Independent association of matrix metalloproteinase-10, cardiovascular risk factors and subclinical atherosclerosis

OBJECTIVES: Circulating levels of matrix metalloproteinase (MMP)-10 are related to inflammation in asymptomatic subjects with cardiovascular risk factors. Whether MMP-10 is associated with the severity of atherosclerosis remains to be determined. This study examines the relationship of systemic MMP-10 levels with atherosclerotic risk factors and subclinical atherosclerosis. METHODS AND RESULTS: Circulating levels of MMP-1, -9 and -10, and markers of inflammation [fibrinogen, interleukin-6, von Willebrand factor, and high-sensitivity C-reactive protein (hs-CRP)] were measured in 400 subjects (mean age 54.3 years, 77.7% men) with cardiovascular risk factors but free from clinical cardiovascular disease. Subclinical atherosclerosis was evaluated by both the mean carotid intima-media thickness (IMT) and the presence of atherosclerotic plaques with the use of B-mode ultrasound in all subjects. MMP-10 levels were positively correlated with fibrinogen (r = 0.24, P < 0.001), hs-CRP (r = 0.14, P < 0.01) and carotid IMT (r = 0.17, P < 0.01). The association between MMP-10 and IMT remained significant in multiple regression analysis (P < 0.02) when controlling for traditional atherosclerotic risk factors and inflammatory markers. Such an association was not observed for MMP-1 and -9. Subjects in the highest MMP-10 tertile had significantly higher carotid IMT (adjusted odds ratio 6.3, 95% confidence interval 1.3-31.4, P = 0.024). In addition, MMP-10 levels were significantly higher in patients with carotid plaques (n = 78) than in those with no plaques after adjusting for age and sex (P < 0.01). CONCLUSION: Higher serum MMP-10 levels were associated with inflammatory markers, increased carotid IMT and atherosclerotic plaques in asymptomatic subjects. Circulating MMP-10 may be useful to identify subclinical atherosclerosis in subjects free from cardiovascular disease.     

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.     

Serum interleukin-18 levels are associated with nephropathy and atherosclerosis in Japanese patients with type 2 diabetes

OBJECTIVE: Interleukin (IL)-18 is a proinflammatory cytokine secreted from mononuclear cells. Serum concentration of IL-18 is a strong predictor of death in patients with cardiovascular diseases. Recent studies have shown that microinflammation is involved in the pathogenesis of diabetic nephropathy as well as of cardiovascular diseases. This study aimed to test the hypothesis that the serum level of IL-18 is a common predictor of nephropathy and atherosclerosis in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Eighty-two Japanese patients with type 2 diabetes and 55 age- and sex-matched healthy control subjects were enrolled. Patients with renal dysfunction (creatinine clearance <1 ml/s) were excluded. We assessed clinical parameters and measured serum and urinary IL-18 levels, serum IL-6 levels, carotid intima-media thickness (IMT), and brachial-ankle pulse wave velocity (baPWV) in all patients. Further, we evaluated changes of urinary albumin excretion rate (AER) after 6 months in 76 diabetic patients. RESULTS: Serum and urinary IL-18 levels were significantly elevated in patients with type 2 diabetes as compared with control subjects (serum IL-18 179 +/- 62 vs. 121 +/- 55 pg/ml, P < 0.001; urinary IL-18 97 +/- 159 vs. 47 +/- 54 pg/ml, P = 0.035). Univariate linear regression analysis showed significant positive correlations between serum IL-18 and AER (r [correlation coefficient] = 0.525, P < 0.001), HbA(1c) (r = 0.242, P = 0.029), high-sensitivity C-reactive protein (hs-CRP) (r = 0.240, P = 0.031), and urinary beta-2 microglobulin (r = 0.235, P = 0.036). Serum IL-18 levels also correlated positively with carotid IMT (r = 0.225, P = 0.042) and baPWV (r = 0.232, P = 0.040). We also found a significant correlation between urinary IL-18 and AER (r = 0.309, P = 0.005). Multivariate linear regression analysis showed that AER (standard correlation coefficients [B] = 0.405, P < 0.001) and hs-CRP (B = 0.207, P = 0.033) were independently associated with serum IL-18 levels. AER was also independently associated with urinary IL-18 levels (B = 0.295, P = 0.005). Moreover, serum and urinary IL-18 levels correlated positively with AER after 6 months (r = 0.489, P < 0.001 and r = 0.320, P = 0.005) and changes in AER during the follow-up period (r = 0.268, P = 0.018 and r = 0.234, P = 0.042). CONCLUSIONS: Serum levels of IL-18 might be a predictor of progression of diabetic nephropathy as well as cardiovascular diseases.     

