Low serum DHEA-S is associated with impaired lung function in women.

BACKGROUND: Emerging evidence suggests that androgens and estrogens have a role in respiratory health, but it is largely unknown whether levels of these hormones can affect lung function in adults from the general population. This study investigated whether serum dehydroepiandrosterone sulfate (DHEA-S), a key precursor of both androgens and estrogens in peripheral tissues, was related to lung function in adult women participating in the European Community Respiratory Health Survey (ECRHS). METHODS: Lung function and serum DHEA-S concentrations were measured in n = 2,045 and n = 1,725 women in 1999-2002 and in 2010-2013, respectively. Cross-sectional associations of DHEA-S levels (expressed as age-adjusted z-score) with spirometric outcomes were investigated, adjusting for smoking habits, body mass index, menopausal status, and use of corticosteroids. Longitudinal associations of DHEA-S levels in 1999-2002 with incidence of restrictive pattern and airflow limitation in 2010-2013 were also assessed. FINDINGS: Women with low DHEA-S (z-score<-1) had lower FEV1 (% of predicted, adjusted difference: -2.2; 95%CI: -3.5 to -0.9) and FVC (-1.7; 95%CI: -2.9 to -0.5) and were at a greater risk of having airflow limitation and restrictive pattern on spirometry than women with higher DHEA-S levels. In longitudinal analyses, low DHEA-S at baseline was associated with a greater incidence of airflow limitation after an 11-years follow-up (incidence rate ratio, 3.43; 95%CI: 1.91 to 6.14). INTERPRETATION: Low DHEA-S levels in women were associated with impaired lung function and a greater risk of developing airflow limitation later in adult life. Our findings provide new evidence supporting a role of DHEA-S in respiratory health. FUNDING: EU H2020, grant agreement no.633212.

Risk of asthma onset after natural and surgical menopause: Results from the French E3N cohort.

BACKGROUND: The gender switch in asthma incidence around puberty has been put forward to suggest a role of sex hormones in asthma. However, there are limited and inconsistent findings on change in asthma incidence with menopause. We aimed to investigate the associations between menopause and asthma incidence, and interactions with overweight/obesity. METHODS: Asthma incidence was assessed in 67,872 women free of asthma at baseline (aged 41-68 years) and regularly followed up as a part of the French E3N cohort. Adjusted hazard ratios (aHR) were derived from Cox models considering age as the time-scale, menopausal status as a time-varying covariate and taking into account menopausal treatment. RESULTS: During 843,243 person-years of follow-up, 1205 new-onset asthma cases were identified. Compared with pre-menopause, surgical menopause was associated with an increased risk of asthma onset (aHR = 1.33 [95%CI 1.01-1.75]) but no association was observed for natural menopause (aHR = 1.05 [0.84-1.32]). In women with natural menopause, a further analysis separating the transition through menopause and the later post-menopausal period did not show any change in asthma incidence with menopause in the total sample or in normal-weight women alone. However, in overweight/obese women, peri-menopausal and post-menopausal women had an increased risk of developing asthma compared with pre-menopausal women of the same age (aHR = 1.91 [1.00-3.66] and aHR = 2.08 [1.07-4.06] respectively). CONCLUSION: Surgical menopause was associated with an increased risk of asthma onset. For natural menopause, no change in asthma incidence was observed in normal-weight women. However, overweight/obese women had an increased risk of developing asthma after natural menopause.

Smoking, telomere length and lung function decline: a longitudinal population-based study.

Telomere shortening is associated with COPD and impaired lung function in cross-sectional studies, but there is no longitudinal study. We used data from 448 participants recruited as part of the French follow-up of the European Community Respiratory Health Survey. We found no relationship between telomere length at baseline and FEV1 decline after 11 years of follow-up. However, heavy smoking was associated with an accelerated FEV1 decline in individuals with short telomeres, but not in subjects with longer telomeres (p for interaction p=0.08). Our findings suggest that short telomere length in peripheral leucocytes might be a marker for increased susceptibility to the effect of smoking.

