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Marion Brisset,
Pierre Boutouyrie,
Fernando Pico,
Yicheng Zhu, Mahmoud Zureik,
Sabrina Schilling,
Carole Dufouil,
Bernard Mazoyer,
Stéphane Laurent,
Christophe Tzourio,
Stéphanie Debette
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ABSTRACT: OBJECTIVE: Our aim was to investigate the relationship of carotid structure and function with MRI markers of cerebral ischemic small-vessel disease. METHODS: The study comprised 1,800 participants (aged 72.5 ± 4.1 years, 59.4% women) from the 3C-Dijon Study, a population-based, prospective cohort study, who had undergone quantitative brain MRI and carotid ultrasound. We used multivariable logistic and linear regression adjusted for age, sex, and vascular risk factors. RESULTS: Presence of carotid plaque and increasing carotid lumen diameter (but not common carotid artery intima-media thickness) were associated with higher prevalence of lacunar infarcts: odds ratio (OR) = 1.60 (95% confidence interval [CI]: 1.09-2.35), p = 0.02 and OR = 1.24 (95% CI: 1.02-1.50), p = 0.03 (by SD increase). Carotid plaque was also associated with large white matter hyperintensity volume (WMHV) (age-specific top quartile of WMHV distribution): OR = 1.32 (95% CI: 1.04-1.67), p = 0.02, independently of vascular risk factors. Increasing Young elastic modulus and higher circumferential wall stress, reflecting augmented carotid stiffness, were associated with increasing WMHV (effect estimate [β] ± standard error: 0.0003 ± 0.0001, p = 0.024; β ± standard error: 0.005 ± 0.002, p = 0.008). Large WMHV was also associated with increasing Young elastic modulus (OR = 1.22 [95% CI: 1.04-1.42], p = 0.01) and with decreasing distensibility coefficient (OR = 0.83 [95% CI: 0.69-0.99], p = 0.04), independently of vascular risk factors. Associations of carotid lumen diameter with lacunar infarcts and of carotid stiffness markers with WMHV were independent of carotid plaque. CONCLUSIONS: In addition to and independently of carotid plaque, increasing carotid lumen diameter and markers of carotid stiffness were associated with increasing prevalence of lacunar infarcts and increasing WMHV, respectively.
Neurology 01/2013; · 8.31 Impact Factor
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ABSTRACT: 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.
Obesity 03/2012; 20(3):628-35. · 4.28 Impact Factor
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Bénédicte Leynaert,
Jordi Sunyer,
Raquel Garcia-Esteban,
Cecilie Svanes,
Deborah Jarvis,
Isa Cerveri,
Julia Dratva,
Thorarinn Gislason,
Joachim Heinrich,
Christer Janson, [......],
Roberto de Marco,
Ernst Omenaas,
Chantal Raherison,
Francisco Gómez Real,
Matthias Wjst,
Elisabeth Zemp, Mahmoud Zureik,
Peter G J Burney,
Josep M Anto,
Françoise Neukirch
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ABSTRACT: Although women with severe non-allergic asthma may represent a substantial proportion of adults with asthma in clinical practice, gender differences in the incidence of allergic and non-allergic asthma have been little investigated in the general population.
Gender differences in asthma prevalence, reported diagnosis and incidence were investigated in 9091 men and women randomly selected from the general population and followed up after 8-10 years as part of the European Community Respiratory Health Survey. The protocol included assessment of bronchial responsiveness, IgE specific to four common allergens and skin tests to nine allergens.
Asthma was 20% more frequent in women than in men over the age of 35 years. Possible under-diagnosis of asthma appeared to be particularly frequent among non-atopic individuals, but was as frequent in women as in men. The follow-up of subjects without asthma at baseline showed a higher incidence of asthma in women than in men (HR 1.94; 95% CI 1.40 to 2.68), which was not explained by differences in smoking, obesity or lung function. More than 60% of women and 30% of men with new-onset asthma were non-atopic. The incidence of non-allergic asthma was higher in women than in men throughout all the reproductive years (HR 3.51; 95% CI 2.21 to 5.58), whereas no gender difference was observed for the incidence of allergic asthma.
This study shows that female sex is an independent risk factor for non-allergic asthma, and stresses the need for more careful assessment of possible non-allergic asthma in clinical practice, in men and women.
