Mingli He

Efficacy of Folic Acid Therapy in Primary Prevention of Stroke Among Adults With Hypertension in China: The CSPPT Randomized Clinical Trial

IMPORTANCE Uncertainty remains about the efficacy of folic acid therapy for the primary prevention of stroke because of limited and inconsistent data. OBJECTIVE To test the primary hypothesis that therapy with enalapril and folic acid is more effective in reducing first stroke than enalapril alone among Chinese adults with hypertension. DESIGN, SETTING, AND PARTICIPANTS The China Stroke Primary Prevention Trial, a randomized, double-blind clinical trial conducted from May 19, 2008, to August 24, 2013, in 32 communities in Jiangsu and Anhui provinces in China. A total of 20,702 adults with hypertension without history of stroke or myocardial infarction (MI) participated in the study. INTERVENTIONS Eligible participants, stratified by MTHFR C677T genotypes (CC, CT, and TT), were randomly assigned to receive double-blind daily treatment with a single-pill combination containing enalapril, 10 mg, and folic acid, 0.8 mg (n = 10,348) or a tablet containing enalapril, 10 mg, alone (n = 10,354). MAIN OUTCOMES AND MEASURES The primary outcome was first stroke. Secondary outcomes included first ischemic stroke; first hemorrhagic stroke; MI; a composite of cardiovascular events consisting of cardiovascular death, MI, and stroke; and all-cause death. RESULTS During a median treatment duration of 4.5 years, compared with the enalapril alone group, the enalapril-folic acid group had a significant risk reduction in first stroke (2.7% of participants in the enalapril-folic acid group vs 3.4% in the enalapril alone group; hazard ratio [HR], 0.79; 95% CI, 0.68-0.93), first ischemic stroke (2.2% with enalapril-folic acid vs 2.8% with enalapril alone; HR, 0.76; 95% CI, 0.64-0.91), and composite cardiovascular events consisting of cardiovascular death, MI, and stroke (3.1% with enalapril-folic acid vs 3.9% with enalapril alone; HR, 0.80; 95% CI, 0.69-0.92). The risks of hemorrhagic stroke (HR, 0.93; 95% CI, 0.65-1.34), MI (HR, 1.04; 95% CI, 0.60-1.82), and all-cause deaths (HR, 0.94; 95% CI, 0.81-1.10) did not differ significantly between the 2 treatment groups. There were no significant differences between the 2 treatment groups in the frequencies of adverse events. CONCLUSIONS AND RELEVANCE Among adults with hypertension in China without a history of stroke or MI, the combined use of enalapril and folic acid, compared with enalapril alone, significantly reduced the risk of first stroke. These findings are consistent with benefits from folate use among adults with hypertension and low baseline folate levels. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00794885.

Prevalence of hyperhomocysteinaemia and its major determinants in rural Chinese hypertensive patients aged 45–75 years

We aimed to investigate the prevalence of hyperhomocysteinaemia (total plasma homocysteine (tHcy) ≥ 10 μmol/l) and its major determinants in rural Chinese hypertensive patients. A cross-sectional investigation was carried out in Lianyungang of Jiangsu province, China. This analysis included 13 946 hypertensive adults. The prevalence of hyperhomocysteinaemia was 51.6 % (42.7 % in women and 65.6 % in men). The OR of hyperhomocysteinaemia were 1.52 (95 % CI 1.39, 1.67) and 2.32 (95 % CI 2.07, 2.61) for participants aged 55-65 and 65-75 v. 45-55 years; 1.27 (95 % CI 1.18, 1.37) for participants with a BMI ≥ 25 v. < 25 kg/m²; 1.14 (95 % CI 1.06, 1.23) for participants with v. without antihypertensive treatment; 1.09 (95 % CI 1.00, 1.18) for residents inland v. coastal; 0.89 (95 % CI 0.82, 0.97) and 0.83 (95 % CI 0.74, 0.92) for participants with moderate and high v. low physical activity levels; 1.54 (95 % CI 1.41, 1.68) and 2.47 (95 % CI 2.17, 2.81) for participants with a glomerular filtration rate 60-90 and < 60 v. ≥ 90 ml/min per 1.73 m²; and 1.20 (95 % CI 1.07, 1.35) and 3.81 (95 % CI 3.33, 4.36) for participants with CT and TT v. CC genotype at methylenetetrahydrofolate reductase 677C>T polymorphism, respectively. Furthermore, higher tHcy concentrations were observed in smokers of both sexes (men: geometric mean 12.1 (interquartile range (IQR) 9.2-14.5) v. 11.9 (IQR 9.-14.) μmol/l, P= 0.005; women: geometric mean 10·3 (IQR 8.3-13.0) v. 9.6 (IQR 7.8-11.6) μmol/l, P= 0.010), and only in males with hypertension grade 3 (v. grade 1 or controlled blood pressure) (geometric mean 12.1 (IQR 9.2-14.4) v. 11.7 (IQR 9.2-14.0), P= 0.016) and in male non-drinkers (yes v. no) (geometric mean 12.3 (IQR 9.4-14.8) v. 11.7 (IQR 9.1-13.9), P= 0.014). In conclusion, there was a high prevalence of hyperhomocysteinaemia in Chinese hypertensive adults, particularly in the inlanders, who may benefit greatly from tHcy-lowering strategies, such as folic acid supplementation and lifestyle change.