Abdominal obesity and late-onset asthma: cross-sectional and longitudinal results: the 3C study.

Whereas global obesity assessed by BMI has been related to asthma risk, little is known as to the potential implication of abdominal adiposity in this relationship. In the elderly, in whom asthma remains poorly studied, abdominal adiposity tends to increase at the expense of muscle mass. The purpose of this study was to investigate the association between abdominal adiposity, assessed by waist circumference (WC), and prevalence and incidence of asthma in a large elderly cohort. Cross-sectional analysis was based on 7,643 participants aged ≥65 years including 592 (7.7%) with lifetime physician-diagnosed asthma. Longitudinal analysis involved 6,267 baseline nonasthmatics followed-up for a period of 4 years, 67 of whom exhibited incident asthma. Baseline WC was categorized according to sex-specific criteria (men/women): <94/80 cm (reference), [94-102[/[80-88[ (abdominal overweight), and ≥102/88 (abdominal obesity). Logistic and Cox regression models estimated asthma risk associated with WC after adjustment for age, sex, educational level, smoking status, BMI, physical ability, dyspnea, chronic bronchitis symptoms and history of cardiovascular disease. At baseline, asthma risk increased with increasing WC independently of BMI and other confounders (adjusted odds ratio (ORa), 95% confidence interval (CI): 1.30, 1.02-1.65 and ORa: 1.76, 1.31-2.36 for abdominal overweight and obesity, respectively). Asthma incidence was related to WC (hazard ratio (HRa), 95% CI: 2.69, 1.21-5.98 and HRa: 3.84, 1.55-9.49, for abdominal overweight and obesity, respectively). Estimates were similar in both sexes. In the elderly, abdominal adiposity was independently associated with increased prevalence and incidence of asthma. Studies aiming to understand the mechanisms involved in the adiposity-asthma link are needed.

Lung function impairment and metabolic syndrome: the critical role of abdominal obesity.

RATIONALE: Increased risk for cardiovascular morbidity and mortality has been related to both lung function impairment and metabolic syndrome. Data on the relationship between lung function and metabolic syndrome are sparse. OBJECTIVES: To investigate risk for lung function impairment according to metabolic syndrome traits. METHODS: This cross-sectional population-based study included 121,965 men and women examined at the Paris Investigations Préventives et Cliniques Center between 1999 and 2006. The lower limit of normal was used to define lung function impairment (FEV(1) or FVC < lower limit of normal). Metabolic syndrome was assessed according to the American Heart Association/National Heart, Lung, and Blood Institute statement. MEASUREMENTS AND MAIN RESULTS: We used a logistic regression model and principal component analysis to investigate the differential associations between lung function impairment and specific components of metabolic syndrome. Lung function impairment was associated with metabolic syndrome (prevalence = 15.0%) independently of age, sex, smoking status, alcohol consumption, educational level, body mass index, leisure-time physical activity, and cardiovascular disease history (odds ratio [OR] [95% confidence interval], 1.28 [1.20-1.37] and OR, 1.41 [1.31-1.51] for FEV(1) and FVC, respectively). Three factors were identified from factor analysis: "lipids" (low high-density lipoprotein cholesterol, high triglycerides), "glucose-blood pressure" (high fasting glycemia, high blood pressure), and "abdominal obesity" (large waist circumference). All factors were inversely related to lung function, but abdominal obesity was the strongest predictor of lung function impairment (OR, 1.94 [1.80-2.09] and OR, 2.11 [1.95-2.29], for FEV(1) and FVC, respectively). Similar results were obtained for women and men. CONCLUSIONS: We found a positive independent relationship between lung function impairment and metabolic syndrome in both sexes, predominantly due to abdominal obesity. Further studies are required to clarify the underlying mechanisms.

Calf circumference is inversely associated with carotid plaques.

