高血压前期颈动脉内-中膜厚度及血管内皮舒张功能的变化

目的探索高血压前期外周动脉血管粥样硬化和血管内皮功能的改变。方法检测颈动脉内-中膜厚度（IMT）和肱动脉内皮舒张功能。结果高血压前期组颈动脉分叉、颈总动脉处内-中膜厚度均较正常血压组增厚（P〈0．05）;高血压前期组反应性充血后肱动脉内径变化率（FMD）显著低于正常血压组（P〈0．05）;含服硝酸甘油后肱动脉内径FMD高血压前期组与正常血压组无明显差异（P〉0．05）。结论高血压前期已存在颈动脉内-中膜增厚,血管内皮功能已经受损。     

Low serum bilirubin levels are independently and inversely related to impaired flow-mediated vasodilation and increased carotid intima-media thickness in both men and women

BACKGROUND: Elevated levels of low-density lipoprotein (LDL) cholesterol and its oxidative modification have been described to be involved in the process of atherogenesis. Bilirubin, an antioxidant, prevents oxidative modification of LDL and therefore may protect from atherosclerosis and coronary heart disease (CHD). Impaired brachial artery flow-mediated dilatation (FMD), which means endothelial dysfunction (ED) and carotid intima-media thickness (IMT) are predictors for the development and progression of atherosclerosis. In the present study, FMD and IMT were studied in healthy subjects with lower and higher serum bilirubin concentrations in physiological ranges. METHODS: Ninety-one healthy subjects between 25 and 45 years of age (47 with lower and 44 with higher serum bilirubin concentrations) were included in this study. Carotid IMT and brachial artery flow-mediated dilatation was measured by means of high-resolution vascular ultrasound. FMD was assessed by establishing reactive hyperemia and endothelium-independent dilatation (EID) was determined by using sublingual isosorbide dinitrate. RESULTS: EDD in subjects with lower serum bilirubin concentrations was significantly worse than in those with higher serum bilirubin concentrations (11.6+/-4.4% versus 7.2+/-4.7%, respectively, p<0.0001). EID measurements were not significantly different between the groups (16+/-5.1% versus 16.8+/-7%, respectively). In addition, carotid IMT was significantly greater in subjects with lower serum bilirubin concentrations (0.5+/-0.13 mm versus 0.42+/-0.07 mm, p<0.0001). Furthermore, FMD in women with lower serum bilirubin concentrations was significantly lower than in women with higher serum bilirubin concentrations (11.5+/-4.9% and 17.5+/-4.7%, respectively, p<0.001). Accordingly, men with lower serum bilirubin concentrations had significantly lower FMD as compared to hyperbilirubinemic ones (11.7+/-3.6% versus 16.7+/-4.8%, respectively, p=0.009). Conversely, carotid IMT was significantly greater in both women and men with lower serum bilirubin concentrations compared to the subjects with elevated serum bilirubin concentrations (0.51+/-0.08 versus 0.41+/-0.08, p<0.001; 0.55+/-0.12 versus 0.40+/-0.07, p=0.002, in women and men, respectively). CONCLUSION: The healthy subjects with lower serum bilirubin concentrations show significant ED and increased carotid IMT, which are predictors for atherosclerosis.     

Flow-mediated vasodilatation of the brachial artery and intima-media thickness of carotid artery in never-treated subjects.

AIM: Data on the association between brachial artery flow-mediated dilatation (FMD) and common carotid intima-media thickness (IMT) are contrasting. The present study investigated the relationship between FMD and IMT and carotid atherosclerosis in never treated subjects. METHODS: Seventy-seven subjects were investigated: 46 had no coronary heart disease (CHD) risk factors, 21 had only one, and 10 had more than one risk factor. IMT of the common carotid was measured by ultrasonography and FMD was evaluated according to standardized methods. RESULTS: IMT increased with increasing number of risk factors (0.66+/-0.12, 0.69+/-0.12 and 0.8+/-0.17 mm, respectively, ANOVA P<0.05). FMD decreased with increasing number of risk factors (10.44+/-5.2, 6.52+/-7.11 and 7.35+/-4.42%, respectively, P<0.05). Endothelium-independent vasodilatation was similar in the 3 groups. IMT and FMD did not correlate neither in subjects without risk factors (r=-0.151, P=0.3), nor in those with 1 (r=-0.196, P=0.4) or with 2 or more risk factors (r=-0.387, P=0.2), while in the group as a whole the correlation was borderline significant (r=-0.217, P=0.058). Eleven subjects had carotid atherosclerosis and higher values of IMT, but not reduced FMD. In multiple regression analysis, diabetes and IMT, but not FMD, were associated with carotid atherosclerosis. CONCLUSIONS: The present findings indicate that, in never treated subjects, FMD is not strictly associated with IMT or atherosclerosis of the carotid arteries.     

