Yongyi Bai

Effect of oral isoflavone supplementation on vascular endothelial function in postmenopausal women: a meta-analysis of randomized placebo-controlled trials

BACKGROUND The effect of isoflavone on endothelial function in postmenopausal women is controversial. OBJECTIVE The objective of this study was to evaluate the effect of oral isoflavone supplementation on endothelial function, as measured by flow-mediated dilation (FMD), in postmenopausal women. DESIGN A meta-analysis of randomized placebo-controlled trials was conducted to evaluate the effect of oral isoflavone supplementation on endothelial function in postmenopausal women. Trials were searched in PubMed, Embase, the Cochrane Library database, and reviews and reference lists of relevant articles. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. RESULTS A total of 9 trials were reviewed in the present meta-analysis. Overall, the results of the 9 trials showed that isoflavone significantly increased FMD (WMD: 1.75%; 95% CI: 0.83%, 2.67%; P = 0.0002). Meta-regression analysis indicated that the age-adjusted baseline FMD was inversely related to effect size. Subgroup analysis showed that oral supplementation of isoflavone had no influence on FMD if the age-adjusted baseline FMD was > or = 5.2% (4 trials; WMD: 0.24%; 95% CI: -0.94%, 1.42%; P = 0.69). This improvement seemed to be significant when the age-adjusted baseline FMD levels were <5.2% (5 trials; WMD: 2.22%; 95% CI: 1.15%, 3.30%; P < 0.0001), although significant heterogeneity was still detected in this low-baseline-FMD subgroup. CONCLUSIONS Oral isoflavone supplementation does not improve endothelial function in postmenopausal women with high baseline FMD levels but leads to significant improvement in women with low baseline FMD levels.

Increase in fasting vascular endothelial function after short-term oral l-arginine is effective when baseline flow-mediated dilation is low: a meta-analysis of randomized controlled trials

BACKGROUND Previous trials suggest that oral l-arginine administration affects endothelial function. However, most of these studies were small, the conclusions were inconsistent, and the precise effects are therefore debatable. OBJECTIVE The objective was to assess the effect of oral l-arginine supplementation on endothelial function, as measured with the use of fasting flow-mediated dilation (FMD). DESIGN We conducted a meta-analysis of randomized, placebo-controlled l-arginine supplementation trials that evaluated endothelial function. Trials were identified in PubMed, Cochrane Library, Embase, reviews, and reference lists of relevant papers. The weighted mean difference (WMD) was calculated for net changes in FMD by using random-effect models. Previously defined subgroup analyses and meta-regression analyses were performed to explore the influence of study characteristics. RESULTS Thirteen trials were included and evaluated. Because there was only one long-term study, we focused on short-term effects of l-arginine (12 studies, 492 participants). In an overall pooled estimate, l-arginine significantly increased FMD (WMD: 1.98%; 95% CI: 0.47, 3.48; P = 0.01). Meta-regression analysis indicated that the baseline FMD was inversely related to effect size (regression coefficient = -0.55; 95% CI: -1.00, -0.1; P = 0.016). A subgroup analysis suggested that l-arginine supplementation significantly increased FMD when the baseline FMD levels were <7% (WMD: 2.56%; 95% CI: 0.87, 4.25; P = 0.003), but had no effect on FMD when baseline FMD was >7% (WMD: -0.27%; 95% CI: -1.52, 0.97; P = 0.67). CONCLUSION Short-term oral l-arginine is effective at improving the fasting vascular endothelial function when the baseline FMD is low.

Patients with metabolic syndrome have prolonged corrected QT interval (QTc).

Prolongation of corrected QT interval (QTc) increases morbidity and mortality and QTc has been found to be longer in patients with diabetes mellitus than in healthy controls. It is still inconclusive whether the metabolic syndrome results in QTc prolongation.

