Health disturbances and exposure to radiofrequency electromagnetic fields from mobile-phone base stations in French urban areas.

The effects of radiofrequency exposure on the health of people living near mobile-phone base stations (MPBSs) have been the subject of several studies since the mid-2000s, with contradictory results. We aimed to investigate the association between measured exposure to radiofrequency electromagnetic fields (RF-EMF) from MPBSs and the presence of self-reported non-specific and insomnia-like symptoms. A cross-sectional survey conducted between 2015 and 2017 in five large cities in France involved 354 people living in buildings located at a distance of 250 m or less from an MPBS and in the main transmit beam of the antennas. Information on environmental concerns, anxiety, and non-specific and insomnia-like symptoms was collected with a questionnaire administrated by telephone. A complete broadband field-meter measurement [100 kHz - 6 GHz] was then made at five points of each dwelling, followed by a spectral analysis at the point of highest exposure, detailing the contribution of each service, including MPBS. The median exposure from MPBS was 0.27 V/m (0.44 V/m for global field), ranging from 0.03 V/m to 3.58 V/m, MPBSs being the main source of exposure for 64% of the dwellings. In this study population, the measured exposure from MPBSs was not associated with self-reported non-specific or insomnia-like symptoms. However, for insomnia-like symptoms, a significant interaction was found between RF-EMF exposure from MPBSs and environmental concerns. These findings do not support the hypothesis of an effect of RF-EMF from MPBSs on non-specific or insomnia-like symptoms in the overall population. Studies are needed to further investigate the positive association observed between exposure from MPBSs and insomnia-like symptoms among people reporting environmental concerns.

Radiofrequency exposure of people living near mobile-phone base stations in France.

In response to the demand from a growing number of people concerned about the possible impact of RF-EMF on health, the French National Frequency Agency (ANFR) has published a standardized protocol for in-situ measurements of radiofrequency electromagnetic fields (RF-EMF). This protocol was based on the search for the point of highest field strength and the use of spot measurement. In the framework of an epidemiological study, such spot measurements were implemented in the homes of 354 participants located in urban areas within 250 m of a mobile-phone base station (MPBS) and in the main beam direction of the antenna. Among the participants, more than half accepted to be enrolled in a longer-term study, among whom 152 were equipped with a personal exposure meter (PEM) for 48 h and 40 for seven continuous days. Both spot and PEM measurements quantified downlink field strengths, i.e. FM, TV3-4-5, TETRA I-II-III, 2 GHz-5GHz Wi-Fi, WiMax, GSM900, GSM1800, UMTS900, UMTS 2100, LTE800, LTE1800, and LTE2600. Spot measurements showed a mean/median field strength of 0.58/0.44 V/m for total RF-EMF and 0.43/0.27 V/m from the MPBS. RF-EMF from the MPBS was the dominant source of exposure in 64% of households. Exposure to RF-EMF was influenced by the position of the windows with respect to the MPBS, in particular line-of-site visibility, the distance of the antenna and the floor of the apartment. The PEM surveys showed the measured exposure to be higher during outings than at home and during the day than at night, but there was no difference between the weekends and working days. There was a strong correlation between exposure quantified by both spot and PEM measurements, although spot measures were approximately three times higher than those by PEMs. This study is the first to assess exposure to RF-EMF of people living near a MPBS in urban areas in France. These preliminary results suggest the value of using spot measurements to estimate the impact of the evolution of the mobile-phone network and technology on the exposure of populations to RF-EMF. The low levels of RF-RMF expressed as mean values do not necessarily rule out possible health effects of this exposure.

All-Cause Mortality up to and After Coronary Heart Disease and Stroke Events in European Middle-Aged Men: The PRIME Study.

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

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.

Excessive daytime sleepiness and vascular events: the Three City Study.

OBJECTIVE: We assessed whether excessive daytime sleepiness (EDS) at baseline was associated with subsequent coronary heart disease (CHD) and stroke events. METHODS: The Three City Study, a French population-based multicenter prospective study, included 7,007 subjects aged ≥65 years with no personal history of CHD, stroke, or dementia, and self-rated EDS as never, rare, regular, or frequent in response to a face-to-face questionnaire. Hazard ratios (HRs) for the first episode of stroke and CHD over 6 years were estimated using a Cox proportional hazards model with age as the time scale. RESULTS: The mean age of the cohort was 73.7 years (standard deviation, 5.37), 63% were women, and 13.3% and 4.3% reported regular and frequent EDS, respectively. After a median follow-up period of 5.1 years, 372 subjects experienced a first event, either stroke (122 subjects) or a CHD event (250 subjects). The increased risk of CHD and stroke was confined to the group with frequent EDS, and was 1.73× as much as in the group that reported never having EDS (HR, 1.73; 95% confidence interval [CI], 1.15-2.60), after adjustment for confounding and mediating factors. This association was seen in those without hypertension but not in those with hypertension at baseline (p for interaction = 0.01). Moreover, the association with frequent EDS was statistically significant for stroke (HR, 2.10; 95% CI, 1.13-3.89) but not for CHD (HR, 1.51; 95% CI, 0.87-2.61). INTERPRETATION: The current study suggests that frequent EDS is independently associated with future vascular events and stroke in particular in healthy community-dwelling elderly subjects.

