Homocysteine levels in acromegaly patients

Acromegaly is associated with a two to three-fold increase in mortality related predominantly to cardiovascular disease. The excess mortality is associated most closely with higher levels of growth hormone (GH). Survival in acromegaly may be normalized to a control age-matched rate by controlling GH levels; in particular, GH levels less than 2.5 ng/mL are associated with survival rates equal to those of the general population. Hyperhomocysteinemia has also been recognized as a risk factor for cardiovascular disease, yet there are limited data on the prevalence of hyperhomocysteinemia in patients with acromegaly. Eighteen acromegaly patients (7 male, 11 female, mean age 42.8 +/- 11.0 years) in our endocrine clinic consented to having the following tests performed: complete blood count (CBC), thyroid hormones, folic acid, vitamin B12, plasma homocysteine levels, uric acid, fibrinogen, CRP, fasting glucose, insulin, C-peptide, total serum cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, GH, insulin-like growth factor-1 (IGF-1) and GH levels after an oral glucose tolerance test (OGTT). By history, fourteen had macroadenomas and four had microadenomas; eight had hypertension; two had glucose intolerance, and four had diabetes. Fifteen had had transsphenoidal or transfrontal surgery: two had been cured, but 13 others were taking long-acting octreotide. Five patients had undergone radiotherapy and the acromegaly in two was treated primarily with long-acting octreotide. CBC, thyroid hormone, folic acid, and vit B12 levels were normal in all patients. We divided the patients into two groups according to mean GH levels after an OGTT: Group 1 (GH<2.5 ng/mL, n=10), and Group 2 (GH<2.5 ng/mL, n=8). Comparison of the two groups using Mann-Whitney U testing revealed statistically significant lower levels in Group 1 of the following parameters: GH (1.91 +/- 0.90 vs. 8.58 +/- 5.55 ng/mL, p=0.002), IGF-1 (338.30 +/- 217.90 vs. 509.60 +/- 293.58 ng/dL, p=0.06), GH after an OGTT (1.42 +/- 0.81 vs. 9.01 +/- 4.53 ng/mL, p=0.001), plasma homocysteine (12.85 +/- 4.47 vs. 18.20 +/- 4.99 micromol/L, p=0.05), total cholesterol (164.0 +/- 20.81 vs. 188.0 +/- 22.26 mg/dL, p=0.05) and LDL cholesterol (81.0 +/- 9.64 vs. 116.70 +/- 13.03 mg/dl, p=0.01). Differences between the other parameters were not significantly different. Acromegaly patients with high GH levels after an OGTT have much higher levels of homocysteine than patients with lower GH levels. The role of elevated homocysteine levels as an independent cardiovascular risk factor in the mortality of acromegaly patients should be determined in future studies.     

Differential effects of the changes of LDL cholesterol and systolic blood pressure on the risk of carotid artery atherosclerosis

ABSTRACT: BACKGROUND: The effects of baseline and changes in blood pressure and low density lipoprotein (LDL) cholesterol on the carotid intima media thickness (IMT) have not been well documented. METHODS: A total of 2572 adults (mean age 53.8 years, 54.6% women) in a Taiwanese community undertook three blood pressure and LDL cholesterol examinations over 6 years. Latent growth curve modeling was used to investigate the effects of baseline and change in blood pressure and LDL cholesterol on IMT. RESULTS: Greater baseline LDL and blood pressure were associated with an increase in IMT (0.005 +/- 0.002 mm per 1 mg/dL [p = 0.006] and 0.041 +/- 0.004 mm mmHg [p <0.0001], respectively. Change in blood pressure was associated with a significant increase in IMT (0.047+/-0.016, P = 0.004), whilst the association between change in LDL and change in IMT was not statistically significant (0.008+/-0.006, P = 0.20). CONCLUSIONS: Carotid IMT was associated with baseline blood pressure and LDL cholesterol, yet only changes of blood pressure, not LDL cholesterol, were related to carotid IMT during the 6- year observation.     