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.     

Relationship of serum uric acid to measures of endothelial function and atherosclerosis in healthy adults

Although uric acid (UA) is considered as an antioxidant, the relationship between serum UA levels and cardiovascular diseases is not clear yet. Higher brachial artery resting diameter (BD), impaired brachial artery flow-mediated dilatation (FMD), increased carotid intima-media thickness (IMT), decreased aortic distensibility (AoD), and increased aortic stiffness index (AoSI) and elastic modulus (AoEM) are predictors for development and/or progression of atherosclerosis. In this study, BD, FMD, carotid IMT, AoD, AoSI and AoEM were studied in healthy subjects with UA concentrations in physiological range. One hundred 24 healthy volunteers between 26 and 55 years of age were included in this study. Each subject had a serum UA levels in normal range. Carotid IMT, BD and brachial FMD were measured by means of high-resolution vascular ultrasound. AoD, AoSI, AoEM were examined by transthoracic echocardiography. Endothelium-dependent dilatation (EDD) was assessed by establishing reactive hyperemia and endothelium-independent dilatation (EID) was determined by using sublingual isosorbide dinitrate. Although carotid IMT and EDD were significantly correlated with UA concentrations (r = 0.346, p < 0.0001; r = -0.255, p < 0.05, respectively), EID measurements were not significantly correlated with serum UA concentrations (r = - 0.105, p > 0.05). In addition, AoSI and AoEM were significantly correlated with serum UA levels (r = 0.368, p < 0.0001; r = -0.366, p < 0.0001, respectively), and there was a significant inverse correlation between AoD and serum UA concentrations (r = -0.366, p < 0.0001). Furthermore, in multivariate analysis, we found that serum UA concentrations were correlated with increased carotid IMT, reduced FMD and increased aortic stiffness independent of other cardiovascular risk factor (beta = 256, p = 0.002; beta = -193, p = 0.03; beta = 0.295, p < 0.0001, respectively). In healthy subjects, increased serum UA concentrations, even in physiological range, are a risk factor for increased carotid IMT, reduced FMD and increased aortic stiffness independent of other cardiovascular risk factor, and other factors related to the metabolic syndrome.     

Decreased endogenous secretory advanced glycation end product receptor in type 1 diabetic patients: its possible association with diabetic vascular complications

OBJECTIVE: The binding of advanced glycation end products (AGEs) to their receptor (RAGE) plays an important role in the development of diabetic vascular complications. In the present study, we examined circulating endogenous secretory RAGE (esRAGE) levels in subjects with type 1 diabetes and explored the possible association between esRAGE levels and the severity of diabetic vascular complications. RESEARCH DESIGN AND METHODS: Circulating esRAGE levels in serum were examined in 67 Japanese type 1 diabetic patients (22 men and 45 women, age 24.0 +/- 4.4 years [means +/- SD]) and 23 age-matched healthy nondiabetic subjects (10 men and 13 women aged 24.9 +/- 1.4 years). Daily urinary albumin excretion, the presence of retinopathy, and intima-media thickness (IMT) of the carotid artery were also evaluated. We further explored the association between esRAGE levels and severity of diabetic vascular complications. RESULTS: Circulating esRAGE levels were significantly lower in subjects with type 1 diabetes than in nondiabetic subjects (0.266 +/- 0.089 vs. 0.436 +/- 0.121 ng/ml, respectively, P < 0.0001) and was inversely correlated with HbA(1c) (A1C) levels (r = -0.614, P < 0.0001). In addition, multivariate regression analysis demonstrated that A1C was an independent risk factor for a low esRAGE value. Furthermore, circulating esRAGE levels were inversely correlated with carotid IMT (r = -0.325, P = 0.0017) and was one of the independent risk factors for IMT thickening. Furthermore, there was a significant difference (P = 0.0124) in esRAGE levels between patients without retinopathy (0.286 +/- 0.092 ng/ml) and those with retinopathy (0.230 +/- 0.074 ng/ml). CONCLUSIONS: Circulating esRAGE levels were significantly lower in type 1 diabetic patients than in nondiabetic subjects and were inversely associated with the severity of some diabetic vascular complications.     

