Excessive daytime sleepiness is an independent risk indicator for cardiovascular mortality in community-dwelling elderly: the three city study.

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 >or=65 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. CONCLUSIONS: EDS might be independently associated with total and cardiovascular mortality in community-dwelling elderly.

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.

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.

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.

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.

Decreased number of circulating CD34+KDR+ cells in asymptomatic subjects with preclinical atherosclerosis.

OBJECTIVES: To assess whether circulating endothelial progenitor cells (CEPCs) can be considered as a cardiovascular risk marker before event has occurred, that is less firmly established than in clinically overt atherosclerosis. METHODS: Number of CD34+KDR+ cell number per ml blood was measured by flow cytometry in 84 untreated subjects without cardiovascular disease. Atherosclerotic plaque was detected by ultrasound in carotid, abdominal aortic and femoral sites and the number of sites affected by plaque among these three sites was counted as 0, 1, 2 or 3. Additionally, intima-media thickness (IMT) was measured by computerized ultrasound imaging of both common carotid segments. RESULTS: CD34+KDR+ cell number decreased by 48, 29 or 30% in the presence of carotid, aortic or femoral plaque (p<0.001, 0.05, 0.05, respectively) as compared to the absence of plaque and by 70% in the presence of three sites affected with plaque as compared with 0 site with plaque (p<0.01) but did not change with increasing IMT tertiles. Adjustment for Framingham risk score, that was also associated with decreased CD34+KDR+ cell number (p<0.001), made CD34+KDR+ cell number associations with plaque insignificant, except at the carotid site (p<0.01). CONCLUSIONS: Reduced CEPC number may participate to preclinical stage of atherosclerosis and provide additional information to traditional risk factors as regards global risk assessment.

New monitoring software for larger clinical application of brachial artery flow-mediated vasodilatation measurements.

BACKGROUND: The reproducibility of brachial artery flow-mediated vasodilatation (FMD) is limited by the operator dependence of most measurement methods. METHODS: A new automated computerized analysis of brachial artery ultrasound scan providing a continuous evolution of the diameter during acute hyperemia, reactive to short hyperemia of the forearm and hand, was tested in 10 normal volunteers and 26 asymptomatic patients with cardiovascular risk factors such as hypertension, hypercholesterolemia, heavy smoking, history of premature coronary heart disease and the metabolic syndrome. FMD was the percentage of the maximum hyperemic diastolic diameter from baseline. Within-reading variations in FMD and diameters were assessed by reading one scan from the same subject twice by two observers. The within-subject variability of FMD was assessed by analysing two repeated measurements in the same subject by the same operator 1 h, 1 week or 1 month apart. RESULTS: Coefficients of variation (CV) of repeated FMD readings were 7.5% in normal volunteers and 6.9% in patients with risk factors. CV of repeated FMD measurements 1 h apart were 7.8% in normal volunteers and 16.5% in patients with risk factors. In normal volunteers, CV of repeated FMD measurements 1 week apart was 9.6%, and in patients with risk factors CV of repeated FMD measurement 1 month apart was 18.1%. CONCLUSION: This method overcomes the variability of FMD measurement seen with conventional manual analysis in normal volunteers, and to a lesser extent in patients with major cardiovascular risk factors, thus supporting its clinical applicability to patients with disease conditions.

Circulating leukocyte-derived microparticles predict subclinical atherosclerosis burden in asymptomatic subjects.

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, platelet-derived, 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. Leukocyte-derived MP level was higher in the presence than in the absence of moderate to high Framingham risk (P<0.05), metabolic syndrome (P<0.01), high C-reactive protein (CRP) (P<0.05), or 2- to 3-sites disease (P<0.01), and correlated positively with number of metabolic syndrome components (P<0.001), tertiles of fibrinogen (P<0.001), and number of diseased sites (P<0.01). In multivariate analysis, 2- to 3-sites disease was independently associated with leukocyte-derived MP level (P<0.05), Framingham risk (P<0.001), and metabolic syndrome (P<0.01). None of the other MP types correlated with risk markers or atherosclerosis. CONCLUSIONS: Leukocyte-derived MP, identified by affinity for CD11a, are increased in subjects with ultrasound evidence of subclinical atherosclerosis, unveiling new directions for atherosclerosis research.