Prevalence of obesity, abdominal obesity and associated factors in hypertensive adults aged 45-75 years.

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 ≥25 kg/m(2). Abdominal obesity was defined as a waist circumference ≥90 cm for men and ≥80 cm 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.

Prevalence of Unrecognized Lower Extremity Peripheral Arterial Disease and the Associated Factors in Chinese Hypertensive Adults

We aimed to examine the prevalence of lower-extremity peripheral artery disease (LE-PAD) and its associated factors in 3,128 Chinese hypertensive adults 45 to 75 years old without known cardiovascular disease, PAD, chronic kidney disease, diabetes, and dyslipidemia. A cross-sectional investigation was carried out in a rural area of Lianyungang, China. An ankle-brachial index ≤0.90 in either leg was used to define LE-PAD. Prevalence of LE-PAD was 9.0% (10.0% in women and 7.4% in men). In the multivariable logistic regression model, odds ratios (95% confidence interval) of having LE-PAD, were 1.82 (1.27 to 2.61) for participants 65 to 75 versus 45 to 55 years old, 1.48 (1.00 to 1.20) for participants with a waist circumference ≥90 versus <90 cm, 1.47 (1.05 to 2.04) and 1.62 (1.15 to 2.27) for participants with grade 2 and 3 hypertension versus controlled blood pressure or grade 1 hypertension, 1.35 (1.00 to 1.83) and 1.61 (1.16 to 2.23) for participants with heart rate at rest 70 to 80 and ≥80 versus <70 beats/min, and 1.41 (1.00 to 1.97) for participants with poor versus good sleeping quality. For other risk factors, gender-related differences were observed. Adjusted odds ratios of having LE-PAD for men and women were 1.07 (0.66 to 1.74) and 0.65 (0.47 to 0.90) for inland versus coastal residents and 1.03 (0.57 to 1.86) and 1.62 (1.09 to 2.41) for participants with body mass index ≥25 versus <25 kg/m(2). In conclusion, there was a high prevalence of LE-PAD in Chinese hypertensive adults without known cardiovascular disease, PAD, chronic kidney disease, diabetes, and dyslipidemia, particularly in women in coastal areas and in participants with higher heart rate and poor sleeping quality. Therefore, ankle-brachial index determinations should be encouraged in clinical practice in Chinese hypertensive adults.

Effect of folic acid supplementation on risk of new-onset diabetes in adults with hypertension in China: Findings from the China Stroke Primary Prevention Trial (CSPPT).

The aim of the present post hoc analysis of the China Stroke Primary Prevention Trial (CSPPT) was to evaluate the effect of folic acid supplementation on the risk of new‐onset diabetes in hypertensive adults in China.

Proteinuria Is an Independent Risk Factor for First Incident Stroke in Adults Under Treatment for Hypertension in China.

Background Conflicting evidence exists regarding whether reduced estimated glomerular filtration rate (eGFR) and proteinuria are independent risk factors for stroke and its subtypes in hypertensive patients. This study investigated the association of these renal measures with first incident stroke in adults under treatment for hypertension in China. Methods and Results The study included 19 599 adults aged 45 to 75 years who participated in the China Stroke Primary Prevention Trial. Baseline eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. Proteinuria was assessed by qualitative dipstick urinalysis and in a subset by the quantitative albumin–creatinine ratio method. Cox regression analysis was used to examine the effects of eGFR and proteinuria on the risk of first incident stroke. During a median of 4.5 years of follow‐up, a total of 585 first strokes (472 ischemic strokes) were identified. Compared to participants without proteinuria, participants with proteinuria (trace or more by dipstick) had a 35% increased risk of first stroke: the adjusted hazard ratio (HR) (95% CI) was 1.35 (1.09–1.66, P=0.005). The results were robust in subgroup analyses. In a subset with data on proteinuria measured by quantitative albumin–creatinine ratio, a similar association was found. In both independent and combined analyses with proteinuria, eGFR was not significantly associated with stroke. Conclusions In adults under treatment for hypertension in China, baseline proteinuria measured by dipstick or quantitative albumin–creatinine ratio, but not reduced eGFR, was found to be an independent risk factor for first incident stroke and ischemic stroke.

