Independent association of von Willebrand factor with surrogate markers of atherosclerosis in middle-aged asymptomatic subjects

Von Willebrand factor (VWF) is considered a reliable marker of endothelial damage. Plasma levels of VWF were measured in 857 middle-aged subjects (80.4% men) free of clinically overt atherosclerotic disease, in relation to cardiovascular risk factors, carotid intima-media thickness (IMT) and microalbuminuria, two established surrogate markers of atherosclerosis. There was linear trend for the increase of VWF, carotid IMT (p < 0.001) and microalbuminuria (p = 0.018). The association between VEF and both markers remained statistically significant after adjusting for cardiovascular risk factors and inflammatory markers (p < 0.01). In conclusion, VWF was independently associated with both structural and functional surrogates of atherosclerosis in asymptomatic subjects, thus representing a systemic biomarker of subclinical atherosclerosis.     

Protective effect of the G-765C COX-2 polymorphism on subclinical atherosclerosis and inflammatory markers in asymptomatic subjects with cardiovascular risk factors

BACKGROUND: Cyclooxygenase (COX)-2, a key regulatory enzyme in prostanoid synthesis, plays an important role in inflammatory processes. The -765G>C COX-2 polymorphism has been associated with lower promoter activity in vitro and reduced levels of C-reactive protein (CRP) in atherosclerotic carriers of the C allele. However, its pathophysiological relevance in vivo has not been fully elucidated. METHODS AND RESULTS: We assessed the -765G>C polymorphism and COX-2 expression in 220 asymptomatic subjects free of cardiovascular disease, in relation to global vascular risk, carotid intima-media thickness (IMT), and inflammatory markers (fibrinogen, C-reactive protein [CRP], von Willebrand factor [vWF] and interleukin-6 [IL-6]). Genotype frequencies were: CC (7.7%), CG (34.5%), GG (57.7%). Among hypercholesterolemic subjects (n=140), C allele carriers had lower COX-2 expression (p<0.05), reduced carotid IMT (p<0.01) and diminished levels of inflammatory markers CRP, vWF and IL-6 (p<0.05), as compared to GG homozygous subjects. The association between carotid IMT and COX-2 polymorphism remained significant after adjusting for cardiovascular risk factors and inflammatory markers (p=0.008). CONCLUSIONS: In asymptomatic hypercholesterolemic subjects the C allele of -765G>C COX-2 polymorphism was associated with lower COX-2 expression, and reduced subclinical atherosclerosis and systemic inflammation compared with GG homozygous, thus conferring atherosclerosis protection in this cardiovascular risk population.     

Endothelial nitric oxide synthase Glu(298)-->Asp polymorphism, carotid atherosclerosis and intima-media thickness in a general population sample

The Glu(298)-->Asp (E298D; 894G-->T) polymorphism of eNOS (endothelial nitric oxide synthase) has been related with cardiovascular disease. In the present study, we investigated the association of Glu(298)-->Asp with atherosclerotic plaques in different carotid vessel segments and with carotid IMT (intima-media thickness). The Glu(298)-->Asp eNOS polymorphism was determined by 5'-exonuclease assay among 2448 participants of the SHIP (Study of Health in Pomerania). Mean and maximum common carotid IMT, as well as carotid atherosclerosis, were measured by high-resolution ultrasound. The Asp/Asp(298) genotype was associated with an increased risk of atherosclerotic plaques at the level of the common carotid arteries [multivariate odds ratio, 1.57 and 95% CI (confidence interval), 1.05-2.34; P=0.025], but not in the carotid bifurcations or internal or external carotid arteries. Glu(298)-->Asp genotype was not associated with carotid IMT in the whole sample. However, the Asp/Asp(298) genotype was independently associated with both higher mean [adjusted increase by 0.046 mm (95% CI, 0.013-0.078); P=0.006] and maximum carotid IMT [0.137 mm (95% CI, 0.064-0.209); P<0.001] in the low-risk group of subjects without carotid atherosclerosis. In conclusion, the Asp/Asp(298) genotype is associated with atherosclerosis in the common carotid arteries and, in a low-risk group, also with carotid IMT. This suggests that the association of the Glu(298)-->Asp genotype with atherosclerosis in the carotid arteries is site-specific and is modified by overall cardiovascular risk.     

