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Abstract: The endogenous catecholamine release-inhibitory peptide catestatin (CST) regulates events leading to hypertension and cardiovascular disease. Earlier we studied the structure of CST by NMR, molecular modeling, and amino acid scanning mutagenesis. That structure has now been exploited for elucidation of interface pharmacophores that mediate binding of CST to its target, with consequent secretory inhibition. Designed pharmacophore models allowed screening of 3D structural domains. Selected compounds were tested on both cultured catecholaminergic cells and an in vivo model of hypertension; in each case, the candidates showed substantial mimicry of native CST actions, with preserved or enhanced potency and specificity. The approach and compounds have thus enabled rational design of novel drug candidates for treatment of hypertension or autonomic dysfunction. [Copyright &y& Elsevier]

Abstract: In Type 2 Diabetes (T2D), adiponectin (AdipoQ) and sulphonylurea receptor genes (ABCC8) are important targets for candidate gene association studies. The single nucleotide polymorphisms (SNPs) in these genes have been associated with features of the metabolic syndrome across various populations. The present case–control study undertaken in the population of Punjab, evaluates the association of +45T>G polymorphism in AdipoQ gene; and Exon16-3C>T as well as Exon18C>T polymorphisms in ABCC8 gene with T2D. These SNPs were genotyped in 200 T2D cases and 200 non-diabetic healthy controls using the PCR-RFLP method. The frequency of the minor G-allele for AdipoQ+45(T>G) polymorphism was significantly higher in T2D cases (29.0%) than in controls (21.5%) [P=0.02, OR=1.49 (1.07–2.04)]. The genetic model analysis revealed that the G-allele cumulatively provides nearly 1.59–1.78 fold increased risk to T2D under the additive (P=0.009; OR=1.59, 1.12–2.25 at 95% CI), dominant (TG/GG vs. TT) (P=0.034, OR=1.64, 1.04–2.56 at 95% CI) and codominant model (TG vs. TT/GG) (P=0.014; OR=1.78, 1.12–2.82 at 95% CI) after adjusting for confounding factors. However, no difference in the distribution of genotype and allele frequencies was observed for both the ABCC8 polymorphisms. The distribution of obesity profiles (BMI, WC and WHR) was also significantly different between cases and controls (P<0.05). Higher BMI and central obesity were observed to increase the risk of T2D. G-allele of +45(T>G) polymorphism in the adiponectin gene appears to be associated with increased risk of T2D, but the polymorphisms in sulphonylurea receptor gene do not seem to be associated with T2D in the population of Punjab. [Copyright &y& Elsevier]

Abstract: There is emerging interest in the potential of the phenolic compounds of Asiatic plantain (Plantago asiatica L.) to attenuate in vitro and in vivo oxidative stress. We hypothesized that a single administration of Asiatic plantain beverage may exert protective effects against postprandial oxidative stress. This preliminary study was designed to compare the ability of different doses of Asiatic plantain beverage to mitigate the postprandial effects of a high-fat meal on the oxidation of lipids and DNA in overweight hyperlipidemic subjects. In a randomized, double-blind, placebo-controlled parallel design (n = 10/group), 40 subjects were administered a single high-fat meal with either a placebo or 1 of 3 Asiatic plantain extract beverages (low, intermediate, or high dose). Blood samples were obtained at fasting and 60, 120, 240, and 360 minutes (total of 5 samples) after intervention. The data showed a tendency for plasma free fatty acid levels to decrease in response to high-dose Asiatic plantain at all time points. Plasma oxidized low-density lipoprotein levels were significantly reduced with high-dose Asiatic plantain at 120 minutes (P = .0251 vs placebo). A comet assay revealed that DNA damage in lymphocytes was significantly decreased by Asiatic plantain at 360 minutes (P = .0225 vs placebo). There were no treatment differences in triglyceride or malondialdehyde levels. The maximum suppression was achieved with a high dose (20 g Asiatic plantain extract/80 mL). These results suggest that by protecting low-density lipoprotein and DNA, an Asiatic plantain beverage may be useful to enhance antioxidant. [Copyright &y& Elsevier]

Abstract: Background: Femoral artery pseudoaneurysm (FAP) is a troublesome complication after transfemoral catheter procedures. The incidence and predictors of FAP as a separate entity have not been extensively studied. Aim: Detect prospectively the incidence and predictors of post catheterization FAP. Methods: From June 2009 till June 2011, we prospectively included all patients who underwent catheterization from the femoral approach. Duplex ultrasound was performed in cases with clinical suspicion of vascular complications. Clinical data and procedural variables were compared with a control group of 200 randomly selected patients. We performed univariate analysis and a logistic regression model for multivariate analysis. Results: The incidence of FAP was 3.42%. Eighty FAPs (66.7%) were related to a diagnostic catheterization while 40(33.3%) were related to an interventional procedure. The mean age of patients with FAP was 55.36±10.68yrs; 57.5% were females. At diagnosis 81.66% of the patients were on antiplatelet therapy, 35% were on heparin or warfarin and 16.66% were on both, with mean value of INR for patients on warfarin 2.2±0.76. FAPs were connected to the common femoral artery in 29.1% of patients, to the SFA in 54.1% and to the profunda in 16.6%. Female gender, obesity and hypertension significantly enhanced the risk for FAP. Also diagnostic angiography, low puncture, multiple punctures and the use of dual antiplatelet and/or anticoagulant therapy were independent procedure-related risk factors for FAP. Conclusion: Femoral artery pseudoaneurysms are not uncommon. Female gender, obesity, hypertension, the use of antiplatelet and/or anticoagulant therapy and faulty puncture techniques are independent risk factors for FAPs. [Copyright &y& Elsevier]

Copyright of Diabetes & Metabolism is the property of Masson Editeur and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: It is hypothesized that healthy dietary and physical activity choices will be inversely associated with coronary heart disease (CHD) risk factors. Results from a cross-sectional study of 294 first-year University of Rhode Island students were used for the analyses. The presence of CHD risk factors was defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines. Diet was assessed by three 24-hour food recalls, and physical activity was assessed by the International Physical Activity Questionnaire. Logistic regression models adjusted for sex estimated the odds of having CHD risk factors. A higher percent of kilocalories from alcohol was associated with a 9.9% increased risk for elevated triacylglycerol (odds ratio [OR], 1.099; 95% confidence interval [CI], 1.000-1.207). Sugar intake (OR, 1.015; 95% CI, 1.004-1.026), saccharin intake (OR, 1.047; 95% CI, 1.015-1.080), and body mass index (BMI; OR, 1.139; 95% CI, 1.037-1.252) were associated with an increased risk of low high-density lipoprotein cholesterol; dietary fiber intake (OR, 0.934; 95% CI, 0.873-1.000) was associated with a decreased risk of low high-density lipoprotein cholesterol. Participants with a higher BMI were 9.4% more likely to have elevated fasting glucose (OR, 1.094; 95% CI, 1.004-1.192) and 193.6% more likely to have a larger waist circumference (OR, 2.936; 95% CI, 1.543-5.586). Dietary factors and BMI are better indicators of CHD risk than physical activity is in this population. [Copyright &y& Elsevier]

Abstract: Objective: Dozens of single nucleotide polymorphisms (SNPs) in the lipoprotein lipase (LPL) gene have been reported to be associated with lipid concentrations. The aim of this study was to validate the association between rs1059611 in the LPL gene and serum lipid concentrations in the Chinese Han population and explore the biological relevance. Methods: A total of 5664 participants were recruited and genotyped for the SNP. Gene expression levels of LPL in blood cells were evaluated by real-time PCR and western blotting analysis. The functional potential of the SNP was examined by luciferase reporter assay and electrophoretic mobility-shift assay (EMSA). Results: We observed significant associations between rs1059611 and increased HDL-C (P = 5.65 × 10−5) and decreased TG concentrations (P = 2.68 × 10−7). We also found that participants with the C allele had higher mRNA expression level (P = 0.0334) and protein expression level (P = 0.0641) of LPL. The luciferase activity of the rs1059611 T construct was 0.69-fold of the rs1059611 C construct (P = 0.0009). The EMSA showed that the binding of the transcription factor(s) differed for the alleles of the SNP. Conclusion: The results of our study demonstrated that rs1059611 was associated with HDL-C and TG concentrations in Chinese Han population and might have a functional effect on the transcription of LPL by differential binding of transcription factors. [Copyright &y& Elsevier]

