Increased intima-media thickness in carriers of the ldl-receptor defective gene versus noncarriers with newly detected asymptomatic severe hypercholesterolemia

Background: The data on the examination of early vascular alterations in carriers of molecular defects of the low‐density lipoprotein‐receptor (LDL‐R) in comparison to noncarriers with severe hypercholesterolemia are controversial. Aims: To examine the difference between patients with severe hypercholesterolemia, who are carriers and noncarriers of LDL‐R defective gene, with respect to their functional (flow‐mediated vasodilation) and structural (intima‐media thickness of carotid artery) characteristics of arterial wall. A total of 250 hypercholesterolemic patients were enrolled. Biochemistry parameters were examined by routine methods. The molecular biological analysis included‐R3500Q‐mutation in the Apolipoprotein‐B (Apo‐B) gene, LDL‐R gene mutation and polymorphism (and the promoter region), as large rearrangements. Determination of flow‐mediated vasodilation and intima‐media thickness of common carotid artery was performed with Hewlett Packard Sonos 5500, using automated computer software MedicaSoft. IMT.lab. Results: There was no significant difference between the groups with respect to total cholesterol, LDL, HDL, Apo‐B, Apolipoprotein A₁ (Apo‐A₁), asymmetric dimethylarginine (ADMA), homocysteine, and cellular adhesion molecules. The Apo‐B/Apo A₁ index differed significantly (t = 11.23, P < 0.001) between the two groups and this difference was found even after adjustment for age and gender. There was no significant difference with respect to the endothelial dependent and independent vasodilatation between the examined groups (P > 0.05). We were founded a significantly higher carotid IMT in the carriers versus noncarriers. This significant difference was confirmed after adjustment for age and gender. Statistically significant correlations we were founded between IMT mean and age (log) (r_xy= 0.45; P < 0.01), cholesterol × years score (log) (r_xy= 0.53; P < 0.01), Apo–B/A₁ (log) (r_xy= 0.66; P < 0.001) in the group of the carriers. Backward selection process selected Apo‐B/A₁ as the most important statistically significant factor related to IMT mean of common carotid artery (F = 105.22; P = 0.001; R²= 0.72). Conclusion: Our data demonstrate that carriers of the LDL‐R defective gene have a higher carotid IMT and Apo B/Apo A₁ index than noncarriers, whereas no difference between the groups was found with respect to the level of lipid parameters, ADMA, total homocysteine, cell adhesion molecules and %FMD. Apo‐B/A₁ is a predictor of IMT mean in the group of the carriers of the LDL‐receptor gene. (Echocardiography 2011;28:223‐234)     

Association of carotid hemodynamics with risk of coronary heart disease in a Taiwanese population with essential hypertension

BACKGROUND: The resistive index (RI) of the carotid artery is a hemodynamic parameter that depends on the degree of vascular resistance in hypertensive patients. The pulsatility index (PI) of the carotid artery was shown to be associated with microangiopathy in diabetic patients. In contrast to carotid intima-media thickness (IMT), no study has yet applied the carotid RI and PI to estimate coronary heart disease (CHD) risk. METHODS: Framingham risk scores (FRS) were determined for 62 patients (32 women; mean age 65 years (range 35-83)) with essential hypertension. Duplex sonography of the common carotid artery (CCA) was performed, with determination of RI, PI, and IMT. RESULTS: The mean FRS of all patients was 14.3% (range 1-30%), the mean IMT value of CCA was 0.89 +/- 0.23 mm, the mean RI was 0.71 +/- 0.07, and the mean PI was 1.46 +/- 0.39. FRS was found to have highly significant correlations with RI and PI (r = 0.47, P < 0.001 and r = 0.45, P < 0.001, respectively). The correlation between FRS and IMT was also significant (r = 0.41, P = 0.001). Multiple stepwise regression analysis showed that RI was an independent determinant of the risk of CHD. CONCLUSIONS: Although RI indirectly reflected the atherosclerotic process, the correlation between RI and CHD risk was comparable to the well-known correlation between cardiovascular event and carotid IMT. Hence, carotid RI can be used as a tool for risk stratification in Taiwanese patients with essential hypertension.     