Carotid Intima-Media Thickness and Brachial Artery Flow-Mediated Dilatation in Patients with and without Metabolic Syndrome

BACKGROUND, Metabolic syndrome has recently emerged as a marker of future cardiovascular risk. However its incremental value for this purpose, over conventional cardiovascular risk factors and diabetes mellitus in particular, is debated. The present study was conducted to determine the extent of subclinical atherosclerosis in patients with metabolic syndrome, and compare it with the same in individuals with cardiovascular risk factors not having metabolic syndrome. METHODS, A total of 156 individuals seeking outpatient cardiac consultation for various indications were included in the study and were divided into four groups - group 1: cardiovascular risk factors present but not metabolic syndrome (n = 60) : group 2 : metabolic syndrome without diabetes mellitus or coronary artery disease (n = 21) ;group 3: metabolic syndrome with diabetes mellitus without coronary artery disease ( n = 27) ;and group 4:patients with documented coronary artery disease (n = 48). Metabolic syndrome was diagnosed on the basis of Adult Treatment Panel III (ATPIII) criteria. All patients underwent assessment of carotid intima-media thickness and brachial artery flow-mediated vasodilatation. RESULTS, Both carotid intima-media thickness and brachial artery flow-mediated vasodilatation were similar in groups 1 and 2 (carotid intima-media thickness: 0.687 -/+ 0.13mm and 0.706 -/+0.23mm, p = 0.963; brachial artery flow-mediated vasodilatation: 11.80 -/+ 5.16% and 12.87 -/+ 7.04%, respectively, p =0.883) , but group 3 patients had significantly higher carotid intima-media thickness (0.774 +/- 0.15mm, p = 0.047) and significantly lower brachial artery flow-mediated vasodilatation (7.37 -/+ 6.12%, p -/+ 0.007) as compared to group 1 patients. There was no significant difference in the two parameters between groups 3 and 4 (carotid intima-media thickness in group 4:0.789 -/+ 0.16mm,p = 0.976 and brachial artery flow-mediated vasodilatation:5.86 -/+ 3.85%, p -/+ 0.709). CONCLUSIONS, In absence of diabetes mellitus, metabolic syndrome was not associated with greater extent of subclinical atherosclerosis compared to individual cardiovascular risk factors. Presence of diabetes mellitus, however, resulted in significant endothelial dysfunction and evidence of subclinical atherosclerosis, similar to that seen in patients with already established coronary artery disease.     

Relationship between carotid artery intima-media thickness and brachial artery flow-mediated dilation in middle-aged healthy men

OBJECTIVES: We aimed to determine the relationship between carotid intima-media thickness (IMT) and brachial artery flow-mediated dilation (FMD) in healthy middle-age men. BACKGROUND: Carotid IMT and brachial artery FMD are frequently used as surrogate measures of subclinical atherosclerosis. Whereas carotid IMT identifies early structural abnormalities, brachial artery FMD, considered a bioassay of endothelial function, measures functional vascular integrity. The relationship between carotid IMT and brachial artery FMD has not been well studied. METHODS: We measured traditional risk factors, carotid IMT, and brachial artery FMD in 1,578 middle-aged men without known cardiovascular disease and analyzed the relationship between carotid IMT and brachial FMD. RESULTS: Carotid IMT correlated with age, systolic blood pressure, body mass index, fasting glucose, total and low-density lipoprotein (LDL) cholesterol, and with the overall Framingham risk score (p < 0.001 for all), whereas impaired brachial artery FMD correlated with systolic and diastolic blood pressure (p < 0.01). No relationship was observed between carotid IMT and brachial artery FMD for the entire cohort (r = -0.006, p = 0.82) and in subgroups defined by traditional risk factors or by quintiles of carotid IMT and brachial FMD. CONCLUSIONS: In middle-aged healthy men, there is no significant correlation between carotid IMT and brachial artery FMD. This finding suggests that these are unique, independent surrogates that measure different aspects and stages of early atherosclerosis. Further studies are needed to define their role in clinical research and in cardiovascular risk assessment.     