颈动脉粥样硬化斑块与多重危险因素关系探讨

目的 探讨颈动脉粥样硬化斑块与多重心血管病危险因素的关系,评估危险因素对亚临床型靶器官损害,减少心血管病总体危险因素.方法 选择2007年5月至2009年5月在我院门诊及病房住院的426例患者给予颈动脉彩色超声检查,根据检查结果分为颈动脉粥样硬化斑块组284例,颈动脉无粥样硬化斑块斑块组142例患者,分别记录年龄、吸烟、体重指数(BMI)、高血压、糖尿病、高脂血症病史.实验室检测血浆总胆固醇(TC)、低密度脂蛋白胆固醇( LDL-C)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)、脂蛋白(a)[LP(a)]、载脂蛋白( ApoA1)、载脂蛋白(ApoB)、超高敏C-反应蛋白(hsCRP)、同型半胱氨酸(HCY)、微量白蛋白尿(MAU)、血尿酸(UA)等,将自变量及单变量数据进行统计学处理,找出致颈动脉粥样硬化斑块的危险因素,并对结果进行分析.结果 年龄、饮酒与颈总动脉内中膜(IMT)增厚相关(P＜0.001).超重、糖尿病、LP(a)增高、高脂血症、年龄、MAU、HCY可独立预测颈动脉粥样硬化及斑块形成(x2 =71.35、38.45、t =3.26、x2=37.23、t=118.51、6.723、3.17,P均＜0.05)危险因素个数聚集的多寡与IMT、颈动脉粥样硬化斑块独立相关(P =0.0001).结论 年龄、饮酒、超重、糖尿病、LP(a)增高、高脂血症、MAU、HCY是预测颈动脉粥样硬化及斑块形成的危险因素,并具有多重、聚集的特点,危险因素的个数越多,危险性越大.     

Preclinical atherosclerosis and inflammation in 61-year-old men with newly diagnosed diabetes and established diabetes

OBJECTIVE: The aim of this study was to investigate the occurrence of subclinical atherosclerosis and underlying mechanisms in men with newly diagnosed diabetes and established diabetes compared with healthy control subjects. RESEARCH DESIGN AND METHODS: In a population-based study of 61-year-old Caucasian men (n = 271) with established diabetes (n = 50) and newly diagnosed diabetes (n = 24) and healthy control subjects (n = 197), standard risk factors and highly sensitive (hs) C-reactive protein (CRP) were measured. Ultrasound measurements of intima-media thickness (IMT) were performed bilaterally in the common carotid artery, and a composite measure was calculated from common carotid and carotid bulb IMT (composite IMT). The plaque status was assessed. RESULTS: Composite IMT and carotid plaque size increased gradually among the healthy control subjects, newly diagnosed diabetic patients, and established diabetic patients (P for trend < or =0.001, respectively). CRP was higher in newly and established diabetes (NS between diabetes groups) compared with healthy control subjects (P < 0.001). Total cholesterol levels were lower in newly diagnosed diabetes (5.51 +/- 1.13 mmol/l, P < 0.05) and established diabetes (5.45 +/- 1.15 mmol/l, P < 0.01) compared with those of healthy control subjects (5.77 +/- 1.03 mmol/l). In men with diabetes (n = 74), diabetes onset status (newly diagnosed versus established), waist-to-hip ratio (WHR), and serum triglycerides, but not CRP, explained 16% of the variance in composite IMT. CONCLUSIONS: This is the first study to show increased preclinical atherosclerotic changes (IMT and plaque size) and increased inflammation (hs-CRP) in men with newly diagnosed diabetes as well as in patients with established diabetes compared with healthy control subjects. WHR, diabetes onset status (newly diagnosed versus established), and triglycerides, but not CRP, were independent correlates of carotid artery IMT in men with diabetes.     