Effects of enhanced external counterpulsation on carotid circulation in patients with coronary artery disease.

BACKGROUND: Enhanced external counterpulsation (EECP) is a noninvasive method previously shown to improve measures of myocardial ischemia in patients with coronary artery disease. However, the concomitant effects of EECP on large and small arterial properties have been poorly examined. In a randomized controlled study, we investigated whether arterial stiffness and resistance of the carotid circulation are altered by EECP. METHODS: Thirty patients with angiographically demonstrated coronary artery disease were randomized into two groups to receive either 'sham' or active EECP therapy for 35 1-hour sessions. The beta stiffness index was calculated by the ln(Ps/Pd)/DD equation where Ps and Pd = systolic and diastolic blood pressure, and DD = the ratio between carotid pulse and diastolic diameter, measured by ultrasound sequential frames during the cardiac cycle. Carotid vascular resistance was calculated as the ratio between mean arterial pressure and mean common carotid blood flow. RESULTS: No significant between-group differences were seen in clinical characteristics or carotid hemodynamics at baseline. The beta stiffness index and carotid vascular resistance were significantly reduced after 35 h of active EECP (p < 0.01), and the decrease was significantly different when compared with controls (p < 0.05 for beta stiffness index and p < 0.001 for carotid vascular resistance). These reductions persisted after multiple covariate adjustment. CONCLUSIONS: This study suggests that EECP exerts clear arterial effects on large and small vessels of the carotid circulation. The combined effects on arterial stiffness and vascular resistance are of particular interest in cardiovascular disease involving reduction in blood flow, in which techniques that increase regional blood flow may be beneficial.

New insight into the association of apolipoprotein E genetic variants with carotid plaques and intima-media thickness.

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Current possibilities for detecting high risk of cardiovascular disease.

Current possibilities for better detecting high risk of coronary heart disease (CHD) and stroke and peripheral arterial disease are described in this review. A first step is based on risk factors assessment that allows establishing high-risk diagnostic, either by detecting a condition termed as "CHD risk equivalent" and defined by one or more severe major risk factor, or by calculating multifactorial risk in asymptomatic subjects with a global risk score integrating several moderate risk factors. A second diagnostic step, concerning subjects not considered at high-risk by risk factors assessment, is based on non-invasive detection of sub clinical atherosclerosis via a wide variety of structural and functional arterial markers. A third step focuses on detection of myocardial ischemia that may add diagnostic and prognostic information in subjects with high CHD risk. The implementation of high-risk strategy is not yet standardized but it should allow improving cost-effectiveness of cardiovascular prevention, particularly in asymptomatic subjects.

Common carotid artery intima-media thickness, carotid plaques, and walking speed.

BACKGROUND AND PURPOSE: Gait dysfunction is an important cause of disability among the elderly and may be, in part, of vascular origin. We studied the association between carotid ultrasound parameters and measures of gait and balance in subjects 65 to 85 years of age who participated in the baseline phase of the Three-City Study in the Dijon center. METHODS: The study population comprised 2572 noninstitutionalized individuals. Carotid plaques and common carotid artery intima-media thickness (CCA-IMT) were measured using ultrasonography. Gait and balance measures included walking speed and a modified version of the Tinetti scale. RESULTS: Mean maximum walking speed (MWS) decreased with increasing CCA-IMT and number of plaques (P<10(-4)). Compared with subjects in the lowest CCA-IMT quintile, the odds ratio (95% CI) for being in the lowest MWS quartile was 1.1 (0.8 to 1.6) in the second, 1.3 (0.9 to 1.8) in the third, 1.7 (1.2 to 2.4) in the fourth, and 2.2 (1.6 to 3.1) in the higher CCA-IMT quintile (P<10(-4)). Mean (SD) CCA-IMT was 0.716 (0.118) mm in subjects with a modified Tinetti score <16 (25th percentile) and 0.685 (0.109) mm in subjects with a score of > or =16 (P=0.006). The proportion of subjects in the lowest MWS quartile (P=0.006) or with a modified Tinetti score <16 (P=0.05) increased with the number of plaques. These relations were attenuated after adjustment for vascular risk factors. CONCLUSIONS: Carotid plaques and higher CCA-IMT values are associated with worse performances on gait and balance tests. Our results suggest that vascular factors may play an important and under-recognized role in motor function.