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.

Personality and the risk of cancer: a 16-year follow-up study of the GAZEL cohort.

OBJECTIVE: Large-scale prospective studies do not support an association between neuroticism and extroversion with cancer incidence. However, research on other personality constructs is inconclusive. This longitudinal study examined the associations between four personality measures, Type 1, "suppressed emotional expression"; Type 5, "rational/antiemotional"; hostility; and Type A with cancer incidence. METHODS: Personality measures were available for 13,768 members in the GAZEL cohort study (baseline assessment in 1993). Follow-up for diagnoses of primary cancers was obtained from January 1, 1994 to December 31, 2009. Associations between personality and cancer incidence were evaluated using Cox proportional hazards analyses and adjusted for potential confounders. RESULTS: During a median follow-up of 16.0 years (range, 9 days-16 years), 1139 participants were diagnosed as having a primary cancer. The mean duration between baseline and cancer diagnosis was 9.3 years. Type 1 personality was associated with a decreased risk of breast cancer (hazard ratio per standard deviation = 0.81, 95% confidence interval = 0.68-0.97, p = .02). Type 5 personality was not associated with prostate, breast, colorectal, or smoking-related cancers, but was associated with other cancers (hazard ratio per standard deviation = 1.17, 95% confidence interval = 1.04-1.31, p = .01). Hostility was associated with an increased risk of smoking-related cancers, which was explained by smoking habits, and Type A was not associated with any of the cancer endpoints. CONCLUSIONS: Several personality measures were prospectively associated with the incidence of selected cancers. These links may warrant further epidemiological studies and investigations about potential biobehavioral mechanisms.

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.

Depressive symptoms, antidepressants and disability and future coronary heart disease and stroke events in older adults: the Three City Study.

To investigate the association between baseline depressive symptoms and first fatal and non fatal coronary heart disease (CHD) and stroke in older adults, taking antidepressants and disability into account. In the Three City Study, a community-based prospective multicentric observational study cohort, 7,308 non-institutionalized men and women aged ≥65 years with no reported history of CHD, stroke or dementia, completed the 20-item Center for Epidemiologic Studies depression scale (CESD) questionnaire. First CHD and stroke events during follow-up were adjudicated by an independent expert committee. Hazard ratios (HRs) were estimated by Cox proportional hazard model. After a median follow-up of 5.3 years, 338 subjects had suffered a first non-fatal CHD or stroke event, and 82 had died from a CHD or stroke. After adjustment for study center, baseline socio-demographic characteristics, and conventional risk factors, depressive symptoms (CESD ≥ 16) were associated with fatal events only: fatal CHD plus stroke (HR = 2.50; 95% CI 1.57-3.97), fatal CHD alone (n = 57; HR = 2.21 ; 95%CI 1.27-3.87), and fatal stroke alone (n = 25; HR = 3.27; 95% CI 1.42-7.52). These associations were even stronger in depressed subjects receiving antidepressants (HR = 4.17; 95% CI 1.84-9.46) and in depressed subjects with impaired Instrumental Activities of Daily Living (HR = 8.93; 95% CI 4.60-17.34). By contrast, there was no significant association with non fatal events (HR for non-fatal CHD or stroke = 0.94; 95% CI 0.66-1.33). In non-institutionalized elderly subjects without overt CHD, stroke or dementia, depressive symptoms were selectively and robustly associated with first fatal CHD or stroke events.

Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta-Analysis of 20 Prospective Studies.

Background The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.

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.

Increased thrombin generation is associated with acute ischemic stroke but not with coronary heart disease in the elderly: the Three-City cohort study.

