Effect of vasodilator and immunosuppressive therapy on the endothelial dysfunction in patients with systemic sclerosis.

A comparative analysis of flow-mediated vasodilation (FMD), vasoactive angiogenic, and fibrogenic mediators between treatment-naive and treated systemic sclerosis (SSc) patients is an unmet need. (1)To assess the FMD and different pathogenic mediators in SSc patients about endothelial dysfunction. (2) To assess the proportion of circulating endothelial cells (CECs) in treatment-naïve patients. SSc patients were grouped into treatment-naïve (Group-I, n = 24) on vasodilator (Group-II, n = 10), on vasodilator + immunosuppressive (Group-III, n = 22)]. Age-sex matched healthy controls (n = 20) were included. Endothelial dysfunction (ED) was measured radiologically using FMD. Serum levels of NO, ET1, NO/ET1, sVCAM, sICAM, TGF, IL-6, and VEGF, as well as gene expressions of eNOS, iNOS, ET-1, and TGF, were measured to assess the status of ED in various study groups. CEC was measured in Group-I and HC. CEC was used as a marker to identify a key regulator of ED in SSc. FMD was significantly decreased in all SSc patients through receiving treatment. Upregulation of serum NO and ET concentrations was noted post-treatment with an unaltered NO/ET1 ratio. NO was positively correlated with FMD (r = 0.6) and negatively with TGFß (r = - 0.5). ET-1 showed a negative correlation with TGFß (r = - 0.5) but no significant correlation with FMD. Circulating endothelial cell (CEC) was significantly higher in Group-I (3.2%) than HC (0.8%) (p = 0.002), and it showed a good correlation with NO (r = - 0.7, p = 0.0001) and NO/ET1 (r = - 0.6, p = 0.007). Persistent ED was observed in all SSc patients irrespective of treatment. Dysbalance in NO/ET1 ratio might be the considering factor for the underlying progression of ED. Based on our findings, it may be hypothesized that reduced NO may be a contributing factor in the pathogenesis of endothelial dysfunction in SSc.

Atorvastatin Reduces Circulating S100A12 Levels in Patients with Carotid Atherosclerotic Plaques - A Link with Plaque Inflammation.

AIMS: Inflammation is involved in various processes of atherosclerosis development. Serum C-reactive protein (CRP) levels, a predictor for cardiovascular risk, are reportedly reduced by statins. However, several studies have demonstrated that CRP is a bystander during atherogenesis. While S100A12 has been focused on as an inflammatory molecule, it remains unclear whether statins affect circulating S100A12 levels. Here, we investigated whether atorvastatin treatment affected S100A12 and which biomarkers were correlated with changes in arterial inflammation. METHODS: We performed a prospective, randomized open-labeled trial on whether atorvastatin affected arterial (carotid and thoracic aorta) inflammation using 18fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) and inflammatory markers. Thirty-one statin-naïve patients with carotid atherosclerotic plaques were randomized to either a group receiving dietary management (n=15) or one receiving atorvastatin (10mg/day, n=16) for 12weeks. 18F-FDG-PET/CT and flow-mediated vasodilation (FMD) were performed, the latter to evaluate endothelial function. RESULTS: Atorvastatin, but not the diet-only treatment, significantly reduced LDL-cholesterol (LDL-C, -43%), serum CRP (-37%) and S100A12 levels (-28%) and improved FMD (+38%). 18F-FDG-PET/CT demonstrated that atorvastatin, but not the diet-only treatment, significantly reduced accumulation of 18F-FDG in the carotid artery and thoracic aorta. A multivariate analysis revealed that reduction in CRP, S100A12, LDL-C, oxidized-LDL, and increase in FMD were significantly associated with reduced arterial inflammation in the thoracic aorta, but not in the carotid artery. CONCLUSIONS: Atorvastatin treatment reduced S100A12/CRP levels, and the changes in these circulating markers mirrored the improvement in arterial inflammation. Our observations suggest that S100A12 may be an emerging therapeutic target for atherosclerosis.

Effect of urolithin A on the improvement of vascular endothelial function depends on the gut microbiota.