Thorax 02/2012; 67(7):625-31. · 6.84 Impact Factor
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ABSTRACT: We sought to address the respective association between carotid intima-media thickness (IMT) in plaque-free sites and plaques with coronary heart disease (CHD) and their usefulness for CHD risk prediction in the Three-City Study.
At baseline, 5895 CHD-free adults aged 65-85 years underwent a bilateral ultrasound examination of carotid arteries. Mean IMT was measured in the far wall of the right and left common carotid arteries (CCA) at plaque-free site while the presence of focal plaques was assessed in the near and the far walls of the CCAs, the bifurcations and the origin of the internal carotid arteries.
After a median follow-up of 5.4 years, 223 subjects had a first ever CHD event. In multivariate analysis, carotid plaques were independent predictors of CHD (Hazard ratio (HR)(plaques at 1 site) = 1.5; 95% confidence interval (CI) = 1.0-2.2; HR(plaques at ≥ 2 sites) = 2.2; 95% CI = 1.6-3.1; p(for trend) < 0.001), contrary to mean CCA-IMT (HR(fifth vs.first quintile) = 0.8; 95% CI = 0.5-1.2; p(for trend) < 0.48). Adding carotid plaques to conventional risk factors significantly improved CHD risk prediction as measured by the area under the ROC curve (from 0.728 to 0.745; p = 0.04), the Harrell's c (from 0.748 to 0.762; p < 0.001), and the integrated discrimination improvement (IDI = 0.007; p = 0.002)/net reclassification improvement (NRI = 13.7%; p < 0.001) indices.
Carotid plaques, but not CCA-IMT measured at a plaque-free site, were independent predictors of CHD and improved CHD risk prediction in older adults.
Atherosclerosis 12/2011; 219(2):917-24. · 3.79 Impact Factor
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ABSTRACT: Few studies have examined the association between global diet, assessed through dietary patterns, and arterial structure and function. The aim of this study was to investigate the relationship between carotid-femoral pulse-wave velocity (PWV), common carotid-arteries intima-media thickness (CCA-IMT) and plaques with dietary patterns measured 7.5 years earlier.
A prospective cohort study between diet and markers of structure and function of large arteries.
Dietary patterns (linear combination of food consumption) were identified using principal component analysis among 1026 middle-aged participants in the SUpplémentation en VItamines et Minéraux AntioXydants (SU.VI.MAX) vascular substudy. Dietary data were based on repeated 24-h dietary records (at least three records during 2 years) obtained at inclusion. Carotid-femoral PWV was used to assess aortic stiffness. Carotid ultrasound examination included measurements of CCA-IMT and carotid plaques.
Four dietary patterns were identified. In multivariate models, a significant positive association was observed between PWV and a dietary pattern positively correlated with meat and alcohol consumption and negatively correlated with fibers, vitamins B9 and C, β-carotene and calcium consumption. Adjusted PWV mean across tertiles of this pattern score was 11.15, 11.26 and 11.58 m/s in the first, second and third tertiles, respectively (P for trend=0.03). Others dietary patterns were not associated with PWV and we detected no association between dietary patterns and IMT or plaques.
This study suggests that a nutritionally poor dietary pattern, characterized by a high meat and alcohol consumption and low micronutrients intake, is related to an increased stiffening of large arteries.
European journal of cardiovascular prevention and rehabilitation: official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology 12/2010; 17(6):718-24. · 2.51 Impact Factor
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Julie Dumont,
Djabaria Meroufel,
Christophe Bauters,
Franck Hansmannel,
Faïza Bensemain,
Dominique Cottel,
Martial Hamon,
Jean-Charles Lambert,
Pierre Ducimetière,
Philippe Amouyel, Mahmoud Zureik,
Thierry Brousseau
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ABSTRACT: Previous studies have suggested that the activity of enzymes involved in the urea cycle may modulate nitric oxide (NO) production, arterial vasomotion, and hypertension. Our aim was to determine whether hypertension and coronary vasomotion could be associated with polymorphisms within the ornithine transcarbamylase (OTC) gene, located on chromosome X and coding for a key-enzyme of the urea cycle.
Among 11 OTC polymorphisms that were originally selected from databases, the tag single-nucleotide polymorphism (SNP) rs5963409 and the independent SNP rs1800321 were tested for association with hypertension in two independent population samples recruited in Northern (Multinational MONItoring of trends and determinants in CArdiovascular disease (MONICA) study, n = 1,138) and Western (Etude du Vieillissement Artériel (EVA) study, n = 1,166) France. The vasomotor response of coronary arteries to methylergonovine maleate and isosorbide dinitrate was also evaluated in an independent sample (the vasomotion study, n = 121).
