Xianhui Qin1, Youbao Li1, Ningling Sun1, Hong Wang1, Yan Zhang1, Jiguang Wang1, Jianping Li1, Xin Xu1, Min Liang1, Jing Nie1, Binyan Wang1, Xiaoshu Cheng1, Nanfang Li1, Yingxian Sun1, Lianyou Zhao1, Xiaobin Wang1, Fan Fan Hou1, Yong Huo2. 1. From the Renal Division, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Guangzhou, China (X.Q., Y.L., X.X., M.L., J.N., B.W., F.F.H.); Department of Cardiology, Peking University People's Hospital, Beijing, China (N.S.); Centers for Metabolic Disease Research, Temple University School of Medicine, PA (H.W.); Department of Cardiology, Peking University First Hospital, Beijing, China (Y.Z., J.L., Y.H.); Center for Epidemiological Studies and Clinical Trials and Center for Vascular Evaluations, Shanghai Institute of Hypertension, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China (J.W.); Department of Cardiology, Second Affiliated Hospital, Nanchang University, China (X.C.); Department of Hypertension, People's Hospital of Xinjiang Uygur Autonomous Region, the Center of Diagnosis, Treatment and Research of Hypertension in Xinjiang, Urumqi, China (N.L.); Department of Cardiovascular Medicine, the First Hospital of China Medical University, Shenyang, China (Y.S.); Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China (L.Z.); and Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.). 2. From the Renal Division, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Guangzhou, China (X.Q., Y.L., X.X., M.L., J.N., B.W., F.F.H.); Department of Cardiology, Peking University People's Hospital, Beijing, China (N.S.); Centers for Metabolic Disease Research, Temple University School of Medicine, PA (H.W.); Department of Cardiology, Peking University First Hospital, Beijing, China (Y.Z., J.L., Y.H.); Center for Epidemiological Studies and Clinical Trials and Center for Vascular Evaluations, Shanghai Institute of Hypertension, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China (J.W.); Department of Cardiology, Second Affiliated Hospital, Nanchang University, China (X.C.); Department of Hypertension, People's Hospital of Xinjiang Uygur Autonomous Region, the Center of Diagnosis, Treatment and Research of Hypertension in Xinjiang, Urumqi, China (N.L.); Department of Cardiovascular Medicine, the First Hospital of China Medical University, Shenyang, China (Y.S.); Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China (L.Z.); and Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.). huoyong@263.net.cn ffhouguangzhou@163.com.
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.
RCT Entities:
OBJECTIVE: We aimed to examine whether baseline homocysteine (Hcy) concentrations affect antihypertensive responses to enalapril treatment among previously untreated hypertensivepatients (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 hypertensivepatients 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 hypertensivepatients.
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