Background: Urolithin A (UA) is a metabolite produced by gut microbiota from ingested ellagic acid. Although the effect of ellagic acid intake on vascular endothelial function (VEF) improvement has been reported, the effect of UA intake on VEF improvement remains obscure. In addition, UA has been reported to improve the intestinal barrier function, and UA may have improved VEF by gut microbiome alteration. Objective: In this study, we conducted a clinical trial to explore and analyze the effects of UA intake on vascular endothelial function (VEF) and characteristics of the intestinal environment, such as gut microbiome profiling and organic acid composition. Methods: A placebo-controlled, randomized, double-blinded, parallel group trial was conducted on participants who could metabolize small amounts of UA from ellagic acid (non-UA producers) and had relatively poor VEF. VEF was assessed using the flow-mediated vasodilatation (FMD) score. Participants were administered placebo, UA 10 mg/day, or UA 50 mg/day for 12 weeks. FMD was measured and fecal samples were collected at 0, 4, 8, and 12 weeks of treatment. Gut microbiome analysis and organic acid level measurements were performed to evaluate the effects of UA intake on the intestinal environment. This clinical trial is publicly registered at the UMIN-CTR, trial number: UMIN000042014. Results: The gut microbiota of the UA 50 mg/day group showed a significant increase in alpha diversity (Faith's phylogenetic diversity). Four and nine microbial genera were significantly altered in the UA 10 mg/day and UA 50 mg/day groups, respectively (p < 0.05, not corrected). Participants whose FMD scores improved with UA intake had poor baseline FMD values as well as a low Bacillota/Bacteroidota ratio. Conclusion: Urolithin A intake alters the gut microbiota and improves their alpha diversity. In addition, the effect of UA on VEF correlated with the individual gut microbiota. Our results have practical implications for a new approach to providing healthcare that focuses on intestinal environment-based diet therapy.

Dependency of flow-mediated vasodilatation from basal nitric oxide activity.

BACKGROUND: Flow-mediated vasodilatation (FMD) has become one of the most widely assessed parameters to analyse endothelial and vascular function in cardiovascular medicine. The degree of contribution of nitric oxide (NO) to FMD is inconclusive and varies widely depending on the device used. In this study, we used a semi-automatic ultrasound device to analyse to what extent basal NO activity contributes to FMD of the brachial artery. METHODS: FMD was assessed with the UNEX EF device in a cross-over single blinded randomized study at baseline and then during infusion of either a NO-synthase-inhibitor (NG-monomethyl-L-arginine (L-NMMA)) or saline. The analysis was repeated after 1 week with the alternative infusion of L-NMMA or saline. All measurements were analysed both automatically and by a technician manually. RESULTS: In total, 25 healthy men subjects completed the study. Diastolic blood pressure and heart rate significantly changed during infusion of L-NMMA. Infusion of L-NMMA reduced FMD significantly (-37%, p = 0.002). Saline solution had no effect on FMD (+14%, p = 0.392). Change in FMD was significantly different between the groups (ΔFMDL-NMMA vs. ΔFMDsaline , p = 0.032). There was a statistically significant correlation between automatically analysed results and those obtained by an experienced technician (FMDsaline : r = 0.822, p < 0.001; FMDL-NMMA : r = 0.645, p = 0.007). CONCLUSION: The influence of NO on FMD is approximately 40% if assessed using the UNEX EF. Prior to use FMD as a marker of endothelial dysfunction, we should explore different methods including various duration of forearm ischaemia to increase NO dependency of FMD.

Linking myeloperoxidase with subclinical atherosclerosis in adults with metabolic syndrome.

BACKROUND: Myeloperoxidase (MPO) is a leukocyte-derived enzyme that has been associated with cardiovascular diseases in many studies. Together with hydrogen peroxide and a halogen, MPO forms a very strong antimicrobial system and there is evidence of links between MPO and inflammation in cardiovascular diseases. Brachial flow-mediated dilation (FMD) refers to a physiologic measure, and carotid intima-media thickness (IMT) is an anatomic structural measure of subclinical atherosclerosis. This research aimed to assess the correlation of MPO serum levels with subclinical atherosclerosis in patients with metabolic syndrome (MS) using the parameters FMD and IMT. METHODS: A total of 88 patients with metabolic syndrome defined according to the International Diabetes Criteria (IDF) criteria were recruited in the study. Doppler ultrasound was used to determine the left and right common carotid artery thickness (left and right CCA IMT) and FMD of brachial artery. The MPO concentrations were measured using the Immundiagnostik MPO ELISA kit. RESULTS: A significant inverse correlation between MPO and brachial FMD (r = -0.354, p < 0.001), a significant positive correlation between MPO and right CCA IMT (r = 0.327, p < 0.001), and a significant positive correlation between MPO and left CCA IMT (r = 0.301, p < 0.001) in patients with MS were obtained in this research study. CONCLUSION: Serum MPO concentration is correlated with subclinical atherosclerosis in patients with MS. The MPO may be a potential therapeutic goal in patients with MS. This finding suggests that new biological markers for MS and subclinical atherosclerosis are helpful for understanding the mechanisms of the risk factors and their role as a considerable burden on the population.