血清MMP-2、TES、E2与高血脂及颈动脉粥样硬化的关系

目的 探讨血清基质金属蛋白酶(MMP-2)、睾酮(TES)、雌二醇(E2)与高血脂及颈动脉粥样硬化的关系.方法 对146例患者分别进行血脂测定、颈动脉超声检查,测定并记录颈动脉内中膜厚度(IMT)、斑块形态、回声强度、斑块数量.根据超声病理形态和血脂水平分为有斑块高血脂组(A组)45例、无斑块高血脂组(B组)41例和血脂正常组(C组)60例.采用酶联免疫双抗体夹心法(ELISA)测定患者血清MMP-2、化学发光法测定血清TES、E2水平.结果 血清MMP-2 A组高于B组和C组,差异有统计学意义(P＜0.05),而B组与C组无统计学差异;血清TES、E2 A组低于B组和C组、B组低于C组,差异有统计学意义(P＜0.05);A组和B组血清MMP-2与TES、E2成负相关(r=-0.597,P＜0.05;r=-0.622,P＜0.05).结论 血清MMP-2、TES、E2水平与高血脂及颈动脉斑块有关.     

胰岛素抵抗与老年高血压病颈动脉粥样硬化关系的研究

目的探讨胰岛素抵抗(IR)与老年高血压颈动脉粥样硬化(AS)的关系及前者在老年高血压发生发展过程中对AS的参与影响作用。方法选取70例老年高血压患者按其是否合并IR分为两组,即高血压合并IR组(34例)和单纯高血压组(36例),并行口服葡萄糖耐量试验和同步胰岛素释放试验。同时做彩超测颈动脉内膜中层厚度(IMT)、斑块厚度(Crouse法计算斑块积分)。根据公式计算出胰岛素敏感指数(ISI),血糖曲线下面积(AG),胰岛素曲线下面积(AI),空腹血胰岛素(FSI)/空腹血糖(FSG),AI/AG,斑块积分,测量体质量、身高计算体质量指数(BMI),同时选取同龄30例正常血压者作为对照,应用直线相关分析观察ISI和斑块积分(PS)与各胰岛素敏感性指标的关系。结果高血压合并IR组的IMT、粥样硬化斑块积分(PS)显著高于对照组(P<0.01),高血压合并IR组的高于单纯高血压组(P<0.05),高血压组高于对照组(P<0.05);IMT与SBP、FSI呈正相关(r值为0.003、0.129,均P<0.01),IMT与ISI呈负相关(r值为-0.125,P<0.01)。PS与SBP、FSI呈正相关(r值为0.018、1.233,均P<0.05),PS与ISI呈负相关(r值为-0.701,P<0.05)。结论IR与老年高血压颈动脉粥样硬化密切相关,老年高血压合并IR加重颈动脉粥样硬化程度和进程,即较单纯老年高血压对颈动脉硬化损害更严重。IR在老年高血压的发生、发展过程中可能起重要作用。与IR相关的高胰岛素血症是参与和促进老年高血压发生动脉粥样硬化的重要影响因素。     

Coronary artery disease and carotid artery intima-media thickness in Japanese type 2 diabetic patients