奥扎格雷钠联合川芎嗪注射液对急性脑梗死患者血清同型半胱氨酸、C 反应蛋白及纤维蛋白原水平的影响

目的:探讨奥扎格雷钠联合川芎嗪注射液对急性脑梗死患者血清同型半胱氨酸(HCY)、C反应蛋白(CRP)及纤维蛋白原(FIB)的水平的影响。方法:选择我院收治的急性脑梗死患者68例,随机分为实验组与对照组,每组34例。对照组患者给予奥扎格雷钠治疗,实验组患者给予奥扎格雷钠联合使用川芎嗪注射液治疗,观察并比较治疗前后两组患者血清HCY,CRP及FIB的水平以及颈内动脉粥样狭窄程度的变化和临床总有效率。结果:与治疗前相比,两组患者血清HCY,CRP及FIB水平均显著降低,颈内动脉粥样硬化情况均好转(P0.05);且与对照组相比,实验组患者血清HCY,CRP及FIB水平较低,颈内动脉粥样硬化情况较轻(P0.05);与对照组相比,实验组患者临床总有效率较高(P0.05)。结论:奥扎格雷钠联合川芎嗪注射液治疗可显著提高急性脑梗死积的临床疗效,并能够降低患者颈内动脉粥样狭窄程度,其机制可能与降低血清HCY,CRP及纤维蛋白原水平有关。     

The cardiovascular profile of soccer referees: an echocardiographic study

Background

Previous studies demonstrated a modest association between C-Reactive Protein (CRP), stenosis of carotid artery, and carotid Intima-Media Thickness (IMT) in general population. During present study, we aimed to evaluate the relationship between High Sensitivity C-Reactive Protein (hsCRP) and Common Carotid Intima-Media Thickness (CCIMT) in patients who candidate for Coronary Artery Bypass Grafting (CABG).

Methods

The study subjects were enrolled from patients with coronary arteries disease referred from Shahid Madani Hospital (Tabriz, Iran), who have been candidate for elective CABG from January 2005 to August 2007. The common carotid arteries were evaluated with high-resolution B-mode ultrasonography using a 7.5- MHz linear-array transducer to determine the IMT and grade of stenosis. Serum hsCRP level was measured using commercially available enzyme linked immunosorbent assay kit.

Results

Finally, information of 176 CABG candidates was analysed. The mean age of participants was 62.71 ± 9.45 years with 1.63 male to female ratio. The mean of CCIMT was 0.69 ± 0.54 mm. Although there was no significant correlation between serum hsCRP level and CCIMT in patients without carotid stenosis (p=0.113, r=0.186), participants with common carotid artery stenosis had higher levels of serum hsCRP than participants without stenosis (2.42+/-1.30 vs. 1.20+/-0.97 mg/dl; p=0.009).

Conclusion

Study results showed that there was no correlation between serum hsCRP level and CCIMT in patients without carotid stenosis, but patients with common carotid artery stenosis had higher levels of serum hsCRP than patients without stenosis.     

HIV-infected patients with lipodystrophy have higher rates of carotid atherosclerosis: the role of monocyte chemoattractant protein-1

Individuals with HIV-1 infection are at increased risk for cardiovascular events, and lipodystrophy is generally associated with pro-atherogenic metabolic disturbances. We conducted a case-control study to assess the presence of sub-clinical atherosclerosis in HIV-1-infected patients with or without lipodystrophy (LD) and to evaluate the influence of monocyte chemoattractant protein-1 (MCP-1) on the development of both carotid atherosclerosis and LD. The study population consisted of 43 patients with LD and 86 patients without LD. We determined carotid intima-media thickness (IMT), MCP-1 concentrations in plasma, and MCP-1 genotype (presence or absence of the -2518G allele). HIV-1-infected patients with LD showed increased risk (OR=3.71, 95% CI=1.10-12.47, p=0.03) for sub-clinical atherosclerosis, and MCP-1 plasma concentration was significantly correlated with IMT in these patients (Pearson=0.31, p=0.03). Furthermore, presence of LD was a determinant for MCP-1 plasma concentration (beta=0.18, p=0.05). In summary, HIV-1-infected patients with clinically manifest LD are at higher risk for atherosclerosis and our observations support the relationship between inflammation and atherosclerotic disease.     