Low insulin sensitivity measured by both quantitative insulin sensitivity check index and homeostasis model assessment method as a risk factor of increased intima-media thickness of the carotid artery

The present study evaluated the association of ultrasonographic manifestations of carotid atherosclerosis with glucose status, various components of the insulin resistance syndrome, and insulin sensitivity measured by a novel quantitative insulin sensitivity check index (QUICKI = 1/[log(I0) + log (G0)]). Carotid ultrasonographic measurements were performed on 54 diabetic subjects, 97 subjects with impaired glucose tolerance and 57 normoglycemic subjects. QUICKI and insulin resistance measured by a HOMA (homeostasis model assessment) method had a high negative correlation (r = -0.995, P < 0.001). QUICKI was lower in diabetic subjects (0.319 +/- 0.022) than in subjects with impaired glucose tolerance (0.334 +/- 0.027) or normoglycemia (0.335 +/- 0.022, P = 0.002). There was an increasing trend in the mean and maximal intima-media thickness (IMT) of the common carotid artery (CCA) with worsening of glucose status. The maximal IMT of the CCA correlated inversely with QUICKI (r = -0.158, P = 0.027). The prevalence of severe CCA atherosclerosis (maximal IMT of the CCA > or = 1.2 mm) was 41% in men and 16% in women (P < 0.001). It was also associated with a long (> or =26 yr) smoking history. The prevalence of severe CCA atherosclerosis was 11% in the highest QUICKI tertile, 36% in the middle tertile, and 33% in the lowest tertile (P = 0.002). Systolic blood pressure was higher and high-density lipoprotein cholesterol lower in subjects with severe CCA atherosclerosis, compared with those without it. In multiple regression analysis, the adjusted odds ratio for severe CCA atherosclerosis was 5.7 (95% confidence interval, 2.2-15.1) in subjects in the two lowest tertiles of QUICKI, compared with those in the highest tertile.     

慢性肾衰竭患者同型半胱氨酸血症与动脉粥样硬化的关系

目的　研究慢性肾功能衰竭 (CRF)患者血浆同型半胱氨酸 (Hcy)水平与动脉粥样硬化及动脉舒张功能障碍的关系。方法　选择CRF患者 197例和健康对照 5 3例 ,采用荧光偏振免疫分析法测定血浆总同型半胱氨酸 (tHcy)水平 ,用高分辨超声技术检测颈总动脉内膜 中层厚度 (IMT)、粥样硬化斑块以及反应性充血后和含服硝酸甘油后肱动脉内径的变化率。结果　CRF患者高同型半胱氨酸血症发生率为 84 4 % ,其血浆tHcy水平 [(2 3 5 6± 11 91) μmol/L]明显高于正常对照组 [(7 97±2 6 5 ) μmol/L](P <0 0 1)。CRF患者平均IMT值和颈动脉粥样斑块检出率均明显高于年龄匹配的正常对照组 ,肱动脉反应性充血后内径增加率 (Dh)为 (4 0 5± 3 81) % ,含服硝酸甘油后内径增加率 (Dn)为 (4 94± 4 2 8) % ,均分别明显低于正常对照组Dh的 (8 81± 6 15 ) %和Dn 的 (11 72± 7 6 4 ) % (P <0 0 1)。按动脉粥样硬化严重程度分级 ,病变越重者血浆tHcy水平越高。多因素逐步回归分析显示 ,影响颈总动脉IMT的因素按影响程度依次为血浆tHcy、透析时间和年龄 (RR =0 4 84 ,P <0 0 0 1) ;影响Dh 的因素为血浆tHcy水平、年龄、透析时间和血清总胆固醇水平 (RR =0 2 6 3,P <0 0 0 1) ;影响Dn 的因素为年龄和血浆tHcy水平 (RR =0 2     

Association between asymmetric dimethylarginine and indices of vascular function in patients with essential hypertension

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is associated with endothelial dysfunction. The aim of the present study was to investigate the relationship between ADMA, indices of arterial stiffness, endothelial function and carotid artery intima-media thickness (IMT) in hypertension patients. Eighty middle-aged (47 ± 10 years) untreated patients with mild to moderate essential hypertension underwent routine physical examination, pulse wave analysis (PWA), measurement of aortic pulse wave velocity (PWV) and IMT. In PWA, administration of salbutamol and nitroglycerine was used to assess endothelium-dependent (EDV) and endothelium-independent vasodilation, respectively. In univariate analysis, ADMA was correlated with EDV (r = -0.26; p = 0.02) and IMT (r = 0.32; p = 0.007). In multiple regression analysis, ADMA was independently associated with the female gender, EDV, IMT and total cholesterol (R(2) = 0.30; p < 0.001). No correlation was detected between ADMA and augmentation index, central/brachial blood pressure or aortic PWV. In hypertension patients, ADMA is independently correlated with IMT and EDV. Thus, ADMA is a marker of endothelial dysfunction and intima-media thickening in patients with hypertension.     