OBJECTIVE: To investigate the association between carotid atherosclerosis, measured as intima-media thickness (IMT), and cardiovascular morbidity in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We investigated the relationship between IMT and coronary artery disease (CAD) in 40 type 2 diabetic patients and 40 control subjects. Diabetic patients with CAD determined by coronary angiography were consecutively recruited, whereas the control subjects were recruited from among diabetic outpatients without CAD at the same institution. IMT was measured in both carotid arteries using B-mode ultrasonography. RESULTS: Carotid IMT was significantly greater in the diabetic patients than in the control subjects (1.27 +/- 0.07 vs. 1.03 +/- 0.04 mm, P < 0.05). IMT was associated with CAD by logistic regression analysis using all independent variables (P = 0.062). When the 40 patients with CAD were divided into a group of 20 patients with coronary artery bypass grafting (CABG) and another 20 patients without CABG, the IMT was significantly greater in the CABG group than in the non-CABG group (1.47 +/- 0.11 vs. 1.07 +/- 0.07 mm, P < 0.05). CONCLUSIONS: These results indicate that the presence of carotid atherosclerosis implies a high probability of coronary involvement in Japanese nonobese subjects with type 2 diabetes.     

2型糖尿病患者趾臂指数与颈动脉及下肢动脉内中膜厚度的相关性研究

目的分析2型糖尿病(T2DM)患者趾臂指数(TBI)与外周动脉内中膜厚度(IMT)的相关性及TBI降低的危险因素。方法选择该院内分泌科住院的T2DM患者292例作为研究对象,分析其TBI与颈、股、腘动脉IMT的相关性及TBI降低的危险因素。结果 TBI降低组(TBI<0.7)与TBI正常组(TBI≥0.7)比较,年龄,DM病程,收缩压(SBP),颈、股、腘动脉IMT,DN患病人数差异均有统计学意义(P<0.05);TBI与颈、股、腘动脉IMT均呈负相关(r=-0.331、-0.288、-0.350,P<0.001);TBI降低的危险因素为年龄(OR=1.060、P<0.001、95%CI:1.027~1.095)、DM病程(OR=1.073、P=0.001、95%CI:1.027~1.121)、SBP(OR=1.021、P=0.018、95%CI:1.004~1.039)和吸烟史(OR=2.406、P=0.008、95%CI:1.251~4.626)。结论 T2DM患者TBI与颈、股、腘动脉IMT均呈负相关,年龄、糖尿病病程、SBP和吸烟史是TBI降低的危险因素。     

Association of NAD(P)H oxidase p22 phox gene variation with advanced carotid atherosclerosis in Japanese type 2 diabetes

OBJECTIVE: To evaluate the association between the C242T polymorphism of the p22 phox gene, an essential component of NAD(P)H oxidase in the vasculature, with intima-media thickness (IMT) of the carotid artery and risk factors for atherosclerosis in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: C242T polymorphism of the p22 phox gene was detected by polymerase chain reaction-restriction fragment-length polymorphism in 200 Japanese type 2 diabetic subjects and 215 nondiabetic subjects. We examined the association with this mutation and carotid atherosclerosis as well as the patients' clinical characteristics and the level of 8-hydroxy-2'deoxyguanosine (8-OHdG) as an index of oxidative DNA damage. RESULTS: The diabetic subjects with the TC+TT genotypes displayed a significantly lower average IMT (1.13 +/- 0.31 vs. 1.31 +/- 0.34 mm; P = 0.0099) and a not significantly lower serum 8-OHdG level than those with the CC genotype, despite no difference in the risk factors. Stepwise multiple regression analysis showed that the risk factors for increased IMT in the diabetic subjects were systolic blood pressure (P = 0.0042) and p22 phox CC genotype (P = 0.0151). In nondiabetic subjects, the average IMT of the TC+TT group was not different from that of the CC group (0.85 +/- 0.14 vs. 0.94 +/- 0.30 mm, P = 0.417). Fasting plasma insulin concentration (41.4 +/- 15.6 vs. 64.2 +/- 59.4 pmol/l, P = 0.0098) and insulin resistance index of homeostasis model assessment (HOMA-R) (1.58 +/- 0.66 vs. 2.60 +/- 2.56, P = 0.0066) were significantly lower in the TC+TT group than in the CC group. CONCLUSIONS: These results show that the C242T mutation in the p22 phox gene is associated with progression of asymptomatic atherosclerosis in the subjects with type 2 diabetes and is also associated with insulin resistance in nondiabetic subjects.     