BACKGROUND AND PURPOSE: The association of carotid atherosclerosis with body composition and fat distribution is poorly understood. We aimed to test the cross-sectional association of carotid plaques and common carotid artery intima-media thickness with calf circumference (CC), representing peripheral fat and lean mass, and with waist circumference and waist-to-hip ratio, 2 markers of abdominal obesity. METHODS: The study was performed on 6265 subjects aged >or=65 years recruited prospectively from the electoral rolls of 3 French cities. Ultrasound examination and anthropometric measures were performed according to a standardized protocol. RESULTS: Carotid plaques were less frequent with increasing CC, the ORs for the second, third, and fourth quartile of CC compared with the first quartile being 0.98 (95% CI, 0.84 to 1.15), 0.85 (95% CI, 0.72 to 1.01), and 0.71 (95% CI,:0.58 to 0.86; P for trend=0.0002), respectively, independently of age, gender, body mass index, and other vascular risk factors. There was an opposite and multiplicative effect of CC and waist-to-hip ratio on the frequency of carotid plaques (55.1% of individuals in the fourth waist-to-hip ratio quartile and the first CC quartile had carotid plaques, against 31.8% in the first waist-to-hip ratio and the fourth CC quartile). Mean common carotid artery intima-media thickness was larger with increasing waist circumference, waist-to-hip ratio, and CC, but the association with CC disappeared after adjusting for body mass index. CONCLUSIONS: The present study shows, for the first time, an inverse relationship between carotid plaques and CC. Although this needs to be confirmed in other populations, it may suggest an antiatherogenic effect of large CC.

Distension of the carotid artery and risk of coronary events: the three-city study.

OBJECTIVE: Arterial mechanical properties are of growing interest in the understanding of cardiovascular disease development. We aimed to determine the predictive value of carotid wall mechanics on coronary heart disease (CHD) in the Three-City study. METHODS AND RESULTS: At baseline, 3337 participants aged > or =65 years underwent a carotid B-mode ultrasonography. During a median follow-up of 43.4 months, 128 CHD occurred. Increased carotid distension (relative stroke change in lumen diameter) was significantly associated with CHD risk. Comparison of subjects in tertile 3 versus those in tertile 1 (reference) showed a hazard ratio (HR) of 1.80 (95% CI, 1.17 to 2.75). Controlling for various confounders including age, heart rate, brachial (or carotid) pulse pressure, and common carotid intima-media thickness did not alter the association between carotid distension and CHD with a HR of 1.79 (95% CI, 1.12 to 2.86; tertile 3 versus tertile 1). Brachial and carotid pulse pressures were also independently associated with CHD. No association was found between CHD and carotid distensibility coefficient, cross-sectional compliance coefficient, Young's elastic modulus, or beta stiffness index. CONCLUSIONS: In the elderly, increased carotid distension was independently predictive of CHD. This simple and noninvasive parameter might be of particular interest for cardiovascular risk assessment.

Tea consumption is inversely associated with carotid plaques in women.

OBJECTIVE: The aim of this study was to assess the relationship of tea consumption with common carotid artery intima-media thickness (CCA-IMT) and carotid plaques. METHODS AND RESULTS: The study was performed on 6597 subjects aged > or = 65 years, recruited in the French population for the Three-City Study. Atherosclerotic plaques in the extracranial carotid arteries and CCA-IMT were measured using a standardized protocol. Results were tested for replication in another, younger, French population sample (EVA-Study, 1123 subjects). In the Three-City Study, increasing daily tea consumption was associated with a lower prevalence of carotid plaques in women: 44.0%, 42.5%, and 33.7% in women drinking no tea, 1 to 2 cups/d, and > or = 3 cups/d (P=0.0001). This association was independent of age, center, major vascular risk factors, educational level, and dietary habits (adjOR=0.68[95%CI:0.54 to 0.86] for women drinking > or = 3 cups/d compared with none). There was no association of tea consumption with carotid plaques in men, or CCA-IMT in both genders. In the EVA-Study, carotid plaque frequency was 18.8%, 18.5%, and 8.9% in women drinking no tea, 1 to 2 cups/d, and > or = 3 cups/d (P=0.08). CONCLUSIONS: In a large sample of elderly community subjects we showed for the first time that carotid plaques were less frequent with increasing tea consumption in women.