Effects of dietary omega3 and omega6 lipids and vitamin E on chemokine levels in autoimmune-prone MRL/MpJ-lpr/lpr mice

Elevated levels of chemokines, such as Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES), Monocyte Chemotactic Protein-1 (MCP-1), Macrophage Inflammatory Protein-1alpha (MIP-1alpha), and Macrophage Inflammatory Protein-1beta (MIP-1beta) have been found in rheumatoid arthritis (RA) and juvenile arthritis (JA), and they may be associated with the pathogenesis of these diseases. These chemokines are implicated in the migration of specific leukocytes into the joints. Omega-3 (omega3) fatty acid rich-fish oil (FO) and vitamin E may delay the progress of certain autoimmune diseases. The present study was designed to understand the effects of dietary lipids (omega-6 and omega-3 fatty acids) and vitamin E on the production of chemokines in autoimmune-prone MRL/lpr (a mouse model for RA) and congenic control MRL/++ mice. The MRL mice were fed for 4.5 months omega-6 and omega-3 diets that varied in lipid sources (corn oil; CO and fish oil; FO) and vitamin E levels (269 I.U./kg and 694 I.U./kg diet). Spleen cells were isolated and cultured aseptically in the presence of PHA for 48 h at 37 degrees C and the levels of chemokines (RANTES, JE/MCP-1 and MIP-1alpha) were determined in the cell-free supernatants. The levels of RANTES and JE/MCP-1 were significantly higher in MRL/lpr mice compared to MRL/++ mice. The FO had differential effect on RANTES and MCP-1 production by spleen cells. The production of RANTES and JE/MCP-1 by spleen cells in mice fed the FO diets was significantly lower than in mice fed the CO diets (p < 0.0001). The levels of vitamin E did not affect the production of RANTES and JE/MCP-1. The levels of vitamin E had a significant effect on MIP-1alpha as the spleen cells of mice fed diets containing 694 IU/kg diet of vitamin E produced significantly higher levels of MIP-1alpha compared to the group of mice fed the diets containing 269 IU of vitamin E (p < 0.0001). The data obtained from this study in MRL/lpr and MRL/++ mice suggest that FO diets containing omega-3 fatty acids are beneficial in decreasing the levels of certain pro-inflammatory chemokines (RANTES and MCP-1) thereby delaying the onset of and severity of autoimmune symptoms in MRL/lpr mouse model.     

von Willebrand factor, C-reactive protein, nitric oxide, and vascular endothelial growth factor in a dietary reversal model of hypercholesterolemia in rabbit

Aims: Endothelial dysfunction is considered a sign of the early vascular changes preceding atherosclerosis. We studied the alteration of von Willebrand Factor (vWF), C - reactive protein (CRP), nitrite and Vascular Endothelial Growth Factor (VEGF) in a dietary reversal model of hypercholesterolemia in rabbit. Methods: This project was designed in two phases. In phase I, male rabbits (n = 11) were fed a 1% high cholesterol diet for 30 days. Then the diet was replaced with normal rabbit chow for other 30 days (cholesterol withdrawal phase, phase II). To compare the fatty streak formation with normal condition, a control group (n = 6) received normal diet during the study. The serum lipid levels, vWF, CRP, nitrite, and VEGF were measured before the experiment and by the end of each phase. Fatty streak formation in the walls of the aortas in both groups (high cholesterol diet and control group) was determined using intima thickness/media thickness (IMT) ratio. Results: The results indicate that the level of cholesterol, Low Density Lipoproteins (LDL), vWF and CRP increased significantly in phase I, and decreased after hypercholesterolemic diet withdrawal (p < 0.05). No statistically significant changes were found in VEGF levels but the serum level of nitrite increased significantly during both phases of the study (p < 0.05). The IMT ratio in the walls of aortas was significantly different between the groups in both phases of studies (p < 0.05). There was a significant correlation between nitrite and cholesterol levels in both phases (r = 0.62 and r = 0.98, p < 0.05). Nitrite concentration also correlated with IMT ratio in both phases of the study (r = 0.75 and r = -0.99, p < 0.05). vWF did not correlate with cholesterol but it correlated with IMT ratio in both phases of the study (r = 0.87 and r = 0.84, p < 0.05). CRP only correlated with cholesterol in the first phase (r = 0.91, p < 0.05). Conclusions: Among the endothelial biomarkers, vWF was found to be a biological marker for identifying the risk of developing atherosclerosis; however a single biomarker may not provide appropriate information.     