A common variant of the eNOS gene (E298D) is an independent risk factor for left ventricular hypertrophy in human essential hypertension

eNOS (endothelial NO synthase) plays a critical role in the development of ventricular remodelling and cardiac hypertrophy. The purpose of the present study was to determine whether three common variants in NOS3 (the eNOS gene) are associated with the risk of LVH [LV (left ventricular) hypertrophy] in patients with essential hypertension. Three NOS3 genetic variants, -T786C (rs2070744), eNOS4a/b and +G894T (rs1799983), were genotyped in two independent case-control studies: the first study consisted of 1061 hypertensive patients with LVH and 1118 hypertensive patients without LVH, and the second sample consisted of 120 patients with LVH and 223 patients without LVH. Echocardiographic measurements were obtained in all of the hypertensive patients. Only the +G894T (E298D) variant of NOS3 was associated with a higher risk of LVH {OR (odds ratio), 1.67 [95% CI (confidence interval), 1.19-2.36]; P<0.01} in the first population, and replicated in the second population [OR, 1.41 (95% CI, 1.01-2.28); P<0.05] in a recessive model. Compared with carriers of the G allele (GT+GG), patients carrying the TT genotype had increased septal wall thickness (16.2%, P<0.01 and 11.7%, P<0.01 respectively), LV posterior wall thickness (8.3%, P<0.01 and 7.1%, P<0.01 respectively), LV mass index (14.0%, P<0.01 and 25.1%, P<0.01 respectively) and relative wall thickness (13.1%, P<0.01 and 16.2%, P<0.01 respectively) in the first and second populations. The results of the present study support that homozygosity for +G894T (E298D) in NOS3 is a genetic risk factor for the development of LVH in patients with hypertension.

Common genetic variation in DDAH2 is associated with intracerebral haemorrhage in a Chinese population: a multi-centre case-control study in China

ADMA (asymmetric omega-NG,NG-dimethylarginine), an endogenous inhibitor of NOS (NO synthase), has been shown to be an independent predictor of cerebrovascular disorders. DDAH2 (dimethylarginine dimethylaminohydrolase 2) promotes the metabolism of ADMA and plays a key role in the regulation of the acute inflammatory response. We hypothesized that genetic variation in DDAH2 might alter the susceptibility to ICH (intracerebral haemorrhage). The hypothesis was tested in two independent case-control studies. We used a haplotype-tagging SNP (single nucleotide polymorphism) approach to identify tag SNPs in DDAH2. The SNPs were genotyped in 1603 stroke patients and 1525 control subjects. The study was replicated in another independent case-control study including 322 stroke patients and 891 control subjects. A promoter variant -449C/G (rs805305) in DDAH2 was identified and found to be in complete linkage disequilibrium with the only tag SNP (rs707916) in the region containing DDAH2. Genotype analyses were conducted for both dominant and additive models. The C allele of the -449 locus resulted in a significantly reduced risk of ICH {dominant model: OR (odds ratio), 0.51 [95% CI (confidence interval), 0.38-0.68], P=6.60x10-6; additive model: OR, 0.64 (95% CI, 0.52-0.80), P=5.21x10-5} than the wild-type genotype. No association was observed between the DDAH2 variant and atherothrombotic stroke. The findings were replicated in the second independent population. In conclusion, our results suggest that the DDAH2 common variant may play a protective role in the development of ICH, implicating that the DDAH2/ADMA pathway may act as a critical regulator of cerebral small-vessel disorders.

Sex Differences in Blood Pressure Response to Antihypertensive Therapy in Chinese Patients with Hypertension