The metabolic syndrome and the carotid artery structure in noninstitutionalized elderly subjects: the three-city study.

BACKGROUND AND PURPOSE: In contrast to the young adult population, limited data are presently available regarding the epidemiology of the metabolic syndrome (MetS) and its relationship with cardiovascular disease risk in the elderly. We have investigated the frequency of the MetS and its association with the carotid artery structure in an elderly free-living population. METHODS: The study population consists of 5585 French noninstitutionalized elderly men and women aged 65 to 85 years, free of diabetes, who participated in the multicenter Three City Study and who underwent ultrasound examination of the carotid arteries at baseline examination between March 1999 and March 2001. The MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: The MetS was present in 12.1% of the study participants, with slightly higher rates in men. Subjects with the MetS had higher frequency of carotid plaques (odds ratio, 1.30; 95% CI, 1.09 to 1.55), higher intima-media thickness of the common carotid artery (odds ratio, 1.81; 95% CI, 1.37 to 2.41), and higher lumen diameter (odds ratio, 2.17; 95% CI, 1.61 to 2.94) (upper quintiles) after adjustment for other cardiovascular risk factors. This association was observed in both genders and in subjects without prevalent cardiovascular disease. Elevated blood pressure as defined in the MetS was the main determinant of the relations between the MetS and the carotid parameters, especially the lumen diameter. CONCLUSIONS: The present data suggest that noninstitutionalized elderly subjects with the MetS have altered structure of the carotid arteries.

Parental longevity, carotid atherosclerosis, and aortic arterial stiffness in adult offspring.

BACKGROUND AND PURPOSE: We examined the associations of parental longevity with carotid intima-media thickness, carotid plaques, and aortic arterial stiffness in adult offspring. METHODS: A population of 1117 volunteers who participated in the SUVIMAX Vascular Study (mean age, 59.7 years; 49.0% women) were included. Carotid-femoral pulse-wave velocity (PWV) was used to assess aortic stiffness. Carotid B-mode ultrasound examination included measurements (at sites free of plaque) of intima-media thickness at the common carotid arteries and assessment of atherosclerotic plaques in the extracranial carotid arteries. RESULTS: The prevalence of carotid plaques in subjects whose fathers had died at <65 years, in those whose fathers were alive at 65 years but who had died by 80 years, and in those whose fathers were alive at 80 years was 40.4%, 30.4%, and 28.9%, respectively (P<0.001). The multivariate odds ratios of carotid plaques in the 3 groups of paternal longevity, adjusted for conventional cardiovascular risk factors, were 1, 0.68 (95% CI, 0.48 to 0.96), and 0.69 (95% CI, 0.49 to 0.98), respectively. The mean common carotid arteries intima-media thickness was higher in subjects with premature paternal death in univariate (P<0.007) but not in multivariate (P=0.39) analyses. Mean PWV decreased with increasing paternal longevity in both univariate and multivariate analyses. The multivariate-adjusted means of PWV in the 3 groups of paternal longevity were 11.9+/-0.14, 11.7+/-0.12, and 11.0+/-0.12 m/s (P<0.0001), respectively. In contrast, neither B-mode ultrasound measurements nor PWV measurements were associated with maternal longevity. CONCLUSIONS: These results may indicate that there are modifications of structure and function of large arteries according to paternal longevity.

Preterm delivery of a first child and subsequent mothers' risk of ischaemic heart disease: a nested case-control study.

Several studies have suggested that preterm delivery is related to a risk of subsequent ischaemic heart disease (IHD) in the mother. We conducted a nested case-control study in the E3N cohort to assess the association between preterm delivery of a first child and IHD, and the effect of major cardiovascular risk factors on this association. The study included 109 cases and 395 controls. Mothers who had preterm delivery were at an increased risk of IHD [multivariate hazard ratio 2.09 (95% confidence interval 1.07-4.09)]. This association was independent of major cardiovascular risk factors.