高血压患者颈动脉内膜中层厚度及血管内皮依赖性舒张功能的改变

目的：观察老年高血压对颈动脉内膜中层厚度（IMT）及血管内皮依赖性舒张功能（EDD）的影响及其临床意义。方法：分别选择对照组40例。高血压组60例。使用E1立EUB-6500彩色多普勒超声诊断仪，探头频率10MHz，测量颈动脉IMT，EDD。结果：高血压组动脉IMT明显增厚，平均（0.912±0．263）mm。血管内皮依赖性舒张功能EDD明显下降，与对照组间均有显著性差异（P〈0.01）。结论：颈动脉内膜中层厚度增厚及血管内皮依赖性舒张功能障碍是老年高血压患者动脉粥样硬化的早期表现。     

Intima-media complex of both the brachial artery and the common carotid artery are associated with left ventricular hypertrophy in patients with previous myocardial infarction

OBJECTIVES: Prospective trials have established intima-media thickness (IMT) of the carotid artery, flow-mediated dilation (FMD) of the brachial artery and cardiac left ventricular hypertrophy (LVH) as predictors of cardiovascular events. The aim of this study was to examine the relationship between intima-media complex of the brachial artery to FMD, intima-media complex of the common carotid artery and cardiac hypertrophy in patients with coronary heart disease. METHODS AND PROCEDURES: Cross-sectional design. Procedures were undertaken within the Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden. A total of 123 patients with a previous acute myocardial infarction (MI) were investigated. Calculated intima-media area (cIMa) of the brachial and common carotid arteries and FMD of the brachial artery and left ventricular dimensions were examined. RESULTS: The brachial cIMa was significantly associated with age, p-triglycerides, common carotid cIMa, ejection fraction, septum thickness, posterior wall thickness and left ventricular mass index (P < 0.05). Brachial cIMa also tended to be associated with systolic blood pressure (P = 0.056). Common carotid cIMa was significantly associated with age, systolic blood pressure, brachial cIMa, FMD and septum thickness (P < 0.05). FMD was significantly associated with age and carotid cIMa (P < 0.05). CONCLUSION: Both cIMa of the common carotid artery and the cIMa of the brachial artery were independently and significantly associated with ventricular septum thickness of the heart in patients with previous myocardial infarction.     

Endothelial-dependent vasodilation is impaired in children with sickle cell disease

Impairment of endothelial-dependent vasodilation has been demonstrated in adults with sickle cell anemia (SCA). We enrolled 21 SCA children, mean age 10.4+/-3.3 yrs, and 23 Afro-Caribbean controls. We examined flow-mediated (FMD) and nitroglycerine-mediated (GTNMD) dilation of the brachial artery, using echotracking techniques, and measured intima-media thickness (IMT) and mechanical properties of the common carotid artery. FMD was significantly decreased in SCA children vs controls (5.6+/-0.2 vs 8.0+/-0.2%, p=0.008), while IMT, stiffness of the common carotid artery, and GTNMD were comparable. In conclusion, endothelial dysfunction is present as early as childhood in SCA patients.     