OBJECTIVE: A high thrombin generation level has been associated with the risk of venous thrombosis. Whether changes in this biomarker are relevant to arterial disease remains unknown. We investigated the association of thrombin generation with coronary heart disease (CHD) and acute ischemic stroke (AIS) in the elderly. METHODS AND RESULTS: We used data from the Three-City study, a prospective cohort including 9294 subjects aged >65 years. After 4 years of follow-up, a case-cohort study was established. Using the calibrated automated thrombography method, endogenous thrombin potential and peak height were measured in plasma samples of all CHD and AIS cases and a random sample of 1177 controls. We did not find any significant association between thrombin generation and CHD. In multivariate analyses, high levels of endogenous thrombin potential and peak height were associated with an increased risk of AIS (hazard ratio=1.16 [95% CI, 0.90 to 1.50] and 1.31 [95% CI, 1.01 to 1.69] for a 1 SD increase, respectively). Data also suggested that these associations might be more important in women (hazard ratio=1.55 [95% CI, 1.05 to 2.33] and 1.71 [95% CI, 1.11 to 2.63], respectively) than in men (P for interaction=0.04 and 0.08, respectively). CONCLUSION: Thrombin generation emerges as an independent predictor of AIS, particularly in women. Hypercoagulability may have an important role in the pathogenesis of AIS.

Lipid-related markers and cardiovascular disease prediction.

CONTEXT: The value of assessing various emerging lipid-related markers for prediction of first cardiovascular events is debated. OBJECTIVE: To determine whether adding information on apolipoprotein B and apolipoprotein A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 to total cholesterol and high-density lipoprotein cholesterol (HDL-C) improves cardiovascular disease (CVD) risk prediction. DESIGN, SETTING, AND PARTICIPANTS: Individual records were available for 165,544 participants without baseline CVD in 37 prospective cohorts (calendar years of recruitment: 1968-2007) with up to 15,126 incident fatal or nonfatal CVD outcomes (10,132 CHD and 4994 stroke outcomes) during a median follow-up of 10.4 years (interquartile range, 7.6-14 years). MAIN OUTCOME MEASURES: Discrimination of CVD outcomes and reclassification of participants across predicted 10-year risk categories of low (<10%), intermediate (10%-<20%), and high (≥20%) risk. RESULTS: The addition of information on various lipid-related markers to total cholesterol, HDL-C, and other conventional risk factors yielded improvement in the model's discrimination: C-index change, 0.0006 (95% CI, 0.0002-0.0009) for the combination of apolipoprotein B and A-I; 0.0016 (95% CI, 0.0009-0.0023) for lipoprotein(a); and 0.0018 (95% CI, 0.0010-0.0026) for lipoprotein-associated phospholipase A2 mass. Net reclassification improvements were less than 1% with the addition of each of these markers to risk scores containing conventional risk factors. We estimated that for 100,000 adults aged 40 years or older, 15,436 would be initially classified at intermediate risk using conventional risk factors alone. Additional testing with a combination of apolipoprotein B and A-I would reclassify 1.1%; lipoprotein(a), 4.1%; and lipoprotein-associated phospholipase A2 mass, 2.7% of people to a 20% or higher predicted CVD risk category and, therefore, in need of statin treatment under Adult Treatment Panel III guidelines. CONCLUSION: In a study of individuals without known CVD, the addition of information on the combination of apolipoprotein B and A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 mass to risk scores containing total cholesterol and HDL-C led to slight improvement in CVD prediction.

Short-term impact of ambient air pollution and air temperature on blood pressure among pregnant women.

BACKGROUND: Epidemiologic studies have reported inconsistent findings for the association between air pollution levels and blood pressure (BP), which has been studied mainly in elderly subjects. Short-term air pollution effects on BP have not been investigated in pregnant women, who may constitute a vulnerable population. METHODS: Between 2002 and 2006, 1500 pregnant women from a mother-child cohort study conducted in Nancy and Poitiers, France, underwent 11,220 repeated BP measurements (average, 7.5 measurements/woman). Nitrogen dioxide (NO2), particulate matter with an aerodynamic diameter below 10 µm (PM10), and meteorologic variables were measured on an hourly basis at permanent monitoring sites. We studied changes of BP in relation to short-term variations of air pollution and temperature with mixed models adjusted for meteorologic and personal characteristics. RESULTS: A 10°C decrease in temperature led to an increase in systolic BP of 0.5% (95% confidence interval = 0.1% to 1.0%). Elevated NO2-levels 1 day, 5 days and averaged over 7 days before the BP measurement were associated with reduced systolic BP. The strongest decrease was observed for the 7-day NO2 average (-0.4% [-0.7% to -0.2%] change for an 11 µg/m³ increase in NO2). PM10 effects on systolic BP differed according to pregnancy trimester: PM10 concentration was associated with systolic BP increases during the first trimester and systolic BP decreases later in pregnancy. CONCLUSIONS: We observed short-term associations of air pollution and of temperature with BP in pregnant women. Whether such changes in BP have clinical implications remains to be investigated.

Relationships between body mass index, cardiovascular mortality, and risk factors: a report from the SCORE investigators.

