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Degree of Blood Pressure Control and Incident Diabetes Mellitus in Chinese Adults With Hypertension.
Zhang, Y, Nie, J, Zhang, Y, Li, J, Liang, M, Wang, G, Tian, J, Liu, C, Wang, B, Cui, Y, et al
Journal of the American Heart Association. 2020;(16):e017015
Abstract
Background The association between blood pressure (BP) control and incident diabetes mellitus remains unknown. We aim to investigate the association between degree of time-averaged on-treatment systolic blood pressure (SBP) control and incident diabetes mellitus in hypertensive adults. Methods and Results A total of 14 978 adults with hypertension without diabetes mellitus at baseline were included from the CSPPT (China Stroke Primary Prevention Trial). Participants were randomized double-masked to daily enalapril 10 mg and folic acid 0.8 mg or enalapril 10 mg alone. BP measurements were taken every 3 months after randomization. The primary outcome was incident diabetes mellitus, defined as physician-diagnosed diabetes mellitus, or use of glucose-lowering drugs during follow-up, or fasting glucose ≥126 mg/dL at the exit visit. Over a median of 4.5 years, a significantly higher risk of incident diabetes mellitus was found in participants with time-averaged on-treatment SBP 130 to <140 mm Hg (10.3% versus 7.4%; odds ratio [OR], 1.37; 95% CI, 1.15‒1.64), compared with those with SBP 120 to <130 mm Hg. Moreover, the risk of incident diabetes mellitus increased by 24% (OR, 1.24; 95% CI, 1.00‒1.53) and the incidence of regression to normal fasting glucose (<100 mg/dL) decreased by 29% (OR, 0.71; 95% CI, 0.57‒0.89) in participants with intermediate BP control (SBP/diastolic blood pressure, 130 to <140 and/or 80 to <90 mm Hg), compared with those with a tight BP control of <130/<80 mm Hg. Similar results were found when the time-averaged BP were calculated using the BP measurements during the first 6- or 24-month treatment period, or in the analysis using propensity scores. Conclusions In this non-diabetic, hypertensive population, SBP control in the range of 120 to <130 mm Hg, compared with the 130 to <140 mm Hg, was associated with a lower risk of incident diabetes mellitus.
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China Stroke Primary Prevention Trial: Visit-to-Visit Systolic Blood Pressure Variability Is an Independent Predictor of Primary Stroke in Hypertensive Patients.
Men, X, Sun, W, Fan, F, Zhao, M, Huang, X, Wang, Y, Liu, L, Liu, R, Sun, W, Peng, Q, et al
Journal of the American Heart Association. 2017;(3)
Abstract
BACKGROUND The optimal range of blood pressure variability remains unclear. We aimed to stratify the degree of risk of stroke based on visit-to-visit systolic blood pressure (SBP) variability in a large Chinese hypertensive population in 32 communities. METHODS AND RESULTS We retrospectively analyzed the data of 20 702 hypertensive patients from the China Stroke Primary Prevention Trial. The participants were randomized into 2 treatment groups to receive either enalapril or enalapril plus folic acid. Their blood pressures were measured every 3 months. The outcome was the first stroke. Three parameters of SBP variability were calculated: standard deviation, coefficient of variation, and average real variability. The records of first 4, 6, 8, 10 and 12 visits at which SBP was measured were used to calculate SBP variability and to predict subsequent stroke risk in adjusted Cox regression models. After median follow-up of 4.5 years, 597 patients had experienced stroke. Visit-to-visit SBP variability was an independent predictor of subsequent stroke (eg, the hazard ratio for the highest quintile of average real variability [22.67-61.07 mm Hg] over 6 visits was 1.55, 95% CI 1.07-2.25, P=0.021), independent of mean SBP over the follow-up period. Its value was more predictive when more blood pressure records were used. CONCLUSIONS Visit-to-visit SBP variability is an independent predictor of primary stroke in Chinese hypertensive patients. This predictive value depends on the number of blood pressure measurements used to calculate variability but is independent of mean SBP. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.
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Plasma Homocysteine and Prognosis of Acute Ischemic Stroke: a Gender-Specific Analysis From CATIS Randomized Clinical Trial.