Correlations between plasma homocysteine and folate concentrations and carotid atherosclerosis in high-risk individuals: baseline data from the Homocysteine and Atherosclerosis Reduction Trial (HART)

Homocysteine has been proposed as a risk factor for atherosclerosis. The association between plasma total homocysteine (tHcy) concentration and carotid atherosclerosis has not been thoroughly studied in high-risk populations with vascular disease. For this study, carotid atherosclerosis was assessed by measurements of carotid intima-media thickness (IMT) and plaque calcification in 923 patients with vascular disease or diabetes. Associations with tHcy and plasma folate concentrations were examined. The mean and single maximum carotid IMT were 1.27 +/- 0.34 mm and 2.41 +/- 0.83 mm, respectively. The mean segment plaque calcification score was 27.8%. tHcy correlated with mean (r = 0.13; p < 0.001) and single maximum (r = 0.12; p < 0.001) carotid IMT. There was a progressive increase in mean and single maximum carotid IMT across quartiles of tHcy (p < 0.0001 for trend). These associations were no longer significant after adjusting for other CV risk factors. A trend towards an inverse association between plasma folate and mean max carotid IMT was found in both univariate and multivariable analyses. However, the plaque calcification score increased across quartiles of tHcy (p < 0.01) and decreased across quartiles of plasma folate concentrations (p < 0.05) after multiple adjustments. In conclusion, in high-risk individuals, tHcy and low folate concentrations were only weakly associated with carotid IMT. In contrast, we found an independent association with the plaque calcification score, a measure of more advanced atherosclerosis. The effect of tHcy lowering on carotid atherosclerosis and stroke prevention warrants further investigation.     

Acute effects of haemodialysis on biochemical modulators of endothelial function

OBJECTIVES: To assess the acute effects of haemodialysis (HD) on biochemical factors modulating endothelial function. SETTING: Academic medical centre. SUBJECTS: Forty patients (age 63.5 +/- 2.2 years, mean +/- SEM) undergoing HD. INTERVENTIONS: Folic acid (F), homocysteine (tHcy), asymmetric dimethylarginine (ADMA), high-sensitivity C-reactive protein (CRP) and malondialdehyde (MDA) were measured pre-HD, 1 h after commencing HD and within the last hour of HD (end-HD). Endothelium-dependent and -independent vasodilatation were measured by applanation tonometry (changes in augmentation index, AIx, postinhaled salbutamol and postsublingual nitroglycerin) in conjunction with biochemical measurements. RESULTS: Marked reductions in serum F (616 +/- 73 vs. 273 +/- 30 nmol L(-1), P < 0.001), tHcy (16.3 +/- 0.7 vs. 11.2 +/- 0.5 micromol L(-1), P < 0.001) and ADMA (0.64 +/- 0.02 vs. 0.47 +/- 0.02 micromol L(-1), P < 0.001) occurred end-HD, whereas CRP and MDA levels did not significantly change. There was no significant change in endothelium-dependent vasodilatation, whereas endothelium-independent vasodilatation improved end-HD (-23.1 +/- 1.9 vs. -17.3 +/- 1.3%, P = 0.018). Regression analysis showed that both higher ADMA (P = 0.029) and lower F levels (P = 0.040) end-HD were determinants of reduced endothelium-dependent vasodilatation end-HD (R(2) = 0.23). CONCLUSIONS: HD is associated with significant reductions in F, tHcy and ADMA serum concentrations. The lack of significant effects of HD on endothelium-dependent vasodilatation could be secondary to the concomitant loss of factors either enhancing (F) or impairing (ADMA) endothelial function.     

