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1.
Interaction of serum calcium and folic acid treatment on first stroke in hypertensive males.
Wu, H, Zhang, Y, Li, H, Li, J, Zhang, Y, Liang, M, Nie, J, Wang, B, Wang, X, Huo, Y, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(4):2381-2388
Abstract
BACKGROUND & AIMS The role of serum calcium on the risk of stroke is still uncertain. We aimed to evaluate the effect of serum calcium on first stroke risk, and on the efficacy of folic acid treatment in prevention of first stroke among hypertensive patients. METHODS Our analyses included a total of 19,644 eligible hypertensive adults from the China Stroke Primary Prevention Trial (CSPPT). In the CSPPT, a total of 20,702 hypertensive patients were randomly assigned to a double-blind, daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. The primary outcome was a first stroke. RESULTS Over a median of 4.5 years, among those not receiving folic acid, a significantly higher risk of first stroke was found in hypertensive males with baseline albumin-corrected serum calcium ≥2.43 mmol/L (median) (vs. <2.43 mmol/L; 6.5% vs. 2.3%; adjusted HR, 2.47; 95% CI: 1.72, 3.55). For those with enalapril and folic acid treatment, compared with the enalapril only group, the risk of first stroke was reduced from 6.5% to 3.0% (adjusted HR, 0.49; 95% CI: 0.35, 0.68) in hypertensive males with baseline albumin-corrected serum calcium ≥2.43 mmol/L, whereas there was no significant effect among hypertensive males with baseline albumin-corrected serum calcium <2.43 mmol/L. However, among hypertensive females, serum calcium did not significantly affect the first stroke risk and the efficacy of folic acid in prevention of first stroke. CONCLUSIONS Among Chinese hypertensive males, those with elevated serum calcium levels had increased risk of first stroke, and this risk was reduced by 51% with folic acid treatment.
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2.
Platelet Count Affects Efficacy of Folic Acid in Preventing First Stroke.
Kong, X, Huang, X, Zhao, M, Xu, B, Xu, R, Song, Y, Yu, Y, Yang, W, Zhang, J, Liu, L, et al
Journal of the American College of Cardiology. 2018;(19):2136-2146
Abstract
BACKGROUND The role of platelets and important effect modifiers on the risk of first stroke is unknown. OBJECTIVES This study examined whether low platelet count (PLT) and elevated total homocysteine (tHcy) levels jointly increase the risk of first stroke, and, if so, whether folic acid treatment is particularly effective in stroke prevention in such a setting. METHODS A total of 10,789 Chinese hypertensive adults (mean age 59.5 years; 38% male, with no history of stroke and myocardial infarction) were analyzed from the China Stroke Primary Prevention Trial, where participants were randomly assigned to daily treatments of 10 mg enalapril and 0.8 mg folic acid (n = 5,408) or 10 mg enalapril alone (n = 5,381). The primary endpoint was first stroke. RESULTS During 4.2 years of follow-up, a total of 371 first strokes occurred. In the enalapril-alone group, the lowest rate of first stroke (3.3%) was found in patients with high PLT (quartiles 2 to 4) and low tHcy (<15 μmol/l); and the highest rate (5.6%) was in patients with low PLT (quartile 1) and high tHcy (≥15 μmol/l) levels. Following folic acid treatment, the high-risk group had a 73% reduction in stroke (hazard ratio: 0.27; 95% confidence interval: 0.11 to 0.64; p = 0.003), whereas there was no significant effect among the low-risk group. CONCLUSIONS Among Chinese hypertensive adults, the subgroup with low PLT and high tHcy had the highest risk of first stroke, and this risk was reduced by 73% with folic acid treatment. If confirmed, PLT and tHcy could serve as biomarkers to identify high-risk individuals who would particularly benefit from folic acid treatment. (China Stroke Primary Prevention Trial [CSPPT]; NCT00794885).
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3.
Effect of long-term low-dose folic acid supplementation on degree of total homocysteine-lowering: major effect modifiers.
Wang, B, Wu, H, Li, Y, Ban, Q, Huang, X, Chen, L, Li, J, Zhang, Y, Cui, Y, He, M, et al
The British journal of nutrition. 2018;(10):1122-1130
Abstract
We sought to examine the potential modifiers in the association between long-term low-dose folic acid supplementation and the reduction of serum total homocysteine (tHcy) among hypertensive patients, using data from the China Stroke Primary Prevention Trial (CSPPT). This analysis included 16 867 participants who had complete data on tHcy measurements at both the baseline and exit visit. After a median treatment period of 4·5 years, folic acid treatment significantly reduced the tHcy levels by 1·6 μmol/l (95 % CI 1·4, 1·8). More importantly, after adjustment for baseline tHcy and other important covariates, a greater degree of tHcy reduction was observed in certain subgroups: males, the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, higher baseline tHcy levels (≥12·5 (median) v. <12·5 μmol/l), lower folate levels (<8·0 (median) v. ≥8·0 ng/ml), estimated glomerular filtration rate (eGFR) <60 ml/min per 1·73 m2 (v. 60-<90 and ≥90 ml/min per 1·73 m2), ever smokers and concomitant use of diuretics (P for all interactions <0·05). The degree of tHcy reduction associated with long-term folic acid supplementation can be significantly affected by sex, MTHFR C677T genotypes, baseline folate, tHcy, eGFR levels and smoking status.