Relationships of plasma interleukin-18 concentrations to hyperhomocysteinemia and carotid intimal-media wall thickness in patients with type 2 diabetes

OBJECTIVE: We compared plasma interleukin (IL)-18 concentrations in patients with type 2 diabetes with those in age-matched control subjects and investigated whether plasma IL-18 was associated with plasma total homocysteine (tHcy) concentration or carotid intimal-media wall thickness (IMT), an early marker of atherosclerosis, in these patients. RESEARCH DESIGN AND METHODS: We measured plasma IL-18 in 103 type 2 diabetic patients and 45 age-matched control subjects. We also measured patients' plasma tHcy and serum high-sensitivity C-reactive protein (hs-CRP). IMT was evaluated for both common carotid arteries. RESULTS: Plasma IL-18 was significantly higher in diabetic patients than in control subjects (203 +/- 153 vs. 118 +/- 37 pg/ml, P < 0.001). High IL-18 was defined as equaling or exceeding the mean + 2 SD of plasma IL-18 in control subjects (192 pg/ml). Patients with high IL-18 showed a greater carotid IMT than those with normal IL-18. Carotid plaques were more numerous in diabetic patients with high IL-18 than in those with normal IL-18. Plasma tHcy concentrations were significantly higher in patients with high IL-18 than in those with normal IL-18. Univariate and multivariate analyses showed a strong independent association between tHcy and IL-18. Plasma IL-18 also correlated positively with serum hs-CRP. CONCLUSIONS: In patients with type 2 diabetes, plasma IL-18 concentrations are greater than in nondiabetic subjects. Plasma IL-18 is an independent determinant of plasma tHcy, which is linked independently with atherosclerotic carotid wall thickening.     

Carotid intima-media thickness in HIV patients treated with antiretroviral therapy

INTRODUCTION: Increased cardiovascular risk in HIV patients in antiretroviral therapy (ART) may be due to HIV infection, direct effect of ART or dyslipidaemia induced by ART. Our aim was to study the relative importance of HIV, ART and dyslipidaemia on atherosclerosis, assessed by the comparison of carotid artery intima-media thickness (IMT) in non-smoking HIV patients with high or low serum cholesterol levels as well as in healthy volunteers. METHODS: HIV patients in ART with normal cholesterol (or=6 x 5 mmol l(-1); n=12) as well as healthy controls (n=14) were included. All were non-smokers and had never received medication for dyslipidaemia or hypertension. IMT was measured by ultrasonography. RESULTS: In HIV patients with normal cholesterol (or=6 x 5 mmol l(-1)) and in controls (5 x 1 +/- 0 x 9 mmol l(-1)) IMT were 683 +/- 119, 656 +/- 99 and 657 +/- 99 microm, respectively. Thus no difference in IMT was found between the three groups. IMT values did not differ between patients receiving and not receiving protease inhibitors (658 +/- 117 microm versus 687 +/- 97 microm, P>0 x 05). In HIV patients IMT correlated inversely with HDL cholesterol levels (r=-0 x 50; P=0 x 01), whereas no correlation was found with total cholesterol or LDL cholesterol. CONCLUSIONS: In non-smoking HIV patients receiving ART no sign of accelerated atherosclerosis was found as assessed by IMT even not in hypercholesterolaemic HIV patients. IMT correlated with HDL cholesterol but not with LDL cholesterol. Based on these observations, one could speculate whether selective lowering of LDL cholesterol will be successful in reducing cardiovascular risk in non-smoking HIV patients.     

Association of postprandial hypertriglyceridemia and carotid intima-media thickness in patients with type 2 diabetes