Resistin and adiponectin levels in subjects with coronary artery disease and type 2 diabetes

BACKGROUND: Resistin and adiponectin are implicated in insulin resistance and atherosclerosis. The objective of this study was to evaluate the association between plasma resistin levels and the presence of coronary artery disease (CAD) or diabetes compared to the controls. In a cross-sectional study, we measured glucose, fasting lipid panel, resistin, adiponectin, insulin, C-reactive protein (CRP) and TNF-alpha in 57 subjects with CAD, 58 subjects with diabetes compared to 45 normal control subjects. Results: Subjects with CAD compared to the control subjects had increased insulin resistance index (39+/-32 vs. 13.45+/-12.73 with p<0.0001), CRP levels (3.8+/-4.03 vs. 2.0+/-2.0 with p<0.05) and decreased levels of adiponectin (12.5+/-4.8 vs. 17.26+/-10.4 with p<0.0003). Subjects with diabetes compared to the controls had had increased insulin resistance index (69+/-19 vs. 13.45+/-12.73 with p<0.001), CRP levels (4.1+/-4.8 vs. 2.0+/-2.0 with p<0.01) and decreased levels of adiponectin (11.58+/-4.8 vs. 17.26+/-10.4 with p<0.001). Compared to the controls, there was no significant difference in the levels of resistin in subjects with CAD (4.92+/-3.2 vs. 4.1+/-2.4) as well as diabetes (4.92+/-3.2 vs. 4.6+/-2.6). Both CRP and resistin levels correlate with TNF-alpha (r=0.557, p<0.000001; r=0.84, p<0.000001). Conclusions: The present study shows decreased plasma adiponectin levels in subjects with diabetes as well as in subjects with CAD is similar to the literature. Plasma levels of resistin in subjects with CAD or diabetes are similar to the controls. However, there was a strong correlation of resistin levels with inflammatory markers. This suggests resistin as an inflammatory marker associated with CAD.     

急性脑出血患者颈动脉斑块与血清hs CRP 及HbAlc的相关性研究

目的:探究急性脑出血患者颈动脉斑块与血清超敏C反应蛋白(hs-CRP)及糖化血红蛋白(Hb Alc)的相关性。方法:随机选取我院2013年5月至2015年1月脑科收治的急性脑出血患者84例,根据颈动脉粥样硬化标准将所有患者分为单纯脑出血组(n=25)、轻度粥样硬化组(n=34)和重度粥样硬化组(n=25)三组,另选取同期我院健康体检者50人(对照组)。对比分析四组颈总动脉膜厚度(IMT)空腹血糖(FPG)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、hs-CRP与Hb Alc水平,分析急性脑出血患者颈动脉斑块的危险因素。结果:四组的IMT、TC、TG、HDL、LDL、hs-CRP和Hb Alc水平差异均具有统计学意义(P0.05),其中hs-CRP和Hb Alc水平在单纯脑出血组轻度粥样硬化组重度粥样硬化组(P0.05);IMT与hs-CRP和Hb Alc均呈现正相关(r=0.388、0.420,P0.05);IMT、hs-CRP和Hb Alc均为颈动脉粥样硬化的危险因素(OR=3.065、1.978、1.647,P0.05)。结论:急性脑出血患者体内hs-CRP及Hb Alc水平是颈动脉斑块形成的危险因素。     

Soluble cell adhesion molecules s-VCAM-1 and s-ICAM-1 in subjects with familial combined hyperlipidemia