Effects of combined supplementation with B vitamins and antioxidants on plasma levels of asymmetric dimethylarginine (ADMA) in subjects with elevated risk for cardiovascular disease

Elevated plasma asymmetric dimethylarginine (ADMA) concentrations have been suggested as a potential risk factor for cardiovascular disease (CVD). Studies indicate a linkage between hyperhomocysteinemia, oxidative stress and ADMA metabolism. We tested the hypothesis that combined supplementation of B vitamins and antioxidants reduces ADMA concentrations in subjects with at least two CVD risk factors. A total of 123 men and women (58+/-8.1 years) were randomly assigned to take either a preparation including B vitamins and antioxidants (verum) or placebo for 6 months in a double-blind design. Blood concentrations of ADMA, symmetric dimethylarginine (SDMA), L-arginine, B vitamins, total homocysteine (tHcy), alpha-tocopherol, antioxidant capacity (TEAC), and oxLDL were measured pre- and post-intervention. Treatment with verum significantly decreased tHcy (-2.14 micromol/L; P<0.001) and significantly increased TEAC values (+39.3 microM; P<0.022), but no effect on ADMA was observed. OxLDL was significantly reduced in verum (-7.3 U/L; P=0.001) and placebo (-9.2U/L; P<0.001). At baseline, significant correlations were found only between ADMA and SDMA (r=0.281; P=0.002), L-arginine/ADMA and SDMA (r=-0.294; P<0.001), L-arginine/ADMA and oxLDL (r=-0.281; P=0.016), and L-arginine/ADMA and age (r=-0.231; P=0.010). Our results indicate that combined supplementation of B vitamins and antioxidants is not an adequate strategy to reduce ADMA plasma levels in subjects with elevated CVD risk.     

老年高血压患者血压昼夜节律与颈动脉粥样硬化的相关性研究

目的探讨老年高血压患者血压昼夜节律与颈动脉粥样硬化的相关性。方法2003￣2004年来我院老年高血压患者共72例(男68例女4例),根据动态血压监测(ABPM)结果分为正常昼夜节律组,即杓型组(n=37,男35例女2例)和异常昼夜节律组,即非杓型组(n=35,男33例女2例)。对所有患者均行颈动脉超声检查,测定右侧颈总动脉(RCCA)、颈内动脉(RICA)内膜中层厚度(IMT)、管腔内径(D),并计算各自的IMT/D值,测定右侧颈动脉分叉处(RBIF)的IMT,观察并记录双侧颈动脉系统斑块的大小、数量。结果(1)两组年龄(Age)、体重指数(BMI)、总胆固醇(TC)、甘油三酯(TG)、全天平均收缩压(24hMSP)、全天平均舒张压(24hMDP)比较均无显著性差异(P>0.05)。(2)两组的RCCA及RICA的IMT、D、IMT/D比较均无显著性差异(P>0.05)。而右颈动脉分叉处IMT,非杓型组明显高于杓型组(P<0.001)。(3)两组总斑块检出率无显著差异,但多发性斑块检出率非杓型组显著高于杓型组(P<0.05)。结论老年高血压患者血压昼夜节律与颈动脉粥样硬化明显相关,异常的血压昼夜节律提示可能存在更严重的靶器官损害。     

The correlation of common carotid arterial diameter with atherosclerosis and diabetic retinopathy in patients with type 2 diabetes mellitus

The clinical significance of the diameter of the common carotid artery (CCA) measured ultrasonographically in diabetic practice has not been sufficiently established. The objective of this study was to investigate the relationship of the ultrasonic CCA diameter with atherosclerotic measures and diabetic retinopathy as a microvascular complication in patients with type 2 diabetes mellitus (T2DM). This hospital-based cross-sectional study included 102 patients with T2DM (men: 65%, mean age: 57 years) who had no apparent carotid arterial stenosis and no history of cardiovascular or severe renal disease. The current smoking status, body mass index, blood pressure, hemoglobin A1c, serum low-density lipoprotein cholesterol, and ultrasonic measures of carotid arteries (CCA diameter, intima-media thickness (IMT), plaque score) were measured. The cardio-ankle vascular index (CAVI) and the presence of diabetic retinopathy were also assessed. The CCA diameter showed a significant positive correlation with the mean IMT or plaque score. The CAVI had a significant positive correlation with the mean IMT, plaque score, and CCA diameter, while diabetic retinopathy had a significant positive correlation with the CCA diameter, but not the mean IMT or plaque score. These results were unaltered after adjusting for multiple confounders. The CCA diameter may serve as a useful marker for atherosclerosis and diabetic retinopathy, and in particular, may be a marker associated with diabetic retinopathy more clearly than the carotid IMT and plaque score, in patients with T2DM.     

