Vascular Ehlers-Danlos syndrome (vEDS) is a rare and severe autosomal dominant disorder caused by variants at the COL3A1 gene. Clinical characteristics and course of disease of 215 molecularly proven patients (146 index cases and 69 relatives) were analysed. We found 126 distincts variants that were divided into five groups: (1) Glycine substitutions (n = 71), (2) splice-site and in-frame insertions-deletions (n = 36), (3) variants leading to haplo-insufficiency (n = 7), (4) non-glycine missense variants within the triple helix (n = 4 variants), and (5) non-glycine missense variants or in-frame insertions-deletions, in the N-or C-terminal part of the protein (n = 8). Overall, our cohort confirmed the severity of the disease with a median age at first complication of 29 years (IQR 22-39), the most frequent being arterial (48%) and digestive (24%) ruptures. Groups 2 and 1 were significantly more severe than groups 3-5, with extreme median ages at first major complication of 23-47 years. Patients of groups 3-5 had a less typical phenotype and remarkably absence of digestive events. The distribution of glycine-replacing amino acids was strongly biased towards more destabilizing residues of the collagen assembly. Thus the natural course of vEDS and the clinical phenotype of patients are influenced by the type of COL3A1 variant. This study also confirms that patients with variants located in the C-and N-termini or leading to haplo-insufficiency have milder course of the disease and less prevalent diagnostic criteria. These findings may help refine diagnostic strategy, genetic counselling and clinical care.

Abstract-Previous reports have investigated associations between carotid intima-media thickness (IMT) and cardiovascular risk factors. Our objective was to investigate this question in greater depth by measuring both femoral and carotid IMT in relation to sex and multifactorial coronary risk. We investigated carotid and femoral artery IMT by using ultrasonography in 326 men and 462 women, 17 to 65 years old. We also evaluated body mass index, blood pressure, blood lipids, glucose, smoking, and Framingham coronary risk. In both vessels, IMT was lower in women than in men. Significant relations between carotid and femoral IMT existed with age and most risk factors in both sexes. After adjustment for age, carotid IMT was related to risk factors in both sexes except for diastolic blood pressure, HDL cholesterol, and smoking in women, whereas femoral IMT was related to triglycerides and smoking in both sexes, systolic blood pressure and blood glucose in men, and total and HDL cholesterol in women. Significant unadjusted and age-adjusted relations of Framingham risk existed with carotid and femoral IMT in both sexes, but slopes of these relations were greater (1) before than after age adjustment, (2) in men than in women at both sites, except the femoral artery after age adjustment, and (3) at the carotid than at the femoral site in both sexes before age adjustment. Carotid IMT in men appears to be a more powerful predictor than it is in women and femoral IMT in both sexes in reflecting multifactorial coronary risk burden, but these differences are partly conditional on age. (Arterioscler Thromb Vasc Biol. 1998;18:584-590.)Key Words: arteries Ⅲ risk factors Ⅲ coronary disease Ⅲ atherosclerosis Ⅲ ultrasound T he early detection of preclinical arterial disease may increase our ability to predict the subsequent risk of cardiovascular complications and lead to optimal disease prevention strategies.1,2 There is growing evidence that the thickening of the arterial wall observable with B-mode ultrasonography represents one initial step of preclinical arterial disease.3 Even in the absence of discrete plaque, the combined thickness of the arterial intima and media, the so-called IMT, can be measured with considerable precision, particularly by coupling high-resolution, B-mode ultrasonography with an automated, computerized system of image analysis. [4][5][6] Several studies of selected patients at risk for cardiovascular disease and a few population-based studies have provided evidence of an association between IMT, as measured in the extracranial carotid arteries, and cardiovascular risk factors. 3,4,[7][8][9][10][11][12] However, little attention has been given to the influence of risk factors on IMT as measured at sites other than the carotid artery, such as the femoral, 8 -13 a vessel considered to be as prone to atherogenesis as the carotid.14 The AXA Study is a prospective, worksite study designed to investigate the influence over time of traditional and new risk factors 15,16 on carotid and femoral IMT as assessed ultr...