Abstract: Background and aim: To verify if the carotid plaque development is concomitant to brachial artery diameter enlargement, in healthy postmenopausal women. Methods and results: This is a retrospective, recall study. We enrolled 40 postmenopausal women, selected from a database for the period 2000–2008, not affected by subclinical carotid atherosclerosis and without risk factors for cardiovascular disease. At the recall visit, carotid and brachial duplex scan was again obtained. The incidence of plaque was 30% after a mean follow-up period of 60 months. There were no differences in baseline characteristics between subjects developing carotid atherosclerosis and subjects who did not, except for the brachial diameter change, follow-up and heart rate. The logistic-regression analysis confirmed that only brachial diameter change resulted to be correlated with the development of carotid atherosclerosis. Conclusion: Brachial artery diameter increase is concomitant to carotid plaque development. Vascular enlargement could not be a focal change but a systemic process associated with atherosclerotic plaque development. Brachial diameter could be a tool with a predictive significance. [Copyright &y& Elsevier]

Background: This study evaluated the feasibility of performing thoracoscopy without lung isolation employing single lumen endotracheal tube (SLET) intubation and carbon dioxide insufflation. Methods: Eighty-two patients underwent a variety of thoracoscopic procedures without lung isolation using SLET intubation and carbon dioxide (CO2) insufflation between January and December 2012. Sixty-five of these patients underwent wedge resections and were isolated for analysis. Operations were accomplished using percutaneously placed laparoscopic trocars and insufflation up to 15 mm Hg. Operative times, length of stay, and vital signs were compared with 52 patients who underwent thoracoscopic wedge resections with double lumen endotracheal tube (DLET) intubation. Results: A retrospective analysis was performed on 65 patients (30 females, mean age 58) who underwent thoracoscopic wedge resections with SLET intubation compared with 52 patients undergoing the same procedure with DLET intubation. Operating room time (111 ± 4.74 minutes), time to incision (49 ± 1.91 minutes), and operative time (48 ± 2.89 minutes) were significantly decreased in the SLET group (p < 0.05). Intraoperative hemodynamic parameters showed no significant aberrations. Two postoperative complications (3.1%) were identified in the SLET group. Length of stay was similar (3 ± 0.49 days versus 3 ± 0.23 days). Conclusions: Single lumen endotracheal tube intubation is a feasible and safe airway management alternative for thoracoscopic procedures. This method resulted in shorter operative times, no aberrant hemodynamic shifts, low complication rates, and similar hospital stays as compared with traditional DLET intubation. [Copyright &y& Elsevier]

Objectives: This study sought to determine the current effectiveness and safety of sympathetic renal denervation (RDN) for resistant hypertension. Background: RDN is a novel approach that has been evaluated in multiple small studies. Methods: We performed a systematic review and meta-analysis of published studies evaluating the effect of RDN in patients with resistant hypertension. Studies were stratified according to controlled versus uncontrolled design and analyzed using random-effects meta-analysis models. Results: We identified 2 randomized controlled trials, 1 observational study with a control group, and 9 observational studies without a control group. In controlled studies, there was a reduction in mean systolic and diastolic blood pressure (BP) at 6 months of –28.9 mm Hg (95% confidence interval [CI]: –37.2 to –20.6 mm Hg) and –11.0 mm Hg (95% CI: –16.4 to –5.7 mm Hg), respectively, compared with medically treated patients (for both, p < 0.0001). In uncontrolled studies, there was a reduction in mean systolic and diastolic BP at 6 months of –25.0 mm Hg (95% CI: –29.9 to –20.1 mm Hg) and –10.0 mm Hg (95% CI: –12.5 to –7.5 mm Hg), respectively, compared with pre-RDN values (for both, p < 0.00001). There was no difference in the effect of RDN according to the 5 catheters employed. Reported procedural complications included 1 renal artery dissection and 4 femoral pseudoaneurysms. Conclusions: RDN resulted in a substantial reduction in mean BP at 6 months in patients with resistant hypertension. The decrease in BP was similar irrespective of study design and type of catheter employed. Large randomized controlled trials with long-term follow-up are needed to confirm the sustained efficacy and safety of RDN. [Copyright &y& Elsevier]

Abstract: Background: The aim of this study was to investigate the individual or combined effects of PPARA-L162V, PPARG-C161T and APOE polymorphisms on hyperlipidemia in coronary heart disease (CHD) patients. Methods: Our study included 223 patients with CHD (103 with type 2 diabetes (T2DM), 120 without diabetes) and 101 controls. All genotypes were determined by PCR–RFLP technique. Results: Genotypic and allelic distributions of PPARA-L162V polymorphism were similar between study and control groups (p >0.05). The serum total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels were higher in PPARA-V162 allele carriers in non-diabetic CHD patients (p =0.007 and p =0.038, respectively). The increasing effect of the PPARA-V162 allele on serum TC and LDL-C levels was weakened with the presence of PPARG-161T allele in the non-diabetic CHD patients. The ApoE4–PPARA-V162 allelic combination of the ApoE/PPARA genes was found to be more frequent in diabetic CHD patients independent of serum lipids (p =0.035). Conclusions: The PPARA V162 allele has an increasing effect on TC and LDL-C levels and this effect was reduced by carrying PPARG T161 allele in non-diabetic CHD patients. On the other hand, the V162 allele may be associated with an increased risk of CHD in diabetic CHD patients due to the presence of ApoE4 allele independent of serum lipids. We suggest that the PPARA L162V polymorphism may have diverse effects on serum lipids and CHD risk depends on the presence of T2DM. [Copyright &y& Elsevier]

Abstract: Objective: To assess the relationship between exercise tolerance test (ETT) performance at 6 weeks poststroke and subsequent performance in a treadmill and overground locomotor training program (LTP). Design: Prospective cohort study. Setting: Exercise testing laboratory in either a primary care hospital or outpatient clinic. Participants: Community-dwelling individuals (N=469), 54.9±19.0 days poststroke, enrolled in the Locomotor Experience Applied Post-Stroke randomized controlled trial. Interventions: Not applicable. Main Outcome Measures: For participants randomly assigned to LTP, the number of sessions needed to attain the training goal of 20 minutes of treadmill stepping was determined. Regression analyses determined the contribution of ETT performance (cycling duration), age, and 6-minute walk test (6MWT) distance to attainment of the stepping duration goal. Results: Age, 6MWT, and ETT performance individually accounted for 10.74%, 10.82%, and 10.76%, respectively, of the variance in the number of sessions needed to attain 20 minutes of stepping. When age and 6MWT were included in the model, the additional contribution of ETT performance was rendered nonsignificant (P=.150). Conclusions: To the extent that ETT performance can be viewed as a measure of cardiovascular fitness rather than neurologic impairment, cardiovascular fitness at the time of the ETT did not make a significant unique contribution to the number of sessions needed to achieve 20 minutes of stepping. The 6MWT, which involves less intensive exercise than the ETT and therefore is likely to be predominantly affected by neurologic impairment and muscular condition, appeared to account for as much variance as the ETT. [Copyright &y& Elsevier]

Abstract: Objective: The aim of this study was to evaluate the relationship of tricipital (TS), abdominal (AS), subscapular (SS), and suprailiac (SIS) skinfolds, Body Mass Index (BMI), and Waist Circumference (WC) with 1) variables related to cardiovascular risk (CVR) and 2) the clustering of cardiovascular risk factors (CVRF) – referenced pediatric cut-off points – in a multivariate analysis. Materials/Methods: The sample was 1672 adolescents. Glucose, lipid profile, blood pressure and anthropometric variables were measured. Results: Adjusting for age, gender, and caloric intake, the highest quartile (Q4) of adiposity markers was associated to Q4 of biochemical and blood pressure variables. However, the association was not found for WC, SS and TS with glucose, and for diastolic blood pressure (DBP) with TS, SS, and SIS. Triglycerides Q4 was related to Q4 of SS, AS, and SIS after further adjustments, as well as HDL cholesterol (HDL-C) Q1 with Q4 of SS and AS. Glucose Q4 was associated to BMI, AS (Not adjusting for BMI and SIS), and SIS Q4 (Not adjusting for BMI and TS). LDL-Cholesterol (LDL-C) Q4 was associated to TS and SS Q4. The associations of LDL-C Q4 and HDL-C Q1 with WC Q4 were not significant after further adjustments. All the adiposity markers, except WC and TS, were associated to CVRF clustering in all the adjustments. Conclusions: In the adolescents, subcutaneous fat from the trunk (SS, AS, SIS) was better and independently associated to CVR variables and with CVRF clustering than visceral fat (WC). Further research is required to explain the specificity in the described associations. [Copyright &y& Elsevier]