Background: Sex-specific responsos to antihypertensive drugs are not very well understood. Objective: To investigate sex-related differences in blood pressure response to antihypertensive drugs in a community-based prospective clinical trial. Methods: We recruited 3535 untreated hypertensive patients (2326 women), aged 40–75 years, from 7 rural communities in China. Subjects were randomized to 1 of 4 drug groups: atenolol, hydrochlorothiazide (HCTZ), captopril, or sustained-released nifedipine; duration of the study was 8 weeks. Mean blood pressure reduction, blood pressure control rates, and frequency of adverse events were compared between men and women. Results: Women had a better response to HCTZ in relation to diastolic blood pressure (1.8 mm Hg lower) than did men (p <0.05) and were 57% more likely to reach the control goal of diastolic blood pressure than were men (p <0.05). In the atenolol group, mean systolic blood pressure decreased 3.9 mm Hg more in women than in men (p <0.05), and women were 65% more likely to reach the control goal of systolic blood pressure and 57% more likely to reach the control goal of diastolic blood pressure than were men (p <0.05). Significant sex-related differences were also found in drug-related adverse events in the nifedipine group (15.8% in women vs 9.8% in men; p = 0.017) and in the captopril group (14.3% in women vs 8.4% in men; p = 0.005), but no differences were seen with HCTZ or atenolol. Conclusions: Women have better blood pressure responses to HCTZ and atenolol and experience more adverse effects with sustained-release nifedipine and captopril than do men, indicating that sex should be taken into account when selecting antihypertensive drugs.

A functional variant in promoter region of platelet-derived growth factor-D is probably associated with intracerebral hemorrhage

BackgroundPlatelet-derived growth factor D (PDGF-D) plays an important role in angiogenesis, vessel remodeling, inflammation and repair in response to injury. We hypothesized that genetic variation in PDGFD gene might alter the susceptibility to stroke.FindingsWe determined the genotypes of a single nucleotide polymorphism (SNP) (-858A/C, rs3809021) in 1484 patients with stroke (654 cerebral thrombosis, 419 lacunar infarction, 411 intracerebral hemorrhage [ICH]) and 1528 control subjects from an unrelated Chinese Han population and followed the stroke patients up for a median of 4.5 years.The -858AA genotype showed significantly increased risk of ICH (dominant model: odds ratio [OR] 1.29, 95% confidence interval [CI] 1.00-1.68, P = 0.05; additive model: OR 1.24, 95% CI 1.01-1.52, P = 0.04) than wild-type genotype. Further analyses showed that -858AA genotype conferred about 2-fold increase in risk of non-hypertensive ICH (dominant model: OR 2.1, 95%CI 1.34-3.29, P = 0.001; additive model: OR 1.75, 95% CI 1.24-2.46, P = 0.001). After a median follow-up of 4.5 years, -858AA genotype was associated with a reduced risk of ICH recurrence (dominant model: adjusted hazard ratio [HR] 0.09, 95%CI 0.01-0.74, P = 0.025; additive model: HR 0.21, 95% CI 0.04-1.16, P = 0.073) in non-hypertensive patients.ConclusionsThe -858AA genotype is probably associated with risk for non-hypertensive ICH. Further studies should be conducted to reveal the role of PDGF-D at various stages of ICH development--beneficial, or deleterious.

Inverse association of plasma level of high-density lipoprotein cholesterol with intracerebral hemorrhage.

This study aimed to investigate whether plasma levels of HDL cholesterol (HDL-C) were associated with the risk of intracerebral hemorrhage (ICH). Plasma HDL-C was determined via enzymatic methods, and ICH was ascertained via medical history, physical examination, and brain imaging (computed tomography or magnetic resonance imaging). The multivariable logistic regression model was used to calculate the odds ratios (OR) and 95% confidence intervals (CI) of ICH according to levels of plasma cholesterol. A total of 170 patients with ICH were identified from 6,046 participants. After adjustment for conventional cardiovascular risk factors, the OR was 2.06 (95% CI, 1.25-3.12; P < 0.01) for participants in the first tertile of HDL-C levels (<1.38 mmol/l) and 1.13 (95% CI, 0.72-1.78; P = 0.59) for participants in the second tertile (1.38-1.64 mmol/l), compared with participants in the third tertile (∩≥1.65 mmol/l). Subgroup analysis indicated that the detrimental effects of HDL-C were more significant in men and lean participants than in their corresponding controls, independent of hypertension. The results presented herein indicate that low plasma HDL-C (<1.38 mmol/l) may be associated with risk of ICH.