Familial combined hyperlipidemia (FCH) is the most common familial hyperlipidemia with a high risk for early atherosclerosis. The aim of this study was to compare levels of soluble intercellular cell adhesion molecule 1 (s-ICAM-1) and soluble vascular cell adhesion molecule 1 (s-VCAM-1) in asymptomatic members of FCH families with healthy controls and to determine the relation between s-ICAM-1, s-VCAM-1 and risk factors accompanying FCH. We also investigated the association between adhesion molecules and the intima-media thickness (IMT) of the common carotid artery, a recognized morphological marker of early atherosclerosis. 82 members of 29 FCH families were divided into the 2 groups: HL (probands and hyperlipidemic first-degree relatives, n = 47) and NL (normolipidemic first-degree relatives, n = 35). The control groups--HL-C (n = 20) and NL-C (n = 20)--consisted of sex- and age-matched healthy individuals. Hyperlipidemic members had significantly higher concentration of s-ICAM-1 (633.7 +/- 169.6 ng/ml versus 546.2 +/- 155.9 ng/ml, p < 0.05). The elevation of s-VCAM-1 was not significant (880.8 +/- 202.9 ng/ml versus 826.5 +/- 174.6 ng/ml, N.S.). Levels of s-ICAM-1 and of s-VCAM-1 in normolipidemic relatives were not significantly different from the control group (530.8 +/- 113.9 ng/ml versus 530.0 +/- 101.0 ng/ml and 860.2 +/- 265.7 ng/ml versus 822.1 +/- 197.0 ng/ml respectively). There was a significant correlation between s-ICAM-1 and apoB (r = 0.42; p < 0.01) in hyperlipidemic subjects and between s-ICAM-1 and proinsulin (r = 0.54; p < 0.01) in normolipidemic subjects. S-ICAM-1 correlated with IMT (r = 0.32; p < 0.05) in all members of FCH families. The increase of s-ICAM-1 in asymptomatic hyperlipidemic members of FCH families reflects their high cardiovascular risk. The positive association between s-ICAM-1 and IMT could indicate s-ICAM-1 as a potential predictor of atherosclerosis manifestation.     

Atherogenic vascular and lipid phenotypes in young patients with Type 1 diabetes are associated with diabetes high-risk HLA genotype

Expression of human leukocyte antigen (HLA) class II molecules on islet endothelial cells is a central vascular event in the pathogenesis of Type 1 diabetes. Previous studies demonstrated the ability of other vascular endothelial cells to express HLA and thereby to process islet autoantigens on their surface. We investigated whether the HLA-DQ2/8 genotype, which confers the highest risk for Type 1 diabetes, is associated with early atherosclerosis in youths with this disease. Brachial artery endothelium-dependent, flow-mediated dilation (BA-FMD) and carotid artery intima-media thickness (CA-IMT), as well as markers of systemic inflammation [C-reactive protein (CRP), fibrinogen, and orosomucoid], HbA(1C), LDL, HDL, and total cholesterol, were assessed in 86 children and adolescents with Type 1 diabetes (mean age and diabetes duration, 15 and 7 yr, respectively) between 2004 and 2006. HLA genotypes were determined in dried blood spots by an oligoblot hybridization method. As a result, HLA-DQ2/8 was detected in 34 patients (DQ2/8). When this group was compared with the remaining patients (non-DQ2/8, n = 52), there were no differences in age, diabetes duration, HbA(1C), body mass index, inflammatory markers, and IMT (P > or = 0.4). In the DQ2/8 group, LDL-to-HDL ratio was elevated compared with that in the non-DQ2/8 group (1.8 vs. 1.3, respectively; P = 0.001), whereas FMD did not significantly differ between the groups (5.3% vs. 6.7%, respectively; P = 0.08). When patients were further categorized in relation to CRP (cut-off value, 1 mg/l), BA-FMD was significantly lower (3%, P < 0.01), whereas LDL-to-HDL ratio increased further (2.2, P < 0.001) in the subgroup of DQ2/8 and CRP > or = 1 patients compared with the remaining three subgroups. These associations remained significant after adjustment for age, diabetes duration, and HbA(1C) by analysis of covariance. The brachial artery responses to nitroglycerine were similar in all subgroups. In conclusion, the diabetes-predisposing HLA-DQ2/8 genotype in children and adolescents with Type 1 diabetes interferes with endothelial and lipid-related mechanisms of early atherosclerosis, possibly in part through inflammatory pathways.     