No abstract

Objectives-We aimed to analyze the influence of hypertension on early large artery remodeling. Methods and Results-Carotid intima-media thickness (IMT) and diameter were measured ultrasonographically in 394 normotensive subjects and 327 untreated and 528 treated hypertensive patients. IMT and diameter were increased in hypertensive groups, treated or untreated, compared with the normotensive group (PϽ0.001). Positive association existed between diameter and IMT in the overall study population (PϽ0.001), and this association interacted with the category of clinical groups (PϽ0.01). Key Words: carotid arteries Ⅲ remodeling Ⅲ hypertension Ⅲ ultrasonics Ⅲ antihypertensive treatment A rterial remodeling is potentially important in atherosclerosis, aiming at counteracting the development of lumen compromise of large artery by mutual adaptation of diameter to wall thickening. 1 At the early stage of atherosclerosis characterized by slightly intrusive or preintrusive wall thickening, the lumen size of the artery remains constant or even increases (compensatory enlargement). 2 Advances in highresolution B-mode ultrasonography offer the possibility of assessing concomitantly intima-media thickness (IMT) and diameter of carotid artery 3 and obtaining in vivo information on the adaptation of IMT to diameter. 4,5 Positive relationships were found between carotid diameter and IMT in populations of healthy subjects, independently of coexisting cardiovascular risk factors. 6 -8 However, these relations have not been examined specifically in patients with hypertension, even though the influence of blood pressure on large artery geometry and structure may change the ability of arteries to remodel their lumen as wall thickness increases. Therefore, the objective of the present study was to assess and compare the adaptation of lumen diameter to IMT in the common carotid artery of 3 groups of untreated and treated hypertensive patients and normotensive subjects. Methods Study SubjectsOne thousand two hundred forty-nine consecutive subjects referred between April 2000 and May 2001 for cardiovascular risk assessment and having undergone appropriate ultrasonographic carotid examination were included in the study. They were divided into 2 groups according to the presence (hypertensive group, nϭ855) or absence (normotensive group, nϭ394) of hypertension defined as blood pressure Ն140 systolic or Ն90 mm Hg diastolic or the current use of antihypertensive treatment. Hypertensive patients were subdivided into 2 groups of untreated (nϭ327) and treated (nϭ528) subjects according to the absence or presence of current antihypertensive treatment for the past 3 months. Among treated hypertensive patients, 314 were treated with a class of drug given alone (monotherapy) or in association with a diuretic (diuretic bitherapy) and subdivided into the following 4 groups according to the class of drug: calcium antagonists, nϭ81; angiotensin converting enzyme inhibitors, nϭ82; ␤ blockers, nϭ93; and angiotensin receptors antagonists, nϭ58. Risk Factors Ev...

Stiffness of aortic walls has been shown to be a marker of coronary and cerebrovascular diseases in patients with myocardial infarction or stroke. However, its value for predicting preclinical atherosclerosis has not been demonstrated. Therefore, this study tested the association of aortic wall stiffness and coronary and extracoronary atherosclerosis in the absence of clinical cardiovascular disease. In 190 asymptomatic men at cardiovascular risk, carotid-to-femoral pulse wave velocity (PWV) was measured mechanographically and the compliance of the aorta (C), as well as the intrinsic compliance (Ci), was deduced after correction for the effect of blood pressure. Also determined noninvasively were 1) the degree of coronary calcium deposit coded as grade 0, 1, 2, or 3 using ultrafast computed tomography; 2) the extent of extracoronary plaque detected by B-mode echography at three different sites (carotid, abdominal aorta, and femoral) coded as 0, 1, 2, or 3 diseased sites; and 3) the estimated Framingham coronary risk. The grade of coronary calcium was not associated with any aortic elastic parameter. The number of extracoronary diseased sites was not associated with PWV and C but correlated negatively with Ci before but not after age adjustment. The coronary risk correlated positively with PWV and negatively with C before but not after age adjustment and was not associated with Ci. In symptom-free subjects aortic stiffening does not predict the presence of coronary and extracoronary atheroma and therefore cannot be considered as a useful surrogate marker of early atherosclerosis.

BACKGROUND: A central distribution of adipose tissue is frequently associated with cardiovascular disease (CVD) and its risk factors. METHODS: Clinical usefulness of waist-to-hip ratio (WHR) for predicting the risk of cardiovascular events, estimated with models based on data from the Framingham and Prospective Cardiovascular Mu È nster (PROCAM) studies was evaluated. SUBJECTS: These were 552 men and 160 women, asymptomatic and at risk for CVD, aged 30 ± 74 y, recruited from an ongoing risk factor screening program conducted at worksites. RESULTS: Abdominal fatness was a strong predictor of cardiovascular complications in subjects whose WHR was in the top quintile (b b 0.98 for men and b b 0.91 for women). The estimated percentage rate of coronary heart disease (CHD, P`0.01) and death (P`0.01), myocardial infarction (P`0.01), stroke (P`0.01), total CVD (P`0.001) and death (P`0.01) increased with increasing quintile of WHR in men and women. In the highest WHR, the number of subjects exceeding a 15% risk of developing a coronary event over the next 10 y was more than two-fold greater (odds ratio (OR) 2.60 (con®dence intervals (CI) 1.09 ± 6.54) than in the lowest WHR quintiles. Similar six-year myocardial infarction (MI) risks at each quintile of WHR were observed in men in both Framingham and PROCAM models. In the overall population, CHD estimates increased with increasing quintiles of WHR with the Framingham model and an adapted model for estimating probabilities of disease in the French population of the Pre  vention Cardiovasculaire en Me  decine du Travail (PCV-METRA) group. CONCLUSION: Abdominal deposition of fat assessed by WHR may be of strong clinical value for predicting high risk of cardiovascular events.

Femoral intima-medial thickness predicted presence of coronary calcium whereas femoral intima-medial thickness and overall multiple plaques predicted extensive coronary calcium. Because coronary calcium is a marker of atherosclerosis and a predictor of coronary events, B-mode ultrasonography could be of clinical value for stratifying coronary risk.

No abstract