Zinc, copper, and magnesium and risks for all-cause, cancer, and cardiovascular mortality.

BACKGROUND: Experimental data suggest that zinc, copper, and magnesium are involved in carcinogenesis and atherogenesis. Few longitudinal studies have related these minerals to cancer or cardiovascular disease mortality in a population. METHODS: Data from the Paris Prospective Study 2, a cohort of 4035 men age 30-60 years at baseline, were used to assess the association between serum zinc, copper, and magnesium and all-cause, cancer, and cardiovascular disease mortality. Serum mineral values measured at baseline were divided into quartiles and classified into low (1st quartile, referent group), medium (2nd-3rd quartiles), and high (4th quartile) values. During 18-year follow up, 339 deaths occurred, 176 as a result of cancer and 56 of cardiovascular origin. Relative risks (RRs) for each element were inferred using Cox's proportional hazard model after controlling for various potential confounders. RESULTS: High copper values (4th quartile) were associated with a 50% increase in RRs for all-cause deaths (RR = 1.5; 95% confidence interval = 1.1-2.1), a 40% increase for cancer mortality (1.4; 0.9-2.2), and a 30% increase for cardiovascular mortality (1.3; 0.6-2.8) compared with low values (1st quartile). High magnesium values were negatively related to mortality with a 40% decrease in RR for all-cause (0.6; 0.4-0.8) and cardiovascular deaths (0.6; 0.2-1.2) and by 50% for cancer deaths (0.5; 0.3-0.8). Additionally, subjects with a combination of low zinc and high copper values had synergistically increased all-cause (2.6; 1.4-5.0) and cancer (2.7; 1.0-7.3) mortality risks. Similarly, combined low zinc and high magnesium values were associated with decreased all-cause (0.2; 0.1-0.5) and cancer (0.2; 0.1-0.8) mortality risks. CONCLUSIONS: High serum copper, low serum magnesium, and concomitance of low serum zinc with high serum copper or low serum magnesium contribute to an increased mortality risk in middle-aged men.

Serum tissue inhibitors of metalloproteinases 1 (TIMP-1) and carotid atherosclerosis and aortic arterial stiffness.

BACKGROUND: The results of experimental studies have suggested that matrix metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), are involved in vascular remodeling. In a population-based study, we report the relationships of serum TIMP-1 with carotid intima-media thickness, carotid plaques and aortic arterial stiffness. METHODS: Free health examinations were performed on 238 men free of coronary heart diseases (aged 56.5 +/- 10.4 years, 57.1% were hypertensive). Carotid-femoral pulse-wave velocity (PWV) was used to assess aortic stiffness. Carotid ultrasound examination included measurements (at sites free of plaques) of intima-media thickness (IMT) at the common carotid arteries (CCA) and assessment of atherosclerotic plaques in the extracranial carotid arteries. RESULTS: The percentage of subjects with plaques was lower in subjects with low TIMP-1 values (P for trend = 0.0001). In multivariate analysis adjusted for age, body mass index, smoking habits, total cholesterol, triglycerides, C-reactive protein, heart rate, diabetes and systolic blood pressure, the odds ratio of carotid plaques in subjects with high values of TIMP-1 (tertile 3) compared to those with low values (tertile 1) was 2.89 (95% confidence interval 1.12-7.47, P < 0.01). TIMP-1 was positively associated with CCA-IMT and PWV in univariate analysis. However, the associations disappeared once age and systolic blood pressure were taken into account in the multivariate analysis. CONCLUSION: This study shows that there is a differential association of TIMP-1 with PWV, CCA-IMT and carotid plaques. Our results suggest that TIMP-1 might be involved in plaque formation.

Parental longevity and 7-year changes in blood pressures in adult offspring.