In males, the frequency of the rs5963409 minor allele was consistently higher in hypertensive (HT) than in normotensive subjects in the MONICA and EVA studies. In the combined sample, the rs5963409 minor allele was associated with an increased risk of hypertension (odds ratio (OR) (95% confidence interval (CI)) = 1.45 (1.10-1.90); P = 0.008). This association was independent of classical confounding factors. Consistently, rs5963409 minor allele was associated with a greater susceptibility to vasoconstriction in response to methylergonovine maleate (P = 0.0072). In contrast, no significant association between rs5963409 and hypertension could be detected in females.
Our results suggest that the OTC rs5963409 polymorphism may be associated with hypertension and coronary vasomotion in males.
American Journal of Hypertension 08/2009; 22(9):993-1000. · 3.18 Impact Factor
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Julie Dumont,
Djabaria Meroufel,
Christophe Bauters,
Franck Hansmannel,
Fa|[iuml]|za Bensemain,
Dominique Cottel,
Martial Hamon,
Jean-Charles Lambert,
Pierre Ducimeti|[egrave]|re,
Philippe Amouyel, Mahmoud Zureik,
Thierry Brousseau
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ABSTRACT: Background Previous studies have suggested that the activity of enzymes involved in the urea cycle may modulate nitric oxide (NO) production, arterial vasomotion, and hypertension. Our aim was to determine whether hypertension and coronary vasomotion could be associated with polymorphisms within the ornithine transcarbamylase (OTC) gene, located on chromosome X and coding for a key-enzyme of the urea cycle.
American Journal of Hypertension 07/2009; 22(9):993-1000. · 3.18 Impact Factor
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ABSTRACT: 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.
To investigate risk for lung function impairment according to metabolic syndrome traits.
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.
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.
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.
American Journal of Respiratory and Critical Care Medicine 02/2009; 179(6):509-16. · 11.08 Impact Factor
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Catherine Bonaïti-Pellié,
Patrick Arveux,
Agathe Billette de Villemeur,
Nicolas Dantchev,
Alexis Elbaz,
Elisabeth Fabre-Guillevin,
Jeanne Fresson,
Christine Saura,
Marie-Josèphe Saurel-Cubizolles,
Jean-Louis Serre,
Dominique Simon,
Isabelle Stucker,
Bertrand Thélot,
Pascale Tubert-Bitter, Mahmoud Zureik
Medecine sciences: M/S 02/2009; 25(1):93-7. · 0.64 Impact Factor
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Rafea Shaaban, Mahmoud Zureik,
David Soussan,
Catherine Neukirch,
Joachim Heinrich,
Jordi Sunyer,
Matthias Wjst,
Isa Cerveri,
Isabelle Pin,
Jean Bousquet,
Deborah Jarvis,
Peter G Burney,
Françoise Neukirch,
Bénédicte Leynaert
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ABSTRACT: A close relation between asthma and allergic rhinitis has been reported by several epidemiological and clinical studies. However, the nature of this relation remains unclear. We used the follow-up data from the European Community Respiratory Health Survey to investigate the onset of asthma in patients with allergic and non-allergic rhinitis during an 8.8-year period.
We did a longitudinal population-based study, which included 29 centres (14 countries) mostly in western Europe. Frequency of asthma was studied in 6461 participants, aged 20-44 years, without asthma at baseline. Incident asthma was defined as reporting ever having had asthma confirmed by a physician between the two surveys. Atopy was defined as a positive skin-prick test to mites, cat, Alternaria, Cladosporium, grass, birch, Parietaria, olive, or ragweed. Participants were classified into four groups at baseline: controls (no atopy, no rhinitis; n=3163), atopy only (atopy, no rhinitis; n=704), non-allergic rhinitis (rhinitis, no atopy; n=1377), and allergic rhinitis (atopy+rhinitis; n=1217). Cox proportional hazards models were used to study asthma onset in the four groups.