The relationship between endothelial function in the brachial artery and intima plus media thickening of the coronary arteries in patients with chest pain syndrome

Endothelial dysfunction precedes the development of clinical atherosclerosis. A decrease in endothelium-derived nitric oxide activity shows impaired vasodilator function and causes arterial intimal hyperplasia or thickening. Others and we have reported the close relation of endothelial function in brachial artery and coronary artery. To compare the flow-mediated endothelium-dependent vasodilation (FMD) in brachial artery and the intima+media area in coronary artery, we measured brachial artery vasodilator response following transient occlusion with high resolution ultrasound transducer and intima+media area in coronary arteries with intravascular ultrasound in 25 patients with normal coronary angiograms (age 61.6+/-8.7 years old, men 14 and women 11). FMD was measured at least 7 days after the cessation of all vasodilators. The mean FMD of 25 patients was 3.83+/-2.38%, the mean intima+media area in coronary arteries of 25 patients was 39.9+/-15.5% of total vessel wall. FMD has a close negative relation with the largest percent intima+media area (r=-0.77, p<0.01). Especially, the patients whose FMD was less than 3.83% had larger percent intima+media area than those whose FMD was 3.83% or more (48.7+/-10.7% versus 30.3+/-14.2%, p<0.01). There is an intima+media thickening even in the patients who had normal coronary angiograms, and that the percent intima+media area correlated with FMD. The measurement of FMD is useful for screening the coronary artery intima+media thickening noninvasively. The pathogenesis of acute coronary syndrome has been reported to be the plaque rupture even in the patients with normal coronary angiograms. Thus, we must pay much attention in the patients with impaired FMD even in the normal coronary angiograms.     

Baroreflex sensitivity normalization after cardiac resynchronization therapy

To evaluate the relation between peripheral vascular endothelial function and coronary flow reserve (CFR), we assessed flow mediated dilation (FMD) of brachial artery and the intima-media thickness (IMT) of the carotid artery in 32 subjects (mean age 58+/-9 years, M/F=9:23 ) with chest pain and normal coronary angiogram. The subjects were divided into 2 groups according to CFR >or=2.1 or <2.1 measured with transthoracic echocardiography in distal left anterior descending coronary artery. We found % FMD was decreased in the group with CFR <2.1 than those of CFR >or=2.1 and CFR was correlated with peripheral FMD. However, IMT was not different between two groups. These results suggest that microvascular dysfunction is primarily related to endothelial dysfunction rather than advanced atherosclerosis and because it is a generalized process that involves the whole arteries, the measurement of brachial FMD can be a useful diagnostic tool to evaluate microvascular dysfunction in patients with chest pain and normal coronary angiogram.     

颈动脉内-中膜厚度和肱动脉血流介导的舒张功能与冠心病的关系

目的探讨颈动脉粥样硬化斑块发生率、颈动脉内-中膜厚度(IMTc)及肱动脉血流介导的舒张功能(FMD)与冠心病的关系。方法应用高分辨率超声检测112例患者的颈动脉粥样硬化斑块、IMTc,同时检测肱动脉FMD,据造影结果将患者分为冠心病组79例与对照组33例,对冠状动脉病变程度进行Gensi-ni评分。结果冠心病组与对照组比较,颈动脉粥样硬化斑块发生率、FMD及IMTc差异具有统计学意义(P<0.05)。直线相关分析表明,FMD与冠状动脉病变Gensini积分呈负相关,(r=-0.362,P<0.01),IMTc与冠状动脉病变Gensini积分呈正相关(r=0.296,P<0.01)。结论联合应用无创高分辨率超声检测颈动脉粥样硬化斑块、IMTc及FMD可间接反映冠心病发生的可能性以及预测冠状动脉病变程度,而且方法简单、无创,为早期诊断冠心病提供了一种安全可靠的手段。     

Usefulness of flow-mediated dilation of the brachial artery and/or the intima-media thickness of the carotid artery in predicting coronary narrowing in patients suspected of having coronary artery disease.