急性脑梗死患者血清基质金属蛋白酶-9超敏C-反应蛋白与颈总动脉内膜中层厚度的相关性

目的 通过观察急性脑梗死(ACI)患者血清基质金属蛋白酶-9(MMP-9)、超敏C-反应蛋白(hs-CRP)水平变化,探讨其与颈总动脉内膜中层厚度(IMT)的相关性.方法 分别采用酶联免疫吸附法(ELISA)及超敏乳胶增强免疫比浊法检测185例ACI患者和45例健康对照组血清MMP-9、hs-CRP水平.结果 (1)ACI患者血清MMP-9、hs-CRP水平显著高于健康对照组(P＜0.01);颈动脉斑块形成组显著高于颈动脉内膜增厚组及颈动脉内膜正常组(P＜0.01);颈动脉内膜增厚组显著高于颈动脉内膜正常组(P＜0.01);颈动脉内膜正常组显著高于健康对照组(P＜0.01).且血清MMP-9、hs-CRP水平随着IMT值增大而升高.(2)ACI患者血清MMP-9、hs-CRP与IMT值呈显著正相关(r=0.357、0.409,P＜0.01),且血清MMP-9与hs-CRP呈显著正相关(r=0.415,P＜0.01),其相关性良好.结论 联合检测血清MMP-9、hs-CRP水平,可作为判断ACI患者疾病严重程度、临床疗效及评估预后的重要参数.     

Elevated C-reactive protein associates with early-stage carotid atherosclerosis in young subjects with type 1 diabetes

OBJECTIVE: To evaluate whether low-grade inflammation contributes to early-stage advanced carotid atherosclerosis in young subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS: The mean and maximum (max) intima-media thicknesses (IMT) of the carotid artery were assessed using ultrasound B-mode imaging in 55 patients with type 1 diabetes (22 men and 33 women, aged 22.1 +/- 3.6 years (+/- SD), duration of diabetes 14.2 +/- 5.7 years) and 75 age-matched healthy nondiabetic subjects (28 men and 47 women). High-sensitive C-reactive protein (hs-CRP) levels were measured with a latex-enhanced immunonephelometer. RESULTS: The patients with type 1 diabetes had significantly higher hs-CRP levels (median 0.35, range 0.05-1.47 mg/l vs. median 0.14, range 0.05-1.44 mg/l; P = 0.001) as well as significantly higher mean IMT and max IMT than the nondiabetic subjects (mean IMT 0.76 +/- 0.09 vs. 0.72 +/- 0.04 mm, P = 0.003; max IMT 0.84 +/- 0.11 vs. 0.77 +/- 0.06 mm, P < 0.0001). Hs-CRP levels were significantly correlated with the mean and max IMT of patients with type 1 diabetes and with the max IMT of nondiabetic patients. Multivariate regression analyses for both diabetic and nondiabetic subjects as a single group showed that hs-CRP levels are independently correlated with the mean IMT and max IMT levels (P = 0.002 and P = 0.023, respectively) as well as with diastolic blood pressure, sex, and duration of diabetes. CONCLUSIONS: Our data indicate that hs-CRP levels are elevated in young patients with type 1 diabetes, possibly corresponding with early-stage advanced carotid atherosclerosis.     