Objectives: The objective of this study was to examine trends in predicted 10-year risk for coronary heart disease (CHD) and cardiovascular disease (CVD) from 1999 to 2000 and from 2009 to 2010 among adults in the United States. Background: Examining trends in predicted risk for CHD and CVD may offer insights into the direction of cardiovascular health. Methods: Data from 7,751 fasting participants, ages 30 to 74 years, of 6 consecutive 2-year cycles of the National Health and Nutrition Examination Survey were used. Predicted 10-year risk for CHD and CVD was calculated using risk equations derived from data from the Framingham Heart Study. Results: Mean predicted 10-year risk for CHD was 7.2% during 1999 to 2000 and 6.5% during 2009 to 2010 (p for linear trend = 0.005), and for CVD it was 9.2% during 1999 to 2000 and 8.7% during 2009 to 2010 (p for linear trend = 0.152). Mean predicted risk for CHD and CVD declined significantly among participants ages 40 to 49 years, 50 to 59 years, 60 to 74 years, and among women. Mean predicted risk for CHD declined significantly among men and whites but nonsignificantly among Mexican Americans (p for linear trend = 0.067). Mean predicted risk increased nonsignificantly among African Americans for both CHD (p for linear trend = 0.063) and CVD (p for linear trend = 0.059). Of the modifiable cardiovascular risk factors included in the risk equations, favorable trends were noted for mean systolic and diastolic blood pressure, mean concentrations of total cholesterol and high-density lipoprotein cholesterol, and smoking status. The prevalence of diabetes mellitus worsened. Conclusions: Predicted 10-year risk for CHD improved modestly. Reversing the seemingly rising trend in risk among African-American adults should be a high priority. [Copyright &y& Elsevier]

Abstract: Objective: We examined the association between the Minnesota Multiphasic Personality Inventory (MMPI) and all-cause mortality in 4462 middle-aged Vietnam-era veterans. Methods: We split the study population into half-samples. In each half, we used proportional hazards (Cox) regression to test the 550 MMPI items' associations with mortality over 15years. In all participants, we subjected significant (p <.01) items in both halves to principal-components analysis (PCA). We used Cox regression to test whether these components predicted mortality when controlling for other predictors (demographics, cognitive ability, health behaviors, and mental/physical health). Results: Eighty-nine items were associated with mortality in both half-samples. PCA revealed Neuroticism/Negative Affectivity, Somatic Complaints, Psychotic/Paranoia, and Antisocial components, and a higher-order component, Personal Disturbance. Individually, Neuroticism/Negative Affectivity (HR =1.55; 95% CI =1.39, 1.72), Somatic Complaints (HR =1.66; 95% CI =1.52, 1.80), Psychotic/Paranoid (HR =1.44; 95% CI =1.32, 1.57), Antisocial (HR =1.79; 95% CI =1.59, 2.01), and Personal Disturbance (HR =1.74; 95% CI =1.58, 1.91) were associated with risk. Including covariates attenuated these associations (28.4 to 54.5%), though they were still significant. After entering Personal Disturbance into models with each component, Neuroticism/Negative Affectivity and Somatic Complaints were significant, although Neuroticism/Negative Affectivity's were now protective (HR =0.73; 95% CI =0.58, 0.92). When the four components were entered together with or without covariates, Somatic Complaints and Antisocial were significant risk factors. Conclusions: Somatic Complaints and Personal Disturbance are associated with increased mortality risk. Other components' effects varied as a function of variables in the model. [Copyright &y& Elsevier]

Abstract: Background: Receptor for advanced glycation end-product (RAGE) gene polymorphism 2245G/A is associated with diabetic retinopathy (DR). However, the mechanism on how it affects the disease development is still unclear. Aim: This study aims to investigate the relationship between 2245G/A RAGE gene polymorphism and selected pro-inflammatory, oxidative-glycation markers in DR patients. Methods: A total of 371 unrelated type 2 diabetic patients [200 with retinopathy, 171 without retinopathy (DNR)] and 235 healthy subjects were recruited. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism method followed by DNA sequencing. The nuclear and cytosolic extracts from peripheral blood mononuclear cells were used for nuclear factor kappa B (NF-κB) p65 and superoxide dismutase activity measurement respectively. Plasma was used for glutathione peroxidase activity, advanced oxidation protein product (AOPP), monocyte chemoattractant protein (MCP)-1, pentosidine and soluble RAGE (sRAGE) measurements. Results: DR patients with 2245GA genotype had significantly elevated levels of activated NF-κB p65, plasma MCP-1, AOPP and pentosidine but lower level of sRAGE when compared to DR patients with wild-type 2245GG. Conclusion: The RAGE gene polymorphism 2245G/A is associated with pro-inflammatory, oxidative-glycation markers and circulating sRAGE in DR patients. Patients with 2245GA RAGE genotype could aggravate DR possibly via NF-κB mediated inflammatory pathway. [Copyright &y& Elsevier]

Abstract: Whole-body cryotherapy (WBC) is an increasing applied cryotherapeutic method, that involves application of a cryotherapeutic factor to stimulate the body by the means of intense hypothermia of virtually the body’s entire area. This method is still not well recognized in Western Europe. However in recent years it is becoming increasingly popular in sports medicine and also in clinical application. Cryotherapeutic agents used in WBC are considered to be a strong stress stimulus which is associated with a variety of changes in functional parameters, particularly of the cardiovascular and autonomic nervous systems. However, such strong influence upon the entire body could be associated with the risk of unexpected reactions which might be dangerous for homeostasis. The present study evaluated the complex hemodynamic physiological reactions in response to WBC exposure in healthy subjects. Thirty healthy male volunteers participated. Each subject was exposed to WBC (−120°C) for 3-min. None of the participants had been exposed to such conditions previously. The research was conducted with modern and reliable measurements techniques, which assessed complex hemodynamic reactions and skin temperature changes non-invasively. All measurements were performed four times (before WBC, after WBC, WBC+3h and WBC+6h) with a Task Force Monitor (TFM – CNSystems, Medizintechnik, Gratz, Austria). Body superficial temperature was measured by infrared thermographic techniques – infra-red camera Flir P640 (Flir Systems Inc., Sweden). Our results show a significant decrease in heart rate, cardiac output, and increase in stroke volume, total peripheral resistance and baroreceptors reflex sensitivity. These changes were observed just after WBC exposure. At stages WBC+3h and WBC+6h there was observed a significant drop in baroreceptors reflex sensitivity due to increased thermogenesis. In conclusion, the present findings suggest that WBC strongly stimulates the baroreceptor cardiac reflex in response to body fluid changes which sequentially modulate HR and BP control in supine and resting healthy subjects. The study was performed on randomized and homogenic group of young healthy subjects. Our findings are important for WBC safety determination in research and clinical studies. [Copyright &y& Elsevier]

Abstract: Objectives: We aimed to investigate the relationship between platelet microRNA (miR-223 and miR-96) expression and clopidogrel responsiveness in patients with coronary heart disease (CHD). Materials and Methods: A total of 33 consecutive non-diabetic CHD patients scheduled for percutaneous coronary intervention were enrolled. Platelet reactivity after clopidogrel loading dose (300mg) was determined by two methods [platelet reactivity index (PRI), measured by vasodilator-stimulated phosphoprotein (VASP) phosphorylation flow cytometry and ADP-induced platelet aggregation (PAG), measured by light transmission aggregometry]. Total platelet RNA was isolated from purified platelets (CD45 magnetic bead negative selection) to quantify miR-223 and miR-96 expression by real-time PCR. Results: All subjects were dichotomized according to PRI medians (normal-responders: PRI<56.5%, n=17 and low-responders: PRI>56.5%, n=16) and PAG medians (normal-responders: PAG<43%, n=17 and low-responders: PAG>43%, n=16). Compared with PRI-determined normal-responders, miR-223 expression, but not miR-96, was significantly decreased in low-responders (P =0.037). No differential expression of miR-223 and miR-96 was observed via PAG determination between normal- and low-responders. In addition, miR-223 expression, but not miR96, was statistically correlated with PRI (Spearman r =−0.403, P =0.020). Stepwise binary logistic regression analysis revealed that among factors that potentially influence platelet reactivity (CYP2C19*2 loss-of-function genotypes, use of calcium channel blockers/proton-pump inhibitors, age, obesity, smoking and platelet microRNAs), decreased miR-223 expression was the only independent predictor associated with the presence of PRI-determined low responders to clopidogrel (OR 0.189, 95% CI 0.043 to 0.836, P =0.028). Conclusions: The present work identifies decreased platelet miR-223 expression as a novel mechanism involved in blunted platelet response to clopidogrel in a Chinese population. [Copyright &y& Elsevier]