Plasma level of asymmetric dimethylarginine (ADMA) as a predictor of carotid intima-media thickness progression: six-year prospective study using carotid ultrasonography

This study was designed to determine the relationship between plasma asymmetric dimethylarginine (ADMA) and the development of carotid atherosclerosis. Cross-sectional studies have revealed that plasma ADMA concentration is correlated with the intima-media thickness (IMT) of the carotid artery, but no prospective studies have appeared. Therefore we prospectively investigated whether or not plasma ADMA level can predict IMT progression. In a community-based cohort, we enrolled 712 subjects who were over 40 years old and who had no apparent cardiovascular diseases according to high-resolution carotid ultrasonography. Blood chemistries including ADMA were measured at baseline. In 575 subjects, IMT was re-measured 6 years later. The value of baseline ADMA for predicting IMT changes was investigated by multivariable analysis. At baseline, there was a significant (beta=0.321; p<0.001) relationship between IMT and ADMA levels. Multiple linear regression analysis revealed that baseline ADMA (beta=0.241; p<0.01) was the only predictor of IMT progression after adjustments for age, sex, baseline IMT, and four major risk factors (hypertension, hypercholesterolemia, diabetes mellitus, and smoking) plus hyperuricacidemia. Plasma ADMA was a predictor of carotid IMT progression.     

Plasma levels of asymmetric dimethylarginine (ADMA) are related to intima-media thickness of the carotid artery: an epidemiological study

Asymmetric dimethylarginine (ADMA) is a circulating endogenous nitric oxide (NO) synthase inhibitor. It has been reported that plasma levels of ADMA are related to intima-media thickness (IMT) in small numbers. We investigated this issue in a large number of subjects without overt cerebro-cardiovascular diseases. A total of 712 subjects (305 men and 407 women; age, 62.6+/-11.2 years) received a health examination in 1999 in a farming community. We measured blood pressure (BP), blood chemistries, and fasting plasma total ADMA levels. IMT of the common carotid artery was determined with the use of duplex ultrasonography as an index of atherosclerosis. Uni- and multi-variate analyses for determinants of IMT were performed. For the total population, the mean ADMA level was 0.50 micromol/l. By the use of multiple stepwise regression analysis, IMT was significantly associated with ADMA (p<0.01), age (p<0.001), and systolic BP (p<0.001). Furthermore, when IMT was analyzed across the ADMA tertiles after adjustments for age, sex, and other confounders, analysis of co-variance showed a significant (p<0.001) and linear association between IMT and ADMA levels. In conclusion, our study indicates that plasma level of ADMA is a strong and independent determinant of IMT of the carotid artery in the large number of subjects without overt cerebro-cardiovascular diseases.     

Asymmetric dimethylarginine is associated with macrovascular disease and total homocysteine in patients with type 2 diabetes

BACKGROUND: The endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) and total homocysteine (tHcy) are elevated in patients at increased cardiovascular risk. Patients with type 2 diabetes (T2DM) have higher incidence of macrovascular disease than the general population. Recent reports suggest a relationship between tHcy and ADMA. To evaluate the connection between ADMA and tHcy and macrovascular disease, we determined both risk factors in T2DM patients with and without macrovascular disease. SUBJECTS AND METHODS: Plasma concentrations of ADMA and tHcy were cross-sectionally determined in 136 T2DM patients. Fifty-five patients had macrovascular disease defined by history of stroke, myocardial infarction, coronary heart disease or peripheral arterial occlusive disease. Logistic regression analysis was performed to examine the relationship between macrovascular disease and these risk factors. Potential confounders were identified by significant Spearman rank correlation coefficients. RESULTS: In unadjusted models ADMA (per 0.1 micromol/l) and tHcy (per 5 micromol/l) were both significantly related to macrovascular disease (OR=1.63, 95% CI: 1.21-2.19 and OR=1.49, 95% CI: 1.04-2.14). In multivariate models, ADMA was significantly associated with macrovascular disease independent of l-arginine, albumin excretion rate, tHcy and glomerular filtration rate (GFR; OR=1.53, 95% CI: 1.04-2.26). The connection between tHcy and macrovascular disease was not independent of diastolic blood pressure, age, ADMA or GFR. Linear regression analyses revealed that ADMA, GFR and low-density lipoprotein cholesterol were independent predictors for tHcy. CONCLUSION: ADMA is associated with macrovascular disease independent of tHcy and traditional cardiovascular risk factors in patients with T2DM.     