A prospective, longitudinal monocentric study on laser Doppler imaging of microcirculation: comparison with macrovascular pathophysiology and effect of adalimumab treatment in early rheumatoid arthritis.

Increased cardiovascular (CV) morbidity and mortality have been found in rheumatoid arthritis (RA). Tumour necrosis factor α (TNF-α) inhibitors may improve vascular function. In the first part of this study, we determined microcirculation during postoocclusive reactive hyperemia (PORH) representing endothelial function. In a nonselected population (n = 46) we measured flow-mediated vasodilation (FMD) of the brachial artery and laser Doppler flow (LDF) by ultrasound. Among LDF parameters, we determined TH1 (time to half before hyperemia), TH2 (time to half after hyperemia), Tmax (time to maximum) and total hyperemic area (AH). We measured von Willebrand antigen (vWF:Ag) by ELISA. In the second part of the study, we assessed the effects of adalimumab treatment on microcirculatory parameters in 8 early RA patients at 0, 2, 4, 8 and 12 weeks. We found significant positive correlations between FMD and LDF Tmax (R = 0.456, p = 0.002), FMD and TH2 (R = 0.435, p = 0.004), and negative correlation between vWF:Ag and Tmax (R = - 0.4, p = 0.009) and between vWF:Ag and TH2 (R = - 0.446, p = 0.003). Upon adalimumab therapy in early RA, TH2 times improved in comparison to baseline (TH2baseline = 26.9 s vs. TH24weeks = 34.7 s, p = 0,032), and this effect prolonged until the end of treatment (TH28weeks = 40.5, p = 0.026; TH212weeks = 32.1, p = 0.013). After 8 weeks of treatment, significant improvement was found in AHa (AHbaseline = 1599 Perfusion Units [PU] vs. AH8weeks = 2724 PU, p = 0.045). The PORH test carried out with LDF is a sensitive option to measure endothelial dysfunction. TH1 and TH2 may be acceptable and reproducible markers. In our pilot study, treatment with adalimumab exerted favorable effects on disease activity, endothelial dysfunction and microcirculation in early RA patients.

Correlation of endothelial dysfunction measured by flow-mediated vasodilatation to severity of coronary artery disease.

OBJECTIVES: Brachial artery ultrasound imaging during reactive hyperemia is widely used tool for quantifying endothelium dependent vasomotion. Angiodefender device is used for non invasive determination of percentage flow mediated vasodilation (FMD). An attempt is made to study whether endothelial dysfunction determined by FMD of brachial artery predicts the presence or absence of coronary artery disease and its correlation with the severity of coronary artery disease. METHODS: One hundred six patients admitted between May 2014 and April 2015 who were posted for coronary angiography diagnosed to have chronic stable angina on clinical basis and/or by exercise stress test, for evaluation of coronary artery disease were submitted to standard clinical evaluation, calculation of percentage FMD by Angiodefender device. Statistical significance of difference of categorical variables was tested using Fisher's exact test. Sensitivity, specificity, positive predictive value and negative predictive value of FMD were studied. RESULTS: There was no correlation between number of risk factors and percentage of FMD. Significantly higher proportion of cases with less FMD had higher prevalence of coronary artery disease and vice-versa. Significantly higher proportion of cases with positive stress test had less percentage of FMD and vice-versa. Significantly higher proportion of cases with less percentage of FMD and positive stress test had higher prevalence of obstructive coronary artery disease and vice-versa. Specificity was 100% when percentage of FMD was ≤10. CONCLUSIONS: FMD an inexpensive and non-invasive test provides information regarding extent and severity of coronary artery disease.

Cross-sectional and longitudinal associations between serum uric acid and endothelial function in subjects with treated hypertension.

