Prevalence and Treatment of Familial Hypercholesterolemia in France.

BACKGROUND: Familial hypercholesterolemia (FH) is known to be underdiagnosed and undertreated. The prevalence of heterozygous FH is estimated to be 1 in 500. Nevertheless, a recent meta-analysis of screening in the general population seems to show that the prevalence of FH is more likely to be 1 in 250. METHODS: Analysis was based on the third French MONICA and MONALISA population surveys. Participants were randomly recruited in 1995 and 2005 from the general population of 3 regions of France. FH was diagnosed using a modified version of the Dutch Lipid Clinic Network (DLCN) without genetic testing. RESULTS: The DLCN score was assessed in 7928 participants aged 35 to 74 years; 50% were men. The prevalence of definite or probable FH was 0.85% (95% CI, 0.63-1.06). Among patients with definite or probable FH, 12% had histories of premature cardiovascular disease (vs less than 1% among subjects without FH; P < 0.0001), 70% were treated (13% with high-intensity, 83% with moderate-intensity, and 4% with low-intensity statin therapy), 90% had cholesterol screening within the past 12 months, and 97% were aware of their hypercholesterolemia. None reached the recommended low-density lipoprotein cholesterol (LDL-C) target (< 2.5 or < 1.8 mmol/L for subjects in primary prevention vs in secondary prevention or with diabetes, respectively), with a mean distance to target of 3.0 mmol/L. CONCLUSIONS: In a sample from the French general population aged 35 to 74 years, the prevalence of FH was close to 1 in 120, and the patients with FH were undertreated.

Score of Adherence to 2016 European Cardiovascular Prevention Guidelines Predicts Cardiovascular and All-Cause Mortality in the General Population.

BACKGROUND: Guidelines on cardiovascular (CV) disease prevention promote healthy lifestyle behaviours and CV risk factor control to reduce CV risk. The effect of adherence to these guidelines on CV and all-cause mortality is not well known. METHODS: We assessed the effect of baseline adherence to "2016 European Guidelines on CV Disease Prevention in Clinical Practice" on long-term CV and all-cause mortality in a sample recruited from the French general population. Analysis was on the basis of the Third French Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) population-based survey (recruitment period: 1994-1997). We built an adherence score to European guidelines, considering adherence to recommendations for smoking, drinking, physical activity, body mass index, blood pressure, low-density and high-density lipoprotein cholesterol, fasting blood glucose, and diet at baseline. Vital status was obtained 18 years after inclusion. Statistical analysis was on the basis of multivariate Cox modelling. RESULTS: Adherence score was assessed in 1311 apparently healthy participants aged 35-64 years (73% men). During the follow-up, 186 deaths occurred (41 were due to a CV cause). Considering CV mortality, the adjusted hazard ratio for subjects in the fourth quartile of the adherence score (worse adherence) was 3.12 (95% confidence interval [CI], 1.62-6.01; P = 0.001), compared with subjects in the first, second, or third quartile (best adherence). Considering all-cause mortality, the adjusted hazard ratio for subjects in the fourth quartile of the adherence score was 2.27 (95% CI, 1.68-3.06; P < 0.001). CONCLUSIONS: Better baseline adherence to European guidelines on CV disease prevention was associated with a significantly reduced long-term CV and all-cause mortality in a sample from the French general population.

Impact of cardiovascular risk factor control on long-term cardiovascular and all-cause mortality in the general population.