Plasma leptin is independently associated with the intima-media thickness of the common carotid artery.

OBJECTIVE: To investigate whether intima-media thickness (IMT) of the common carotid artery (CCA), an early marker of asymptomatic atherosclerosis, is significantly and independently associated with plasma concentrations of leptin, an adipose tissue hormone that has recently been proposed as a cardiovascular risk factor in obese patients. DESIGN: Cross-sectional sample of normal-weight and obese men and women. SUBJECTS: One-hundred and twenty healthy subjects (52 men and 68 women), aged 18-45 y and with a wide range of BMI, were recruited for the study. MEASUREMENTS: Fasting plasma leptin concentrations and the IMT of the CCA were measured in all subjects. Leptin concentrations were measured by radioimmunoassay and the IMT of the CCA was quantified by high resolution B-mode ultrasound imaging. Central fat (measured by waist circumference), smoking habits, blood pressure, insulin sensitivity (measured by the insulin tolerance test), and fasting plasma glucose, insulin and lipid pattern (cholesterol, HDL-cholesterol, triglycerides, LDL-cholesterol) were also measured. RESULTS: IMT of the CCA was positively correlated with log leptin concentrations (P<0.005 in men and P<0.001 in women), body mass index (P<0.001 in men and women), waist circumference (P<0.001 in men and women), age (P<0.001 in men and P<0.05 in women), and negatively associated with insulin sensitivity in both sexes (P<0.05). IMT was also directly correlated with cholesterol (P<0.05), LDL-cholesterol (P<0.01) and systolic blood pressure in men (P<0.05), and with diastolic blood pressure levels in women (P<0.05). When a multiple linear regression model was used without body mass index (BMI), the correlation between leptin and IMT was maintained in both men (P<0.01) and women (P<0.005), independent of age, insulin sensitivity, smoking habits, systolic blood pressure, fasting glucose, triglycerides, cholesterol, LDL-cholesterol and HDL-cholesterol. By contrast, BMI-adjusted leptin concentrations were not significantly associated with IMT (Pc (partial correlation): 0.41 in men and 0.15 in women). Moreover, when BMI was entered into a multiple linear regression model without leptin, the correlation between BMI and IMT was maintained in both men (P<0.005) and women (P<0.01), independent of the same parameters. CONCLUSION: Plasma leptin concentrations are independently associated with the IMT of the CCA, suggesting that the increase of adipose tissue mass (or leptin per se) may have an unfavourable influence on the development of atherosclerosis. However, the association between IMT and leptin seems to be dependent and/or confounded by the relationship between IMT and obesity.     

Endothelial dysfunction in patients with peripheral arterial disease and chronic hyperhomocysteinemia: potential role of ADMA

Hyperhomocysteinemia is associated with an enhanced risk for cardiovascular disease. Patients with peripheral arterial disease (PAD) show an increased prevalence of hyperhomocysteinemia. A decreased biological activity of nitric oxide (NO) may contribute to homocysteine-associated endothelial dysfunction. This study was designed to investigate whether elevated levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) are involved in endothelial dysfunction in patients with chronic hyperhomocysteinemia and PAD. A total of 76 patients (58 males and 18 females; mean age 65.2 +/- 2.0 years) with PAD were included in the analysis and characterized according to demographic variables and cardiovascular risk factors. Flow-dependent vasodilation (FDD) was determined by high-resolution ultrasound in the radial artery. Total plasma homocysteine (plasma tHcy) and ADMA levels were measured by HPLC. Urinary nitrate was quantified using gas chromatography-mass spectrometry. Patients with plasma tHcy in the highest tertile (n = 27; i.e. > 10.6 micromol/l) had a mean plasma level of 14.4 +/- 1.21 mol/l compared with 9.9 +/- 0.1 micromol/l in those patients in the middle tertile (n = 22; p < 0.05) and 9.4 +/- 0.1 micromol/l in those in the lowest tertile (n = 27; i.e. <9.6 micromol/l; p < 0.05). The hyperhomocysteinemic individuals (highest tertile) had a significantly decreased FDD compared with healthy age-matched controls (n = 15) (7.6 +/- 1.0 vs 13.0 +/- 0.4%; p < 0.05), higher plasma ADMA concentrations (4.0 +/- 0.3 vs 2.6 +/- 0.3 micromol/l; p < 0.05), and a lower urinary nitrate excretion rate (89.5 +/- 13.4 vs 131.3 +/- 17.9 micromol/mmol creatinine; p < 0.05) compared with patients with plasma tHcy in the lowest tertile. Multivariate regression analysis including plasma tHcy, ADMA, total cholesterol, diabetes mellitus, smoking, and systolic blood pressure revealed ADMA as the only significant factor determining FDD (p < 0.05). In conclusion, we demonstrated a stronger relationship between impaired endothelial function and elevated ADMA levels in comparison with plasma tHcy concentrations in patients with PAD and chronic hyperhomocysteinemia. This may raise the question of whether different therapeutical options that interact indirectly with plasma tHcy, i.e. treatment with ACE inhibitors and AT1-receptor blockers to reduce ADMA plasma concentrations or L-arginine, could be a beneficial tool for treating patients with hyperhomocysteinemia.     