OBJECTIVES: The endothelial dysfunction-arterial stiffness-atherosclerosis continuum plays an important pathophysiological role in hypertension. The aim of this study was to investigate the cross-sectional association between serum uric acid (SUA) and vascular markers related to this continuum, and to assess the longitudinal association between SUA and endothelial function that represents the initial step of the continuum. METHODS: We evaluated the baseline associations between SUA levels and vascular markers that included flow-mediated vasodilatation (FMD), brachial-ankle pulse wave velocity (baPWV), and common carotid artery intima-media thickness (CCA-IMT) in 648 subjects receiving antihypertensive treatment. The longitudinal association between baseline SUA levels and FMD measured at 1.5 and 3 yr of follow-up was also investigated. RESULTS: At baseline, modest, but significant correlations were observed between SUA and FMD in females (r = -0.171), baPWV in males with SUA >368.78 µmol/L (r = -0.122) and in females with a SUA level ≤ 362.83 µmol/L (r = 0.217), mean CCA-IMT in females with a SUA level ≤ 333.09 µmol/L (r = 0.139), and max CCA-IMT in females with SUA level ≤ 333.09 µmol/L (r = 0.138). A longitudinal association between SUA and FMD was less observed in males. In females, the baseline SUA was associated significantly with FMD values at 1.5 yr (r = -0.211), and SUA levels >237.92 µmol/L were associated significantly and independently with FMD values at 3 yr (r = -0.166). CONCLUSIONS: Lower SUA levels were associated with better vascular markers of the continuum, especially in females. Furthermore, we observed a longitudinal association between SUA and endothelial function, suggesting SUA level may be a potential marker of the continuum in hypertension.

Association Between Waist-to-Height Ratio and Endothelial Dysfunction in Patients With Morbidity　- A Report From the FMD-J Study.

BACKGROUND: Waist circumference (WC), waist-to-height ratio (WHtR) and body mass index (BMI) are known as easy anthropometric markers of abnormal obesity and screening tools for predicting cardiovascular outcomes, but which indices are best is unclear. We therefore investigated the superiority and association between each index and low flow-mediated dilatation (FMD) as a surrogate marker for cardiovascular outcomes in patients with morbidity in a large Japanese prospective cohort.Methods and Results:A total of 1,645 Japanese patients who had coronary artery disease and hypertension or diabetes mellitus were enrolled, and 1,087 of them were analyzed. The high-WHtR group (≥0.5) showed greater morbidity and increased inflammation in association with atherosclerosis compared with the low-WHtR group. High WHtR and advanced age were identified as predictors of low FMD (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.02-1.88, P=0.037 and OR 1.55, 95% CI 1.19-2.01, P=0.001, respectively). However, WC was not associated with that risk in either sex (male: OR 1.37, 95% CI 0.97-1.93, P=0.076; female: OR 1.08, 95% CI 0.68-1.73, P=0.74), and no association was evident between high BMI and low FMD (OR 0.92, 95% CI 0.71-1.19, P=0.54). CONCLUSIONS: WHtR offers a superior predictor of decreased FMD than other anthropometric indices, and progression of arteriosclerosis might be detected more sensitively. Further study is needed to investigate the relationship between cardiovascular mortality and WHtR.

Endothelial dysfunction and abnormal vascular structure are simultaneously present in patients with heart failure with preserved ejection fraction.

BACKGROUND: Endothelial dysfunction and abnormal vascular structure may be involved in the pathogenesis of chronic heart failure (HF). The purpose of this study was to evaluate simultaneously vascular function and vascular structure in patients with heart failure with preserved ejection fraction (HFpEF). METHODS: We measured flow-mediated vasodilatation (FMD) and nitroglycerine-induced vasodilation as indices of vascular function and intima-media thickness (IMT) as an index of vascular structure of the brachial artery in 41 patients with HFpEF (23 men and 18 women; mean age, 66±12yr) and 165 patients without HF (95 men and 70 women; mean age, 54±16yr). RESULTS: FMD was significantly smaller in patients with HFpEF than in patients without HF (2.9±2.1% versus 4.6±2.7%, P=0.0002). Nitroglycerine-induced vasodilation was significantly smaller in patients with HFpEF than in patients without HF (9.3±4.1% versus 12.9±4.9%, P<0.0001). Brachial artery IMT was significantly larger in patients with HFpEF than in patients without HF (0.35±0.06mm versus 0.31±0.07mm, P=0.0002). After adjustment for age, sex, hypertension, dyslipidemia, and diabetes mellitus, the associations remained significant between HFpEF and FMD (odds ratio, 0.79; 95% confidence interval, 0.66-0.92; P=0.0032), nitroglycerine-induced vasodilation (odds ratio, 0.88; 95% confidence interval, 0.80-0.96; P=0.0039), and brachial artery IMT (odds ratio, 1.08; 95% confidence interval, 1.01-1.17; P=0.033). CONCLUSIONS: These findings suggest that both endothelial dysfunction and abnormal vascular structure may contribute to the pathogenesis and maintenance of HFpEF. Endothelial function and vascular structure may be potential therapeutic targets for HFpEF.