脑梗死颈动脉粥样硬化患者血清MMP-9水平的测定及临床意义

目的探讨脑梗死患者颈动脉粥样硬化与血清基质金属蛋白酶-9（MMP-9）水平的关系。方法应用彩色Doppler超声诊断仪检测颈动脉内膜中层厚度（IMT）,以及有无斑块形成及斑块形态。应用双抗体夹心酶联免疫吸附法（ELISA）检测100例脑梗死患者的血清MMP-9水平,并进行相关分析。结果不稳定斑块组空腹血清MMPO浓度为（549．93±153．12）ng／ml,高于稳定斑块组和无斑块组的（281．45±120．34）ng／ml和（87．36±23．62）ng／ml,差异具有统计学意义（P〈0．01）。结论血清MMP-9水平的升高,可成为颈动脉粥样硬化斑块易损性的独立预测因素。血清MMP-9水平增高与颈动脉粥样硬化斑块不稳定性密切相关。     

糖尿病患者血清超敏C反应蛋白与动脉粥样硬化的关系

目的：探讨2型糖尿病（T2DM）患者血清超敏C反应蛋白（hs—CRP）水平与动脉粥样硬化之间的关系。方法：将141例T2DM患者具有大血管危险因素的数量分为三组，以颈动脉内膜中层厚度（IMT）反应动脉粥样硬化程度，并测定患者血清CRP、血脂水平和胰岛素抵抗相关指标。结果：具有3或4个危险因素即患者体重指数（BMI）、胰岛素抵抗指数（HOMA—IR）、血清甘油三酯（TG）和hs—CRP水平，较具有其中1或2个危险因素患者的水平高。随着危险因素增多，3个组颈动脉IMT依次为0．68mm、0．82mm、0．97mm；颈动脉斑块检出率依次为12．5％、24．1％、42．9％。颈动脉IMT随着危险因素的增加而显著增加，斑块检出率未见显著差异。颈动脉IMT与收缩压、HOMA—IR、hs—CRP呈显著正相关。CRP与HOMA—IR、BMI及TG呈显著正相关。经多元线形回归分析认为，hs—CRP和HOMA—IR是颈动脉IMT的独立危险因素。结论：T2DM患者血清hs—CRP水平与胰岛素抵抗和颈动脉IMT程度呈显著相关，hs-CRP是颈动脉IMT增厚的一个独立危险因素。     

Vascular stiffness in familial hypercholesterolaemia is associated with C-reactive protein and cholesterol burden

BACKGROUND: Familial hypercholesterolaemia (FH) is characterized by very high serum cholesterol and premature coronary atherosclerosis. Arterial stiffness and atherosclerosis are two major underlying pathophysiologies of arterial disease that are predictive of future cardiovascular events. The aims of this study were to quantify atherosclerosis and arterial stiffness and to evaluate their relationship with high sensitive C-reactive protein (hs-CRP) and the level of exposure to high serum cholesterol in FH patients. Materials AND METHODS: We measured traditional risk factors, hs-CRP, intima-media thickness (IMT) of carotid artery, and brachial-ankle pulse wave velocity (baPWV) in 35 heterozygous FH subjects and 17 healthy control subjects. Cholesterol-year score (CYS) was calculated to estimate the lifetime cholesterol burden in FH subjects. RESULTS: FH subjects had significantly elevated total cholesterol, low-density lipoprotein cholesterol, and carotid IMT compared with those without mutations. Among FH patients, the baPWV and carotid IMT were higher in cases with high cholesterol burden than those without. Similarly, the baPWV and carotid IMT were also higher in cases with elevated hs-CRP (> 1 mg L(-1)) than those without. Multiple linear regression analysis demonstrated CYS and hs-CRP were significant independent predictors of baPWV and IMT in FH patients. CONCLUSIONS: Both high cholesterol burden and vascular inflammation are not only associated with atherosclerosis, but also contribute to the development of arterial stiffness in FH patients. Early detection of hypercholesterolaemia in FH patients is warranted to prevent the untoward pathophysiologies.     

Serum metalloproteinase 9 levels in patients with coronary artery disease: a novel marker of inflammation.

