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.

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.

Hostility and the risk of peptic ulcer in the GAZEL cohort.

OBJECTIVE: Evidence for an association between hostility and peptic ulcer mainly relies on cross-sectional studies. Prospective studies are rare and have not used a validated measure of hostility. This prospective study aimed to examine the association between hostility and peptic ulcer in the large-scale French GAZEL cohort. METHOD: In 1993, 14,674 participants completed the Buss and Durkee Hostility Inventory. Participants were annually followed-up from 1994 to 2011. Diagnosis of peptic ulcer was self-reported. The association between hostility scores and ulcer incidence was measured by hazard ratios (HR) and 95% confidence intervals computed through Cox regression. RESULTS: Among 13,539 participants free of peptic ulcer history at baseline, 816 reported a peptic ulcer during a mean follow-up of 16.8 years. Adjusting for potential confounders, including smoking, occupational grade, and a proxy for nonsteroidal anti-inflammatory drug exposure, ulcer incidence was positively associated with total hostility (HR per SD: 1.23, confidence interval: 1.14-1.31), behavioral hostility (HR per SD: 1.13, confidence interval: 1.05-1.21), cognitive hostility (HR per SD: 1.26, confidence interval: 1.18-1.35), and irritability (HR per SD: 1.20, confidence interval: 1.12-1.29). The risk of peptic ulcer increased from the lowest to the highest quartile for all hostility measures (p for linear trend < .05). CONCLUSIONS: Hostility might be associated with an increased risk of peptic ulcer. Should these results be replicated, further studies would be needed to explore the underlying mechanisms.

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.

Influence of calendar period on the association between BMI and coronary heart disease: a meta-analysis of 31 cohorts.

OBJECTIVE: The association between obesity and coronary heart disease (CHD) may have changed over time, for example due to improved pharmacological treatment of CHD risk factors. This meta-analysis of 31 prospective cohort studies explores the influence of calendar period on CHD risk associated with body mass index (BMI). DESIGN AND METHODS: The relative risks (RRs) of CHD for a five-BMI-unit increment and BMI categories were pooled by means of random effects models. Meta-regression analysis was used to examine the influence of calendar period (>1985 v ≤1985) in univariate and multivariate analyses (including mean population age as a covariate). RESULTS: The age, sex, and smoking adjusted RR (95% confidence intervals) of CHD for a five-BMI-unit increment was 1.28(1.22:1.34). For underweight, overweight and obesity, the RRs (compared to normal weight) were 1.11(0.91:1.36), 1.31(1.22:1.41), and 1.78(1.55:2.04), respectively. The univariate analysis indicated 31% (95%CI: -56:0) lower RR of CHD associated with a five-BMI-unit increment and a 51% (95%CI: -78: -14)) lower RR associated with obesity in studies starting after 1985 (n = 15 and 10, respectively) compared to studies starting in or before 1985 (n = 16 and 10). However, in the multivariate analysis, only mean population age was independently associated with the RRs for a five-BMI-unit increment and obesity (-29(95%CI: -55: -5)) and -31(95%CI: -66:3), respectively) per 10-year increment in mean age). CONCLUSION: This study provides no consistent evidence for a difference in the association between BMI and CHD by calendar period. The mean population age seems to be the most important factor that modifies the association between the risk of CHD and BMI, in which the RR decreases with increasing age.

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.

Lipoprotein(a) plasma levels and the risk of cancer: the PRIME study.