Carotid atherosclerosis,intima media thickness and risk factors--an analysis of 1781 asymptomatic subjects in Taiwan

The aim of this study was to investigate the association of intima media thickness (IMT) and plaque with risk factors for atherosclerosis in asymptomatic subjects in Taiwan. Between 1998 and 2001, the study recruited 1781 asymptomatic subjects (1131 men and 650 women [mean age, 49 years; range 18-85 years]). These were examined by B-mode ultrasound to measure the IMT at the far wall of the common carotid artery (CCA) and the extent of plaque formation. A wide range of vascular risk factors including age, gender, smoking, body mass index, blood chemistry, and previous history were surveyed. The mean (+/-S.D.) IMT observed was 0.68 (+/-0.12) and 0.66 (+/-0.11) mm for men and women, respectively, (P=0.0008). The mean (S.D.) IMT of the CCA was 0.66 (+/-0.12) mm on the right side and 0.68 (+/-0.12) mm on the left side (P=0.0004). IMT increased with aging, according to the equation IMT=(0.005xage in years)+0.403 [corrected]. Higher IMT was associated with male gender, and IMT was greater in the left CCA. About 36.9% of subjects had carotid plaques. The percentage of plaque increased with aging. The plaque prevalence was positively associated with IMT. The value of IMT over the cut point of 0.68 mm correlated with obviously increased risk of carotid atherosclerosis. Age, systolic blood pressure and fasting blood sugar were independent risk factors related to both carotid atherosclerosis and thick IMT.     

Augmentation index and carotid intima-media thickness are differently related to age, C-reactive protein and oxidized low-density lipoprotein

OBJECTIVE: Ageing, plasma circulating C-reactive protein (CRP), oxidized low-density lipoprotein (OxLDL) and homocysteine (Hcy) are associated with atherosclerosis. The aim of this study was to evaluate the relationship between age, inflammatory and oxidative stress-related markers with functional and structural changes of the arteries in asymptomatic persons. METHODS: CRP, OxLDL and Hcy were measured in 175 clinically healthy subjects, aged 40-70 years. Ultrasonography and pulse wave analysis were used to measure carotid intima-media thickness (IMT) and augmentation index (AIx). RESULTS: OxLDL was correlated with IMT (r = 0.24, P = 0.003), whereas CRP was correlated with AIx (r = 0.21, P = 0.005). No correlation was detected between Hcy and AIx or age-adjusted IMT. There was a significant association between AIx and age 50 years (r = 0.40; P = 0.001). In stepwise regression analysis age, weight, white blood cell count, OxLDL, heart rate and timing of the reflected waveform adjusted for height were significantly and independently associated with IMT (R = 0.41; P < 0.001). At the same time, AIx as the dependent variable correlated positively with age, gender, CRP and mean arterial pressure, and negatively with heart rate, weight and height, in stepwise regression analysis (R = 0.63; P < 0.001). CONCLUSION: The results of the present study showed that CRP, OxLDL, Hcy and age are not similarly related to AIx and IMT in asymptomatic persons. The results suggest that CRP and younger age are related to arterial stiffness, whereas OxLDL and older age become more important determinants of structural changes of the arteries in asymptomatic persons.     