BACKGROUND: The finding that expression of metalloproteinases (MMPs) is induced in atherosclerotic plaques prone to rupture suggests the possibility that patients with atherosclerotic diseases would show enhanced blood levels of MMPs and that MMPs might represent a potential inflammatory risk factor for atherosclerosis. Therefore, the present study was aimed at verifying whether MMPs may represent sensitive markers of inflammation in patients with coronary artery disease. METHODS: MMP-2, MMP-9, interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen levels were measured in blood samples obtained from 66 cases with previous acute myocardial infarction and 66 control subjects similar for age, sex, and major atherosclerotic risk factors but without history or evidence of atherothrombotic diseases. RESULTS: Biohumoral markers of inflammation and MMP-9 levels were significantly elevated in cases compared with controls (median values 40.6 versus 9.8 ng/mL; p < .0001), whereas MMP-2 levels did not differ between the two groups (median values 839 versus 873 ng/mL; p = .53). A direct correlation was found among MMP-9, CRP, IL-6, and fibrinogen levels. Conditional logistic regression analysis showed that MMP-9 is related to myocardial infarction (p = .006) even after adjusting for cardiovascular medications and CRP. CONCLUSION: These findings suggest that measurement of serum MMP-9 levels may represent a novel marker of inflammation in patients with known coronary artery disease and might provide an index of plaque activity in this clinical setting.     

Reduced endothelial progenitor cells in European and South Asian men with atherosclerosis

BACKGROUND: Circulating endothelial progenitor cells (EPCs) play a role in the repair and regeneration of the endothelium and may represent a novel cardiovascular risk factor. South Asian subjects have an increased risk of cardiovascular disease which is not fully explained by known risk factors. This study examined associations of EPCs with atherosclerosis and possible ethnic differences in EPCs. MATERIALS AND METHODS: A population sample of 58 European and South Asian adult men was enriched with the recruitment of an additional 59 European and South Asian men with known coronary disease. The coronary artery calcification score was measured by multi-slice computerized tomography (CT), carotid and femoral intima-media thickness (IMT), and femoral plaques were measured by ultrasound. The subjects were further subdivided into three categories of coronary artery disease on the basis of coronary artery calcification score and clinical history. Total EPCs and non-senescent EPCs (ns-EPCs) were quantified after 5 days cell culture and the number of late outgrowth colonies was measured over a 6-week test period. Circulating CD34+ haematopoietic precursor cells were measured by flow cytometry. RESULTS: Individuals with femoral plaques had reduced total and ns-EPCs. The number of ns-EPCs were reduced in individuals with the most coronary atheroma and were inversely related to the coronary calcification score and femoral IMT. These relationships persisted after multivariate adjustment for other risk factors. The numbers of late outgrowth colonies or circulating CD34+ cells were unrelated to the presence of atherosclerosis. There were no differences in the number of EPCs between European and South Asian subjects. CONCLUSION: The number of EPCs are reduced in subjects with atherosclerosis independent of other risk factors. Reduction in EPC numbers may be an independent risk factor for atherosclerosis but does not explain ethnic differences in cardiovascular risk.     

颈动脉内膜中层厚度在尿白蛋白正常的不同糖耐量人群中的变化及相关危险因素探讨

目的观察尿白蛋白排泄率(AER)在临床正常值范围内的不同糖耐量人群颈动脉内膜中层厚度(IMT)变化情况并分析其相关危险因素。方法选取AER在临床正常值范围内的正常糖耐量(NGT)25例、糖耐量减低(IGT)29例和新诊断2型糖尿病(T2DM)163例受试者,检测其颈动脉IMT及分析相关心血管危险因素。结果 T2DM组患者AER较非糖尿病组高(P<0.001);其颈动脉IMT比NGT组厚(P=0.03)。IGT组患者异常颈动脉IMT与空腹血糖正相关,调整了年龄和性别因素影响后相关性依然良好(r=0.461,P=0.020);空腹血糖升高致其发生异常颈动脉IMT的优势比(OR)达8.06(95%CI1.09～59.49)。结论 T2DM患者AER较非糖尿病患者高,且已出现亚临床性心血管疾病。IGT患者的空腹血糖水平与异常颈动脉IMT的发生独立相关,可作为心血管疾病危险预测因子。     

