Increased intima-media thickness (IMT) is a non-invasive marker of early arterial wall alteration, which is easily assessed in the carotid artery by B-mode ultrasound, and more and more widely used in clinical research. Methods of IMT measurement can be categorized by two approaches: (i) measurement at multiple extracranial carotid sites in near and far walls and (ii) computerized measurement restricted to the far wall of the distal common carotid artery. Because IMT reflects global cardiovascular risk, its normal value might be better defined in terms of increased risk rather than in terms of statistical distribution within a healthy population. The available epidemiological data indicate that increased IMT (at or above 1 mm) represents a risk of myocardial infarction and/or cerebrovascular disease. Close relationships have been shown between: (i) most traditional cardiovascular risk factors; (ii) certain emerging risk factors such as lipoproteins, psychosocial status, plasma viscosity, or hyperhomocysteinemia; and (iii) various cardiovascular or organ damages such as white matter lesion of the brain, left ventricular hypertrophy, microalbuminuria or decreased ankle to brachial systolic pressure index. Thus, IMT gives a comprehensive picture of the alterations caused by multiple risk factors over time on arterial walls. Prospective primary and secondary prevention studies have also shown that increased IMT is a powerful predictor of coronary and cerebrovascular complications (risk ratio from 2 to 6) with a higher predictive value when IMT is measured at multiple extracranial carotid sites than solely in the distal common carotid artery. Therapeutic double-blind trials have shown that lipid-lowering drugs, such as resin and overall statines, and to a lesser extent antihypertensive drugs, such as calcium antagonists, may have a beneficial effect on IMT progression in asymptomatic or in coronary patients. However, methodological standardization of IMT measurement still needs to be implemented before routine measurement of IMT can be proposed in clinical practice as a diagnostic tool for stratifying cardiovascular risk in primary prevention and for aggressive treatment decision. It can be anticipated however, that the presence of increased carotid IMT in one individual with intermediate cardiovascular risk would lead to his classification into the high-risk category and thus influence the aggressiveness of risk factor modifications.

Objective-To clarify circulating microparticles (MP) relationships with preclinical atherosclerosis. Methods and Results-In 216 subjects without cardiovascular disease, we assessed: (1) annexin V-positive, plateletderived, endothelium-derived and leukocyte-derived circulating MP by capture on annexin V, anti-GPIb, anti-CD105, and anti-CD11a antibody-coated wells, respectively; (2) Framingham risk, metabolic syndrome, and low-grade inflammation by risk factors measurement including hsCRP; and (3) subclinical atherosclerosis by ultrasound examination of carotid, abdominal aorta, and femoral arteries. Number of sites with plaque ranged from 0 to 3 and plaque burden was classified into 0 to 1 or 2 to 3 sites disease.

Background and Purpose-Excessive daytime sleepiness, one of the most frequent sleep complaints in the elderly, may affect survival, but inconsistent results have been observed in that population so far. We therefore estimated the risk of mortality for excessive daytime sleepiness (EDS) in community-dwelling elderly participating in the Three City Study. Methods-The Three City Study is a French population-based multicenter prospective study including 9294 subjects (60% women) aged Ն65 years at recruitment between 1999 to 2001. At baseline, 8269 subjects rated EDS and nocturnal sleep complaints as never, rare, regular, and frequent in response to an administered questionnaire and provided information on medication use for sleep or anxiety. Hazard ratios (HR) of EDS (regular or frequent) for mortality over 6 years were estimated by a Cox proportional hazard model. Results-At baseline, 18.7% of the study participants had regular or frequent EDS. After 6 years of follow-up, 762 subjects had died including 260 from cancer and 196 from cardiovascular disease. EDS was associated with a significant 33% increased risk of mortality (95% CI: 1.13 to 1.61) after adjustment for age, gender, study center, body mass index, previous cardiovascular disease, Mini Mental State Examination score, and cardiovascular risk factors. Further adjustment for current use of medication for sleep and for depressive symptoms slightly diminished the HRs. EDS was equally predictive of mortality in those who snored loudly and in those who did not. EDS was related to cardiovascular mortality but not to mortality attributable to cancer. Conclusion-EDS

Abstract-The matrix Gla protein (MGP) is an important inhibitor of vessel and cartilage calcification that is strongly expressed in human calcified, atherosclerotic plaques and could modulate plaque calcification and coronary heart disease risk. Using a genetic approach, we explored this possibility by identifying polymorphisms of the MGP gene and testing their possible association with myocardial infarction (MI) and plaque calcification. Eight polymorphisms were identified in the coding and 5Ј-flanking sequences of the MGP gene. All polymorphisms were investigated in 607 patients with MI and 667 control subjects recruited into the ECTIM Study (Etude Cas-Témoins de l'Infarctus du Myocarde) and in 717 healthy individuals with echographically assessed arterial calcification and atherosclerosis who were participating in the AXA Study. In the ECTIM Study, alleles and genotypes were distributed similarly in patients and controls in the whole study group; in only 1 subgroup of subjects defined as being at low risk for MI were the concordant AϪ7 and Ala 83 alleles more frequent in patients with MI than in controls (PϽ0.003). In the AXA Study among subjects with femoral atherosclerosis, the same alleles were more common in the presence than the absence of plaque calcification (PϽ0.025). The other MGP polymorphisms were not associated with any investigated clinical phenotype. Transient transfection experiments with allelic promoter-reporter gene constructs and DNA-protein interaction assays were carried out to assess possible in vitro functionality of the promoter variants detected at positions Ϫ814, Ϫ138, and Ϫ7 relative to the start of transcription. When compared with the Ϫ138 T allele, the minor Ϫ138 C allele consistently conferred a reduced promoter activity of Ϫ20% (PϽ0.0001) in rat vascular smooth muscle cells and of Ϫ50% (PϽ0.004) in a human fibroblast cell line, whereas the other polymorphisms, including Ϫ7, displayed no evidence of in vitro functionality. We conclude that the AϪ7 or Ala 83 alleles of the MGP gene may confer an increased risk of plaque calcification and MI; however, the observed relationships are weak or limited to subgroups of patients and therefore need confirmation. (Arterioscler Thromb Vasc

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A difference in early carotid wall changes is shown between 2 equally effective antihypertensive treatments.

Shear-mediated arterial vasodilation and vasoconstriction were more pronounced in women than in men, suggesting different gender-related sensitivity in the regulation of large-artery vascular tone.

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...