Although experimental studies have shown lipoprotein(a) antiangiogenic and antitumoral effects, the association of lipoprotein(a) levels with cancer in population studies remains elusive and poorly documented. The aim of this study was to analyse the relationship between lipoprotein(a) plasma levels and the incidence of cancer over 10 years of follow-up. Data from two French centres of the PRIME cohort were used, representing 5237 men aged 50-59 years and free from a history of cancer at baseline. Data on medical history, socioeconomic and lifestyle factors were obtained by questionnaire. Lipoprotein(a) plasma levels were analysed from fasting blood samples collected at baseline. The relationship between lipoprotein(a) levels and first incident cancer was studied using the multivariate Cox proportional hazards models for all-site and the main-site-specific cancers, adjusted for various potential confounders including age, centre, smoking status and alcohol consumption. During follow-up, 456 new cancers were identified. No significant association was found between lipoprotein(a) and the all-site or main-site-specific cancers (hazard ratios for quartiles 2-4 vs. 1, respectively: 1.24, 1.11, 1.29, P=0.23). However, a higher risk seemed to be observed for highest lipoprotein(a) levels in all sites, lung, colorectal or tobacco/alcohol-related cancers. For prostate cancer, the lowest risk was observed for the highest levels of lipoprotein(a) (P=0.12). In conclusion, no evident association was found between the lipoprotein(a) levels and the incidence of cancer. Nevertheless, a higher cancer risk seemed to be observed for the highest lipoprotein(a) levels. Further research focusing on the lipoprotein(a) qualitative structure, that is, apolipoprotein(a) polymorphism could help clarify this highly complex relation.

High level of plasma estradiol as a new predictor of ischemic arterial disease in older postmenopausal women: the three-city cohort study.

BACKGROUND: Despite evidence that estrogens may be involved in atherothrombosis, the role of endogenous sex steroid hormones in ischemic arterial disease among postmenopausal women remains uncertain. METHODS AND RESULTS: In the Three-City prospective cohort study of subjects (n=9294) >65 years of age, we investigated the association of total 17ß-estradiol, bioavailable 17ß-estradiol, and total testosterone with the 4-year incidence of ischemic arterial disease among postmenopausal women who did not use any hormone therapy. We designed a case-cohort study including a random sample of 537 subjects and 106 incident cases of first cardiovascular events. Weighted Cox proportional-hazards models with age as the time scale were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for ischemic arterial disease by a 1-standard deviation increase in sex steroid hormones. In univariate analysis, HR of ischemic arterial disease was positively and significantly associated with both total and bioavailable estradiol levels. These associations remained significant after adjustment for traditional cardiovascular risk factors, including body mass index, diabetes, hypercholesterolemia, hypertension, and smoking status (HR: 1.42, 95% CI: 1.12-1.79, P<0.01; and HR: 1.42, 95% CI: 1.12-1.78, P<0.01, respectively). Separate analysis for coronary heart disease yielded similar results (adjusted HR: 1.49, 95% CI: 1.10-2.02, P=0.01; and adjusted HR: 1.50, 95% CI: 1.11-2.04, P<0.01, respectively), and a borderline significant trend was observed for ischemic stroke (HR: 1.34, 95% CI: 0.95-1.89, P=0.08; and HR: 1.32, 95% CI: 0.94-1.84, P=0.11, respectively). By contrast, no significant association was found between total testosterone and ischemic arterial disease in both univariate and adjusted analyses. CONCLUSIONS: High plasma level of endogenous estradiol emerges as a new predictor of ischemic arterial disease in older postmenopausal women. (J Am Heart Assoc. 2012;1:e001388 doi: 10.1161/JAHA.112.001388.).

Heart rate and risk of cancer death in healthy men.

BACKGROUND: Data from several previous studies examining heart-rate and cardiovascular risk have hinted at a possible relationship between heart-rate and non-cardiac mortality. We thus systematically examined the predictive value of heart-rate variables on the subsequent risk of death from cancer. METHODS: In the Paris Prospective Study I, 6101 asymptomatic French working men aged 42 to 53 years, free of clinically detectable cardiovascular disease and cancer, underwent a standardized graded exercise test between 1967 and 1972. Resting heart-rate, heart-rate increase during exercise, and decrease during recovery were measured. Change in resting heart-rate over 5 years was also available in 5139 men. Mortality including 758 cancer deaths was assessed over the 25 years of follow-up. FINDINGS: There were strong, graded and significant relationships between all heart-rate parameters and subsequent cancer deaths. After adjustment for age and tobacco consumption and, compared with the lowest quartile, those with the highest quartile for resting heart-rate had a relative risk of 2.4 for cancer deaths (95% confidence interval: 1.9-2.9, p<0.0001) This was similar after adjustment for traditional cardiovascular risk factors and was observed for the commonest malignancies (respiratory and gastrointestinal). Similarly, significant relationships with cancer death were observed between poor heart rate increase during exercise, poor decrease during recovery and greater heart-rate increase over time (p<0.0001 for all). INTERPRETATION: Resting and exercise heart rate had consistent, graded and highly significant associations with subsequent cancer mortality in men.