PURPOSE: In clinical trials, lowering cardiovascular risk factors (CVRFs) reduces cardiovascular (CV) morbidity and mortality. We assessed the impact of controlling CVRFs at baseline on long-term all-cause and CV mortality in the general population. METHODS: Analysis was based on the Third French MONICA population-based survey (1994-1997). Vital status was obtained 18 years after inclusion. Statistical analysis was based on Cox-modelling. RESULTS: About 3402 participants aged 35-64 were included and 569 (17%) presented with 2 or more uncontrolled CVRFs, 1194 (35%) had one uncontrolled CVRF, 770 (23%) had all CVRFs controlled under treatment (or were former smokers) and 869 (25%) exhibited no CVRF. During the follow-up, 389 deaths occurred (76 were due to CV causes). Considering all-cause mortality, the adjusted hazard ratios (aHR) for subjects with one uncontrolled CVRF and for those with two or more were 1.38 [1.03-1.83] (p = 0.029) and 1.80 [1.33-2.43](p < 0.001), respectively, as compared with subjects presenting with all their CVRFs controlled. For subjects exhibiting no CVRF, the aHR was 0.66 [0.44-0.98] (p = 0.042). Considering CV mortality, aHRs for subjects presenting with one and two or more uncontrolled CVRF were 1.70 [0.84-3.42] (p = 0.138) and 3.67 [1.85-7.29] (p < 0.001), respectively, as compared with subjects who had either all their CVRFs controlled or exhibited no CVRF. CONCLUSIONS: Failing to control CVRFs significantly increases long-term all-cause and CV mortality in the French general population. Key messages Only 30% of patients with cardiovascular risk factors were controlled. Failing to control cardiovascular risk factors significantly increased long-term cardiovascular and all-cause mortality. A residual risk for all-cause mortality remained even when patients were controlled.

Isolated negative T waves in the general population is a powerful predicting factor of cardiac mortality and coronary heart disease.

BACKGROUND: 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. METHODS: 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. RESULTS: After multivariate adjustment, INTW < 1 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. CONCLUSIONS: In middle-age men, INTW is associated with a 2 to 3-fold higher risk of death, myocardial infarction and angina pectoris.

Expired-air carbon monoxide as a predictor of 16-year risk of all-cause, cardiovascular and cancer mortality.

BACKGROUND: Measurement of expired-air carbon monoxide (EACO) is commonly used to ascertain non-smoking status, although it can also reflect exposures not related to smoking. Our aim was to assess 16-year mortality according to EACO measured at baseline, in a general population. METHODS: Our analysis was based on the Third French MONICA population survey (1994-1997). Causes of death were obtained 16 years after inclusion, and assessment of determinants of mortality was based on Cox modeling. RESULTS: EACO was measured in 2232 apparently healthy participants aged 35-64. During follow-up, 195 deaths occurred (19% were due to cardio-vascular (CV) causes and 49% to cancer). At baseline, the mean EACO was 11.8 (±7.4)ppm, 4.6 (±2.5)ppm, 4.3 (±2.2)ppm for current, former and never smokers, respectively (P<0.001). After adjustment for main mortality risk factors and smoking, the hazard ratio (HR) for total mortality was 1.03[95% confidence interval: 1.01-1.06] per 1-unit increase in EACO, and it was 1.04[1.01-1.07] for cancer mortality. Adjusted HR for CV mortality was 1.05[1.01-1.10] but did not remain significant after additional adjustment for smoking (0.98[0.91-1.04]). Interactions between EACO and smoking were not significant. CONCLUSIONS: In a general population, baseline EACO is an independent predictor of 16-year all-cause and cancer mortality, after adjustment for confounders including smoking. Given that the effect of EACO is similar among smokers and non-smokers, EACO is probably not solely related to smoking but could also be a marker of inhaled ambient carbon monoxide and/or endogenous production. Besides, smoking better predicts CV mortality than EACO.

Validation of a short, qualitative food frequency questionnaire in French adults participating in the MONA LISA-NUT study 2005-2007.