Role of CC chemokines (macrophage inflammatory protein-1 beta, monocyte chemoattractant protein-1, RANTES) in acute lung injury in rats

The role of the CC chemokines, macrophage inflammatory protein-1 beta (MIP-1 beta), monocyte chemotactic peptide-1 (MCP-1), and RANTES, in acute lung inflammatory injury induced by intrapulmonary deposition of IgG immune complexes injury in rats was determined. Rat MIP-1 beta, MCP-1, and RANTES were cloned, the proteins were expressed, and neutralizing Abs were developed. mRNA and protein expression for MIP-1 beta and MCP-1 were up-regulated during the inflammatory response, while mRNA and protein expression for RANTES were constitutive and unchanged during the inflammatory response. Treatment of rats with anti-MIP-1 beta Ab significantly decreased vascular permeability by 37% (p = 0.012), reduced neutrophil recruitment into lung by 65% (p = 0.047), and suppressed levels of TNF-alpha in bronchoalveolar lavage fluids by 61% (p = 0.008). Treatment of rats with anti-rat MCP-1 or anti-rat RANTES had no effect on the development of lung injury. In animals pretreated intratracheally with blocking Abs to MCP-1, RANTES, or MIP-1 beta, significant reductions in the bronchoalveolar lavage content of these chemokines occurred, suggesting that these Abs had reached their targets. Conversely, exogenously MIP-1 beta, but not RANTES or MCP-1, caused enhancement of the lung vascular leak. These data indicate that MIP-1 beta, but not MCP-1 or RANTES, plays an important role in intrapulmonary recruitment of neutrophils and development of lung injury in the model employed. The findings suggest that in chemokine-dependent inflammatory responses in lung CC chemokines do not necessarily demonstrate redundant function.     

Elevated levels of matrix metalloprotein-3 in patients with coronary aneurysm: A case control study

BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of arterial aneurysms through increased proteolysis of extracellular matrix proteins. Increased proteolysis due to elevated matrix degrading enzyme activity in the arterial wall may act as a susceptibility factor for the development of coronary aneurysms. The aim of this study was to investigate the association between MMPs and presence of coronary aneurysms. METHODS: Thirty patients with aneurysmal coronary artery disease and stable angina were enrolled into study (Group 1). Fourteen coronary artery disease patients with stable angina were selected as control group (Group 2). MMP-1, MMP-3 and C-reactive protein (CRP) were measured in peripheral venous blood and matched between the groups. RESULTS: Serum MMP-3 level was higher in patients with aneurismal coronary artery disease compared to the control group (20.23 +/- 14.68 vs 11.45 +/- 6.55 ng/ml, p = 0.039). Serum MMP-1 (13.63 +/- 7.73 vs 12.15 +/- 6.27 ng/ml, p = 0.52) and CRP levels (4.78 +/- 1.47 vs 4.05 +/- 1.53 mg/l, p = 0.13) were not significantly different between the groups. CONCLUSION: MMPs can cause arterial wall destruction. MMP-3 may play role in the pathogenesis of coronary aneurysm development through increased proteolysis of extracellular matrix proteins.     

Plasma and urine levels of resistin and adiponectin in chronic kidney disease

BACKGROUND: Subjects with chronic kidney disease (CKD) have an increased risk of developing coronary atherosclerosis. Adipocyte hormones, resistin and adiponectin are implicated in insulin resistance and atherosclerosis. However, few studies in the literature address the role of adipocyte hormones in CKD. The aim of this study was to compare the levels of resistin, adiponectin and other inflammatory markers in subjects with CKD with those of the control subjects. MATERIALS AND METHODS: In a cross-sectional study, we measured basal metabolic panel, fasting lipid panel and levels of glucose, resistin, adiponectin, insulin, C-reactive protein (CRP) and TNF-alpha in 43 subjects with CKD compared with those of 34 control subjects. We also measured the resistin and adiponectin levels in urine samples (16). RESULTS: Subjects with CKD have increased insulin levels and insulin resistance index (IRI). Compared with controls, subjects with CKD had increased levels of resistin (5.12+/-3.2 vs.7.5+/-5.9; p<0.05), CRP (1.7+/-2.2 vs. 5.97+/-6.0; p<0.0005), and TNF-alpha (3.4+/-2.0 vs. 5.2+/-3.5; p<0.005). Resistin levels correlate with CRP and TNF-alpha, even with BMI as a covariate. Although 60% of subjects with CKD have CAD, e plasma levels of adiponectin were not decreased in subjects with CKD compared with controls (17.02+/-9.8 vs. 16.40+/-9.0 with p value 0.78). Urinary adiponectin levels correlate inversely with GFR (r=-0.4; p<0.05) and plasma adiponectin levels (r=0.9; p<0.0001). CONCLUSIONS: Subjects with CKD had normal levels of plasma adiponectin despite the adverse metabolic environment for CAD. In addition, this study demonstrates the relationship between resistin and TNF-alpha in subjects with CKD and suggests that resistin may play a role in the sub-clinical inflammation associated with CKD, suggesting that adiponectin clearance may be decreased as shown by the inverse correlation of urinary adiponectin with GFR.     