Assessment of novel risk factors in patients at low risk for cardiovascular events based on Framingham risk stratification

BACKGROUND: Coronary heart disease (CHD) risk assessed by the Framingham risk score does not take into account the various "novel" markers that are of increasing interest. In this paper we examine a low-risk population to determine which novel markers may be of additive value to the Framingham assessment of CHD risk. METHODS: Levels of high-sensitivity C-reactive protein (hs-CRP), soluble vascular cell adhesion molecule (s-VCAM), soluble intercellular adhesion molecule (s-ICAM-1), endothelial selectin (e-selectin), homocysteine and von Willebrand factor (vWF) were measured in 53 apparently healthy subjects recruited from a risk-reduction referral clinic. Carotid intima medial thickness (IMT) and number of plaques were determined by ultrasonography. Brachial ultrasound flow-mediated dilation (FMD) was also measured. Framingham risk scores were calculated and univariate and multivariate analyses of the resulting percent CHD risk over 10 years and novel markers were undertaken. RESULTS: Abnormal carotid IMT and presence of plaques, hs-CRP, homocysteine, FMD and s-ICAM-1 were detected with a high frequency in this low-risk cohort. Average IMT, number of plaques and homocysteine were highly correlated with the calculated percent CHD whereas measures of hs-CRP, s-ICAM-1 and FMD were independent of the percent CHD calculation. CONCLUSIONS: FMD, as a reflection of the functional status of the vasculature, and hs-CRP and s-ICAM-1, as indicators of inflammatory processes, were independent of Framingham risk assessment in patients at low risk for cardiovascular disease.     

High rate of increased carotid intima-media thickness and atherosclerotic plaques in Chinese asymptomatic subjects with central obesity

Both central obesity and increased carotid intima-media thickness (IMT) are markers of atherosclerosis and associated with cardiovascular diseases (CVD). Information of IMT in Chinese subjects with central obesity is limited. This study was performed to assess the rate of atherosclerosis and abnormal IMT in asymptomatic Chinese subjects with central obesity, and to investigate the association between IMT values and CVD risk factors including hypertension, hyperglycaemia and dyslipidaemia. We studied 122 centrally obese adults who had good past health. IMT measurements on carotid arteries were performed and fasting blood taken for plasma glucose and lipid profiles. Abnormal IMT was defined as > 0.9 mm. Atherosclerosis was defined as the presence of one or more visible plague. Of the 122 subjects, the mean (±SD) age was 59.4 ± 5.8 years (median [range]: 59.0 [45–75] years). The median IMT value was 0.70 mm (range: 0.53–1.19 mm) [men vs. women: 0.74 mm vs. 0.66 mm, P-value: < 0.001]. IMT values and the rate of atherosclerosis increased with age and the number of CVD risk factors (P-value for trend: < 0.05). Using binary logistic regression to predict the presence of atherosclerosis with the presence of abnormal IMT, age, gender, and other CVD risk factors as independent variables, age (OR [95% CI] = 1.13 [1.03, 1.23], P = 0.009) and abnormal IMT (OR [95% CI] = 4.05 [1.09, 15.03], P = 0.037) were independently associated with atherosclerosis. In conclusion, among Hong Kong Chinese asymptomatic subjects with central obesity, there was a high rate of CVD risk factors. We found that 19% of these subjects had carotid atherosclerotic plaques and 10% of them had abnormal IMT (>0.9 mm). Carotid IMT study may serve as an appropriate screening tool to diagnose atherosclerosis in the centrally obese middle-aged population.     