In this report, we examined the cross-sectional and the 7-year longitudinal changes in blood pressures in adult offspring according to parental longevity. A population of volunteers free of symptomatic cardiovascular diseases who participated to the Supplementation en Vitamines et en Minéraux Antioxydants (SUVIMAX) Vascular Study (mean age 52.3 years; 48.3% women) were examined at baseline and 7 years later. Paternal (n=994) and maternal (n=896) longevity were analyzed separately. The prevalence of hypertension at baseline in subjects whose father died at <65 years of age, in those whose fathers were alive by age 65 but died by 80 years of age, and in those whose fathers were alive by age 80 was respectively 34.9%, 28.5%, and 20.2% (P<0.001). The means of systolic blood pressure in the 3 groups of paternal longevity were respectively 128.4 (+/-16.0), 125.3 (+/-14.2), and 123.6 (+/-14.4) mm Hg (P<0.001). During the follow-up, the mean systolic blood pressure increases in the 3 groups of paternal longevity were respectively 5.3 (+/-17.0), 4.2 (+/-14.0), and 1.6 (+/-13.2) mm Hg (P<0.001). In subjects without hypertension at baseline, hypertension occurred during the follow-up in 26.6%, 17.7%, and 15.3% (P<0.009), respectively. Multivariate analyses adjusted for baseline or changes in cardiovascular risk factors did not modify these results. In contrast, there was no relationship between maternal longevity and blood pressure measurements in either cross-sectional or longitudinal analyses. This study suggests that paternal premature death was associated with accelerated progression of systolic blood pressure and higher occurrence of hypertension in offspring. These results indicate that there are dynamic and continuous processes linking paternal longevity to blood pressure in adults.

Heart-rate profile during exercise as a predictor of sudden death.

BACKGROUND: Changes in heart rate during exercise and recovery from exercise are mediated by the balance between sympathetic and vagal activity. Since alterations in the neural control of cardiac function contribute to the risk of sudden death, we tested the hypothesis that among apparently healthy persons, sudden death is more likely to occur in the presence of abnormal heart-rate profiles during exercise and recovery. METHODS: A total of 5713 asymptomatic working men (between the ages of 42 and 53 years), none of whom had clinically detectable cardiovascular disease, underwent standardized graded exercise testing between 1967 and 1972. We examined data on the subjects' resting heart rates, the increase in rate from the resting level to the peak exercise level, and the decrease in rate from the peak exercise level to the level one minute after the termination of exercise. RESULTS: During a 23-year follow-up period, 81 subjects died suddenly. The risk of sudden death from myocardial infarction was increased in subjects with a resting heart rate that was more than 75 beats per minute (relative risk, 3.92; 95 percent confidence interval, 1.91 to 8.00); in subjects with an increase in heart rate during exercise that was less than 89 beats per minute (relative risk, 6.18; 95 percent confidence interval, 2.37 to 16.11); and in subjects with a decrease in heart rate of less than 25 beats per minute after the termination of exercise (relative risk, 2.20; 95 percent confidence interval, 1.02 to 4.74). After adjustment for potential confounding variables, these three factors remained strongly associated with an increased risk of sudden death, with a moderate but significantly increased risk of death from any cause but not of nonsudden death from myocardial infarction. CONCLUSIONS: The heart-rate profile during exercise and recovery is a predictor of sudden death.

Alcohol consumption and carotid artery structure in older French adults: the Three-City Study.