BACKGROUND: Food frequency questionnaires (FFQs) are often used to evaluate individuals' food intakes in epidemiologic studies because of their simplicity and low cost. OBJECTIVE: To assess the validity of a short (24 items), qualitative FFQ used in the MONA LISA-NUT study. DESIGN: Cross-sectional study of a representative sample in three French counties. PARTICIPANTS/SETTING: The sample included 2,630 participants aged 35 to 65 years from the MONA LISA-NUT study. MAIN OUTCOME MEASURES: Food consumption was measured with the FFQ and via food records for 3 consecutive days. Plasma fatty acids were measured from a subset of participants. STATISTICAL ANALYSES PERFORMED: The FFQ items' validity was assessed by calculating crude and deattenuated Pearson correlation coefficients between frequencies reported by the FFQ and average weights reported by the food records. Furthermore, the validity of some items of the FFQ measuring the consumption of fatty foods was assessed by calculating Pearson correlation coefficients between frequencies of consumption of these foods and dosages of the corresponding plasma fatty acids: fish and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), olive oil and oleic acid, margarine and elaidic acid, and dairy products and pentadecanoic and heptadecanoic acids. RESULTS: The mean of the deattenuated Pearson correlation coefficients for all items was 0.46, with values ranging from 0.22 (fried food) to 0.77 (breakfast cereal). The correlation coefficient was ≤ 0.4 for one third of the 24 items. Moderate correlations were found between fish and EPA/DHA (EPA: r=0.43, 95% CI 0.33 to 0.51; DHA: r=0.39, 95% CI 0.30 to 0.47), but not for other food items. CONCLUSIONS: One third of the 24 items in the short, qualitative FFQ evaluated here were not sufficiently valid. However, for the food groups most commonly studied in the literature, this FFQ had the same degree of validity as other questionnaires designed to classify subjects according to their level of intake.

Gender- and age-specific trends in coronary heart disease mortality in France from 2000 to 2007: results from the MONICA registers.

BACKGROUND: Several recent studies in the USA, the UK and Australia have raised concern about a possible plateau or even reverse trend in coronary heart disease (CHD) mortality in younger populations. We aimed to assess the recent gender- and age-specific trends in CHD mortality among inhabitants aged 35-74 years from the three geographical areas covered by the French MONICA population registers. METHODS: Registered events were fatal myocardial infarctions and coronary deaths selected after a thorough investigation by the physician who signed the death certificate, general practitioners and cardiologists, and by public and private hospitals for in-hospital deaths. RESULTS: From 2000 to 2007 age-standardized CHD mortality rates decreased significantly by 24% in men and 38% in women. In the age group 55-74, the estimated annual percentage change (EAPC) in mortality was -5.2 (95% confidence interval: -6.6 to -3.7; p < 10(-4)) among men and -9.0 (-11.6 to -6.4; p < 10(-4)) among women. In the 35-54 age group, the EAPC in mortality was -4.1 (-7.2 to -1.1; p < 10(-2)) among men and -2.5 (-8.7 to 3.7; p = 0.43) among women. These trends remained similar when possible coronary deaths were also accounted for, except in young men where the decline was no longer significant. CONCLUSIONS: A clear decline in recent CHD mortality rates was observed among subjects above 54 years, but not among younger subjects, particularly in women. These results may be due to unfavourable trends in some risk factors in the latter age group and call for a strengthening of primary prevention.

External validation of the 2008 Framingham cardiovascular risk equation for CHD and stroke events in a European population of middle-aged men. The PRIME study.

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.

Multiple biomarkers for the prediction of ischemic stroke: the PRIME study.