Associations between parameters of flow-mediated vasodilatation obtained by continuous measurement approaches and the presence of coronary artery disease and the severity of coronary atherosclerosis.

We investigated the associations between the parameters of flow-mediated vasodilatation (FMD) obtained by continuous measurement approaches and the presence of coronary artery disease (CAD) and the severity of coronary atherosclerosis. The subjects consisted of 282 consecutive patients who underwent coronary angiography (CAG) and in whom we could measure FMD. Using continuous measurement approaches, we measured FMD as the magnitude of the percentage change from brachial artery diameter from baseline to peak (bFMD), the maximum FMD rate calculated as the maximal slope of dilation (FMD-MDR), and the integrated FMD response calculated as the area under the dilation curve during the 60- and 120 s dilation periods (FMD-AUC60 and FMD-AUC120). We divided the patients into two groups, the CAD group and the non-CAD group, and defined the severity of coronary atherosclerosis according to the Gensini score. The CAD group showed significantly lower %FMD, FMD-MDR, FMD-AUC60, and FMD-AUC120. Gender, smoking, dyslipidemia (DL), and diabetes mellitus (DM), in addition to FMD-AUC120, were identified as significant independent variables that predicted the presence of CAD by a multivariate logistic regression. In addition, a multiple regression analysis indicated that gender, DL, and hypertension, in addition to FMD-AUC120, were predictors of the Gensini score. Finally, we defined the cutoff value of FMD-AUC120 for the prediction of CAD in all patients as 11.1 (sensitivity 0.582, specificity 0.652) by a receiver-operating characteristic (ROC) curve analysis. In conclusion, FMD-AUC120 as assessed by continuous measurement approaches may be a superior marker for evaluating the presence of CAD and the severity of coronary atherosclerosis.

The Impact of Cocoa Flavanols on Cardiovascular Health.

The aim of the study was to review the effect of cocoa flavanols on cardiovascular health, with emphasis on the doses ingested, and to analyze a range of cocoa products for content of these compounds. PubMed was searched from 2010 to locate systematic reviews (SR) on clinical effects of chocolate consumption. Thirteen SRs were identified and reviewed, and provided strong evidence that dark chocolate did not reduce blood pressure. The evidence was however strong for an association with increased flow-mediated vasodilatation (FMD) and moderate for an improvement in blood glucose and lipid metabolism. Our analysis showed that cocoa products with around 100 mg epicatechin can reliably increase FMD, and that cocoa flavanol doses of around 900 mg or above may decrease blood pressure in specific individuals and/or if consumed over longer periods. Out of 32 cocoa product samples analyzed, the two food supplements delivered 900 mg of total flavanols and 100 mg epicatechin in doses of 7 g and 20 g and 3 and 8 g, respectively. To achieve these doses with chocolate, around 100 to 500 g (for 900 mg flavanols) and 50 to 200 g (for 100 mg epicatechin) would need to be consumed. Chocolate products marketed for their purported health benefits should therefore declare the amounts of total flavanols and epicatechin. Copyright © 2016 John Wiley & Sons, Ltd.

Vascular Endothelial Function Assessed by Postischemic Diastolic Blood Pressure Is Associated with Acclimatization and Acute Mountain Sickness.