Effect of folic acid supplementation on risk of new‐onset diabetes in adults with hypertension in China: Findings from the CSPPT

The aim of the present post hoc analysis of the China Stroke Primary Prevention Trial (CSPPT) was to evaluate the effect of folic acid supplementation on the risk of new‐onset diabetes in hypertensive adults in China.

Methylenetetrahydrofolate reductase C677T polymorphism is associated with estimated glomerular filtration rate in hypertensive Chinese males

BackgroundPlasma level of total homocysteine (tHcy) is negatively correlated with kidney function in general population. However, the causal mechanism of this correlation is poorly understood. The purpose of this study is to investigate the association of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, which is a major genetic determinant of the plasma tHcy level, with estimated glomerular filtration rate (eGFR) in Chinese.MethodsA total of 18 814 hypertensive patients (6 914 males, 11 900 females) were included in the study.ResultsAssociation between the eGFR and MTHFR C677T genotype was examined by sex-specific regression analyses. In males, TT genotype was associated with 1.37 ml/min/1.73 m2 decrease in eGFR (p = 0.004) and with an increased risk (OR = 1.32, p = 0.008) for the lowest quintile of eGFR after adjusting for age, BMI, and blood pressures. However, such association was not observed in females (p > 0.05). This association suggests MTHFR C677T polymorphism may play a role in the regulation of eGFR in males.ConclusionsMTHFR 677 T is a risk allele for decreased kidney function in Chinese males, implicating this gene in the pathogenesis of chronic kidney disease (CKD).

Prospective study of serum uric acid levels and stroke in a Chinese hypertensive cohort

ABSTRACT Our aim was to investigate the association between serum uric acid (SUA) levels and the risk of first stroke in a Chinese population of hypertensive patients. This prospective study enrolled 20,577 hypertensive participants who without a history of stroke, and was conducted from May 2008 to August 2013 in Anqing and Lianyungang (China). A total of 632 (3.1%) first stroke events (510 ischemic events, 120 hemorrhagic events and 2 unspecified stroke events) were identified during a mean 4.5-year follow-up period. The risk of first stroke was not significantly associated with the increased SUA levels; this conclusion was also found after adjustment for gender and age. However, a statistically significant decreased risk of hemorrhagic stroke for the second SUA quartile (Q2) compared to the first quartile (Q1) (HR 0.56, 95%CI: 0.32–0.97, P = 0.037) was found. In addition, when grouped by tertiles of diastolic blood pressure (DBP), the results showed that high SUA lowered the risk of total stroke in participants in the third SUA quartile (Q3) (HR 0.69, 95%CI: 0.49–0.96, P = 0.028) and fourth SUA quartile (Q4) (HR 0.70, 95%CI: 0.50–0.99, P = 0.043) as compared with that in the first quartile (Q1). To sum up, no significant evidence in present study indicates that increased SUA levels are predictive of first stroke in a Chinese population of hypertensive patients.

Impact of Achieved Blood Pressure on First Stroke in Uncomplicated Grade 1 Hypertension

Background We aimed to test the impact of achieved blood pressure (BP) on first stroke among patients with grade 1 hypertension and without cardiovascular diseases in the China Stroke Primary Prevention Trial. Methods and Results A total of 3187 patients with uncomplicated grade 1 hypertension were included. The risk of outcomes was assessed according to: (1) the proportion of visits in which BP was reduced to <140/90 mm Hg, and (2) the time‐averaged systolic BP (SBP) or diastolic BP levels during the study treatment period. The median antihypertensive treatment duration was 4.6 years. Only 1.5% of the participants discontinued the treatments because of adverse reaction. Overall, the risk of stroke decreased with the increase of the proportion of study visits with BP <140/90 mm Hg (for per 5% increase; hazard ratio, 0.92 [95% CI, 0.87–0.98]). Consistently, compared with patients with time‐averaged SBP ≥140 or diastolic BP ≥90 mm Hg, the risk of stroke was lower in patients with time‐averaged SBP of 120 to <140 mm Hg (1.1% versus 2.9%; hazard ratio, 0.39 [95% CI, 0.22–0.69]) or diastolic BP <90 mm Hg (1.5% versus 2.7%; hazard ratio, 0.41 [95% CI, 0.17–0.98]). The beneficial results were consistent across age (<60 versus ≥60 years), sex, baseline SBP (<150 versus 150 to <160 mm Hg), study treatment groups (enalapril or enalapril‐folic acid), and hypertension subtypes (isolated systolic hypertension or systolic‐diastolic hypertension). However, a time‐averaged SBP <120 mm Hg (versus 120–140 mm Hg) was associated with an increased risk for stroke. Similar results were observed for composite cardiovascular events or all‐cause death. Conclusions Achieved BP <140/90 mm Hg was significantly associated with a decreased risk of stroke or all‐cause death in patients with uncomplicated grade 1 hypertension.