OBJECTIVE: To simultaneously evaluate 14 biomarkers from distinct biological pathways for risk prediction of ischemic stroke, including biomarkers of hemostasis, inflammation, and endothelial activation as well as chemokines and adipocytokines. METHODS AND RESULTS: The Prospective Epidemiological Study on Myocardial Infarction (PRIME) is a cohort of 9771 healthy men 50 to 59 years of age who were followed up over 10 years. In a nested case-control study, 95 ischemic stroke cases were matched with 190 controls. After multivariable adjustment for traditional risk factors, fibrinogen (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.03-2.28), E-selectin (OR, 1.76; 95% CI, 1.06-2.93), interferon-γ-inducible-protein-10 (OR, 1.72; 95% CI, 1.06-2.78), resistin (OR, 2.86; 95% CI, 1.30-6.27), and total adiponectin (OR, 1.82; 95% CI, 1.04-3.19) were significantly associated with ischemic stroke. Adding E-selectin and resistin to a traditional risk factor model significantly increased the area under the receiver-operating characteristic curve from 0.679 (95% CI, 0.612-0.745) to 0.785 and 0.788, respectively, and yielded a categorical net reclassification improvement of 29.9% (P=0.001) and 28.4% (P=0.002), respectively. Their simultaneous inclusion in the traditional risk factor model increased the area under the receiver-operating characteristic curve to 0.824 (95% CI, 0.770-0.877) and resulted in an net reclassification improvement of 41.4% (P<0.001). Results were confirmed when using continuous net reclassification improvement. CONCLUSIONS: Among multiple biomarkers from distinct biological pathways, E-selectin and resistin provided incremental and additive value to traditional risk factors in predicting ischemic stroke.

Interregional differences in the clinical, biological and electrical characteristics of first acute coronary events in France: results from the MONICA registries.

BACKGROUND: In France, there is a large north-to-south, decreasing gradient in case fatality rates of hospitalized patients for an acute coronary event. This gradient may be explained by differences in the presenting patients' clinical, biological and electrocardiographic characteristics. GOAL: To compare the characteristics of patients hospitalized for an acute episode of coronary insufficiency in three regions of France with contrasting fatality rates. METHODS: We assessed all men and women (aged 35-74 years) covered by the MONICA registries in three geographical areas (north, east and south-west France) and hospitalized in 2006 for a first acute coronary event. The symptoms, electrocardiogram features, left ventricular ejection fraction (LVEF) and troponin levels were systematically transcribed from medical files. Vital status was followed up for one year. RESULTS: Fatality rates at 28 days and 1 year were higher in the north (7% and 12%, respectively) than in the east (5% and 7%) and in the south-west (2% and 5%). Major symptoms (such as cardiac arrest, acute pulmonary oedema and cardiac shock), altered LVEF and ST+ myocardial infarction (STEMI) were more frequent in the north than in the south-west (all p < 0.0001) - pointing to marked inter-regional differences in the presentation of acute coronary syndromes (ACSs). In multivariate analyses, age, major symptoms, altered LVEF and STEMI remained strongly associated with 28-day lethality, whereas the relationship with geographical area was attenuated. Similar results were observed for 1-year outcomes. CONCLUSIONS: The clinical, biological and electrocardiographic presentations of hospitalized incident ACSs differ from one region of France to another. These differences explain (at least in part) the 28-day and 1-year decreasing case fatality gradient in hospitalized patients from northern France to south-western France.

The major element of 1-year prognosis in acute coronary syndromes is severity of initial clinical presentation: Results from the French MONICA registries.

BACKGROUND: While the death rate from acute coronary syndromes (ACS) has been in decline for more than 50 years, out-of-hospital mortality remains high despite improvements in care. AIM: To evaluate the importance of out-of-hospital mortality and identify the main predictors of in-hospital and 1-year mortality in France. METHODS: Analyses were based on data from the French MONICA population-based registry, which included all cases of ACS occurring in people aged 35-74 years during 2006 in three geographic areas in France. We first evaluated out-of-hospital mortality; then, using data from patients with incident ACS who reached hospital alive, Cox models were performed to determine the main predictors of 1-year mortality. The number of attributable deaths was assessed for variables of interest. RESULTS: After 1-year follow-up, case-fatality was 29.3% for incident events (n=2547); the proportion of out-of-hospital deaths was 70.3%, and 91.5% of deaths occurred in the 28 days following the ACS. On multivariable analysis, the number of attributable deaths associated with three scenarios (out-of-hospital life-and-death emergency, hospitalization before ACS occurrence, and lack of coronary angiography) was 130 (accounting for 59% of deaths occurring after reaching the hospital) during 1-year follow-up. These scenarios corresponded to patients with an initial severe clinical presentation in whom rates of use of specific treatments and invasive procedures were very low. CONCLUSION: A large proportion of fatalities after an ACS occurs in the out-of-hospital phase. Moreover, the major component of 1-year mortality is associated with a poor prognosis at initial presentation. This finding highlights the importance of cardiovascular prevention, population education and better out-of-hospital emergency management in improving prognosis after an ACS.