BACKGROUND: This study assessed whether the brachial diastolic blood pressure (DBP) decline induced by 5-minute arm ischemia is associated with acclimatization and acute mountain sickness (AMS). METHODS: Forty-two age- and body mass index-matched young male residents at sea level (<400 m) or moderate altitude (1000-2000 m above sea level) were enrolled. All subjects had never been to 3200 m before. Brachial BP was measured at a station at 1380 m altitude before and 1, 5, and 10 minutes after right arm ischemia. AMS score was evaluated after 3-day training at a high altitude of 3200 m. RESULTS: In moderate altitude versus sea-level residents: (1) systolic BP curves for both arms overlapped well; (2) mean right arm DBP decline post right arm ischemia was larger, while left arm, which was not subjected to ischemia, did not show DBP decline in either group; and (3) AMS scores were significantly lower (3.19 ± 2.16 vs. 5.52 ± 4.58, p = 0.043) in those residing at moderate altitude compared to those from low altitude. There was a low negative correlation between AMS score and right arm area between curves-DBP (r = -0.320, p = 0.039). CONCLUSION: Moderate altitude relative to sea-level residents had a larger mean postischemic DBP decline in weak but significant association with lower mean AMS score at 3200 m. These data suggest that differences in vascular endothelial function related to altitude of residence persist during travel to high altitude and might contribute to AMS risk.

Study of endothelial dysfunction in patients of psoriatic arthritis by flow mediated and nitroglycerine mediated dilatation of brachial artery.

OBJECTIVE: To study endothelial dysfunction in patients with psoriatic arthritis (PsA) without risk factors for cardiovascular disease. METHODS: Forty patients with PsA according to Classification Criteria for Psoriatic Arthritis (CASPAR) criteria and forty age- and sex-matched controls were included. Patients with risk factors for cardiovascular disease were excluded. Endothelial function was assessed by measuring endothelial-dependent flow-mediated vasodilatation (FMD%) and endothelial-independent nitroglycerin-mediated dilatation (NMD%) in the brachial artery. RESULTS: There was a significant impairment of FMD% in patients as compared to controls (mean 8.3% vs. 10.8%, P = 0.007), but there was no significant difference in NMD%. CONCLUSIONS: There is presence of endothelial dysfunction in patients with PsA independent of risk factors for cardiovascular disease.

Pitavastatin calcium improves endothelial function and delays the progress of atherosclerosis in patients with hypercholesterolemia.

BACKGROUND: Statins have proven efficacy in inhibiting the onset and progress of atherosclerosis. The effectiveness of pitavastatin in reversing carotid atherosclerosis associated with hypercholesterolemia (HC) is unknown. OBJECTIVES: To explore the simultaneous effects of pitavastatin calcium on brachial arterial flow-mediated vasodilatation (FMD), carotid intima-media thickness (IMT), and arterial stiffness (ß), three surrogate markers of atherosclerosis were studied in HC patients. METHODS: A randomized, double-blind trial was performed with 40 HC subjects who fulfilled the inclusion/exclusion criteria. Patients were given pitavastatin calcium 1 mg/d (Group 1) or 2 mg/d (Group 2) for 8 weeks. There were 20 patients in each group, and 30 gender- and age-matched healthy subjects as controls were recruited. FMD of the brachial artery, carotid IMT, and arterial stiffness indicated by ß were measured at baseline and at 8 weeks after starting pitavastatin calcium therapy using ultrasound techniques. Biochemical tests were also made on all subjects. RESULTS: At baseline, higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), reduced FMD, and increased ß and IMT were observed in HC patients (P<0.001 for all) compared with controls. After 8 weeks, TC was decreased by 20.59%/27.56% and LDL-C 30.92%/35.64%, respectively, in comparison to baseline groups; the HC groups had reduced ß and improved endothelial function over the 8-week follow-up (P<0.05-0.001); nonetheless, no significant alterations of IMT were found (P>0.05). Significant negative interactions between TC/LDL and FMD (P<0.05-0.001), positive interactions between TC and IMT (P=0.003) and between TC/LDL and ß (P<0.001-0.000) were found. CONCLUSIONS: Treatment with pitavastatin calcium exerted favorable effects on endothelial function and arterial stiffness. It also improved carotid atherosclerosis in patients with HC.

Non-alcoholic Fatty Liver Disease and Metabolic Syndrome-Position Paper of the Indian National Association for the Study of the Liver, Endocrine Society of India, Indian College of Cardiology and Indian Society of Gastroenterology.

Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic syndrome. Prevalence of metabolic risk factors including diabetes mellitus, obesity, etc. is rapidly increasing in India putting this population at risk for NAFLD. Patients with NAFLD are at increased risk for liver-related morbidity and mortality and also cardiovascular disease risk and increased incidence of diabetes mellitus on long-term follow-up. Management of patients with NAFLD may require a multi-disciplinary approach involving not only the hepatologists but also the internists, cardiologists, and endocrinologists. This position paper which is a combined effort of the Indian National Association for Study of the Liver (INASL), Endocrine Society of India (ESI), Indian College of Cardiology (ICC) and the Indian Society of Gastroenterology (ISG) defines the spectrum of NAFLD and the association of NAFLD with insulin resistance and metabolic syndrome besides suggesting preferred approaches for the diagnosis and management of patients with NAFLD in the Indian context.