Differences between markers of atherogenic lipoproteins in predicting high cardiovascular risk and subclinical atherosclerosis in asymptomatic men.

OBJECTIVE: As main markers of atherogenic lipoproteins, apolipoprotein B (apoB), non-HDL cholesterol (non-HDLC), and LDL cholesterol (LDLC) do not seem equipotent to predict cardiovascular complications, we have compared simultaneously their capacity to predict high cardiovascular risk and subclinical atherosclerosis in a primary prevention population. METHODS: In 723 asymptomatic men, we measured apoB, non-HDLC, and LDLC, and we determined concomitantly coronary heart disease (CHD) risk equivalent defined by National Cholesterol Education Program guidelines, ultrasound-assessed extra-coronary plaques at multiple sites, and electron beam computed tomography-assessed high coronary calcium. RESULTS: Odds ratios (95% confidence interval) per standard deviation of apoB, non-HDLC, and LDLC of having: (i) CHD risk equivalent were 1.90 (1.53-2.37), 1.78 (1.43-2.21), 1.47 (1.19-1.81); (ii) extra-coronary plaques were 1.37 (1.16-1.61), 1.31 (1.11-1.56), 1.19 (1.01-1.39); (iii) high coronary calcium were 1.35 (1.09-1.68), 1.33 (1.07-1.64), 1.26 (1.01-1.39), respectively. Risk factors and treatment did not confound the above associations, except triglycerides for which adjustment weakened the risk predictions of lipids and annihilated lipids differences in predicting CHD risk equivalent and atherosclerosis markers. CONCLUSIONS: ApoB was the best predictor, non-HDLC the second best predictor, and LDLC the poorest predictor of high cardiovascular risk and subclinical extra-coronary and coronary atherosclerosis, and triglycerides participated to these differences.

Differential associations of statin and fibrate treatment with carotid arterial remodeling.

BACKGROUND: The effects of statins on intima-media thickness (IMT) are well documented, whereas those of fibrates are unknown. Therefore we compared IMT under treatment with each class of drugs. METHODS: We studied a cohort of consecutive dyslipidemic subjects treated with statin (n = 291) or fibrate (n = 82) drugs. Fibrate-treated subjects were matched with the same number of statin-treated subjects to obtain two subgroups of similar demographic and risk factors including LDL cholesterol. Common carotid far wall IMT and lumen diameter were measured by ultrasonography. RESULTS: In the entire study population, IMT was greater in the fibrate group than in the statin group (P < .001), even after adjustment for LDL cholesterol and other covariates (P < .05). In the matched groups, IMT was greater in fibrate group than in the statin group (P < .01), even after adjustment for LDL cholesterol and other covariates including treatment duration (P < .01). The IMT correlated positively with treatment duration in the fibrate group (P < 0.05) but not in the statin group. In addition, IMT correlated positively with carotid lumen diameter in both the fibrate and statin groups (P < .05, P < .01) but with a lower slope in the former (P < .05). CONCLUSIONS: In this study fibrate treatment was associated with greater IMT, steeper IMT-time relationship, and lower compensatory carotid enlargement than was statin treatment. These differences were not explained by differences in LDL cholesterol.