The 8.8-year cumulative incidence of asthma was 2.2% (140 events), and was different in the four groups (1.1% (36), 1.9% (13), 3.1% (42), and 4.0% (49), respectively; p<0.0001). After controlling for country, sex, baseline age, body-mass index, forced expiratory volume in 1 s (FEV(1)), log total IgE, family history of asthma, and smoking, the adjusted relative risk for asthma was 1.63 (95% CI 0.82-3.24) for atopy only, 2.71 (1.64-4.46) for non-allergic rhinitis, and 3.53 (2.11-5.91) for allergic rhinitis. Only allergic rhinitis with sensitisation to mite was associated with increased risk of asthma independently of other allergens (2.79 [1.57-4.96]).
Rhinitis, even in the absence of atopy, is a powerful predictor of adult-onset asthma.
The Lancet 09/2008; 372(9643):1049-57. · 38.28 Impact Factor
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Stéphanie Debette,
Nathalie Leone,
Dominique Courbon,
Jérôme Gariépy,
Christophe Tzourio,
Jean-François Dartigues,
Karen Ritchie,
Annick Alpérovitch,
Pierre Ducimetière,
Philippe Amouyel, Mahmoud Zureik
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ABSTRACT: 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.
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.
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.
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.
Stroke 08/2008; 39(11):2958-65. · 5.73 Impact Factor
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Nathalie Leone,
Pierre Ducimetière,
Jerôme Gariépy,
Dominique Courbon,
Christophe Tzourio,
Jean-François Dartigues,
Karen Ritchie,
Annick Alpérovitch,
Philippe Amouyel,
Michel E Safar, Mahmoud Zureik
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ABSTRACT: 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.
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.
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.
Arteriosclerosis Thrombosis and Vascular Biology 07/2008; 28(7):1392-7. · 6.37 Impact Factor
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Stéphanie Debette,
Dominique Courbon,
Nathalie Leone,
Jérôme Gariépy,
Christophe Tzourio,
Jean-François Dartigues,
Pascale Barberger-Gateau,
Karen Ritchie,
Annick Alpérovitch,
Philippe Amouyel,
Pierre Ducimetière, Mahmoud Zureik
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ABSTRACT: 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.
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).
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.
Arteriosclerosis Thrombosis and Vascular Biology 02/2008; 28(2):353-9. · 6.37 Impact Factor
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Rafea Shaaban, Mahmoud Zureik,
David Soussan,
Josep M Antó,
Joachim Heinrich,
Christer Janson,
Nino Künzli,
Jordi Sunyer,
Matthias Wjst,
Peter G Burney,
Françoise Neukirch,
Bénédicte Leynaert
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ABSTRACT: Patients with allergic rhinitis have more frequent bronchial hyperresponsiveness (BHR) in cross-sectional studies.
To estimate the changes in BHR in nonasthmatic subjects with and without allergic rhinitis during a 9-year period.
BHR onset was studied in 3,719 subjects without BHR at baseline, who participated in the follow-up of the European Community Respiratory Health Survey.
BHR was defined as a >or=20% decrease in FEV(1) for a maximum dose of 1 mg of methacholine. Allergic rhinitis was defined as having a history of nasal allergy and positive specific IgE (>or=0.35 IU/ml) to pollen, cat, mites, or Cladosporium. The cumulative incidence of BHR was 9.7% in subjects with allergic rhinitis and 7.0% in subjects with atopy but no rhinitis, compared with 5.5% in subjects without allergic rhinitis and atopy (respective odds ratios [OR] and their 95% confidence intervals [95% CI] for BHR onset, 2.44 [1.73-3.45]; and 1.35 [0.86-2.11], after adjustment for potential confounders including sex, smoking, body mass index and FEV(1)). Subjects with rhinitis sensitized exclusively to cat or to mites were particularly at increased risk of developing BHR (ORs [95% CI], 7.90 [3.48-17.93] and 2.84 [1.36-5.93], respectively). Conversely, in subjects with BHR at baseline (n = 372), 35.3% of those with allergic rhinitis, compared with 51.8% of those without rhinitis had no more BHR at follow-up (OR [95% CI], 0.51 [0.33-0.78]). BHR "remission" was more frequent in patients with rhinitis treated by nasal steroids than in those not treated (OR [95% CI], 0.33 [0.14-0.75]).
Allergic rhinitis was associated with increased onset of BHR, and less chance for remission except in those treated for rhinitis.
American Journal of Respiratory and Critical Care Medicine 11/2007; 176(7):659-66. · 11.08 Impact Factor
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ABSTRACT: Proliferation and migration of vascular smooth muscle cells (VSMCs) are striking features shared by vascular ageing, atherosclerosis, and in-stent restenosis. VSMC biology depends in part on polyamines whose metabolism is closely regulated by ornithine decarboxylase antizyme 1 (OAZ1). Therefore, we sought for association between OAZ1 gene polymorphisms and various outcomes involving VSMC proliferation.