Abstract: Objectives: Both decreased and increased risk of cardiovascular events/mortality have been reported with high adiponectin levels. Only a few studies have reported an association of adiponectin with markers of hemostasis/endothelial dysfunction which might explain the reported discrepancies. Design and methods: We evaluated the association of total adiponectin with von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), soluble thrombomodulin (sTM), adhesion molecules sICAM-1 and sVCAM-1, lipids and markers of insulin resistance (IR) in 308 asymptomatic dyslipidemic subjects and healthy controls. Subjects were divided into 4 dyslipidemic phenotypes (DLP): DLP1 (TG<1.5mmol/L+ApoB<1.2g/L), DLP2 (TG≥1.5+ApoB<1.2), DLP3 (TG<1.5+ApoB≥1.2) and DLP4 (TG≥1.5+ApoB≥1.2). The results were evaluated also according to the presence (+) and absence (−) of metabolic syndrome (MS). Results: In hyperlipidemic subjects (DLP2–4), PAI-1, t-PA and sICAM-1 correlated with markers of IR but only t-PA correlated inversely with adiponectin. In contrast positive association of adiponectin with vWF, sTM and sVCAM-1 was found but none of these parameters correlated with markers of insulin resistance. In multiple regression analysis, adiponectin remained independently associated with vWF [in DLP3, DLP4, DLP2–4, MS(−)], with sTM [in DLP2, DLP4, DLP2–4, MS(+)] and with sVCAM-1 [in DLP2, DLP3, DLP4, DLP2–4, MS(+)]. In healthy controls (DLP1), no association between adiponectin and markers of hemostasis/endothelial dysfunction was found. Conclusion: The independent positive association of adiponectin with vWF, sTM and sVCAM-1 deserves further evaluation in connection with the risk of atherothrombotic cardiovascular events. [Copyright &y& Elsevier]

Abstract: Objectives: The study aimed to analyze the relationship between metabolic variables and estimated glomerular filtration rate (eGFR) and explore the potential risk factors for a mildly reduced eGFR in a community-based population. Design and methods: Cross-sectional study in 643 adults without a history of kidney disease whose eGFR levels were greater than 60mL/min/1.73m2 according to the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). Anthropometric measurements, blood pressure, fasting lipid profile and levels of fasting and post-load glucose, insulin, serum creatinine and uric acid (UA) were tested. The eGFR was calculated, and the correlations between eGFR and each variable were analyzed. Results: The subjects were divided into two groups by using 90mL/min/1.73m2 as the cut-off value of the eGFR. In the lower eGFR group, the age, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), waist circumference (WC), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), 2h post-load plasma glucose (2h-PG) levels and UA were significantly increased, and the incidences of hypertension, diabetes, obesity, hypertriglyceridemia and hypercholesterolemia were also higher (P <0.05). A multiple linear stepwise regression analysis showed that the WC, SBP, FPG and UA were independently correlated with the eGFR after adjusting for the other covariables. Conclusions: The WC, SBP, FPG and UA were closely related to the eGFR in the subjects whose eGFR levels were greater than 60mL/min/1.73m2. The increased WC, SBP, FPG and UA may be the main risk factors for a mildly reduced eGFR. [Copyright &y& Elsevier]

Abstract: The aim of this study was to investigate orthostatic reactions in females with Rett syndrome (RTT), and also whether the severity of the syndrome had an impact on autonomic reactions. Based on signs of impaired function of the central autonomic system found in RTT, it could be suspected that orthostatic reactions were affected. The orthostatic reactions in 21 females with RTT and 14 normally developed females matched by age were investigated when they rose from a sitting position, and during standing for 3min. Reactions of the heart, the blood pressure and the time for recovery of systolic blood pressure, were studied in real time, heartbeat by heartbeat, simultaneously. There was no difference between participants with RTT and the normally developed controls regarding general orthostatic reactions (heart rate, systolic and diastolic blood pressure, and mean arterial pressure) when getting up from a sitting position, and when standing erect for 3min. In the specific immediate response by the heart to standing up, the 30:15 ratio, significantly lower values were found for females with RTT. In the RTT group, the maximum fall of systolic blood pressure showed a tendency to a larger decrease, and the initial decrease in systolic blood pressure was significantly faster. The time for recovery of systolic blood pressure from standing erect did not differ between groups. At baseline the females with RTT had significantly lower systolic blood pressure and a tendency to a higher heart rate. The results do not indicate any autonomic limitations for people with RTT in getting up from a sitting position and standing. The participants with RTT had normal orthostatic reactions indicated by the heart and blood pressure responses when standing erect for 3min. A faster initial drop in systolic blood pressure in people with RTT was notable. [Copyright &y& Elsevier]

Summary: Background & aims: We aimed to examine the prevalence of obesity, abdominal obesity and associated factors in 17,656 Chinese hypertensive adults aged 45–75 years. Methods: A cross-sectional investigation was carried out in Lianyungang, China. Overweight or obesity was defined as a body mass index of ≥25kg/m2. Abdominal obesity was defined as a waist circumference ≥90cm for men and ≥80cm for women. Results: The prevalence of overweight or obesity and abdominal obesity was 54.4% (women 59.3% and men 46.0%) and 59.4% (women 73.8% and men 35.1%), respectively. In the multivariable logistic-regression models, higher hypertension grades and standard of living, greater red meat consumption, lower physical activity levels, and antihypertensive treatment were independently associated with overweight or obesity and abdominal obesity in both sexes. Inland residence (versus coastal) was an independent associated factor for abdominal obesity in both sexes. Furthermore, a positive family history of diabetes in both sexes, a positive family history of hypertension, men with a positive family history of coronary heart disease, and men with inland residence were all independently associated with overweight or obesity. Conclusions: We found a high prevalence of overweight or obesity and abdominal obesity in Chinese hypertensive adults, particularly in inland areas. [Copyright &y& Elsevier]

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Background and aims: Specific Suppressor of Cytokine Signaling (SOCS) members, such as SOCS7, may play a role in the development of insulin resistance (IR) owing to their ability to inhibit insulin signaling pathways. The objective was to explore the association between common variants and related haplotypes in SOCS7 gene and metabolic traits related to obesity, lipid metabolism and IR. Methods and Results: 780 unrelated men were included in a cross-sectional study. We selected three tagged SNPs that capture 100% of SNPs with minor allele frequency ≥ 0.10. Analyses were done separately for each SNP and followed up by haplotype analysis. rs8074124C was associated with both obesity (p = 0.005) and abdominal obesity (p = 0.002) and allele C carriers showed, in comparison with TT carriers, lower BMI (p = 0.001) and waist circumference (p = 0.001). rs8074124CC- carriers showed lower fasting insulin (p = 0.017) and HOMA-IR (p = 0.018) than allele T carriers. rs12051836C was associated with hypertriglyceridemia (p = 0.009) and hypertriglyceridemic waist (p = 0.006). rs12051836CC- carriers showed lower fasting insulin (p = 0.043) and HOMA-IR (p = 0.042). Haplotype-based association analysis (rs8074124 and rs12051836 in that order) showed associations with lipid and obesity -related phenotypes, consistent with single locus analysis. Haplotype analysis also revealed association between haplotype CT and both decreased HDL-C (p = 0.026) and HDL-C (p = 0.014) as a continuous variable. Conclusions: We found, for the first time, significant associations between SOCS7 common variants and related haplotypes and obesity, IR and lipid metabolism disorders. [Copyright &y& Elsevier]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