Depressive symptoms, a time-dependent risk factor for coronary heart disease and stroke in middle-aged men: the PRIME Study.

BACKGROUND AND PURPOSE: To date, the association between depressive symptoms and the risk of cardiovascular diseases remains controversial. We investigated prospectively, within the same population, the time course of the association between baseline depressive symptoms and first stroke or coronary heart disease event. METHODS: In the Prospective Epidemiological Study of Myocardial Infarction (PRIME) Study, a multicenter, observational, prospective cohort, 9601 men from France and Northern Ireland were surveyed for the occurrence of first coronary heart disease (n=647) and stroke events (n=136) over 10 years. At baseline, the fourth quartile of a 13-item modified Center for Epidemiological Studies questionnaire was used to define the presence of depressive symptoms. We sought the best time-dependent function to assess the association between depressive symptoms and outcomes. Thus, the hazard ratios were estimated by a Cox proportional hazard model after splitting the follow-up before and after 5 years of follow-up time periods. RESULTS: Depressive symptoms at baseline were associated with coronary heart disease in the first 5 years of follow-up (hazard ratio, 1.43; 1.10-1.87) and with stroke in the second 5 years of follow up (hazard ratio, 1.96; 1.21-3.19) after adjustment for age, study centers, baseline socioeconomic factors, traditional vascular risk factors, and antidepressant treatment. The association was even stronger for ischemic stroke (n=108; hazard ratio, 2.48; 1.45-4.25). CONCLUSIONS: The current study suggests that in healthy, European, middle-aged men, baseline depressive symptoms are associated with an increased risk of coronary heart disease in the short-term, and for stroke in the long-term.

Adipocytokines and the risk of ischemic stroke: the PRIME Study.

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.

Ten-year risk of all-cause mortality: assessment of a risk prediction algorithm in a French general population.

While assessment of global cardiovascular risk is uniformly recommended for risk factor management, prediction of all-cause death has seldom been considered in available charts. We established an updated algorithm to predict absolute 10-year risk of all-cause mortality in apparently healthy subjects living in France, a country with high life expectancy. Analyses were based on the Third French MONICA Survey on cardiovascular risk factors (1995-1996) carried out in 3,208 participants from the general population aged 35-64. Vital status was obtained 10 years after inclusion and assessment of determinants of mortality was based on multivariable Cox modelling. One-hundred-fifty-six deaths were recorded. Independent determinants of mortality were living area (Northern France), older age, male gender, no high-school completion, smoking, systolic blood pressure ≥ 160 mmHg, LDL-cholesterol ≥ 5.2 mmol/l, and diabetes. Score sheets were developed to easily estimate 10-year risk of death. For example, a non diabetic, heavy smoker, 46-year old man, living in South-Western France, who did not complete high-school, with LDL-cholesterol ≥ 5.2 mmol/l and systolic blood pressure < 160 mmHg, has a 17% probability of death in the ten coming years. The C-statistic of the prediction model was 0.76 [95% CI: 0.72-0.80] with a degree of overoptimism estimated at 0.0058 in a bootstrap sample. Calibration was satisfying: P value for Hosmer-Lemeshow χ(2) test was 0.483. This prediction algorithm is a simple tool for guiding practitioners towards a more or less aggressive management of risk factors in apparently healthy subjects.

Patterns of alcohol consumption and ischaemic heart disease in culturally divergent countries: the Prospective Epidemiological Study of Myocardial Infarction (PRIME).