Systematic screening of the OAZ1 gene enabled to detect 21 variants. The impact of 4 selected tag polymorphisms (+849C/T, +851G/T, +1804G/A, and +2222A/G) was evaluated in 3 independent association studies. In a sample of 205 patients, the +2222G allele was associated with an increased risk of 6-month coronary in-stent restenosis (OR [95%CI]=2.1 [1.2 to 3.6]; P=0.0071). In a sample of 1001 subjects participating to the EVA study, the +2222G allele was longitudinally associated with a 4-year increase in common carotid intima-media thickness (P=0.047). In a case-control study (466 cases versus 466 controls), the risk of coronary heart disease associated with the +2222G allele was 1.3 (95%CI=[1.1 to 1.6]; P=0.026). No other significant association was consistently detected.
We identified the OAZ1+2222A/G polymorphism as a potential genetic marker of vascular events. Our findings strengthen the hypothesis that the polyamine metabolism plays a role in vascular diseases.
Arteriosclerosis Thrombosis and Vascular Biology 11/2007; 27(10):2120-6. · 6.37 Impact Factor
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ABSTRACT: Recently, it was suggested that arginase (ARG)1 plays an important role in atherogenesis. However, because of its complex functions depending on vascular cell type, its impact on atherogenesis remains unclear.
To evaluate the association between ARG1 polymorphisms and phenotypes related to atherosclerosis.
Among 10 ARG1 polymorphisms selected from databases, 4 single-nucleotide polymorphisms (rs2781666; rs2781667; rs2781668; rs17599586) were tested for association with myocardial infarction (MI) in a case-control study (350 cases vs 581 controls), and with common carotid artery (CCA) intima-media thickness (CCA-IMT) in an independent sample of 963 subjects (Etude du Vieillissement Artériel (EVA) study).
The genotype distribution of the rs2781666 G/T polymorphism differed significantly between MI cases and controls (p = 0.005), and the risk of MI was consistently increased for both GT heterozygotes (OR (95% CI) 1.5 (1.1 to 2.0)) and TT homozygotes (OR (95% CI) 2.2 (1.1 to 4.4)). In the EVA study, the rs2781666 polymorphism was also associated with an increase in CCA-IMT (p = 0.010), a surrogate marker of MI.
The ARG1 rs2781666 polymorphism was consistently associated with MI and an increased CCA-IMT. These findings reinforce the hypothesis of a significant role of ARG1 in vascular pathophysiology.
Journal of Medical Genetics 09/2007; 44(8):526-31. · 6.36 Impact Factor
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Rafea Shaaban,
Bénédicte Leynaert,
David Soussan,
Josep M Antó,
Susan Chinn,
Roberto de Marco,
Judith Garcia-Aymerich,
Joachim Heinrich,
Christer Janson,
Deborah Jarvis,
Jordi Sunyer,
Cecilie Svanes,
Matthias Wjst,
Peter G Burney,
Françoise Neukirch, Mahmoud Zureik
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ABSTRACT: Identification of the risk factors for bronchial hyperresponsiveness (BHR) would increase the understanding of the causes of asthma. The relationship between physical activity and BHR in men and women aged 28.0-56.5 years randomly selected from 24 centres in 11 countries participating in the European Community Respiratory Health Survey II was investigated.
5158 subjects answered questionnaires about physical activity and performed BHR tests. Participants were asked about the frequency and duration of usual weekly exercise resulting in breathlessness or sweating. BHR was defined as a decrease in forced expiratory volume in 1 s of at least 20% of its post-saline value for a maximum methacholine dose of 2 mg.
Both frequency and duration of physical activity were inversely related to BHR. The prevalence of BHR in subjects exercising <or=1, 2-3 and >or=4 times a week was 14.5%, 11.6% and 10.9%, respectively (p<0.001). The corresponding odds ratios were 1.00, 0.78 (95% CI 0.62 to 0.99) and 0.69 (95% CI 0.50 to 0.94) after controlling for potential confounding factors. The frequency of BHR in subjects exercising <1 h, 1-3 h and >or=4 h a week was 15.9%, 10.9% and 10.7%, respectively (p<0.001). The corresponding adjusted odds ratios were 1.00, 0.70 (95% CI 0.57 to 0.87) and 0.67 (95% CI 0.50 to 0.90). Physical activity was associated with BHR in all studied subgroups.