There is keen interest in continuous and noninvasive blood pressure (BP) measurement. However, many technologies have a shortcoming of complex mechanical structure. In our study, two arterial pulses are acquired by photoplethysmography (PPG) at ear and toe in order to explore a new method of measuring BP by pulse wave velocity (PWV). We previously validated and reported a BP-PWV mathematical model with measurements from humans with no evidence of cardiovascular disease, but were only able to determine PWV related to diastolic blood pressure (DBP). In this paper, we propose methods of identifying pulse transmit time (PTT) in low, normal and high systolic blood pressure (SBP) conditions. By averaging the PTT's of incident wave and reflected wave for non-systematic error reduction, we obtain a PWV that is suitable for estimating SBP. SBP and DBP are estimated by two separate PWV's based on the previously calibrated models. Experimental measurements are conducted on 26 subjects (age 19 ± 1 and 60 ± 1) with no evidence of cardiovascular disease. The measurement errors (Mean Deviation = 2.16 mmHg (SBP) and 1.49 mmHg (DBP); Standard Deviation = 6.23 mmHg (SBP) and 6.51 mmHg (DBP)) satisfy the accuracy criteria of Association for the Advancement of Medical Instrumentation. The results verify that SBP and DBP can be estimated by one mathematical model with the same model parameters and two separate PWV's. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe the pattern of blood pressure (BP) distribution in a multiethnic primary care practice in relation to sociodemographic characteristics, lifestyle and risk factors. Another aim was to analyse the quality of diagnosis and effectiveness of hypertension (HT) treatment. In all, 470 adult patients (16 years old) who visited the Jordbro Health Centre (JHC), Haninge Municipality, participated in this study. A general questionnaire with questions about sociodemographic characteristics, lifestyle, health status and chronic disease was used. Medical records: information on consultations with the general practitioner and prescriptions were collected from the medical records for the year 2001. Furthermore, a medical examination was performed: this consisted of weight, height, systolic (SBP) and diastolic (DBP) blood pressure, and laboratory analyses including fasting blood glucose, serum cholesterol, serum triglycerides, electrocardiogram and spirometry. Out of 464 patients, 114 (24.6%) reported HT. Among the HT patients, 93 (81.6%) had SBP 140 mmHg and 52 (45.6%) DBP 90 mmHg. Among the nonhypertensive patients (n=350), 120 (34.3%) had SBP 140 mmHg and 50 (14.3%) DBP 90 mmHg. Furthermore, there are some patients with high BP who are unknown or undetected. HT treatment among this population is unsatisfactory and greater efforts are required to identify people with high BP and to ensure that they are managed according to the best available evidence.Journal of Human Hypertension (2005) 19, 775–786. doi:10.1038/sj.jhh.1001902; published online 23 June 2005 [ABSTRACT FROM AUTHOR]

Abstract: Estrogen is likely involved in the gender specific differences in coping with stress. Activation of catecholamine (CA) biosynthetic enzyme gene expression in central and peripheral CA systems plays a key role in response to stress and in regulation of the cardiovascular system. Here we examined whether estradiol can modulate response of hypothalamic-pituitary-adrenal axis (HPA), gene expression of enzymes related to CA biosynthesis in several noradrenergic locations, tetrahydrobiopterin (BH4) concentration and blood pressure (BP) in response to immobilization stress (IMO) of ovariectomized female rats. Rats were injected with 25 μg/kg estradiol benzoate (EB) or sesame oil once daily for 16 days and subsequently exposed to two hours of IMO. The IMO triggered elevation in plasma ACTH was lessened in EB-pretreated animals. However, estradiol did not alter the IMO-elicited rise of tyrosine hydroxylase mRNA levels in adrenal medulla (AM) and in the nucleus of solitary track (NTS) compared with controls. The response of GTP cyclohydrolase I (GTPCH) mRNA in AM to IMO was also similar in both groups. Several responses to IMO in EB-treated rats were reversed. Instead of IMO-elicited elevation in dopamine β-hydroxylase mRNA levels in the locus coeruleus, GTPCH mRNA and BH4 levels in the NTS, they were reduced by IMO. In a parallel experiment, BP was monitored during restraint stress. The elevation of BP in response to single or repeated restraint stress was sustained during 2 h in controls and reduced after 70 min stress in EB treated rats. One month after withdrawal of EB treatment, the BP response to restraint was similar to that of rats which never received EB. The results demonstrate that estrogen can modulate responses to stress affecting HPA axis, CA biosynthesis, in central and peripheral noradrenergic systems, and BP. [Copyright &y& Elsevier]

Purpose: The purpose of this study is to examine whether the prevalence of hypertension differs by acculturation status among Hispanics in Dallas County, Texas. The authors test the hypothesis that compared with those of low acculturation, those of mid- and high-level acculturation will be at greater risk for having hypertension. Methods: Conducted from July 2000 through October 2002, the Dallas Heart Study (DHS) is a general population cross-sectional study of cardiovascular risk factors among Dallas County residents. These analyses focus on the 1163 DHS participants who self-reported Hispanic ethnicity, completed a household interview, and had blood pressures measured. Acculturation was assessed with a validated 12-item scale that measured the following dimensions of cultural adaptation: language; media preference; social interaction; and ease of relationships with those of other ethnicities. Results: The majority of participants were born in Mexico (57.5%) and ranged in age from 18 to 65 years (mean age 33 years). Women made up just under half of the sample (47.81%). The unadjusted prevalence of hypertension was 9.78%. When age-adjusted for the 2000 US Standard Population, the prevalence was 17.27%. The χ2 analysis showed that those of low acculturation were significantly less likely to have hypertension (6.05%) than those of mid- and high-level acculturation (10.78% and 12.80%, respectively). After controlling for the effects of possible confounders (i.e., sociodemographic factors, health care access and utilization, health behaviors, and health status), logistic regression showed that when compared with Hispanics of low acculturation, those of middle and high acculturation were at greater risk of having hypertension (OR=3.04, 95% CI, 1.27, 7.29 and OR=2.62, 95% CI, 1.04, 6.59, respectively). Conclusion: These findings demonstrate that acculturation is significantly associated with hypertensive status. [Copyright &y& Elsevier]

Objective: to determine the relationship between acute-phase proteins and microalbuminuria in type 2 diabetic patients without clinical evidence of macrovascular disease. Research design and methods: We studied cross-sectionally 64 non-smoking outpatients with type 2 diabetes mellitus without clinical evidence of cardiovascular disease attended at Brazilian University General Hospital aged 59.5±8.1 years and with a known duration of diabetes of 11.5±8 years. Urinary albumin excretion rate (AER) was determined in timed overnight urine samples. Serum α1-acid glycoprotein (AGP) and plasma fibrinogen were determined by immunoturbidimetry assay and serum C-reactive protein (CRP) was measured by a high-sensitive immunonephelometry assay. Results: A higher levels of AGP (P=0.0000), CRP (P=0.003) and fibrinogen (P=0.0001) were found in microalbuminuric (n=26) than in normoalbuminuric patients (n=38). All the acute-phase proteins were correlated with each other and with AER, respectively (r=0.67 for AGP; 0.35 for fibrinogen, and 0.41 for CRP, P<0.01 for all). Stepwise multiple regression analysis showed that AGP was independently associated with AER along with systolic blood pressure (r2=0.49, P=0.000). Logistic regression analysis showed that AGP was independently related to microalbuminuria with an odds ratio (95% CI) of 1.16 ((1.08–1.24), P=0.000). Conclusions: According to our results acute-phase proteins a known markers of chronic inflammation were associated with microalbuminuria independently of clinical cardiovascular disease. The influence of AGP on AER and microalbuminuria needs to be confirmed in prospective studies. Intervention studies are necessary to assess whether anti-inflammatory treatment would have a beneficial effect on this chronic complication of diabetes. [Copyright &y& Elsevier]

Objectives: The goal of this study was to examine the age-associated differences in ventricular-vascular coupling, defined by the ratio of arterial elastance (EaI) to left ventricular systolic elastance (ELVI), and its components, at rest and during exercise.Background: Ejection fraction (EF) increases during exercise, but the EF reserve decreases with aging. Ejection fraction is inversely related to EaI/ELVI, an index of the interaction between arterial and ventricular properties, which is an important determinant of cardiac performance. Thus, age differences in EaI/ELVI during exercise, due to age differences in EaI, ELVI, or both, may help to explain the age deficit in EF reserve.Methods: We noninvasively characterized EaI/ELVI = end-systolic volume index (ESVI)/stroke volume index (SVI) and its two determinants EaI = end-systolic pressure/SVI, and ELVI = end-systolic pressure/ESVI, at rest and during exercise in 239 healthy men and women (age range, 21 to 87 years). Blood pressures were assessed with cuff sphygomanometry, and cardiac volumes with gated blood pool scintingraphy.Results: Resting EaI/ELVI was not age related in men or women. In both sexes, EaI/ELVI decreased during exercise and declined to a lesser extent in older subjects. There were gender differences in the components of EaI/ELVI during exercise: EaI was greater in older versus young women (p = 0.01) but was unaffected by age in men. Left ventricular systolic elastance increased to a greater extent in young versus older subjects (p = 0.0001 for men, p = 0.07 for women).Conclusions: Age-associated differences in EaI/ELVI occur in both genders during exercise. Sub-optimal ventricular-vascular coupling helps to explain the age-associated blunting of maximal exercise EF, and its underlying mechanisms appear to differ between men and women. [Copyright &y& Elsevier]