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4.
Optimal Systolic Blood Pressure Levels for Primary Prevention of Stroke in General Hypertensive Adults: Findings From the CSPPT (China Stroke Primary Prevention Trial).
Fan, F, Yuan, Z, Qin, X, Li, J, Zhang, Y, Li, Y, Yu, T, Ji, M, Ge, J, Zheng, M, et al
Hypertension (Dallas, Tex. : 1979). 2017;(4):697-704
Abstract
We aimed to investigate the relationship of time-averaged on-treatment systolic blood pressure (SBP) with the risk of first stroke in the CSPPT (China Stroke Primary Prevention Trial). A post hoc analysis was conducted using data from 17 720 hypertensive adults without cardiovascular disease, diabetes mellitus, and renal function decline from the CSPPT, a randomized double-blind controlled trial. The primary outcome was first stroke. Over a median follow-up duration of 4.5 years, the association between averaged on-treatment SBP and risk for first stoke followed a U-shape curve, with increased risk above and below the reference range of 120 to 130 mm Hg. Compared with participants with time-averaged on-treatment SBP at 120 to 130 mm Hg (mean, 126.2 mm Hg), the risk of first stroke was not only increased in participants with SBP at 130 to 135 mm Hg (mean, 132.6 mm Hg; 1.5% versus 0.8%; hazard ratio, 1.63; 95% confidence interval, 1.01-2.63) or 135 to 140 mm Hg (mean, 137.5 mm Hg; 1.9% versus 0.8%; hazard ratio, 1.85; 95% confidence interval, 1.17-2.93), but also increased in participants with SBP <120 mm Hg (mean, 116.7 mm Hg; 3.1% versus 0.8%; hazard ratio, 4.37; 95% confidence interval, 2.10-9.07). Similar results were found in various subgroups stratified by age, sex, and treatment group. Furthermore, lower diastolic blood pressure was associated with lower risk of stroke, with a plateau at a time-average on-treatment diastolic blood pressure <80 mm Hg. In conclusion, among adults with hypertension and without a history of stroke or myocardial infarction, diabetes mellitus, or renal function decline, a lower SBP goal of 120 to 130 mm Hg, as compared with a target SBP of 130 to 140 mm Hg or <120 mm Hg, resulted in the lowest risk of first stroke.
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5.
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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6.
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).
Qin, X, Li, J, Zhang, Y, Chen, D, Wang, B, He, M, Fu, J, Tang, G, Cai, Y, Shi, X, et al
Journal of diabetes. 2016;(2):286-94
Abstract
BACKGROUND 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. METHODS In all, 20 702 hypertensive adults with no history of stroke and/or myocardial infarction (MI) were randomly assigned to receive double-blind daily treatment with tablets containing either: (i) 10 mg enalapril and 0.8 mg folic acid (n = 10 348); or (ii) 10 mg enalapril alone (n = 10 354). New-onset diabetes was defined as either self-reported physician-diagnosed diabetes or the use of glucose-lowering drugs during the follow-up period of the CSPPT. RESULTS Over a median treatment duration of 4.5 years, new-onset diabetes occurred in 198 (2.0%) and 214 (2.1%) subjects in the enalapril-folic acid and enalapril groups, respectively (hazard ratio [HR] 0.92; 95% confidence interval [CI] 0.76-1.12). Similar results were observed when analyses were limited to subjects with baseline fasting glucose (FG) <7.0 mmol/L (HR 0.85; 95% CI 0.62-1.14). Furthermore, there was no significant group difference in: (i) the risk of new-onset FG ≥7.0 mmol/L (defined as FG <7.0 at baseline and ≥7.0 mmol/L at the last visit; relative risk [RR] 1.07; 95% CI 0.96-1.20); or (ii) the composite of new-onset diabetes or new-onset FG ≥7.0 mmol/L (RR = 1.06; 95% CI 0.95-1.19). CONCLUSIONS Among adults with hypertension with no history of stroke and/or MI in China, folic acid supplementation had no significant effect on the risk of new-onset diabetes.