OBJECTIVE: To investigate the effect of alcohol intake patterns on ischaemic heart disease in two countries with contrasting lifestyles, Northern Ireland and France. DESIGN: Cohort data from the Prospective Epidemiological Study of Myocardial Infarction (PRIME) were analysed. Weekly alcohol consumption, incidence of binge drinking (alcohol >50 g on at least one day a week), incidence of regular drinking (at least one day a week, and alcohol <50 g if on only one occasion), volume of alcohol intake, frequency of consumption, and types of beverage consumed were assessed once at inclusion. All coronary events that occurred during the 10 year follow-up were prospectively registered. The relation between baseline characteristics and incidence of hard coronary events and angina events was assessed by Cox's proportional hazards regression analysis. SETTING: One centre in Northern Ireland (Belfast) and three centres in France (Lille, Strasbourg, and Toulouse). PARTICIPANTS: 9778 men aged 50-59 free of ischaemic heart disease at baseline, who were recruited between 1991 and 1994. MAIN OUTCOME MEASURES: Incident myocardial infarction and coronary death ("hard" coronary events), and incident angina pectoris. RESULTS: A total of 2405 men from Belfast and 7373 men from the French centres were included in the analyses, 1456 (60.5%) and 6679 (90.6%) of whom reported drinking alcohol at least once a week, respectively. Among drinkers, 12% (173/1456) of men in Belfast drank alcohol every day compared with 75% (5008/6679) of men in France. Mean alcohol consumption was 22.1 g/day in Belfast and 32.8 g/day in France. Binge drinkers comprised 9.4% (227/2405) and 0.5% (33/7373) of the Belfast and France samples, respectively. A total of 683 (7.0%) of the 9778 participants experienced ischaemic heart disease events during the 10 year follow-up: 322 (3.3%) hard coronary events and 361 (3.7%) angina events. Annual incidence of hard coronary events per 1000 person years was 5.63 (95% confidence interval 4.69 to 6.69) in Belfast and 2.78 (95% CI 2.41 to 3.20) in France. After multivariate adjustment for classic cardiovascular risk factors and centre, the hazard ratio for hard coronary events compared with regular drinkers was 1.97 (95% CI 1.21 to 3.22) for binge drinkers, 2.03 (95% CI 1.41 to 2.94) for never drinkers, and 1.57 (95% CI 1.11 to 2.21) for former drinkers for the entire cohort. The hazard ratio for hard coronary events in Belfast compared with in France was 1.76 (95% CI 1.37 to 2.67) before adjustment, and 1.09 (95% CI 0.79 to 1.50) after adjustment for alcohol patterns and wine drinking. Only wine drinking was associated with a lower risk of hard coronary events, irrespective of the country. CONCLUSIONS: Regular and moderate alcohol intake throughout the week, the typical pattern in middle aged men in France, is associated with a low risk of ischaemic heart disease, whereas the binge drinking pattern more prevalent in Belfast confers a higher risk.

C-reactive protein, interleukin 6, fibrinogen and risk of sudden death in European middle-aged men: the PRIME study.

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.

Characteristics of current smokers, former smokers, and second-hand exposure and evolution between 1985 and 2007.

AIMS: The aim of this study was to assess trends in the prevalence of adult smoking habits between 1985-1987 and 2005-2007 in three distinct areas of France and their contribution to coronary heart disease (CHD) death rates. METHODS: Participants were recruited as part of the French Monitoring trends and determinants in Cardiovascular disease survey in 1985-1987 (n=3760), 1995-1997 (n=3347), and 2005-2007 (n=3573). They were randomly selected from electoral rolls after stratification for sex, 10-year age group (35-64 years), and town size. Smoking habits were analyzed by questioning the participants about earlier or current consumption, the number of cigarettes smoked per day, age at first cigarette, pipe tobacco and cigarillo consumption, quit attempts, age at quitting, and second-hand exposure. Predicted CHD death rates as a function of smoking were predicted with the SCORE risk equation. RESULTS: In men, a significant decrease in tobacco exposure (from 40 to 24.3%) between 1985-1987 and 2005-2007 was observed. In women, the prevalence of current smokers increased from 18.9 to 20% and that of former smokers rose from 8.7 to 25.5%. In both men and women, average daily cigarette consumption and second-hand exposure to smoke fell between 1995-1997 and 2005-2007. Predicted CHD death rates as a function of smoking trends decreased in men (range 10-15%) but increased in women (range 0.1-3.6%). CONCLUSION: This study found divergent trends in the prevalence of smoking in men and women aged between 35 and 64 years over the period of 1985 to 2007. These changes may have contributed to the decline in CHD death in men but not in women.