Purpose: To study adiponectin, a circulating adipocytokine secreted by adipocytes inversely associated with diabetes and insulin resistance, and factors affecting its levels in the Coronary Artery Risk Development in Young Adults (CARDIA) study.Methods: Adiponectin in serum was measured by radioimmunoassay in 3355 participants (ages: 23–45 years) categorized by fasting glucose levels as normal, impaired fasting glucose, or diabetes mellitus.Results: Levels of adiponectin were higher in women, in white participants, and with age. Waist circumference, estimating visceral fat, strongly and inversely correlated with levels of adiponectin, more than body mass index. Adiponectin values adjusted for gender and race were lower with higher fasting glucose values in the normal range and still lower with impaired fasting glucose and untreated diabetes mellitus, even further adjusting for waist circumference and fasting insulin levels (p < 0.0001). Gender- and race-adjusted adiponectin levels were inversely associated with insulin resistance at year 15 and with insulin resistance measured 15 years previously and with its change from baseline to year 15 (p < 0.0001).Conclusions: These data suggest complex and significant physiologic interactions among circulating levels of adiponectin and measures of insulin action throughout young adulthood, even from several years earlier. Central obesity, as measured with waist circumference, is a primary factor affecting levels of circulating adiponectin. Furthermore, levels of glucose and levels of adiponectin may directly influence one another. [Copyright &y& Elsevier]

Objectives: We sought to investigate the relationship between target organ damage (TOD) in hypertension and a prothrombotic/hypercoagulable state, using a new technique of “platelet lysis” to quantify the amount of P-selectin per platelet (pP-sel), and to correlate it with other platelet markers (e.g., mass, volume and granularity, soluble P-selectin [sP-sel], and beta-thromboglobulin [beta-TG]).Background: The increased risk of TOD in hypertension may be related to a prothrombotic/hypercoagulable state, with abnormalities in platelets, such as increased expression of P-selectin.Methods: We studied 199 patients (mean age 68 years, 75% men) with hypertension. Of these, 125 had TOD (e.g., stroke, previous myocardial infarction, angina, left ventricular hypertrophy). Values obtained were compared with those from 59 healthy normotensive control subjects (mean age 68 years, 58% men).Results: Hypertensive patients had a higher mean platelet volume, mass, pP-sel, sP-sel, and beta-TG and lower platelet granularity (all p < 0.01), but a similar platelet count, as compared with controls. Within the hypertensive group, those with evidence of TOD had significantly larger platelets with greater mass but had lower granularity, sP-sel, and pP-sel levels than those without TOD, possibly reflecting increased aspirin use. On multivariate analysis, aspirin use was a determinant of pP-sel (p = 0.03) and sP-sel (p = 0.01), but the use of other drugs or other co-morbidity (e.g., diabetes, smoking) did not influence either P-selectin value.Conclusions: Patients with hypertension have evidence of changes in platelet physiology, as reflected by a higher level of pP-sel. Patients with TOD also had larger platelets, with greater mass, and the use of aspirin lowered pP-sel and sP-sel levels. These changes may have implications for the pathophysiology of cardiovascular and cerebrovascular disease in hypertension. [Copyright &y& Elsevier]

: ObjectivesWe sought to evaluate whether the clustering of multiple components of the metabolic syndrome (MS) has a greater impact on these vascular parameters than individual components of MS.: BackgroundIntima-media thickness (IMT) and vascular stiffness have been shown to be independent predictors of adverse cardiovascular events. The MS is defined as the clustering of three or more of the cardiovascular risk factors of dysglycemia, hypertension, dyslipidemia, and obesity.: MethodsCarotid IMT and stiffness were derived via B-mode ultrasonography in 471 participants from the Baltimore Longitudinal Study on Aging, who were without clinical cardiovascular disease and not receiving antihypertensive therapy.: ResultsThe MS conferred a disproportionate increase in carotid IMT (+16%, p < 0.0001) and stiffness (+32%, p < 0.0001), compared with control subjects. Multiple regression models, which included age, gender, smoking, low-density lipoprotein, as well as each individual component of MS as continuous variables, showed that MS was an independent determinant of both IMT (p = 0.002) and stiffness (p = 0.012). The MS was associated with a greater prevalence of subjects whose values were in the highest quartiles of IMT, stiffness, or both.: ConclusionsEven after taking into account each individual component of MS, the clustering of at least three of these components is independently associated with increased IMT and stiffness. This suggests that the components of MS interact to synergistically impact vascular thickness and stiffness. Future studies should examine whether the excess cardiovascular risk associated with MS is partly mediated through the amplified alterations in these vascular properties. [Copyright &y& Elsevier]

: ObjectivesWe examined whether common coronary heart disease (CHD) risk factors measured in mid-life predict erectile dysfunction (ED) 25 years later.: BackgroundRetrospective and cross-sectional studies have suggested that ED is associated with classic CHD risk factors, but few prospective studies have studied these associations.: MethodsIn this prospective study of community-dwelling men age 30 to 69 years, seven classic CHD risk factors (age, smoking, hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, and obesity) were assessed from 1972 to 1974. In 1998, after an average follow-up of 25 years, surviving male participants were asked to complete the International Index of Erectile Function (IIEF-5), which allows stratification of ED into five groups.: ResultsSixty-eight percent of the surviving men returned, and 60% completed the IIEF-5 questionnaire. Respondents had more favorable levels of all heart disease risk factors at baseline than non-respondents. At baseline, the average age of the 570 ED study participants was 46 years; at follow-up, their average age was 72 years. Mean age, body mass index, cholesterol, and triglycerides were each significantly associated with an increased risk of ED. Cigarette smoking was marginally more common in those with severe/complete ED, as compared with those without ED. Blood pressure and fasting blood glucose were not significantly associated with ED, likely due to selective mortality.: ConclusionsImproving CHD risk factors in mid-life may decrease the risk of ED as well as CHD. Erectile dysfunction should be included as an outcome in clinical trials of lipid-lowering agents and lifestyle modifications. [Copyright &y& Elsevier]

: ObjectivesThis study was designed to determine the effects of obesity on left ventricular (LV) structure and function in young obese women.: BackgroundSevere prolonged obesity in older adults results in increased plasma volume, eccentric LV hypertrophy, and systolic and diastolic dysfunction. Obese women are at increased risk for the development of heart failure. However, the effects of the obesity on cardiac structure and function in young, otherwise-healthy women are controversial.: MethodsFifty-one women were evaluated: 20 were obese (body mass index [BMI] ≥30 kg/m2) and 31 were non-obese (BMI <30 kg/m2). Left ventricular structure and systolic and diastolic function were assessed by two-dimensional echocardiography and tissue Doppler imaging, including the load-independent systolic myocardial velocity (Sm global) and early diastolic myocardial velocity (Em global), respectively. The effects of BMI on LV structure and function were assessed using multivariate regression analyses.: ResultsObese women had higher end-diastolic septal and posterior wall thickness, LV mass, and relative wall thickness than non-obese women; BMI values showed significant correlations with these variables (r = 0.58, p < 0.0001; r = 0.50, p < 0.0002; r = 0.52, p < 0.0001, and r = 0.40, p < 0.005, respectively). The Sm global and Em global were lower in obese women, suggesting systolic and diastolic function are decreased; both were negatively correlated with BMI (r = −0.43, p <. 002 and r = −0.61, p < 0.0001, respectively). Multivariate analysis showed BMI was the only independent predictor of relative wall thickness, Sm global, and Em global.: ConclusionsObesity in young otherwise-healthy women is associated with concentric LV remodeling and decreased systolic and diastolic function. These early abnormalities in LV structure and function may have important implications for explaining the myocardial dysfunction that is associated with increased cardiovascular morbidity and mortality caused by obesity. [Copyright &y& Elsevier]

Introduction: Thrombospondin-1 (TSP-1) is very important in platelet adhesion and aggregation, inflammation, cell to cell interaction, and vascular smooth muscle cell proliferation. Therefore, it may play an important role in the progression of cardiovascular disease. Recently, the TSP-1 N700S variant was proposed to be a new genetic predictor for myocardial infarction (MI) in American population, but the hypothesis was not verified in two other populations. We investigated a possible association between the N700S polymorphism and MI in a Chinese Han population. Materials and methods: We performed a case-control study including 406 patients who survived an acute MI before age 60 years and 400 age- and sex-matched controls. The N700S polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism. Results: Of the 806 subjects participating in the study, only 7 of the heterozygotes and none of the homozygotes were detected for the 700S allele. The prevalence of the S allele in the healthy controls was less frequent than those of the west populations (0.3% vs. 11%). No association of the N700S polymorphism with an altered risk of MI was found in our study (GA vs. AA: OR=2.48; 95% CI, 0.48 to 12.86; P=0.46). Conclusions: Our study suggested that the TSP-1 N700S polymorphism was rare and unrelated to MI in the Chinese Han population. Additional investigations should be performed in populations at different risk for coronary events in order to further elucidate the possible contribution of the polymorphism to cardiovascular disease. [Copyright &y& Elsevier]