It has been reported that flow-mediated dilation (FMD) of the brachial artery and the carotid intima-media thickness (IMT), markers of atherosclerosis, are altered in patients with coronary artery disease (CAD), but it is still not known if the presence of CAD can be detected using these markers. We examined whether the presence of CAD can be detected by FMD of the brachial artery and/or IMT. Eighty-one patients who underwent coronary angiography for the first time were enrolled. In each patient, brachial artery diameter responses to FMD and the administration of nitroglycerin spray, and carotid IMT were measured using high-resolution ultrasound (10 MHz) before coronary angiography. CAD was defined as >50% stenosis of a major coronary artery. Fifty-six patients had CAD. FMD was lower and IMT was greater in patients with CAD (FMD, 2.9 +/- 0.2% vs 9.4 +/- 0.5%; IMT, 1.09 +/- 0.05 vs 0.79 +/- 0.04 mm, both p <0.0001). Nitroglycerin-induced dilation did not differ in the 2 groups. Multivariate analysis showed that FMD was the only predictor of the presence of CAD (p = 0.0026). Receiver-operating characteristic analysis demonstrated that a cutoff value for FMD for detecting the presence of CAD was 6%, with a sensitivity of 0.93 (52 of 56) and a specificity of 0.88 (22 of 25). These findings suggest that FMD but not IMT may be used to detect the presence of CAD in patients with suspected CAD.     

Population-based twin study of the effects of migration from Finland to Sweden on endothelial function and intima-media thickness

Finnish men have higher coronary heart disease (CHD) mortality than Swedish men do. To assess the impact of migration to a country with lower CHD mortality on subclinical atherosclerosis, we measured early functional and structural atherosclerotic vascular changes in twins discordant for migration from Finland to Sweden. Conventional CHD risk factors, flow-mediated dilatation (FMD) of the brachial artery, carotid intima-media thickness, and carotid artery compliance were measured in 74 male twin pairs (20 monozygous, 54 dizygous), aged 42 to 69 years, in which co-one twin had migrated more than 20 years ago permanently to Sweden. There were no significant differences in CHD risk factors except for diastolic blood pressure and body fat percentage, which were higher in Sweden. In all subjects, mean FMD was non-significantly higher in Sweden (5.7+/-4.3% vs 4.9+/-4.2%, P=0.22), but in monozygous twins the difference in FMD was highly significant (7.2+/-4.4 vs 3.7+/-2.9%, P=0.003). There was no significant difference in intima-media thickness or carotid artery compliance between Sweden and Finland. We conclude that in Finnish monozygous twins the endothelial function is better among the twins that have migrated to a country with lower CHD prevalence.     

Type IIb von Willebrand disease: role of qualitative defects in atherosclerosis and endothelial dysfunction.

OBJECTIVE: To verify whether a hereditary bleeding tendency, such as von Willebrand disease (vWD) type IIB, protects against the onset of atherosclerosis. PARTICIPANTS AND METHODS: Twenty-four patients with vWD type IIB and 24 healthy controls, matched for common atherosclerotic risk factors. All patients were evaluated by color Doppler ultrasound of the common carotid, carotid bifurcation, common femoral artery, brachial artery, and abdominal aorta, investigating intima-media thickness (IMT) and presence of plaques in each arterial district. Flow mediated dilation (FMD) of the brachial artery was used to test endothelial function. RESULTS: vWD type IIB patients presented no significant difference in IMT in any arterial district. FMD showed no differences between the 2 groups. CONCLUSIONS: The quantitative clotting defect characteristic of vWD type IIB does not seem to protect against atherosclerosis.     

冠心病患者冠状动脉病变血管数与高敏C反应蛋白、颈动脉斑块分级和内皮功能的相关性

目的探讨冠心病患者冠状动脉病变血管数与高敏C反应蛋白(hsCRP)、内皮依赖血管舒张功能、颈动脉内膜中层厚度(IMT)和斑块积分的相关性。方法采用高分辨率血管超声法检测76例冠心病患者与30例非冠心病对照组肱动脉血流介导的内皮依赖性血管舒张功能(FMD)、颈动脉IMT及斑块积分;并检测患者血液中hsCRP水平,对冠心病患者进行冠状动脉造影,根据冠状动脉病变血管数将冠心病患者分为3组:单支病变组、双支病变组及三支病变组。结果冠心病患者的血浆hsCRP显著高于对照组,FMD在冠心病各亚组中明显降低,与对照组比较差异有统计学意义(均为P<0.05);IMT在冠心病组中明显增厚,与对照组比较差异有统计学意义(均为P<0.05);颈动脉斑块积分在冠心病各亚组间比较差异有统计学意义(P<0.05)。冠心病患者冠状动脉病变血管数与血浆hsCRP及斑块积分呈正相关,与FMD呈负相关。结论血浆hsCRP、FMD及颈动脉斑块积分的检测与冠心病患者冠状动脉病变支数相关。     