Asymmetric dimethylarginine is associated with carotid atherosclerosis in patients with essential hypertension

Abstract

This study was to assess the relationship between asymmetric dimethylarginine (ADMA) and carotid atherosclerosis in patients with essential hypertension. A total of 182 individuals with never-treated essential hypertension and 182 age-matched healthy controls were studied. Plasma ADMA levels, mean intima-media thickness (IMT) and plaque score were significantly greater in hypertensive patients than normotensive controls. ADMA was positively correlated with mean IMT. On multiple logistic regression analysis, ADMA was a crucial independent predictor of carotid plaque formation (plaque score ≥1.1). Our results suggest that increased levels of ADMA are associated with the development of carotid atherosclerosis in hypertensive patients.     

Plasma fibronectin level and its association with coronary artery disease and carotid intima-media thickness

BACKGROUND: The exact relation of fibronectin with coronary atherosclerosis is unknown. The aim of the present study was to examine the association of fibronectin level with presence and extent of coronary artery disease (CAD) and intima-media thickness (IMT) of common carotid artery (CCA). DESIGN: The IMTs of CCA of 86 patients who underwent coronary angiography were measured; traditional vascular risk factors were also evaluated in these patients. Fibronectin, lipids, C-reactive protein (CRP) and fibrinogen levels were determined. RESULTS: Plasma fibronectin levels of the patients with CAD were found to be significantly elevated compared to patients with normal vessels (0.46+/-0.11 and 0.36+/-0.12 mg/dl respectively, P = 0.001). Fibronectin levels were not associated with extent of CAD. No significant association was observed between fibronectin level and traditional risk factors. IMTs of right and left CCA in patients with CAD were found to be elevated compared to patients with normal vessels (0.89+/-0.1 mm compared with 0.76+/-0.1 mm, P = 0.001 and 0.93+/-0.2 mm compared with 0.71+/-0.1 mm, respectively P < 0.001). Fibronectin levels were positively correlated with CRP (r = 0.45, P < 0.001), low-density lipoprotein-cholesterol (r = 0.23, P = 0.03) and total cholesterol (r = 0.21, P = 0.04) levels and negatively correlated with high-density lipoprotein-cholesterol (HDL-C) levels (r = -0.24, P = 0.02). IMT of left CCA was positively correlated with CRP levels (r = 0.23, P = 0.04) and negatively correlated with HDL-C levels (r = 0.2, P = 0.04). Logistic regression analysis showed that age (P < 0.01) and fibronectin levels (P = 0.01) were independent predictors for the existence of CAD. CONCLUSIONS: The results suggest that fibronectin levels may be a significant predictor of CAD. However, it was shown that fibronectin levels were not associated with extent of CAD and IMT of CCA.     

Abnormal asymmetric dimethylarginine/nitric oxide balance in patients with documented coronary artery disease: relation to renal function and homocysteine

Background As an endogenous inhibitor of nitric oxide production, asymmetric dimethylarginine (ADMA) is reported to be associated with coronary artery disease (CAD). Methods We measured plasma levels of ADMA, nitrate + nitrite (NOx), total homocysteine (tHCY), and renal function in 106 people with angiographic evidence of coronary artery disease (CAD), including 46 with single vessel disease and 60 with double/triple vessel disease, and in 70 age-matched individuals without any angiography evidence of CAD. Also the levels of these parameters were evaluated according to their history of MI. Plasma tHcy and ADMA were measured by HPLC and the levels of NOx using the Griess reaction. Results Levels of ADMA, ACE and tHcy levels were significantly higher and NO level was significantly lower in CAD patients compared with controls but there were no significant differences among patients with or without history of MI and between patients with single compared to those with double/triple vessel disease. Additionally a negative correlation was found between ADMA-NOx (r = −0.396, p = 0.001) and between tHcy-NOx (r = −0.262, p = 0.027). In the entire study group, ADMA level was significantly higher in patients with creatinine clearance (CrCl) < 91 mL/min than in patients with CrCl ≥ 91 mL/min (0.60 ± 0.23 micromoles/L versus 0.49 ± 0.25 micromoles/L, p = 0.05). Conclusions We suggest that there is an abnormal plasma ADMA-to-NO balance in patients with documented CAD and that this may be due at least in part to an associated reduction in renal function.