Guangyun Mao

Efficacy of folic acid supplementation in stroke prevention: a meta-analysis

BACKGROUND The efficacy of treatments that lower homocysteine concentrations in reducing the risk of cardiovascular disease remains controversial. Our aim was to do a meta-analysis of relevant randomised trials to assess the efficacy of folic acid supplementation in the prevention of stroke. METHODS We collected data from eight randomised trials of folic acid that had stroke reported as one of the endpoints. Relative risk (RR) was used as a measure of the effect of folic acid supplementation on the risk of stroke with a random effect model. The analysis was further stratified by factors that could affect the treatment effects. FINDINGS Folic acid supplementation significantly reduced the risk of stroke by 18% (RR 0.82, 95% CI 0.68-1.00; p=0.045). In the stratified analyses, a greater beneficial effect was seen in those trials with a treatment duration of more than 36 months (0.71, 0.57-0.87; p=0.001), a decrease in the concentration of homocysteine of more than 20% (0.77, 0.63-0.94; p=0.012), no fortification or partly fortified grain (0.75, 0.62-0.91; p=0.003), and no history of stroke (0.75, 0.62-0.90; p=0.002). In the corresponding comparison groups, the estimated RRs were attenuated and insignificant. INTERPRETATION Our findings indicate that folic acid supplementation can effectively reduce the risk of stroke in primary prevention.

Ser1369Ala Variant in Sulfonylurea Receptor Gene ABCC8 Is Associated With Antidiabetic Efficacy of Gliclazide in Chinese Type 2 Diabetic Patients

OBJECTIVE—The purpose of this study was to investigate whether genetic variants could influence the antidiabetic efficacy of gliclazide in type 2 diabetic patients. RESEARCH DESIGN AND METHODS—A total of 1,268 type 2 diabetic patients whose diabetes was diagnosed within the past 5 years and who had no recent hypoglycemic treatment were enrolled from 23 hospitals in China. All of the patients were treated with gliclazide for 8 weeks. Fasting and oral glucose tolerance test 2-h plasma glucose, fasting insulin, and A1C were measured at baseline and after 8 weeks of treatment. We used two independent cohorts to test the associations of 25 single nuclear polymorphisms in 11 candidate genes with the antidiabetic efficacy of gliclazide. A general linear regression model was used to test the association with adjustment for important covariates. RESULTS—After 8 weeks of gliclazide therapy, mean fasting plasma glucose (FPG) was reduced from 11.1 mmol/l at baseline to 7.7 mmol/l. In cohort 1, we genotyped all 25 SNPs (n = 661) and found that Ser1369Ala of the ABCC8 gene and rs5210 of the KCNJ11 gene were significantly associated with decreases in FPG (P = 0.002). We further genotyped Ser1369Ala in cohort 2 (n = 607) and confirmed the association identified in cohort 1. In the pooled analysis, compared with subjects with the Ser/Ser genotype, subjects with the Ala/Ala genotype had a 7.7% greater decrease in FPG (P < 0.001), an 11.9% greater decrease in 2-h plasma glucose (P = 0.003), and a 3.5% greater decrease in A1C (P = 0.06) after 8 weeks of treatment with gliclazide. CONCLUSIONS—In two independent cohorts of Chinese type 2 diabetic patients, we found consistent evidence that the Ser1369Ala variant in the ABCC8 gene can influence the antidiabetic efficacy of gliclazide.

Individual and joint association of α1A-adrenergic receptor Arg347Cys polymorphism and plasma irbesartan concentration with blood pressure therapeutic response in Chinese hypertensive subjects

Individual variability in the therapeutic response to an antihypertensive drug could have a genetic basis. We investigated whether the α1A‐adrenergic receptor (α1A‐AR) Arg347Cys polymorphism is associated with the blood pressure (BP) therapeutic response to irbesartan and whether the association could be altered by the plasma irbesartan level.

Efficacy of folic acid and enalapril combined therapy on reduction of blood pressure and plasma glucose: A multicenter, randomized, double-blind, parallel-controlled, clinical trial

OBJECTIVE We compared the efficacy of folic acid (FA) plus enalapril with enalapril alone on the reduction of blood pressure (BP) and fasting plasma glucose (FPG) in adult Chinese hypertensive patients. METHODS Four hundred eighty subjects with mild to moderate BP were randomly assigned to one of three treatment groups: 1) 10 mg of enalapril (control group), 2) 10 mg of enalapril plus 0.4 mg of FA (low-FA group), or 3) 10 mg of enalapril plus 0.8 mg of FA (high-FA group) daily for 8 wk. Generalized linear mixed models were used to compare the reduction in BP and FPG level from baseline to week 8 of the treatment and the difference among the three treatment groups, adjusting for pertinent covariates. RESULTS Four hundred forty-three subjects (57.3% women, 27-75 y of age) successfully completed the trial. After the 8-wk treatment, compared with baseline, all treatment groups showed significant reduction of BP but not of FPG. There was no significant difference in BP or FPG reduction among the three treatment groups. In subgroup analysis, we found that in subjects with hyperglycemia (FPG >or=6.1 mmol/L) at baseline, FPG reduction was significantly greater in the high-FA group (-0.80 +/- 1.20 mmol/L) than in the low-FA group (-0.39 +/- 1.44 mmol/L) and the control group (-0.23 +/- 1.30 mmol/L). Regression analysis further confirmed that FPG reduction in the high-FA group was -0.68 +/- 0.28 mmol/L greater than in the control group (P = 0.015), even after adjustment for important covariates. A dose-response trend was evident (P for trend = 0.025) and the test for an interaction between treatment group and baseline FPG was significant (P < 0.001). CONCLUSION In this sample of adult Chinese hypertensive patients, FA combined with enalapril showed a greater beneficial effect on reduction of FPG in a dose-related fashion than did enalapril alone among subjects with hyperglycemia.