Association of APOE genotype with carotid atherosclerosis in men and women: the Framingham Heart Study

The aim of this study was to determine the association between APOE genotype and carotid atherosclerosis, defined as intimal-medial thickness (IMT) and stenosis, and to assess if other cardiovascular risk factors modify this association. A total of 1,315 men and 1,408 women from the Framingham Offspring Study underwent carotid ultrasound during examination cycle 6 and had complete data on APOE genotype. Three APOE genotype groups were defined: APOE2 (including E2/E2, E3/E2 genotypes), APOE3 (E3/E3), and APOE4 (including E4/E3, E4/E4 genotypes). Carotid IMT and the presence of carotid stenosis > 25% were determined by ultrasonography. In women, the APOE2 group was associated with lower carotid IMT (0.67 vs. 0.73 mm) and lower prevalence of stenosis (odds ratio = 0.49; 95% confidence interval = 0.30-0.81) compared with the APOE3 group. In men, APOE genotype was not associated with carotid IMT or stenosis in the whole group; however, diabetes modified the association between APOE genotype and carotid IMT (P for interaction = 0.044). Among men with diabetes, the APOE4 group was associated with a higher internal carotid artery IMT (1.22 mm) than the APOE3 group (0.90 mm) or the APOE2 group (0.84 mm). The E2 allele was associated with lower carotid atherosclerosis in women, and the E4 allele was associated with higher internal carotid IMT in diabetic men.     

Markers of inflammation are inversely associated with VO2 max in asymptomatic men.

We investigated whether markers of inflammation, including a cytokine (IL-6), acute-phase reactants [C-reactive protein (CRP) and fibrinogen], and white blood cell (WBC) count are associated with maximal O(2) consumption (Vo(2 max)) in men without coronary heart disease (CHD). In asymptomatic men (n = 172, 51 +/- 9.3 yr old), Vo(2 max) was measured during a symptom-limited graded treadmill exercise test. Physical activity level was assessed by a standardized questionnaire. IL-6 and CRP were measured by immunoassays, fibrinogen by the Clauss method, and WBC count with a Coulter counter. IL-6 and CRP were logarithmically transformed to reduce skewness. Multivariable regression was used to assess whether markers of inflammation were associated with Vo(2 max) after adjustment for age, body mass index, CHD risk factors, and lifestyle variables (physical activity level, percent body fat, and alcohol intake). Vo(2 max) was 34.5 ml.kg(-1).min(-1) (SD 6.1). Log IL-6 (r = -0.38, P < 0.001), log CRP (r = -0.40, P < 0.001), fibrinogen (r = -0.42, P < 0.001), and WBC count (r = -0.22, P = 0.004) were each correlated with Vo(2 max). In separate multivariable linear regression models that adjusted for age, body mass index, CHD risk factors, and lifestyle variables, log IL-6 [beta-coeff = -1.66 +/- 0.63 (SE), P = 0.010], log CRP [beta-coeff = -0.99 +/- 0.33 (SE), P = 0.003], fibrinogen [beta-coeff = -1.51 +/- 0.44 (SE), P = 0.001], and WBC count [beta-coeff = -0.52 +/- 0.30 (SE), P = 0.088] were each inversely associated with Vo(2 max). In conclusion, higher circulating levels of IL-6, CRP, and fibrinogen are independently associated with lower Vo(2 max) in asymptomatic men.     