Flow-dependent vasomotor dysfunction of the popliteal artery related to common carotid artery intima-media thickness

This study was designed to assess a possible correlation between flow-mediated endothelium-dependent vasodilation in the popliteal artery and the intima-media thickness of the common carotid artery. Impaired vasodilation is one of early markers of atherosclerosis that has not been studied on the popliteal artery. An increase in intima-media thickness of the common carotid artery is also considered to be an indication of early stages of atherosclerosis. With use of ultrasound, the diameter of the popliteal artery was measured at rest and during reactive hyperemia after 5-minute arterial occlusion. Subsequently, the intima-media thickness was measured in left common carotid arteries in 27 patients with hyperlipidemia, in 10 patients with confirmed coronary artery disease, and in 20 healthy individuals. In healthy individuals, popliteal artery diameter increased by mean of 6.6 +/- 3.5% (p < 0.01) in relation to hyperemia. In patients with hyperlipidemia before therapy and in patients with coronary disease, no increase in diameter occurred (mean, 0.44% and -1.6%, respectively). The difference between healthy individuals and patients was statistically significant at p < 0.001. The popliteal artery seems to respond similarly to the brachial artery. When comparing the change in popliteal artery diameter and intima-media thickness of common carotid arteries, a strong negative correlation (r = -0.5713, p < 0.001) was observed in all subjects.     

Increased arterial intima-media thickness and in vivo LDL oxidation in young men with borderline hypertension

We used borderline hypertension as a model for prehypertension to examine the early influences of elevated blood pressure on subclinical atherosclerosis, lipoprotein oxidation, and cardiac adaptation. Healthy men (age 37+/-4 years) were classified prospectively into 2 groups on the basis of having either borderline hypertension (systolic 130 to 140 mm Hg or diastolic 85 to 89 mm Hg, n=16) or normal (<130/85 mm Hg, n=22) blood pressure values during the previous 2 years. The groups were matched for age, body size, and serum cholesterol levels. High-resolution ultrasound was used to measure intima-media thickness (IMT) of the carotid and brachial arteries, cardiac dimensions, and brachial artery endothelial function. Baseline low-density lipoprotein (LDL)-diene conjugation was measured as an estimate of in vivo LDL oxidation (ox-LDL). Compared with normotensive controls, men with borderline hypertension had higher IMT of the carotid artery (0.58+/-0.06 versus 0.75+/-0.07 mm, P<0.001) and IMT of the brachial artery (0.45+/-0.05 versus 0.57+/-0.07 mm, P<0.001), and increased levels of ox-LDL (29+/-9 versus 47+/-17 mol/L, P<0.001), but similar endothelial function. Left ventricular mass was similar in both groups, but there were significant differences in left ventricular geometry. In multivariate analyses, the predictors of carotid IMT were 24-hour systolic blood pressure (P<0.001) and ox-LDL (P=0.10). The current study demonstrates evidence of increased subclinical atherosclerosis and ox-LDL in borderline hypertension. These results are consistent with the idea that enhanced ox-LDL may be one of the pathophysiological events related to development of atherosclerosis in men with borderline elevated blood pressure.     

颈动脉粥样硬化和肱动脉内皮功能与冠状动脉病变的关系

目的 探讨颈动脉不同部位内膜中膜厚度及斑块积分,反应性充血后肱动脉血管内径变化与冠状动脉粥样硬化程度的关系,从而为临床筛查冠状动脉粥样硬化积累新的临床资料与经验.方法 入选对象31例,依冠状动脉积分分为高、中、低三组,对每组对象行超声检测颈动脉不同部位内膜中膜厚度和肱动脉血流介导的血管舒张功能.结果 颈动脉各部位内膜中膜厚度与冠状动脉粥样硬化病变程度呈正相关,且分叉处的内膜中膜厚度与冠心病有更强的相关性(r=0.679,P<0.01);颈动脉粥样斑块积分与冠状动脉粥样硬化病变程度呈正相关,颈动脉分叉处最易形成斑块(P<0.05);肱动脉血管内皮舒张功能与冠状动脉粥样硬化病变程度呈负相关(r=-0.646,P<0.01).硝酸甘油诱导的非内皮依赖性血管舒张功能在三组间虽呈现逐渐减弱的趋势,但未达到统计学差异(P>0.05).结论 颈动脉内膜中膜厚度及肱动脉血流介导的血管舒张功能测定可较好地反映冠状动脉硬化程度.     