Long-term influence of diet and/or omega-3 fatty acids on matrix metalloproteinase-9 and pregnancy-associated plasma protein-A in men at high risk of coronary heart disease

BACKGROUND: Matrix metalloproteinases (MMPs) are important in the atherosclerotic process. The relationship between MMPs and traditional risk factors for cardiovascular disease (CVD) and any influence of lifestyle changes are largely unknown. OBJECTIVES: In a factorial design, we studied the effects of 3 years of dietary counselling and/or n-3 PUFA supplementation (2.4 g/d) on the levels of MMP-9, tissue inhibitor of metalloproteinase (TIMP-1) and pregnancy-associated plasma protein (PAPP-A) in a population of elderly men at high risk of CVD (n = 563, age 70+/-6 years). We further explored the association between these markers and different disease entities, carotid intima media thickness (IMT) and traditional risk factors for CVD. RESULTS: Smokers had significantly higher levels of MMP-9 (p<0.0001), and TIMP-1 levels were lower in subjects with previous AMI (p = 0.021). MMP-9 was significantly correlated with LDL-C and inversely with HDL-C (both p<0.0001). There were no significant correlations between the measured variables and IMT. Significant reductions in MMP-9 and PAPP-A levels after 36 months were found in all study groups, however, with no between-group differences. CONCLUSIONS: The elevated levels of MMP-9 in smokers and the reduced levels of TIMP-1 in patients with previous AMI reflect an importance of MMPs in the development of CVD. Intervention with diet and/or n-3 PUFA supplementation did not influence the levels of MMP-9, TIMP-1 or PAPP-A in the present population.     

Prediction of cerebrovascular and cardiovascular events in patients with subclinical carotid atherosclerosis: the role of C-reactive protein.

BACKGROUND: Several studies have suggested that inflammation and infection may be important for accelerated progression of atherosclerosis, but few data are available on subjects with early stages of atherosclerosis. METHODS AND RESULTS: We included, in a prospective 5-year follow-up study, 150 patients with subclinical carotid atherosclerosis, evaluating at baseline all established traditional cardiovascular risk factors (eg, older age, male sex, obesity, hypertension, diabetes, smoking, family history of coronary artery disease, and dyslipidemia); 2 markers of inflammation, fibrinogen, and high-sensitivity C-reactive protein (CRP); and the seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus. After follow-up, cardiovascular and cerebrovascular events were registered in the 19% of patients, and the increment in CRP levels (in quintiles) was significantly associated with ischemic stroke (P = 0.0253), acute myocardial infarction (P = 0.0055), cardiovascular or cerebrovascular death (P = 0.0145), and the presence of any event (P = 0.0064). Most traditional cardiovascular risk factors (eg, older age, hypertension, diabetes, and dyslipidemia) were significantly associated with the events but only in the unadjusted analysis; in fact, at logistic regression analysis, among all baseline variables, only elevated CRP levels showed a predictive role (odds ratio, 7.0; 95% confidence interval, 2.2-18.4; P = 0.0247). CONCLUSIONS: Our findings suggest that elevated CRP concentrations may significantly influence the occurrence of cerebrovascular and cardiovascular events in patients with baseline subclinical carotid atherosclerosis. Notably, null findings were obtained by viral and bacteria titers, suggesting a greater role of inflammation (and not of infection) in the progression of atherosclerosis in our cohort. However, further studies are needed to evaluate the therapeutic implications in this category of patients.     

Family history of type 2 diabetes is associated with increased carotid artery intimal-medial thickness in Mexican Americans

OBJECTIVE: To evaluate whether the joint risk of diabetes and atherosclerosis tracked within families, we assessed the correlation between a family history of diabetes and intimal-medial thickness (IMT) of the common carotid artery (CCA). RESEARCH DESIGN AND METHODS: Study subjects included 620 nondiabetic individuals from 24 families enrolled in the San Antonio Family Heart Study. The thickness of the far walls of the CCA was measured by B-mode ultrasonography. Statistical analyses included familial correlations to account for the nonindependence of family data. RESULTS: After adjusting for sex, age, and IMT reader effects, the heritability of IMT in this population was 16% (P = 0.009). Using a more comprehensive family history score that accounted for diabetes status of the individual's parents and older siblings, we observed a significant correlation between family history score and increased CCA IMT (0.006 mm increase in CCA IMT for every point increase of diabetes family history score, P = 0.016). This association remained even after further adjustment for BMI, smoking, and fasting insulin and glucose levels. After adjusting for several cardiovascular risk factors, the mean CCA IMT in those with high family history scores for diabetes was still 0.037 mm thicker than those with low family history scores for diabetes (P = 0.040). CONCLUSIONS: These results suggest that the genetic contribution to CCA IMT variability is modest. Also, the small increase in subclinical atherosclerosis observed even among nondiabetic Mexican Americans with a positive family history of diabetes is probably transmitted along with the risk of diabetes through shared etiologic risk factors between diabetes and cardiovascular disease.     