These results suggest that BHR is strongly and independently associated with decreased physical activity. Further studies are needed to determine the mechanisms underlying this association.
Thorax 05/2007; 62(5):403-10. · 6.84 Impact Factor
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ABSTRACT: 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.
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.
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.
The present data suggest that noninstitutionalized elderly subjects with the MetS have altered structure of the carotid arteries.
Stroke 04/2007; 38(3):893-9. · 5.73 Impact Factor
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ABSTRACT: Reduced pulmonary function is an important predictor of cardiovascular morbidity and mortality. The mechanisms underlying this association are unknown but may involve systemic inflammation. We assessed the cross-sectional and longitudinal relationships between C-reactive protein (CRP) levels and forced expiratory volume in 1s (FEV1) and its decline in the general population, over a period of 8.5 years. The analyzes were based on 531 subjects (mean age at baseline: 37+/-7 years, 50% women and 42% non-smokers), recruited at two French centers participating in the European Community Respiratory Health Survey. Lung function was expressed as a percentage of predicted FEV1. CRP was measured centrally, by means of a highly sensitive assay. In cross-sectional analysis, FEV1 as a % of predicted values was negatively associated with serum CRP concentration (P=0.002). Multivariate adjustment did not alter these results (P=0.002). In longitudinal analysis, annual FEV1 decline tended to increase from the lower to the upper tertile for baseline CRP concentration but the association was borderline significant (P=0.14). Mean values of annual FEV1 decline were 26+/-32, 31+/-32, and 34+/-32 ml/year for the lower, middle and upper tertiles of baseline CRP concentration, respectively, after adjusting for potential confounders (P=0.09). Changes in CRP levels during follow-up were associated with annual FEV1 decline. The mean annual FEV1 declines in subjects with increasing CRP, in those with stable CRP and in those with decreasing CRP were 36+/-31, 30+/-31 and 24+/-31 ml/year, respectively (P<0.001). These findings were not affected by adjustment for potential confounders (P=0.002). In conclusion, increases in CRP levels over time were associated with a steeper FEV1 decline.
Respiratory Medicine 01/2007; 100(12):2112-20. · 2.47 Impact Factor
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Stéphanie Debette,
Jean-Charles Lambert,
Jérôme Gariépy,
Nathalie Fievet,
Christophe Tzourio,
Jean-Françoise Dartigues,
Karen Ritchie,
Anne-Mary Dupuy,
Annick Alpérovitch,
Pierre Ducimetière,
Philippe Amouyel, Mahmoud Zureik
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ABSTRACT: Carotid plaques and elevated carotid artery intima-media thickness (IMT) are major predictors of vascular morbidity and mortality. Our aim was to test their association with 2 polymorphisms of the apolipoprotein E (apoE) gene, epsilon and -219G/T.
The study was performed on 5856 subjects aged > or =65 years recruited from the French population for the Three-City Study. Carotid ultrasound examination included an assessment of atherosclerotic plaques in the extracranial carotid arteries and a measurement of IMT in the common carotid arteries (CCA) at a site free of plaques. The genetic association was tested using genotype and haplotype analyses.
In a multivariate analysis including both polymorphisms and vascular risk factors, carotid plaques were more frequent in epsilon4 homozygotes (adjusted odds ratio=2.12, 95% CI=1.27 to 3.53) and less frequent in epsilon2 carriers (adjusted odds ratio=0.79, 95% CI=0.66 to 0.95) compared with epsilon3 homozygotes. Adjusting for and stratifying on lipid levels did not modify these results. CCA-IMT was higher in carriers of the epsilon34 genotype (mean CCA-IMT=0.744 mm versus 0.732 mm for the epsilon33 genotype, P=0.002), but the association disappeared after excluding subjects with carotid plaques. No association was found between the -219 polymorphism and either carotid plaques or CCA-IMT, and there was no interaction or cis-effect between -219 and epsilon.
This study, conducted on a large population cohort of French elderly, demonstrated that carotid plaques were significantly associated with the apoE epsilon polymorphism independently of the -219 polymorphism and vascular risk factors, in particular lipid levels.
Stroke 01/2007; 37(12):2917-23. · 5.73 Impact Factor