Association between a thyroid hormone receptor-α gene polymorphism and blood pressure but not with coronary heart disease risk.

BACKGROUND: Thyroid hormones (THs) exert multiple biological roles including effects on the cardiovascular system (lipid profile, blood pressure (BP) and cardiac output). The lipid-lowering actions of TH are mediated by the TH receptor-ß whereas the mechanisms explaining the BP variations concomitant with the thyroid disorders are less understood. As the TH receptor-α (TR-α) has been associated with many of TH actions on the cardiovascular system in mice models, we hypothesized that it could be involved in the latter. We thus tested whether polymorphisms in TR-α (THRA gene) could be associated with BP level variation. Secondarily, we tested for association with coronary heart disease (CHD) risk. METHODS: We analyzed the associations between five THRA polymorphisms and (i) BP level in two population-based studies (MONICA Lille n = 1,155; MONICA Toulouse n = 1,170) and (ii) the risk of CHD in two case-control studies (Lille CHD n = 558 cases/568 controls; PRIME n = 527 cases/584 controls). RESULTS: Individuals carrying the rs939348 T allele had higher systolic BP (~+1.3 mm Hg) than CC individuals in both the MONICA Lille (P = 0.02) and Toulouse (P = 0.03) studies. The odds ratio (OR) for hypertension was 1.25 (P = 0.02) in the combined sample. Concerning the CHD risk, no significant association could be detected. CONCLUSIONS: For the first time, our study showed associations between the THRA rs939348 polymorphism and systolic BP and the risk of hypertension but not with CHD, although we admit that the statistical power available to study any relationship with CHD was very limited. Further larger association studies are needed to confirm our findings.

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.

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.

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.

Hostility may explain the association between depressive mood and mortality: evidence from the French GAZEL cohort study.

UNLABELLED: Depressive mood is associated with mortality. Because personality has been found to be associated with depression and mortality as well, we aimed to test whether depressive mood could predict mortality when adjusting for several measures of personality. METHODS: 20,625 employees of the French national gas and electricity companies gave consent to enter in the GAZEL cohort in 1989. Questionnaires were mailed in 1993 to assess depressive mood, type A behavior pattern, hostility, and the six personality types proposed by Grossarth-Maticek and Eysenck. Vital status and date of death were obtained annually for all participants. The association between psychological variables and mortality was measured by the Relative Index of Inequality (RII) computed through Cox regression. RESULTS: 14,356 members of the GAZEL cohort (10,916 men, mean age: 49 years; 3,965 women, mean age: 46 years) completed the depressive mood scale and at least one personality scale. During a mean follow-up of 14.8 years, 687 participants had died. Depressive mood predicted mortality, even after adjustment for age, sex, education level, body mass index, alcohol consumption, and smoking [RII (95% CI) = 1.56 (1.16-2.11)]. However, this association was dramatically reduced (RII reduction: 78.9%) after further adjustment for cognitive hostility (i.e. hostile thoughts) [RII (95% CI) = 1.12 (0.80-1.57)]. Cognitive hostility was the only personality measure remaining associated with mortality after adjustment for depressive mood [RII (95% CI) = 1.97 (1.39-2.77)]. CONCLUSIONS: Cognitive hostility may either confound or mediate the association between depressive mood and mortality.

Higher level of systemic C-reactive protein is independently predictive of coronary heart disease in older community-dwelling adults: the three-city study.