Association between serum testosterone concentration and carotid atherosclerosis in men with type 2 diabetes

OBJECTIVE: There is evidence to suggest that low concentrations of testosterone are associated with an increased risk of cardiovascular disease in men. The aim of this study was to evaluate the relationship between serum testosterone concentration and carotid atherosclerosis as well as major cardiovascular risk factors in men with type 2 diabetes. RESEARCH DESIGN AND METHODS: Serum free and total testosterone concentrations were measured in 253 consecutive men with type 2 diabetes. The relationships between serum testosterone concentration and carotid atherosclerosis, determined by ultrasonographically evaluated intima-media thickness (IMT) and plaque score (PS) in a subgroup of 154 diabetic patients, as well as major cardiovascular risk factors, including age, blood pressure, and lipid concentrations, were evaluated. RESULTS: Inverse correlations were found between free testosterone (F-tes) concentration and IMT (r = -0.206, P = 0.0103) and between F-tes concentration and PS (r = -0.334, P < 0.001). The IMT and PS were significantly greater in patients with lower concentrations of F-tes (<10 pg/ml) than in patients with higher concentrations of F-tes (1.01 +/- 0.29 vs. 0.91 +/- 0.26 mm, P = 0.038; 4.5 +/- 3.8 vs. 2.4 +/- 3.2, P = 0.0003; respectively). An inverse correlation was found between serum F-tes concentration and age (r = -0.420, P < 0.0001). A positive correlation was found between serum F-tes and total cholesterol concentrations (r = 0.145, P = 0.0238). CONCLUSIONS: Serum F-tes concentration is inversely associated with carotid atherosclerosis determined by ultrasonographically evaluated IMT and PS in men with type 2 diabetes.     

Increased carotid intima-media thickness in men born in east Finland: a twin study of the effects of birthplace and migration to Sweden on subclinical atherosclerosis

BACKGROUND: There is a clear east-west difference in coronary heart disease (CHD) mortality and incidence in Finland, people living in east Finland having higher CHD rate. A study of Finnish immigrants to Sweden has suggested that a long stay in Sweden would be associated with reduced CHD risk. AIM: To determine whether structural and functional markers of subclinical atherosclerosis differ between men originating from east and west Finland, and whether migration to Sweden influences subclinical atherosclerosis. METHOD: Carotid intima-media thickness (IMT) and brachial artery flow-mediated dilatation (FMD) with high-resolution ultrasound and a set of cardiovascular risk factors were measured in 76 middle-aged male twin pairs (55 pairs from east and 21 pairs from west Finland) discordant for migration to Sweden. RESULTS: Among men living in Finland, IMT was significantly higher in men originating from east Finland compared to those from west Finland (0.796 +/- 0.212 versus 0.704 +/- 0.123 mm, P = 0.02). A similar east-west difference was observed in men who had migrated to Sweden (0.766 +/- 0.220 versus 0.686 +/- 0.089 mm, P = 0.03). The east-west difference in IMT persisted after adjustment for the major traditional cardiovascular risk factors. No east-west difference was seen in FMD. Smoking, Framingham risk score and physical activity had a greater impact on IMT in men originating from east compared to west Finland. CONCLUSIONS: Men originating from east Finland, irrespective of their current residence, have a greater degree of subclinical atherosclerosis and they may be more susceptible to the impact of conventional cardiovascular risk factors than men originating from west Finland.