: ObjectivesThe goal of this study was to determine if a low-dose combination of the angiotensin-converting enzyme inhibitor perindopril (Per) and the diuretic indapamide (Ind) reduces central (thoracic aorta, carotid artery) as well as brachial systolic blood pressure (SBP) more than the beta-blocker atenolol and to determine the hemodynamic factors influencing independently brachial and central SBP: pulse wave velocity (PWV) and pattern of wave reflections.: BackgroundIn high cardiovascular risk populations, angiotensin blockade improves survival without affecting brachial SBP and diastolic blood pressure (DBP). Whether central SBP, which is physiologically lower than brachial SBP, is significantly reduced has never been investigated.: MethodsThis study was a double-blind randomized trial for one year in patients with essential hypertension.: ResultsFor a similar DBP reduction, Per/Ind decreased SBP significantly more than atenolol, with a more pronounced reduction for central than for brachial SBP. After one year, the difference between brachial and central SBP was maintained by Per/Ind (8.28 ± 1.53 mm Hg) and significantly attenuated by atenolol (0.29 ± 1.61 mm Hg). Under atenolol, the principal factor modulating SBP reduction was mean blood pressure. Under Per/Ind, this parameter played a minor role, and the central SBP reduction implied a major role for disturbed PWV and wave reflections.: ConclusionsUnder Per/Ind, but not atenolol, normalization of brachial SBP is achieved with a significantly greater reduction of central SBP. This hemodynamic profile reflects changes of wave reflections issued from distal arterial and arteriolar territory, where Per/Ind, but not atenolol, is known to improve vessel wall structure. [Copyright &y& Elsevier]

: ObjectivesThe goal of our study was to define the structural characteristics of the heart in Japanese 100-km ultramarathon runners.: BackgroundDuring screening of participants in a 100-km ultramarathon, we found some participants who had larger cardiac chambers than had ever been previously reported.: MethodsA total of 291 male participants in a 100-km ultramarathon age from 20 to 73 years were examined using echocardiography.: ResultsThe mean heart rate (HR) was 50.6 ± 5.6 beats/min (38 to 79 beats/min), the systolic blood pressure (SBP) was 110.5 ± 5.6 mm Hg (94 to 138 mm Hg), the diastolic blood pressure (DBP) was 65.9 ± 6.6 mm Hg (58 to 90 mm Hg), the left ventricular end-diastolic diameter (Dd) was 61.8 ± 6.9 mm (42 to 75 mm), the left ventricular end-systolic diameter (Ds) was 39.6 ± 6.0 mm (23.0 to 55.0 mm), the interventricular septal thickness (IVS) was 10.2 ± 1.9 mm (5 to 19 mm), the posterior wall thickness (PW) was 10.0 ± 1.4 mm (5 to 15 mm), the aortic diameter (Ao) was 38.5 ± 4.0 mm (27 to 50 mm), the left atrial diameter (LA) was 40.2 ± 4.8 mm (26 to 49 mm), and the systolic wall stress (WS) was 221.5 ± 52.9 kdyne/cm2 (108.0 to 537.6 kdyne/cm2). Significant predictors of these parameters were the monthly running distance for HR, SBP, DBP, Dd, Ds, Ao, LA, and WS, as well as the age for IVS, PW, and Ao.: ConclusionsThirty-three participants had a Dd larger than 70 mm. Moreover, some athletes had a larger aorta and left atrium than had ever been previously reported. The oldest runner was 73 years old. [Copyright &y& Elsevier]

It has been previously shown that essential hypertension (EH) is associated with coagulation–fibrinolytic balance disorders. Our study was conducted in order to investigate disturbances in coagulation–fibrinolysis in offsprings of hypertensive parents. Two groups were studied: 44 healthy normotensive individuals (17 male, 27 female, age range 12–22 years) with a documented family history of hypertension and 33 individuals (14 male, 19 female, age range 11–21 years) without a family history of essential hypertension. The following parameters were determined in both groups: plasminogen activator inhibitor-1 antigen, tissue plasminogen activator antigen, fibrinogen, fibrin degradation products, thrombomodulin, protein S antigen, protein C activity, von Willebrand factor Ag, factor VII and factor XII activity. Additionally, systolic and diastolic blood pressure, insulin levels, blood lipids and heart rate were determined. The two groups were not found to have differences with respect to age, gender, body mass index, blood lipids and insulin levels. Hypertensive offsprings had significantly higher plasma levels of plasminogen activator inhibitor-1 antigen, fibrinogen, fibrin degradation products, protein S antigen and factor XII activity, while no differences were observed to the other haemostatic variables studied. Hence, offsprings of hypertensives had significantly higher diastolic blood pressure and heart rate. In conclusion, alterations regarding blood pressure, heart rate and fibrinolytic function exist in offsprings of hypertensive parents compared to individuals without family history of hypertension. [Copyright &y& Elsevier]

The percentage of spontaneously activated platelets and the platelet response to several agonists were studied in 26 hypertensive patients. The percentage of platelets expressing glycoprotein (GP) IIb/IIIa in its active conformation (GPIIb/IIIa*), P-selectin and phosphatidylserine (PS) was measured by flow cytometry at baseline and 1 and 2 months after treatment with doxazosin (4 mg/day). The response to ADP and Ca2+ ionophore was also evaluated. The results were compared with those of a control group of 71 normotensive volunteers. Spontaneous platelet activation was higher in patients than in controls (P-selectin-positive results in 4.4±2.0% patients vs. 2.7±1.7 controls, p<0.05; phosphatidylserine-positive results in 0.7±0.4% vs. 0.5±0.3%, respectively, p<0.05), and higher in response to ionophore action (phosphatidylserine-positive results 51.8±11.1% vs. 43.4±11.7%, p<0.01). Platelet activation in patients decreased after 2 months of doxazosin administration compared to baseline (P-selectin-positive results 2.7±1.4% vs. 4.4±2.0%, p<0.05; phosphatidylserine-positive results 0.3±0.2% vs. 0.7±0.4%, p<0.05). No significant differences were noted in GPIIb/IIIa*. The clinical significance of normalization of platelet activity by doxazosin remains to be established. [Copyright &y& Elsevier]

Introduction: The clinical use of cyclosporin A (CsA) is commonly associated with the development of hypertension and increased risk of thromboembolic events. Decreased endothelium-dependent relaxation and increased platelet activation seems to be involved on those side effects, but the underlying mechanisms are not yet elucidated. The present study aimed to evaluate the CsA effect on the platelet NO–cyclic guanosine-3′,5′-monophosphate (cGMP) pathway and the putative benefits of concomitant isosorbide-5-mononitrate (IS-5-MN) administration on CsA-induced hypertension and on platelet hyperactivation. Materials and Methods: Blood pressures, platelet NO synthase activity and cGMP content, intracellular free calcium concentration ([Ca2+]i) and whole blood platelet aggregation were assessed in three rat groups orally treated, during 7 weeks, with the following diets: orange juice (control group), 5 mg/kg/day of CsA (CsA group) and 150 mg/kg/day, b.i.d., of IS-5-MN for 2 weeks and IS-5-MN plus 5 mg/kg/day of CsA for 7 weeks (IS-5-MN+CsA group). Results: IS-5-MN treatment has prevented hypertension development obtained in the solely CsA-treated rats. CsA treatment has inhibited NOS activity, which was reverted by the concomitant IS-5-MN and CsA administration. On the contrary, platelets from CsA-treated rats had cGMP content increased when compared with the control rats. The variation obtained when ISMN was present was less predominant. Therefore, the organic nitrate treatment has prevented platelet hyperactivation, namely, by decreasing thrombin-evoked [Ca2+]i and collagen-evoked platelet aggregation, when compared with the solely CsA-treated group. The preventive effect of IS-5-MN was reinforced by electron microscopy studies of platelet activation. Conclusions: By increasing [Ca2+]i and aggregation, CsA induces platelet hyperactivation and simultaneously increases cGMP content, which might represent a compensatory inhibitory mechanism. The concomitant IS-5-MN treatment prevents the above-mentioned platelet hyperreactivity and tends to normalize the NO–cGMP pathway as well as the development of hypertension. [Copyright &y& Elsevier]