BACKGROUND: Although cardiovascular disease (CVD) is the biggest global cause of death, CVD mortality is falling in developed countries. There is concern that this trend may be offset by increasing levels of obesity. DESIGN: We used the Systematic Coronary Risk Evaluation (SCORE) data set to examine relationships between body mass index (BMI), conventional risk factors and CVD mortality. METHODS: The SCORE data set comprises data from 12 European cohort studies. The relationship between BMI and CVD mortality was examined in each BMI category using univariable and multivariable (Cox) analyses. The SCORE population was also divided into gender and age strata: under 40, 40-49, 50-59, and over 60. The rate of CVD mortality in each BMI category was calculated within each gender and age stratum. Relationships between BMI and other CVD risk factors were also examined. RESULTS: There was a strong, graded but J-shaped univariable relationship between BMI and CVD mortality in both genders. Each 5-unit increase in BMI was associated with an increase in CVD mortality of 34% in men and 29% in women. The hazard ratios remained significant when adjusted for age, self-reported smoking status, total cholesterol, and systolic blood pressure (SBP). On additional adjustment for diabetes and high-density lipoprotein cholesterol (HDL), the association between BMI and CVD mortality did not persist. In all age groups except those over 60 there were significant relationships between increased BMI and CVD mortality. In the over-60 age group the only significant relationships with mortality were in underweight and severely overweight women and mildly obese men. After adjustment for age, each 1-unit increase in BMI was associated with a 1.14 mmHg increase in SBP, 0.055 mmol/l increase in total cholesterol, and a 0.024 mmol/l decrease in HDL in men. Figures were slightly lower in women. CONCLUSIONS: Overall, overweight and obesity relate to CVD mortality in a strong and graded manner. The effects are greater in women and markedly so in younger persons. It is likely that a substantial part of the BMI-associated risk of CVD mortality is mediated through other known CVD risk factors. This increases the public health importance of BMI as both a simple indicator and mediator of CVD 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.

Could clinical decision rules relying on cardiovascular risk models increase psychosocial inequalities in health? Results from the PRIME cohort study.

OBJECTIVE: Guidelines on cardiovascular prevention relying on common cardiovascular risk scoring could result in delayed drug therapy for patients with low psychosocial status because of underestimation of true cardiovascular risk. We aimed to assess the potential delay in drug therapy for subjects with adverse psychosocial factors. METHOD: The study population consisted of 6185 French men from the PRIME (Prospective Epidemiological Study of Myocardial Infarction) cohort study (1991-2003). The number of extra years to reach a risk threshold for subjects without adverse psychosocial factor compared to subject with adverse psychosocial factor was estimated using a coronary risk model including biomedical factors and a psychosocial variable (education, occupation, living conditions or a depression score). RESULTS: Coronary risk was significantly higher only for subjects with a high depression score (odds ratio=1.34; 95% confidence interval 1.04, 1.72) or low educational attainment (odds ratio=1.39; 95% confidence interval=1.07, 1.81). For a given risk threshold, subjects with high depression scores were 4.5 years (95% confidence interval=0.0, 15.4 years) younger than subjects with low depression scores. The age difference was 4.1 years (95% confidence interval=-0.5, 15.8 years) between subjects with low and high educational attainment. CONCLUSION: Clinical decision rules relying on classic cardiovascular risk scoring could result in delayed drug therapy for patients with depression or low educational attainment.

Evolution of obesity prevalence in France: an age-period-cohort analysis.

BACKGROUND: A rapid increase in the prevalence of obesity has been reported in France since 1990. We investigated the impact of birth cohort on the changes in obesity prevalence after taking into account age and survey period. METHODS: We analyzed data from 4 national surveys in 1997, 2000, 2003, and 2006. For each survey, self-reported data on weight and height were recorded on mailed questionnaires sent to a sample of 20,000 households, representative of the French population. Obesity was defined according to World Health Organization criteria as body mass index >or=30 kg/m. We modeled the prevalence of obesity using logistic regression with age, cohort, and period as explanatory variables. As these variables are linearly dependent, only nonlinear effects can be estimated uniquely and interpreted, after including specific chosen constraints in the models. RESULTS: There was a progressive increase in the prevalence of obesity between 1997 and 2006, attributable either to a period effect or to a cohort effect. There was a substantial departure from a linear trend for the cohort effect only, which seemed to be stronger in women: there was an acceleration in the prevalence of obesity with birth cohort for individuals born after the mid-1960s, in both sexes. CONCLUSIONS: Our results are consistent with previous studies in other countries. Compared with older generations, men and women born in the late 1960s may have been subject to early exposures that increased their lifelong susceptibility to obesity.

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.

Relative contribution of lipids and apolipoproteins to incident coronary heart disease and ischemic stroke: the PRIME Study.

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.