Arterial structure and function in young adults with the metabolic syndrome: the Cardiovascular Risk in Young Finns Study.

AIMS: To study the relations between the metabolic syndrome (MS) and subclinical atherosclerosis in young adults. METHODS AND RESULTS: International Diabetes Federation (msIDF), National Institute of Health Adult Treatment Panel III (msNCEP), and European Group for the Study of Insulin Resistance (msEGIR) definitions of MS were related to carotid artery intima-media thickness (cIMT), brachial flow-mediated dilatation (FMD), and carotid artery compliance (CAC) in 2163 Finnish adults (aged 32 +/- 5years). All definitions associated with increased cIMT and decreased CAC in both sexes. The cIMT values (mean+/-SD) were 0.576 +/- 0.088 mm in subjects without the syndrome, 0.615 +/- 0.102 mm in msIDF, 0.617 +/- 0.104 mm in msNCEP, and 0.607 +/- 0.097 mm in msEGIR (P < 0.0001). Corresponding CAC values were 2.26 +/- 0.72, 1.76 +/- 0.66, 1.73 +/- 0.66, 1.72 +/- 0.66%/10 mmHg (P < 0.001). Impaired brachial FMD was not related to MS but it modified the relations between MS and cIMT: MS correlated with increased cIMT in subjects with an impaired FMD response (P = 0.003) but not in subjects with an enhanced FMD response (P = 0.75). CONCLUSION: All current definitions of MS identify a population of young adults with evidence of increased subclinical atherosclerosis. Impaired brachial endothelial response is not a hallmark of MS in young adults, but the status of endothelial function modifies the association between metabolic risk factors and atherosclerosis.     

Endothelial nitric oxide synthase and methylenetetrahydrofolate reductase gene polymorphisms are associated with endothelial dysfunction in young, healthy men

BACKGROUND: The guanine to thymine polymorphism at position 894 of the eNOS gene (resulting in a change from glutamate to aspartate [Asp] at codon 298 [Asp298]) and the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism (C677T) have been reported to be associated with atherosclerosis and cardiovascular disease. Endothelial dysfunction is considered to be the earliest stage of atherosclerosis. OBJECTIVES: To examine whether common eNOS and MTHFR gene polymorphisms are associated with endothelial dysfunction in young, healthy men without overt cardiovascular disease. SUBJECTS AND METHODS: Flow-mediated, endothelium-dependent vasodilation (FMD) and glyceryl trinitrate-induced, endothelium-independent vasodilation (GTN) were measured using high-resolution ultrasound of the brachial artery in 53 young, healthy men assigned to eNOS and MTHFR genotypes. RESULTS: Subjects with the eNOS Asp298 allele (n=15) showed significantly reduced FMD:GTN compared with those without this allele (n=38) (0.23+/-0.13 [mean +/- SD] versus 0.35+/-0.14, P=0.0072), whereas there was no significant difference in GTN between these two groups. Although subjects with the MTHFR T677 allele did not show significantly reduced levels of FMD:GTN, subjects with the eNOS Asp298 allele and who were carriers of the MTHFR T677 allele demonstrated markedly reduced levels of FMD:GTN compared with noncarriers (0.14+/-0.05 versus 0.28+/-0.13, P=0.04). CONCLUSIONS: The data suggest that even in young men, the eNOS Asp298 allele may be involved in endothelial dysfunction before any overt vascular disease has occurred. Furthermore, a combination of the eNOS Asp298 and MTHFR T677 alleles may exaggerate endothelial dysfunction and may contribute to a comparatively earlier development of atherosclerosis.