: ObjectivesThe purpose of this study was to evaluate the efficacy and tolerability of monotherapy with the selective aldosterone blocker eplerenone in both black and white patients with hypertension.: BackgroundEssential hypertension and cardiovascular-renal-target organ damage is more prevalent in black than white adults in the U.S.: MethodsBlack (n = 348) and white (n = 203) patients with mild-to-moderate hypertension were randomized to double-blind treatment with eplerenone 50 mg, the angiotensin II receptor antagonist losartan 50 mg, or placebo once daily. Doses were increased if blood pressure remained uncontrolled. The primary end point was change in mean diastolic blood pressure (DBP) after 16 weeks of therapy.: ResultsAdjusted mean changes from baseline in DBP were −5.3 ± 0.7, −10.3 ± 0.7, and −6.9 ± 0.6 mm Hg in the placebo, eplerenone-treated, and losartan-treated groups, respectively (mean ± SE, p < 0.001 eplerenone vs. placebo, p < 0.001 eplerenone vs. losartan). In black patients, DBP decreased by −4.8 ± 1.0, −10.2 ± 0.9, and −6.0 ± 0.9 mm Hg for the placebo, eplerenone-treated, and losartan-treated groups, respectively (mean ± SE, p < 0.001 eplerenone vs. placebo, p < 0.001 eplerenone vs. losartan), whereas in white patients, DBP decreased by −6.4 ± 1.0, −11.1 ± 1.1, and −8.4 ± 1.0 mm Hg, respectively (p = 0.001 eplerenone vs. placebo, p = 0.068 for eplerenone vs. losartan). For reduction of systolic blood pressure (SBP), eplerenone was superior to placebo and losartan in all patients combined and in black patients, and was superior to placebo in white patients. Eplerenone was as effective as losartan in reducing SBP and DBP in the high renin patient, but more effective than losartan in the low renin patient. Similarly, eplerenone was at least as effective as losartan in patients with differing baseline levels of aldosterone. Both eplerenone and losartan were well tolerated.: ConclusionsThe antihypertensive effect of eplerenone was equal in black and white patients and was superior to losartan in black patients. [Copyright &y& Elsevier]

To investigate the relationship between hypertension and Alzheimer''s disease(AD) and the change of Alzheimer''s patients'' blood pressure(BP) before and after the onset of AD, we conducted this epidemiological study. Subjects for this study were individuals who participated in a large scale, randomized controlled trial of nutritional intervention from 1984 to1991. Participants were initially screened for dementia using Chinese Mini-Mental State Examination (CMMS) and Activities of Daily Living (ADL). Positive subjects were subsequently administered a detailed neuropsychological and neurobehavioral examination. The diagnosis of AD was made by a consensus conference of psychiatrists using Diagnostic And Statistical Manual Of Mental Disorders-Fourth Edition(DSM-IV) criteria. 16 488 subjects were examined and 301 were diagnosed as AD. We compared the prevalence of AD in different populations that were stratified with 1984''s systolic or diastolic blood pressure(those four stratifications being high blood pressure, borderline blood pressure, normal, low blood pressure), and compared the change of blood pressure of 301 AD patients between 1984 and 1999–2000, which is before and after the onset of AD respectively. Multiple Logistic Regression (1:1 nested case-control study) was used to assess if hypertension is an independent risk factor for AD, and Trend test was used to assess the relationship between blood pressure and AD. Here we demonstrate that there was a significant difference in AD prevalence among different populations stratified by systolic or diastolic blood pressure (P < 0.01).The prevalence is highest in hypertension group, and lowest in hypotension group. Multiple Logistic Regression identified high blood pressure as a risk factor for AD (OR = 1.97, 95%CI:1.09–3.54, P = 0.02). Trend test showed that there is a significant dose-response relationship between blood pressure and AD (P < 0.0002). For hypertensive AD patients, there was no significant difference in systolic blood pressure(SBP) before and after the onset of AD, but diastolic blood pressure(DBP) decreased dramatically after the onset of AD (P < 0.01), howerver, the result also showed that DBP decrease occurred in the non-demented group. Based on this, we think the DBP decrease is not related to AD. We further investigated whether BP values differed crossed-sectionally between the AD-patients and non-demented individuals. We found that regardless of SBP or DBP, the BP values of the AD group were all significantly higher than that of non-demented. In summary, these data suggest there is a strong relationship between hypertension and AD; however, the mechanism remains to be studied. [Copyright &y& Elsevier]

Background: Up-regulation of ICAM-1 at the vascular endothelial level is one of the most important promoters in the slow progression of a healthy vessel to an atherosclerotic one. The current study aimed to evaluate whether low dose of the antioxidant α-tocopherol affects the circulating soluble (s) ICAM-1 in healthy subjects. Methods: Either α-tocopherol E (50 I.U./day) or placebo was randomly, double-blindly given to 39 healthy male volunteers (mean age 41.6±5.9 years) over a period of 20 weeks. Results: At the baseline, sICAM-1 levels were inversely correlated with α-tocopherol concentrations (r=−0.525, p<0.0001). Twenty weeks of α-tocopherol supplementation (n=20 subjects) significantly decreased the circulating sICAM-1 levels (from 149.2±18.4 to 131.5±17.2 μg l−1, p<0.004) while it increased the α-tocopherol concentrations (from 25.8±5.0 to 31.2±5.7 μmol l−1, p<0.003). No significant changes in plasma sICAM-1 and α-tocopherol levels were observed in placebo-treated subjects (n=19). In actively treated subjects, changes in circulating sICAM-1 were inversely correlated with changes in α-tocopherol concentrations (r=−0.597, p=0.005). Conclusions: Plasma sICAM-1 concentrations are stable in healthy subjects over a period of 20 weeks while they significantly decreased with low dose of α-tocopherol. Thus, antioxidant vitamins are likely to counteract with endothelial changes that could potentially trigger the atherogenetic process. [Copyright &y& Elsevier]

Sudden physical exertion is associated with an increased risk of acute myocardial infarction (MI) and sudden cardiac death. In addition, activation of the coagulation cascade and/or reduced fibrinolytic capacity after physical exercise has been reported in patients with cardiovascular disease. We investigated the haemostatic responses to an acute submaximal physical exercise in middle-aged women with a history of MI compared with healthy, age-matched controls. Resting plasma von Willebrand factor antigen (vWF Ag) and tissue plasminogen activator (tPA) antigen concentrations and plasminogen activator inhibitor-1 (PAI-1) activity were higher in the patients compared with control subjects. After 30 min of submaximal exercise on a bicycle ergometer, small, but still significant, increases in fibrinogen and vWF Ag concentrations were found in both groups. However, exercise did not induce thrombin generation and fibrin formation, as assessed by thrombin–antithrombin complex and fibrin D-dimer, in either group. Both tPA antigen concentration and activity increased and PAI-1 activity decreased significantly with exercise in both groups. Interestingly, the magnitude of changes in these latter variables did not differ between the groups (P=.99, P=.88 and P=.24, respectively). The present study demonstrates that some middle-aged women with previous MI have no signs of coagulation activation and retained fibrinolytic response after submaximal exercise. The clinical implication of these results might be that women with stable coronary heart disease can participate in rehabilitative exercise training without exhibiting a procoagulative state. [Copyright &y& Elsevier]

We sought to determine whether maternal plasma lipoprotein(a) [Lp(a)] levels are elevated in the second trimester, before the development of preeclampsia and other obstetrical complications, in women at risk. In the first part of the study (cross-sectional), plasma concentrations of Lp(a) were compared among 16 women with preeclampsia, 35 normotensive pregnant women and 18 healthy nonpregnant women. In the second part (nested case–control), blood samples were collected prospectively from 82 women at risk of preeclampsia, at 14–24 weeks of gestation, and Lp(a) levels were compared between those in whom preeclampsia or other obstetrical complications developed and those in whom they did not. In the cross-sectional study, plasma concentrations of Lp(a) were significantly higher in women with preeclampsia than in normotensive pregnant and healthy nonpregnant women (41±31 vs. 24±16 and 15±10 mg/dl, respectively; P=.001). Of the 82 women in the second part of the study, 9 (11%) developed preeclampsia and 19 (23%) had complications such as intrauterine growth restriction, preterm delivery and fetal or neonatal loss. There were no differences in plasma Lp(a) concentrations between the women with preeclampsia and those without complications, though Lp(a) levels were significantly higher in women with other complications than in those with either preeclampsia or uncomplicated pregnancies (40±29 vs. 17±13 or 28±18 mg/dl, respectively; P=.05). In conclusion, elevated plasma levels of Lp(a), associated with clinically established preeclampsia, are not detected before the appearance of the disorder in pregnant women at risk. [Copyright &y& Elsevier]