Respective contribution of conventional risk factors and antihypertensive treatment to stable angina pectoris and acute coronary syndrome as the first presentation of coronary heart disease: the PRIME Study.

OBJECTIVE: To test whether conventional risk factors and antihypertensive treatment were more predictive of stable angina (SA) than acute coronary syndrome (ACS) as the first presentation of coronary heart disease (CHD). DESIGN: We used data from the PRIME Study (Prospective Epidemiological Study of Myocardial Infarction), a prospective cohort of 9758 asymptomatic middle-aged men recruited from WHO MONICA centers in Northern Ireland and France between 1991 and 1993. SA and ACS events were registered during 5 years of follow-up. METHODS: Hazard ratios (HRs) of each risk factor measured at baseline for SA and ACS events were assessed using separate Cox proportional hazard models. Difference between HRs was estimated by the bootstrap method. RESULTS: After 5 years of follow-up, there were 114 SA and 178 ACS as the first presentation of CHD. Diastolic blood pressure [adjusted HRs for 1 standard deviation increase = 1.34; 95% confidence interval (CI): 1.17-1.54 vs. 1.04; 95% CI: 0.87-1.25; P for comparison between HRs = 0.012], and possibly cigarette smoking over or equal to 20 pack-years (adjusted HR = 2.07; 95% CI: 1.43-2.99 vs. 1.29; 95% CI: 0.83-2.01; P for comparison between HRs = 0.062) were more predictive of ACS than SA, whereas this was the opposite for antihypertensive treatment (adjusted HR = 2.18; 95% CI: 1.39-3.41 for SA vs. 1.28; 95% CI: 0.85-1.93 for ACS, P for comparison between HRs = 0.049). CONCLUSION: The present data support that SA and ACS, as the first presentation of CHD, may not share exactly the same determinants.

Relative risks for stroke by age, sex, and population based on follow-up of 18 European populations in the MORGAM Project.

BACKGROUND AND PURPOSE: Within the framework of the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project, the variations in impact of classical risk factors of stroke by population, sex, and age were analyzed. METHODS: Follow-up data were collected in 43 cohorts in 18 populations in 8 European countries surveyed for cardiovascular risk factors. In 93 695 persons aged 19 to 77 years and free of major cardiovascular disease at baseline, total observation years were 1 234 252 and the number of stroke events analyzed was 3142. Hazard ratios were calculated by Cox regression analyses. RESULTS: Each year of age increased the risk of stroke (fatal and nonfatal together) by 9% (95% CI, 9% to 10%) in men and by 10% (9% to 10%) in women. A 10-mm Hg increase in systolic blood pressure involved a similar increase in risk in men (28%; 24% to 32%) and women (25%; 20% to 29%). Smoking conferred a similar excess risk in women (104%; 78% to 133%) and in men (82%; 66% to 100%). The effect of increasing body mass index was very modest. Higher high-density lipoprotein cholesterol levels decreased the risk of stroke more in women (hazard ratio per mmol/L 0.58; 0.49 to 0.68) than in men (0.80; 0.69 to 0.92). The impact of the individual risk factors differed somewhat between countries/regions with high blood pressure being particularly important in central Europe (Poland and Lithuania). CONCLUSIONS: Age, sex, and region-specific estimates of relative risks for stroke conferred by classical risk factors in various regions of Europe are provided. From a public health perspective, an important lesson is that smoking confers a high risk for stroke across Europe.