Efficacy of Combined Amlodipine/Terazosin Therapy in Male Hypertensive Patients With Lower Urinary Tract Symptoms: A Randomized, Double-blind Clinical Trial

OBJECTIVES To investigate the therapeutic efficacy and safety of Amlodipine alone or in combination with terazosin for the presence of lower urinary tract symptoms (LUTS) and hypertension. LUTS and hypertension often coexist in elderly men. METHODS A total of 355 patients with Stage 1 or 2 hypertension and LUTS (as defined by an International Prostate Symptom Score of > or =10) were randomly assigned to receive 2 mg of terazosin (n = 117), 5 mg of Amlodipine (n = 119), or 5 mg of Amlodipine plus 2 mg of terazosin (n = 119) once daily for a total of 28 days. The primary outcomes were a reduction in the total and subscores of the International Prostate Symptom Score and blood pressure. Analyses were performed by intention to treat. This trial is registered with ClinicalTrials.gov (No. NCT00693199). RESULTS At day 28 of the trial, the Amlodipine plus terazosin group demonstrated comparable efficacy in lowering the total International Prostate Symptom Score and significant improvement in the presence of overactive bladder compared with the terazosin group (P < .05) and significant improvement in quality of life compared with the Amlodipine group (P < .05). The Amlodipine plus terazosin group also achieved the greatest blood pressure control compared with either the terazosin group (P < .01) or Amlodipine group (P < .05). All 3 treatment regimens were well tolerated by the study patients. CONCLUSIONS The results of this 4-week, double-blind, randomized trial have demonstrated that in Chinese male hypertensive patients with LUTS, low-dose Amlodipine plus terazosin therapy appears to be a safe and effective combination therapy to control both conditions, especially for those with predominant overactive bladder symptoms.

H-type hypertension and risk of stroke in chinese adults: A prospective, nested case–control study

Abstract Objectives: To investigate the independent and joint associations of hyperhomocysteinemia and hypertension with incident stroke and stroke death in Chinese adults. Methods: About 39,165 rural Chinese adults aged 35 years or older who had no history of stroke at the baseline study were prospectively followed to determine major cardiovascular events, with an average follow-up of 6.2 years. Using a nested case–control design, this report includes 179 incident stroke cases (121 stroke deaths) and 179 controls without vascular events from the original cohort matched by age, sex, community, and length of plasma storage. Baseline plasma total homocysteine (tHcy) measurements were obtained for all subjects. Logistic regression analysis was performed to investigate the independent and joint associations between H-type hypertension, defined as subjects with concomitant hypertension and elevated homocysteine (≥10 μmol/L), and risk of incident stroke and stroke death, after adjusting for important covariates. Results: We analyzed each risk factor independently and jointly. For analysis, homocysteine was divided into three groups: low (tHcy <10 µmol/L), moderate (≥10 µmol/L tHcy <20 µmol/L), and high (tHcy≥20µmol/L). Compared to subjects in the low group, the odds ratios (95% CI) of incident stroke for those in the moderate group and the high group were 1.7 (0.8–3.7) and 3.1 (1.2–8.6), respectively. The odds ratios (95% CI) of stroke death for the moderate and high groups were 2.8 (1.1–7.4) and 5.1 (1.6–16.4), respectively. Hypertension was also independently associated with a higher risk of incident stroke and stroke death: 3.8 (2.3–6.4) and 3.2 (1.8–6.0), respectively, compared to those without hypertension. When analyzed jointly, the highest risk was found among patients with H-type hypertensive with both hyperhomocysteinemia and hypertension: 12.7 (2.8–58.0) for incident stroke and 11.7 (2.5–54.7) for stroke death. Conclusions: This study provides strong evidence that hyperhomocysteinemia and hypertension are two independent, modifiable risk factors, which act additively to increase the risk of incident stroke and stroke death. The results strongly suggest that H-type hypertension is a major risk factor for vascular disease and mortality, and those with H-type hypertension may particularly benefit from homocysteine-lowering therapy along with anti-hypertension therapy in Chinese populations.

Renin-Angiotensin-Aldosterone System Gene Polymorphisms and Antihypertensive Response to Irbesartan in Chinese Hypertensives

The aim of this study was to determine whether specific single nucleotide polymorphisms (SNPs) and their reconstructed haplotypes in renin-angiotensin-aldosterone system (RAAS) genes were associated with antihypertensive reduction to irbesartan treatment. Thousand one forty-two hypertensives were recruited and received 150 mg irbesartan daily for 4 weeks. Blood pressures (BPs) and blood samples, at postdose on the 28th day, were measured. Predose BPs and plasma irbesartan concentrations were also measured. Involved SNPs in RAAS pathway genes were genotyped. Genotype (-344 TC) in the CYP11B2 had a significantly greater systolic blood pressure (SBP) reduction versus the TT genotype (p = 0.001). Subjects with the 174MM genotype of the angiotensinogen (AGT) gene had a significantly greater average SBP reduction (p = 0.025). The C-344T and T1016C polymorphisms in the CYP11B2 gene were both significantly associated with diastolic blood pressure (DBP) reduction (p = 0.026 or p = 0.003). Overall, the three loci-constructed haplotypes of the CYP11B2 gene were associated with DBP reduction (p = 0.008). Haplo-GLM analyses demonstrated that subjects with haplotype CTA had a significantly greater SBP and DBP reductions (p < 0.001 or p = 0.020), whereas subjects with haplotype TAA had a significantly lower SBP and DBP reductions (p < 0.001). Our findings suggested that SNPs and their reconstructed haplotypes in RAAS genes might be involved in the regulation of BP-lowering response to irbesartan in Chinese hypertensives.