Metformin improves endothelial function and carotid intima media thickness in patients with PCOS.

OBJECTIVE: Oral contraceptive pills (OCP) are widely used for treating women with polycystic ovary syndrome (PCOS). Metformin has beneficial effects on insulin resistance and endothelial functions. The aim of this study was to investigate the effects of treatment with drospirenone/ethinyl estradiol (EE) alone or in combination with metformin on the flow-mediated vasodilatation (FMD) and carotid intima media thickness (CIMT) in women with PCOS. METHODS: Fifty women with PCOS (mean age 23 ± 5) were randomized to oral treatment of OCP alone (n = 25) or an OCP combination with metformin (n = 25) for 6 months. FMD from the brachial artery and CIMT were calculated. The hormonal profile, HOMA-IR score, basal insulin and glucose levels were studied in both groups. Before and after 6 months' treatment, echocardiographic measurements and laboratory tests were also obtained. RESULTS: After 6 months' treatment we observed a small decrease in FMD in the OCP group (14.9 ± 9.4 versus 14.4 ± 9.9, p = 0.801) and a slight increase in the combination group (14.5 ± 9.1 versus 15.0 ± 8.0, p = 0.715) but neither of them reached significance. CIMT increased in the OCP group (0.048 ± 0.011 to 0.050 ± 0.010 cm, p = 0.433) and decreased slightly in the combination group (0.049 ± 0.012, 0.048 ± 0.011 cm, p = 0.833). CONCLUSION: We demonstrated that adding metformin to OCP treatment may have beneficial effect on FMD and CIMT that represent vascular function in patients with PCOS. These results suggest that adding metformin to OCP treatment for PCOS could preserve the cardiovascular system and improve it.

Effects of vaginal delivery, cesarean section and exposure to labor on endothelial function of pregnant women.

INTRODUCTION: This study was undertaken to assess the influence of labor and cesarean section on endothelial function. MATERIALS AND METHODS: Flow-mediated vasodilatation (FMD) was measured before and after delivery for an assessment of endothelial function in three groups: (1) the Vaginal delivery group (with spontaneous labor or induction of labor, n = 48), (2) the Elective C/S group (with a cesarean planned, n = 20), and (3) the C/S after FP group (scheduled for vaginal delivery but required to have an emergency cesarean section because of failure in progress, n = 11). RESULTS: There were statistically significant changes between the antepartum and postpartum FMD values in the Vaginal delivery group and the Elective C/S group but not in the C/S after FP group (P < 0.001, P = 0.023 and P = 0.22 respectively). CONCLUSIONS: These observations suggest that labor may enhance endothelial function and that cesarean section may impair endothelial function.

Ischemic postconditioning does not improve peripheral endothelial function in ST-segment elevation myocardial infarction patients.

The purpose of this study was to determine whether ischemic postconditioning (IPC) could improve peripheral endothelial function in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Of 102 patients randomly assigned to an IPC or standard protocol to study infarct size utilizing cardiovascular magnetic resonance imaging, 84 patients had peripheral endothelial function assessed with brachial ultrasound measures and peripheral arterial tonometry (PAT) during reactive hyperemia 3 days after PCI. Overall IPC was not associated with a smaller infarct size compared to controls, though there was a trend towards greater myocardial salvage with IPC. Patients randomized to IPC (n=43; age 56 ± 11 years; 85% male) and standard protocol (n=41; age 56 ± 10 years; 88% male) underwent endothelial function assessment. Flow mediated vasodilatation was not significantly greater in the IPC group than in the standard group (7.4 ± 4.9% versus 6.6 ± 4.0% respectively, p=0.40) nor was peak hyperemic velocity-time integral (78 ± 26 cm versus 71 ± 30 cm respectively, p=0.28). Similarly, the PAT hyperemic ratio was not significantly greater in the IPC group than in the standard group (2.0 ± 0.9 versus 1.8 ± 0.6 respectively, p=0.14). In conclusion, IPC did not improve early peripheral endothelial function in patients with STEMI undergoing primary PCI.