Zhong, C, Xu, T, Xu, T, Peng, Y, Wang, A, Wang, J, Peng, H, Li, Q, Geng, D, Zhang, D, et al
Molecular neurobiology. 2017;(3):2022-2030
Abstract
Elevated total homocysteine level (tHcy) has been hypothesized to be associated with morbidity and mortality of stroke; however, results regarding the association between plasma tHcy status and prognosis of acute ischemic stroke are inconsistent. Moreover, the gender effect on this association has yet to be explored. We thus prospectively investigated whether higher tHcy concentrations predicted poor stroke prognosis in Chinese adults. A total of 3309 acute ischemic stroke patients were included in this prospective multicenter study from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Baseline tHcy concentrations were quantitatively determined via enzymatic cycling assay. The primary outcome was a combination of death and major disability at 3 months (modified Rankin scale scores 3-6) after hospitalization. Multivariate logistic regression models with restricted cubic splines were used to determine the association between baseline plasma tHcy and the subsequent outcome. Higher plasma tHcy concentrations were associated with increased risks of the primary outcome in women but not in men (P interaction = 0.016). Adjusted odds ratios comparing two extreme tHcy quartiles were 1.83 (95 % confidence interval 1.12-2.98; P trend = 0.02) in women and 0.87 (95 % confidence interval 0.61-1.25; P trend = 0.37) in men. The significant association between baseline tHcy status and stroke prognosis in women, but not in men, persisted in further subgroup analyses, stratified by age, baseline systolic blood pressure, and other pre-specified factors. Elevated tHcy is positively associated with poor prognosis of acute ischemic stroke in women, but not in men. Further studies are needed to replicate our findings and to clarify the potential sex-specific mechanisms.
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Elevated Homocysteine Concentrations Decrease the Antihypertensive Effect of Angiotensin-Converting Enzyme Inhibitors in Hypertensive Patients.
Qin, X, Li, Y, Sun, N, Wang, H, Zhang, Y, Wang, J, Li, J, Xu, X, Liang, M, Nie, J, et al
Arteriosclerosis, thrombosis, and vascular biology. 2017;(1):166-172
Abstract
OBJECTIVE We aimed to examine whether baseline homocysteine (Hcy) concentrations affect antihypertensive responses to enalapril treatment among previously untreated hypertensive patients (n=10 783) in the CSPPT (China Stroke Primary Prevention Trial). APPROACH AND RESULTS After a 3-week run-in treatment with a daily dose of 10 mg enalapril, eligible hypertensive patients were randomly assigned to a double-blind daily treatment of a tablet of either enalapril (10 mg) and folic acid (0.8 mg) or enalapril (10 mg) alone for a median of 4.5 years. After the 3-week treatment period with enalapril alone, the systolic blood pressure-lowering effect was significantly reduced by 1.39 (95% confidence interval 0.40-2.37) and 3.25 (95% confidence interval 1.98-4.52) mm Hg, respectively, in those with baseline Hcy concentrations of 10 to 15 and ≥15 μmol/L (P for trend <0.001) as compared with those with Hcy concentration of <10 μmol/L. Similar results were observed after a 15-week treatment period with enalapril alone. After a median 4.5-year enalapril-based antihypertensive treatment period, compared with those with Hcy concentration of <10 μmol/L, the systolic blood pressure-lowering effect was still significantly reduced by 0.77 (95% confidence interval 0.01-1.53) and 1.70 (95% confidence interval 0.72-2.68) mm Hg, respectively, in those with Hcy concentrations of 10 to 15 and ≥15 μmol/L (P for trend <0.001). In addition, participants with higher baseline Hcy concentrations had persistently higher systolic blood pressure levels across the entire study treatment period. Similarly, baseline Hcy concentrations were inversely associated with diastolic blood pressure reduction during the short-term enalapril alone treatment. However, the inverse association between baseline Hcy and diastolic blood pressure reduction was attenuated and became insignificant after the long-term enalapril-based treatment period. CONCLUSIONS Elevated Hcy concentrations significantly decreased the antihypertensive effect of the short-term and long-term enalapril-based antihypertensive treatment in previously untreated hypertensive patients.
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Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial.
Huo, Y, Li, J, Qin, X, Huang, Y, Wang, X, Gottesman, RF, Tang, G, Wang, B, Chen, D, He, M, et al
JAMA. 2015;(13):1325-35
Abstract
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.
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Effects of combined enalapril and folic acid therapy on the serum uric acid levels in hypertensive patients: a multicenter, randomized, double-blind, parallel-controlled clinical trial.
Li, H, Qin, X, Xie, D, Tang, G, Zhang, Y, Li, J, Hou, F, Wang, X, Huo, Y, Xu, X
Internal medicine (Tokyo, Japan). 2015;(1):17-24
Abstract
Objective The efficacy of combined treatment consisting of enalapril and folic acid (FA) was compared to that of enalapril alone in reducing the serum uric acid (UA) levels in adult hypertensive patients in China. Methods Patients with mild to moderate hypertension (n=480) were randomly assigned to one of three treatment groups: (1) 10 mg enalapril (control group), (2) 10 mg enalapril plus 0.4 mg FA (low-FA group) or (3) 10 mg enalapril plus 0.8 mg FA (high-FA group) daily for eight weeks. The primary outcome was the UA ratio (week 8 UA: baseline UA). Results The final analysis included 450 patients (43.1% men, 27-75 years of age). An adjusted multivariable regression analysis revealed no significant differences in the UA ratio between the three groups after eight weeks of treatment. In the subgroup analysis stratified according to the baseline UA level, the high-FA group demonstrated a significantly greater UA-lowering response among the patients with an elevated baseline UA concentration (UA ≥310 μmol/L) [median UA ratio (25th percentile, 75th percentile): 0.94 (0.83, 1.01)], compared with that observed in the control group [0.97 (0.90, 1.00), p=0.025]. Similar results were found in the participants with baseline hyperuricemia (HUA; UA: men >420 μmol/L, women >350 μmol/L). Conclusion In this sample of adult hypertensive patients, the administration of a daily dose of 10 mg of enalapril combined with 0.8 mg of FA had a greater beneficial effect on the serum UA levels than did that of 10 mg of enalapril alone in patients with either an elevated UA concentration or HUA.