BACKGROUND AND PURPOSE: Several epidemiological studies have suggested a U-shaped association between alcohol consumption and cardiovascular risk. However, the modifications of vascular structure associated with alcohol consumption are largely unknown. METHODS: The study population sample comprised 6216 subjects (3780 women and 2436 men) aged 65 years or older who were recruited from 3 French cities (Bordeaux, Dijon, and Montpellier, which are located in the 3 principal wine-growing regions). Usual alcohol consumption was assessed by a standardized questionnaire. Carotid ultrasound examination included measurements (at sites free of plaques) of intima-media thickness (IMT) at the common carotid arteries (CCA), CCA-lumen diameter, and assessment of atherosclerotic plaques in the extracranial carotid arteries. RESULTS: Neither CCA-IMT nor carotid plaques were associated with alcohol consumption categories in the overall population. Weak and marginal positive associations were observed between categories of alcohol consumption and carotid plaques in men (P=0.02 for linear trend). CCA-lumen diameter was positively and independently associated with alcohol consumption in overall population and in men and in women. Similar results were found between alcohol consumption and carotid measurements in subjects free of cardiovascular disease (90.1% of the population). CONCLUSIONS: This very large population sample of French older adults shows no marked relationships of alcohol consumption with atherosclerosis. The positive association of alcohol intake with carotid arterial diameter may reflect the ability of alcohol to maintain adaptive enlargement to preserve lumen area.

Genes encoding endothelin-converting enzyme-1 and endothelin-1 interact to influence blood pressure in women: the EVA study.

BACKGROUND: Endothelin-1 (ET-1) is a potent vasoactive peptide that has been implicated in the regulation of basal vascular tone. Endothelin-converting enzyme-1 (ECE-1), the main enzyme responsible for ET-1 generation, may contribute to blood pressure (BP) control. A possible association between a polymorphism of the gene encoding ECE-1 (ECE1B C-338A) and BP values in untreated hypertensive women was recently reported. OBJECTIVE: We studied the influence of the ECE1B C-338A polymorphism on BP levels in 1189 subjects participating in the Etude du Vieillissement Artériel (EVA study), and looked for an interaction between this variant and a polymorphism of the ET-1 gene (EDN1 K198N). METHODS: The ECE1B C-338A polymorphism was genotyped in 491 men and 698 women; 477 men and 669 women could also be genotyped for the EDN1 K198N polymorphism. Associations between BP levels and genotypes were assessed by ANOVA; ANCOVA was used to control for covariates. RESULTS: We found an association between the ECE1B C-338A polymorphism and BP levels in women but not in men. Specifically, females homozygous for the A allele had significantly higher systolic, diastolic and mean BP levels (P = 0.01, 0.02, 0.006 respectively, after adjustment for age and body mass index). Genotyping of the EDN1 K198N polymorphism showed that this variant was not associated with BP values in either men or women, but interacted with the ECE1 variant to influence systolic and mean BP levels in women. CONCLUSION: Results from this large association study suggest that the genes encoding ECE-1 and ET-1 interact to modulate BP levels in women.

Bronchial hyperresponsiveness to methacholine is associated with increased common carotid intima-media thickness in men.

BACKGROUND: Respiratory alterations have been associated with subsequent coronary heart diseases in numerous population-based studies. The underlying mechanisms remain largely unknown. The objective of this study was to examine the association between bronchial hyperresponsiveness (BHR) to methacholine (which reflects local inflammation in the bronchus) and common carotid intima-media thickness (CCA-IMT). METHODS AND RESULTS: As part of the European Community Respiratory Health Survey follow-up, in Paris Center, we assessed BHR to methacholine (> or =20% decrease in FEV1 for a maximum methacholine dose of 4 mg) and measured CCA-IMT by ultrasonography in 255 adults free of cardiovascular diseases aged 29 to 56 years (123 men, 132 women; mean age 44.5 years, 43.5% never smokers). In men, CCA-IMT mean value was higher in subjects with BHR than in those without (0.68+/-0.11 versus 0.62+/-0.09 mm, P=0.002). No association was found in women. Multivariate analysis confirmed the independent association between BHR and CCA-IMT in men (adjusted odds ratio for a 0.10-mm increase in CCA-IMT=2.1, 95% confidence interval: 1.1 to 4.3; P=0.02). These results remained similar after exclusion of asthmatic subjects (n=11). In each strata of smoking status (nonsmoker, ex-smoker, and current smokers), CCA-IMT mean values tended to be higher in subjects with BHR than in those without, although the difference between the 2 groups was more pronounced in current smokers. CONCLUSIONS: The results of the present study suggest that BHR is independently associated with CCA-IMT in men. The interrelationships between cardiovascular and respiratory alterations should be further investigated.