OBJECTIVES: To assess the association between systemic C-reactive protein (CRP) and incident coronary heart disease (CHD) in community-dwelling elderly people. DESIGN: A French population-based multicenter prospective cohort study. SETTING: Three cities in France: Bordeaux in the southwest, Dijon in the northeast, and Montpellier in the southeast. PARTICIPANTS: After 4 years of follow-up, a case-cohort study was designed including 1,004 subjects randomly selected from the initial cohort of 9,294 subjects free of CHD at baseline and 174 subjects who developed first CHD events during follow-up. MEASUREMENTS: Hazard ratios (HRs) were estimated using a Cox proportional hazard model adapted for the case-cohort design using a CRP level less than 1 mg/L as the reference category. RESULTS: Of the random sample, 24.3% had a CRP level less than 1.0 mg/L, 45.8% had a CRP level of 1.0 to 2.9 mg/L, and 29.9% had a CRP level of 3.0 to 10.0 mg/L. The HRs for CHD, adjusted for age, sex, and study center, were 1.69 (95% confidence interval (CI)=1.04-2.75) for CRP from 1.0 to 2.9 mg/L and 2.32 (95% CI=1.41-3.82) for CRP from 3.0 to 10.0 mg/L (P for trend <.001). After additional adjustment for smoking, body mass index, diabetes mellitus, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, statin use, and antihypertensive treatment, a baseline CRP of 3.0 to 10.0 mg/L remained associated with risk of CHD (HR=1.87, 95% CI=1.09-3.25), although CRP did not improve the discriminative ability of a predicting model based on traditional risk factors (receiver operating characteristic curves from 0.740 to 0.749). CONCLUSION: CRP is an independent CHD risk marker but does not improve CHD risk prediction in community-dwelling elderly people.

Slow walking speed and cardiovascular death in well functioning older adults: prospective cohort study.

OBJECTIVE: To study the relation between low walking speed and the risk of death in older people, both overall and with regard to the main causes of death. DESIGN: Prospective cohort study. SETTING: Dijon centre (France) of the Three-City study. PARTICIPANTS: 3208 men and women aged >or=65 living in the community, recruited from 1999 to 2001, and followed for an average of 5.1 years. MAIN OUTCOME MEASURES: Mortality, overall and according to the main causes of death, by thirds of baseline walking speed (measured at maximum speed over six metres), adjusted for several potential confounders; Kaplan-Meier survival curves by thirds of baseline walking speed. Vital status during follow-up. Causes of death. Results During 16 414 person years of follow-up, 209 participants died (99 from cancer, 59 from cardiovascular disease, 51 from other causes). Participants in the lowest third of baseline walking speed had an increased risk of death (hazard ratio 1.44, 95% confidence interval 1.03 to 1.99) compared with the upper thirds. Analyses for specific causes of death showed that participants with low walking speed had about a threefold increased risk of cardiovascular death (2.92, 1.46 to 5.84) compared with participants who walked faster. There was no relation with cancer mortality (1.03, 0.65 to 1.70). In stratified analyses, cardiovascular mortality was increased across various strata defined by sex, median age, median body mass index (BMI), and level of physical activity. Conclusion Slow walking speed in older people is strongly associated with an increased risk of cardiovascular mortality.

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.

Contribution of cardiovascular risk factors to coronary risk in patients with intermittent claudication in the PRIME Cohort Study of European men.

BACKGROUND: Intermittent claudication (IC) is associated with an increased cardiovascular morbidity. The goal of the present study was to assess the contribution of conventional cardiovascular risk factors (CVRFs) to this increased risk. METHOD: The PRIME Study is a multicenter Prospective Cohort Study of 10 602 men recruited in 1991-1993, aged 50-59 at baseline and followed over 10 years. At baseline, a questionnaire on socio demographic data was self-administered and CVRFs were measured. Composite outcome consisted of incident MI, effort angina, unstable angina and coronary death. The standardized questionnaire of the London School of hygiene was used to identify claudicants. Data were analyzed using multivariate Cox models. RESULTS: Probable and possible cases of IC were reported by 1.4% (135) and 4.6% (442) of subjects, respectively. Compared to subjects with no claudication, the probable cases demonstrated higher rates of CVRFs. The incidence of CAD events was 7.23/1000 person-year. Compared to non claudicants, probable claudicants had an increased age and country adjusted risk of coronary events (HR (95% CI), 2.4 (1.5-3.7), p<0.0001). After further adjustments for school duration, family history of early myocardial infarction, tobacco consumption, alcohol consumption, BMI, systolic blood pressure, antihypertensive treatment, diabetes, total cholesterol, HDL-cholesterol, triglycerides and lipid-lowering treatment, participants with probable claudication had an increased risk of coronary events but this was no longer significant (HR (95% CI), 1.3 (0.8-2.1), p=0.23). CONCLUSION: IC is associated with an increased risk of developing coronary events. This association is largely explained by the coexistence of CVRFs.