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The combination of amlodipine and angiotensin receptor blocker or diuretics in high-risk hypertensive patients: rationale, design and baseline characteristics.
Wang, W, Ma, L, Zhang, Y, Deng, Q, Liu, M, Liu, L
Journal of human hypertension. 2011;(4):271-7
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Abstract
The Chinese Hypertension Intervention Efficacy Study (CHIEF) is a multi-centre randomized controlled clinical trial comparing the effects of amlodipine+angiotensin II receptor blocker and amlodipine+diuretics on the incidence of cardiovascular events, represented as a composite of non-fatal stroke, non-fatal myocardial infarction and cardiovascular death events in high-risk Chinese hypertensive patients. The study also evaluates the long-term effects of lipid-lowering treatment and lifestyle modification. From October 2007 to October 2008, 13,542 patients were enrolled into the study in 180 centres in China. Patients will be followed up for 4 years. There was no difference in baseline characteristics between the two blood pressure arms.
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The Felodipine Event Reduction (FEVER) Study: a randomized long-term placebo-controlled trial in Chinese hypertensive patients.
Liu, L, Zhang, Y, Liu, G, Li, W, Zhang, X, Zanchetti, A, ,
Journal of hypertension. 2005;(12):2157-72
Abstract
OBJECTIVE To compare the incidence of stroke and other cardiovascular events in hypertensive patients receiving a low-dose diuretic and low-dose calcium antagonist combination with those receiving low-dose diuretic monotherapy, and assess the effects of a small blood pressure difference at achieved levels lower than those achieved in previous placebo-controlled trials. METHODS The Felodipine Event Reduction (FEVER) trial was an investigator-designed, prospective, multicentre, double-blind, randomized, placebo-controlled, parallel group trial. It enrolled 9800 Chinese patients, of either sex, aged 50-79 years, with one or two additional cardiovascular risk factors or disease, whose blood pressure, 6 weeks after switching from previous antihypertensive therapy to low-dose (12.5 mg a day) hydrochlorothiazide, was in the range 140-180 mmHg (systolic) or 90-100 mmHg (diastolic). These patients were randomly assigned either to low-dose felodipine extended release or placebo, and followed at 3-month intervals for an average of 40 months. RESULTS The intention-to-treat analysis included 9711 randomly selected patients with only 30 (0.3%) lost to follow-up. A total of 31 842 patient-years of follow-up were accumulated, with 85.9% of patients remaining on blinded randomized treatment. Add-on therapy was given to 33.9% of the hydrochlorothiazide-felodipine patients and to 42.3% of the hydrochlorothiazide-placebo patients. In the felodipine group, systolic blood pressure (SBP)/diastolic blood pressure (DBP) decreased (from randomization to study end) from 154.2/91.0 to 137.3/82.5 mmHg, and in the placebo group from 154.4/91.3 to 142.5/85.0 mmHg, with an average difference throughout the trial of 4.2/2.1 mmHg. In the felodipine group, the primary endpoint (fatal and non-fatal stroke) was reduced by 27% (P = 0.001). Among secondary endpoints, all cardiovascular events were reduced by 27% (P < 0.001), all cardiac events by 35% (P = 0.012), death by any cause by 31% (P = 0.006), coronary events by 32% (P = 0.024), heart failure by 30% (P = 0.239), cardiovascular death by 33% (P = 0.019), cancer by 36% (P = 0.017) in the felodipine group. No significant differences were found in new-onset diabetes. Both treatments were very well tolerated. CONCLUSIONS In moderately complicated hypertensive patients from China even a difference in SBP/DBP as small as 4/2 mmHg, such as that induced by adding low-dose felodipine to low-dose hydrochlorothiazide, is associated with very substantial reductions in the incidence of most types of cardiovascular events. As the SBP achieved in the felodipine group was below the recommended goal of less than 140 mmHg, and SBP in the placebo group was slightly above that level, FEVER provides the required evidence in support of the guidelines recommended goal, even for a hypertensive population not entirely consisting of patients with diabetes or previous cardiovascular events.