Polymorphism R92Q of the tumour necrosis factor receptor 1 gene is associated with myocardial infarction and carotid intima-media thickness--the ECTIM, AXA, EVA and GENIC Studies.

The TNFRSF1A gene was screened for polymorphisms in 95 subjects with premature myocardial infarction (MI), who also had one parent who had an MI. A total of 10 polymorphisms were found: three in the promoter region, two in exons and five in introns. All polymorphisms were genotyped in ECTIM, a case-control study of MI (1815 subjects). The nonsynonymous 92Q allele was found in 1.8, 1.0 and 1.7% of controls from Strasbourg, Belfast and Glasgow - respectively; in cases: 4.2, 2.2 and 3.2%. The population-adjusted odds ratio (OR) for MI associated with allele Q carrying was 2.15 (95% CI: 1.09-4.23). To check its possible implication in atherosclerosis, this polymorphism was then genotyped in the AXA Study (ultrasound examinations of carotid and femoral arteries in the context of an employment medical examination, 733 subjects), the EVA Study (ultrasound examinations of carotid arteries in a study of cognitive and vascular ageing, 1092 subjects) and the GENIC Study (on brain infarction (BI), 912 subjects). In the AXA Study, among smokers, carrying the 92Q allele was positively associated with the presence of a carotid plaque (OR 5.07; 95% CI: 1.64-15.63) and with a thickening of the carotid intima-media thickness (IMT) (0.59 (0.11) vs 0.54 (0.11), P=0.045). In the EVA Study, carriers of allele 92Q had an increased mean carotid IMT (0.70 (0.09) vs 0.67 (0.13), P=0.02). No significant association of the 92Q allele was found with BI in the GENIC Study. Overall, these results may suggest that carriers of the 92Q allele may be at increased risk of atherosclerosis.

Echogenic carotid plaques are associated with aortic arterial stiffness in subjects with subclinical carotid atherosclerosis.

A better understanding of the interrelationships between the structure and function of the large arteries would lead to optimize cardiovascular disease prevention strategies. In this study, we investigated the relationships of aortic arterial stiffness assessed by carotid-femoral pulse-wave velocity (PWV), with carotid plaque echogenicity assessed by B-mode ultrasound. We analyzed 561 subjects (without coronary heart disease or stroke) who were volunteers for free health examinations (age, 58.3+/-10.8 years; 32.6% women). Extracranial carotid plaque echogenicity was graded from 1 (plaque appearing black or almost black) to 4 (plaque appearing white or almost white) according to the Gray-Weale classification. Plaques of grades 1 and 2 were defined as echolucent plaques, and plaques of grades 3 and 4 were defined as echogenic plaques. Fifty-one subjects (9.1%) had echolucent carotid plaques, 109 (19.4%) had echogenic plaques, and 401 (71.5%) had no plaques. Subjects with echogenic plaques had higher PWV mean (12.9+/-2.8 m/s) compared with those without plaques (11.1+/-2.3 m/s, P<0.001) and compared with those with echolucent plaques (11.3+/-2.3 m/s, P<0.01). The PWV means in subjects without plaques and those with echolucent plaques were similar and not statistically different (P=0.55). When multivariate adjustment for major known cardiovascular risk factors was performed, these results were not markedly modified. Similar patterns of results were also observed in many subgroups according to age, gender, and hypertensive status. This study provides the first evidence that echogenic but not echolucent carotid plaques are associated with aortic arterial stiffness. This association applies to individuals with normal blood pressure and those with elevated blood pressure. Assessment of the joint and interaction effects of plaque morphology and arterial stiffness on the occurrence of cardiovascular events would permit a better identification of high-risk subjects.