Serum C-reactive protein (CRP) levels and insulin resistance in non-obese women with polycystic ovarian syndrome, and effect of bicalutamide on hirsutism, CRP levels and insulin resistance

BACKGROUND/AIMS: Insulin resistance is associated with serum C-reactive protein (CRP) levels. We aimed to evaluate the effect of bicalutamide on insulin resistance and serum CRP levels in non-obese polycystic ovarian syndrome (PCOS) patients. METHODS: 40 non-obese patients (BMI < or =25 kg/m2) with PCOS and, 40 age- and BMI-matched healthy women were studied. Patients received bicalutamide orally at the dose of 25 mg/day. Serum CRP levels were measured with immunometric assay. Homeostasis model assessment (HOMA-IR) index was used for insulin resistance. RESULTS: Mean Ferriman-Gallwey score (FGS) (p = 0.001), insulin (p = 0.001), serum glucose (p = 0.001), prolactin (p < 0.003), total (p < 0.04) and free testosterone (p = 0.001) and free androgen index (FAI) levels (p = 0.001) of PCOS subjects were higher than in the control group. Mean HOMA-IR of PCOS patients was higher than in control subjects (2.43 +/- 1.2 and 0.94 +/- 0.37, p = 0.001). CRP levels in subjects with PCOS was also higher than in control subjects (4.27 +/- 1.33 and 0.98 +/- 0.19, p = 0.001). After bicalutamide treatment, FGS, free and total testosterone and FAI decreased (p = 0.001). HOMA-IR, prolactin and CRP levels did not show any statistical difference with bicalutamide treatment. CONCLUSIONS: PCOS patients had insulin resistance and a high CRP level. Bicalutamide treatment did not influence insulin resistance and CRP level in PCOS, and this ineffectiveness of bicalutamide on CRP levels may be the result of insulin resistance and/or high prolactin levels at this time.     

Circulating oxidized low-density lipoprotein and common carotid artery intima-media thickness in a random sample of middle-aged men

Circulating oxidized low-density lipoprotein (oxLDL) has been suggested to play an important role in atherosclerosis development. According to previous observations, oxLDL correlates with clinically manifest coronary and carotid artery disease. We investigated the association between the oxLDL concentration measured directly in plasma and common carotid artery intima-media thickness (IMT) in a population-based, case-control study in middle-aged men from Southern Finland. oxLDL was determined in 214 men by a commercially available sandwich ELISA test (Mercodia). Carotid artery IMT was measured at 12 standardized segments by B-mode ultrasonography (at the near and far wall of the left and right common carotid arteries, bifurcations and internal carotid arteries), and the overall mean maximum IMT (MMaxIMT) was calculated. The MMaxIMT of the carotid arteries was significantly associated with circulating oxLDL (r_s=0.16, p=0.018). In a stepwise multiple regression model with MMaxIMT as dependent variable and systolic blood pressure, smoking, oxLDL, HDL cholesterol and apolipoprotein B as covariates, systolic blood pressure (=0.22, p<0.001), oxLDL (=0.15, p=0.022) and smoking (=0.17, p=0.014) showed an independent association with IMT (R²=0.10, p<0.001). Our results show that oxLDL measured directly from plasma is independently associated with subclinical carotid artery atherosclerosis in middle-aged men.     

Influence of age, body mass index, and blood pressure on the carotid intima-media thickness in normotensive and hypertensive patients.

We investigated whether body mass index and blood pressure have an additive influence on the carotid intima-media thickness (IMT). In 27 patients treated for hypertension (47.2+/-8.7 years) and 23 normotensive subjects (44.1+/-8.1 years), 24-h recording of blood pressure was performed. The carotid IMT was determined by ultrasonography and baroreflex sensitivity by a spectral method from 5-min recordings of blood pressure. Significant differences between hypertensive and normotensive subjects were observed for carotid IMT (0.60+/-0.08 vs. 0.51+/-0.07 mm; p<0.001) and baroreflex sensitivity (3.5+/-1.8 vs. 5.6+/-2.1 ms/mm Hg; p<0.001). Hierarchical multiple regression analysis (p<0.01) showed that carotid IMT was positively correlated with age (p<0.001) and body mass index (p<0.05) in normotensive subjects. The increased carotid IMT in hypertensive patients was not additively influenced by either age or body mass index. Baroreflex sensitivity decreased with age (p<0.01) and with carotid IMT (p<0.05) in normotensive subjects only. Multiregression analysis showed that an additive influence of age and body mass index on the development of carotid IMT is essential only in normotensive subjects. In hypertensive subjects the influence of blood pressure predominates, as documented by a comparison of the carotid IMT between hypertensive and normotensive subjects.