Influence of hypertension on early carotid artery remodeling.

OBJECTIVE: 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 (P<0.001). Positive association existed between diameter and IMT in the overall study population (P<0.001), and this association interacted with the category of clinical groups (P<0.01). The slope of the diameter-IMT relationship was different between normotensive, untreated hypertensive, and treated hypertensive groups (P<0.01), with higher value in the treated hypertensive group than in untreated hypertensive and normotensive groups (P<0.05, P<0.01). Adjustment for blood pressure, lipid-lowering therapy, or multiple covariates (age, sex, systolic and diastolic blood pressures, body mass index, lipid-lowering therapy, smoking, and previous cardiovascular disease) did not abolish the diameter-IMT slope difference between clinical groups (P<0.01). CONCLUSIONS: The sensitivity of carotid artery enlargement in response to increase in wall thickness was unchanged in untreated hypertension but altered by antihypertensive therapy compared with the normotensive condition.

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.

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.

Characterization of polymorphic structure of SREBP-2 gene: role in atherosclerosis.

Sterol regulatory element binding proteins (SREBPs) are membrane-bound transcription factors that control the metabolism of cholesterol and fatty acids in mammalian cells. We postulated that polymorphisms (SNPs) in SREBP-2 gene might influence lipid parameters and the risk of coronary atherosclerosis. PCR-SSCP analysis and direct sequencing of DNA from 64 asymptomatic hypercholesterolemic men revealed seven genetic SREBP-2 SNPs. The genotype distribution of four of these SNPs (1668G>T, 1784G>C, 3474T>C and 3705C>T), and their influence on plasma lipid values and clinical parameters was studied in 655 asymptomatic men previously selected for the presence of at least one cardiovascular risk factor (hypertension, hypercholesterolemia, tobacco consumption). No significant relation was found with lipid parameters but there was a significant association between the 1784G>C polymorphism and intima-media thickness (IMT) measured in 497 subjects. Thus, a common variation in the SREBP-2 gene is related with early-stage carotid atherosclerosis in subjects with a risk of cardiovascular events without detectable change in plasma lipid levels.

Intima-media thickness: a new tool for diagnosis and treatment of cardiovascular risk.

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.

Large artery wall thickening and its determinants under antihypertensive treatment: the IMT-INSIGHT study.

BACKGROUND: Calcium antagonists retard progression of intima-media thickness (IMT), but whether this retardation covers heterogeneous individual patient responses of IMT change is unknown. METHODS: Hypertensive patients treated for 4 years with nifedipine (n = 115) or coamilozide (n = 127) underwent ultrasound measurements of carotid IMT at baseline, 4 months later, and then every year. RESULTS: A histogram of individual slopes of IMT change (least square regression of IMT to time) during treatment identified three categories of slopes according to the 20th and 80th percentiles of distribution: lower, intermediate and higher percentiles of IMT slope; the proportion of categories of IMT slope differed between treatments (P < 0.05), due to a more frequent lower slope percentile under nifedipine (27%) than under coamilozide (14%); within-group differences between IMT slope categories were: (i) increased baseline IMT associated with lower IMT slope percentile in nifedipine group (P < 0.001) and (ii) more frequent carotid plaque associated with higher IMT slope percentile in both treatment groups (P < 0.05). Analysis of overall patients showed that IMT slope was associated negatively with nifedipine treatment (P < 0.01) and baseline IMT (P < 0.001) and positively with carotid plaque (P < 0.01); the relationship between IMT slope and baseline IMT was negative under nifedipine and flat under coamilozide, and the presence of plaque reset both relationships towards a higher IMT slope; the between-treatment difference in IMT slope was different between tertiles of baseline IMT (P = 0.016). CONCLUSIONS: The differences in IMT slope between nifedipine and coamilozide increase with increasing baseline IMT.