OBJECTIVE: Serum triglyceride levels are important in the development of atherosclerosis. Although triglyceride levels are generally increased in the postprandial periods, the association between postprandial triglyceride (pTG) levels and atherosclerosis has not been investigated in diabetic patients. To investigate the role of pTG levels in atherosclerosis, we examined the correlation between pTG levels and carotid intimal-medial thickness (IMT). RESEARCH DESIGN AND METHODS: Carotid IMT was measured by ultrasonography in 61 patients with type 2 diabetes. Plasma glucose (PG), insulin, total cholesterol, triglycerides, and HDL cholesterol levels were measured after overnight fasting and 4 h after a meal. RESULTS: Carotid IMT of the patients with fasting hypertriglyceridemia was greater than that of the patients with normal fasting triglyceride (fTG) levels (0.85+/-0.12 vs. 0.76+/-0.14 mm; P = 0.02). The carotid IMT was increased in the patients with pTG levels >2.27 mmol/l. The normo-normo (NN) and normo-hyper (NH) groups consisted of patients with normal fTG levels but with pTG levels <2.27 and >2.27 mmol/l, respectively. Patients with both hypertriglyceridemia and pTG levels >2.27 mmol/l formed the hyper-hyper (HH) group. Carotid IMT was significantly increased in the NH (0.86+/-0.13 mm) and HH (0.85+/-0.12 mm) groups compared with the NN group (0.73+/-0.13 mm; P<0.01). Although postprandial PG, pTG, and fasting LDL cholesterol levels were all independently correlated with carotid IMT, pTG levels had the strongest statistical influence (P = 0.002). CONCLUSIONS: Postprandial hypertriglyceridemia despite normal fTG levels may be an independent risk factor for early atherosclerosis in 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.     

糖尿病患者心踝血管指数与颈动脉硬化的相关性及其危险因素分析

目的 探讨糖尿病患者心踝血管指数( CAVI)与颈动脉硬化的相关性及其危险因素.方法 入选60例2型糖尿病患者以及同期入院治疗的60例非糖尿病患者,对受试者进行病史采集,检测血糖、血脂等生化指标,行颈动脉彩色多普勒超声检查及CAVI测定,分析CAVI与颈动脉硬化的相关性;以CAVI为因变量,年龄、血压、体质量指数、血脂、空腹血糖、糖化血红蛋白(HbAlc)等指标为自变量进行多元线性回归分析.结果 糖尿病组患者体质量指数、甘油三酯、空腹血糖、HbAlc、颈动脉内膜中层厚度(IMT)、CAVI值及颈动脉斑块发生率均显著高于非糖尿病组[(27.6±3.6)、(25.3±3.3)kg/m2,(2.26±1.12)、(1.74±0.97) mmol/L,(8.86±2.64)、(5.26±0.92)mmol/L,(8.28±1.28)、(5.38±0.86),(1.16±0.16)、(0.86±0.14) mm,(9.55±1.13)、(8.54±0.94),46.7％ (28/60)与25.0％(15/60)],两组间差异均有统计学意义(t值分别为3.648、2.719、9.974、14.567、10.930、5.323,x2=6.125,P均＜0.05);CAVI与受试者颈动脉IMT呈正相关(r=0.435,P＜0.01);多元线性回归显示,CAVI与年龄(β=0.458,P＜0.01)、甘油三酯(β=0.058,P=0.012)、空腹血糖(β=0.168,P=0.002)、HbAlc(β =0.228,P=0.003)存在显著正相关.结论 CAVI与糖尿病患者颈动脉IMT呈正相关,糖尿病患者年龄、甘油三酯、空腹血糖及HbAlc是动脉僵硬的独立危险因素.     

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.     

Low testosterone and high C-reactive protein concentrations predict low hematocrit in type 2 diabetes

