24.2 kg/m2) compared with the bottom fifth (body mass index

Objective: To determine and describe the extent to which European dietary data collected in disparate surveys can be meaningfully compared. Design: Seven independent population-based surveys from six European countries were initially included. Differences in study designs and methodological approaches were examined. Risk factor data for 31, 289 adults aged 40–59 y were harmonized and pooled in a common, centralized database. Results: Direct comparisons of dietary measures across studies were not deemed appropriate due to methodological heterogeneity. Nonetheless, comparisons of intra-population contrasts by gender across sites were considered valid. Women consumed fruit and vegetables more often than men. Age-standardized gender differences in the prevalence of low fruit and vegetable consumption ranged from 7 to 18% and 5 to 15%, respectively. Data on energy intake showed good agreement across study populations. The proportion of total energy from macronutrients was similar for women and men. Gender differences for relative intakes of saturated fatty acids (percentage energy) were small and only in France were they significant. Dietary fibre density was significantly higher in women than in men. Overall, the participating Southern European populations from Italy and Spain exhibited more healthful food composition patterns. Conclusions: Contrasts in dietary patterns by gender across populations may provide the basis for health promotion campaigns. The most favourable patterns observed may serve as attainable goals for other populations. An international risk factor surveillance programme based upon locally run, good quality studies has the potential to provide the needed data. Sponsorship: European Community (DG V), project 96CVVF3-446-0; Swiss Federal Office for Education and Science, OFES 96.0089. European Journal of Clinical Nutrition (2000) 54, 253–262

Elevation in plasma homocysteine concentration has been associated with vascular disease and neural tube defects. Methionine synthase is a vitamin B(12)-dependent enzyme that catalyses the remethylation of homocysteine to methionine. Therefore, defects in this enzyme may result in elevated homocysteine levels. One relatively common polymorphism in the methionine synthase gene (D919G) is an A to G transition at bp 2,756, which converts an aspartic acid residue believed to be part of a helix involved in co-factor binding to a glycine. We have investigated the effect of this polymorphism on plasma homocysteine levels in a working male population (n = 607) in which we previously described the relationship of the C677T "thermolabile" methylenetetrahydrofolate reductase (MTHFR) polymorphism with homocysteine levels. We found that the methionine synthase D919G polymorphism is significantly (P = 0.03) associated with homocysteine concentration, and the DD genotype contributes to a moderate increase in homocysteine levels across the homocysteine distribution (OR = 1.58, DD genotype in the upper half of the homocysteine distribution, P = 0.006). Unlike thermolabile MTHFR, the homocysteine-elevating effects of the methionine synthase polymorphism are independent of folate and B(12) levels; however, the DD genotype has a larger homocysteine-elevating effect in individuals with low B(6) levels. This polymorphism may, therefore, make a moderate, but significant, contribution to clinical conditions that are associated with elevated homocysteine.

The American Diabetes Association recently proposed a new, lower, cut-point of 7.0 mmol/l for diagnosis of diabetes mellitus. We examined data from the Caerphilly and Speedwell cohorts to determine possible cut-points of fasting plasma glucose for increased risk of subsequent ischaemic heart disease (IHD). Men (n = 4860) from the general population of a town in South Wales and a practice-based population in Bristol aged 45-63 years were first examined in 1979-83, and re-examined at intervals, and these data relate to follow-up at about 10 years (120 months, Caerphilly) (112 months, Speedwell). Clinically recognized diabetics (n = 94) experienced a higher mortality rate and an excess number of major IHD events. Among non-diabetics, mean blood glucose was 5.0 mmol/l and a significant excess of major IHD events occurred above this point even when the data were fully adjusted for all other IHD risk factors. Risk of major IHD was greatest for non-diabetic men with plasma glucose levels between 7.0 and 7.7 mmol/l. Under 7.0 mmol/l, the excess event rate was modest, however. Glucose levels were not associated with excess all-cause mortality among these non-diabetic men. These data, based on the excess risk of macrovascular disease experienced by a British cohort of non-diabetic men, accord with the proposals to base the diagnosis of diabetes on a cut point of 7.0 rather than 7.8 mmol/l.

The relationships of three measurements of the factor VIII/von Willebrand factor (VWF) complex (factor VIII activity, FVIIIc (one-stage assay); VWF antigen, VWF Ag (ELISA); and VWF activity, VWF act, measured by a recently-developed ELISA) to major ischaemic heart disease (IHD) events were studied in 1997 men aged 49-65 years, in the second phase of the Caerphilly Heart Study. These variables were related using logistic regression analysis to myocardial infarction or IHD death, which occurred in 129 men during an average follow-up period of 61 months. All three measurements were highly correlated (r = 0.63-0.77), and each was significantly associated with incident major IHD on univariate analyses (relative odds in highest fifth compared to lowest fifth, 1.68-1.90; P = 0.028-0.006) and on multivariate analyses adjusting for major IHD risk factors and for baseline IHD. Neither FVIIIc nor VWF act was significantly related to incident IHD following adjustment for VWF Ag. We therefore suggest that the associations between these three measurements of the factor VIII/VWF complex and incident IHD might have at least three explanations: VWF Ag is a marker of arterial endothelial disturbance; VWF act promotes platelet adhesion/aggregation and hence the platelet component of arterial thrombosis; and FVIIIc promotes fibrin formation and hence the fibrin component of arterial thrombosis.