OBJECTIVE: After the demonstration that one-third of male patients with type 2 diabetes have hypogonadotrophic hypogonadism, we have shown that patients with hypogonadotrophic hypogonadism also have markedly elevated C-reactive protein (CRP) concentrations. We have now hypothesized that type 2 diabetic subjects with hypogonadotrophic hypogonadism may have a lower hematocrit because testosterone stimulates, whereas chronic inflammation suppresses, erythropoiesis. RESEARCH DESIGN AND METHODS: Seventy patients with type 2 diabetes at a tertiary referral center were included in this study. RESULTS: The mean hematocrit in patients with hypogonadotrophic hypogonadism (n = 37), defined as calculated free testosterone (cFT) of <6.5 ng/dl, was 40.6 +/- 1.1%, whereas that in eugonadal patients (n = 33) was 43.3 +/- 0.7% (P = 0.011). The hematocrit was related to cFT concentration (r = 0.46; P < 0.0001); it was inversely related to plasma CRP concentration (r = 0.41; P < 0.0004). Patients with CRP <3 mg/l had a higher hematocrit (42.7 +/- 0.7%) than those with CRP >3 mg/l (39.9 +/- 1.1%; P < 0.05). The prevalence of normocytic normochromic anemia (hemoglobin <13 g/dl) was 23% in the entire group, whereas it was 37.8% in the men with hypogonadotrophic hypogonadism and 3% in the eugonadal men (P < 0.01). Erythropoietin concentration was elevated or high normal in all 11 patients with anemia in whom it was tested. CONCLUSIONS: We conclude that hypogonadotrophic hypogonadism in male type 2 diabetic subjects is associated with a lower hematocrit and a frequent occurrence of mild normocytic normochromic anemia with normal or high erythropoietin concentrations. In these patients, hematocrit is also inversely related to CRP concentration. Thus, low testosterone and chronic inflammatory mechanisms may contribute to mild anemia. Such patients may also have a high risk of atherosclerotic cardiovascular events in view of their markedly elevated CRP concentrations.     

颈动脉粥样硬化与缺血性卒中危险分层相关性分析

目的观察急性缺血性卒中患者的颈动脉粥样硬化与卒中复发风险分层的关系。方法采用Essen卒中风险评分量表(ESRS)对82例急性缺血性卒中患者的危险因素评估后分为ESRS≥3分组(40例)和ESRS 0～2分组(42例),经彩色多普勒超声仪对两组进行评估,比较两组颈动脉粥样硬化特征和程度。结果 ESRS≥3分组与ESRS 0～2分组相比,ESR≥3分组中高龄、高血压、糖尿病和本次卒中之前有TIA或缺血性卒中的比例明显较高(P<0.05)。ESRS≥3分组颈动脉内-中膜厚度(IMT),斑块(尤其多发斑块)发生率,脂质性、钙化性斑块发生率,中、重度粥样硬化发生率明显高于ESRS 0～2分组(P<0.05)。经多因素非条件Logistic回归分析,颈总动脉IMT≥1.0 mm,脂质性、钙化性斑块,颈动脉粥样硬化程度与ESRS≥3分组卒中复发的危险因素成正相关。结论颈动脉粥样硬化与缺血性卒中复发高危风险密切相关。颈总动脉IMT、颈动脉粥样硬化的严重程度可作为卒中高危复发风险的预测指标。     

Combination of multiple genetic risk factors is synergistically associated with carotid atherosclerosis in Japanese subjects with type 2 diabetes

OBJECTIVE: Several genetic risk factors, such as single nucleotide polymorphisms (SNPs), in candidate genes have been reported to be responsible for intima-media thickness (IMT), which is one of the surrogate end points of cardiovascular events. However, the synergistic effects of SNPs have not been evaluated in detail. RESEARCH DESIGN AND METHODS: We measured the average IMT of the common and internal carotid artery in Japanese type 2 diabetic patients (n = 690) (>50 years old) using ultrasonography. We also determined their genotypes regarding 106 SNPs in candidate genes responsible for cardiovascular diseases. Among the 106 SNPs, we selected 40 common (frequency of minor allele >/=10%) SNPs. We compared the average IMT of subjects with and without any pairs of four genotypes selected from the 40 common SNPs. RESULTS: The combination of methylen-tetrahydrofolate reductase 677 TT genotype and lymphotoxin-alpha (LTA) 252 GG genotype and that of ACE DD genotype and LTA 252 GG genotype were evaluated as responsible for a statistically significant (P = 2.7 x 10(-9) and 3.5 x 10(-6), respectively) increase in average IMT (mean [+/-SD] 1.54 +/- 0.60 and 1.43 +/- 0.58 mm, respectively) compared with those of the subjects without these combinations (1.04 +/- 0.34 and 1.04 +/- 0.34 mm, respectively). No single genotype was shown to be responsible for the statistically significant difference in average IMT after Bonferroni's multiple comparison procedure. CONCLUSIONS: The present analysis demonstrates an approach to evaluate combinations of multiple genetic risk factors that are synergistically associated with carotid atherosclerosis.