Xiao Huang1, Youbao Li1, Ping Li1, Jianping Li1, Huihui Bao1, Yan Zhang1, Binyan Wang1, Ningling Sun1, Jiguang Wang1, Mingli He1, Delu Yin1, Genfu Tang1, Yundai Chen1, Yiming Cui1, Yining Huang1, Fan Fan Hou1, Xianhui Qin2, Yong Huo2, Xiaoshu Cheng2. 1. From the Department of Cardiology (X.H., P.L., H.B., X.C.), Second Affiliated Hospital, Nanchang University; Division of Nephrology (Y.L., B.W., F.F.H., X.Q.), Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease (Y.L., B.W., F.F.H., X.Q.); State Key Laboratory of Organ Failure Research (Y.L., B.W., F.F.H., X.Q.); Guangdong Provincial Institute of Nephrology (Y.L., B.W., F.F.H., X.Q.); Departments of Cardiology (J.L., Y.Z., Y. Huo), Pharmacy (Y. Cui), and Neurology (Y. Huang), Peking University First Hospital; Department of Cardiology (N.S.), Peking University People's Hospital, Beijing; Department of Hypertension (J.W.), The Shanghai Institute of Hypertension, Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai; Departments of Neurology (M.H.) and Cardiology (D.Y.), First People's Hospital, Lianyungang; Institute for Biomedicine and School of Health Administration (G.T.), Anhui Medical University, Hefei; and Department of Cardiology (Y. Chen), Chinese PLA General Hospital, Beijing, China. 2. From the Department of Cardiology (X.H., P.L., H.B., X.C.), Second Affiliated Hospital, Nanchang University; Division of Nephrology (Y.L., B.W., F.F.H., X.Q.), Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease (Y.L., B.W., F.F.H., X.Q.); State Key Laboratory of Organ Failure Research (Y.L., B.W., F.F.H., X.Q.); Guangdong Provincial Institute of Nephrology (Y.L., B.W., F.F.H., X.Q.); Departments of Cardiology (J.L., Y.Z., Y. Huo), Pharmacy (Y. Cui), and Neurology (Y. Huang), Peking University First Hospital; Department of Cardiology (N.S.), Peking University People's Hospital, Beijing; Department of Hypertension (J.W.), The Shanghai Institute of Hypertension, Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai; Departments of Neurology (M.H.) and Cardiology (D.Y.), First People's Hospital, Lianyungang; Institute for Biomedicine and School of Health Administration (G.T.), Anhui Medical University, Hefei; and Department of Cardiology (Y. Chen), Chinese PLA General Hospital, Beijing, China. pharmaqin@126.com huoyong@263.net.cn xiaoshumenfan@126.com.
Abstract
OBJECTIVE: To examine whether a change in serum total homocysteine (tHcy) levels is associated with first stroke risk in a post hoc analysis of the China Stroke Primary Prevention Trial (CSPPT). METHODS: We analyzed 16,867 participants of the CSPPT with tHcy measurements at both baseline and exit visits. The primary outcome was first stroke. The secondary outcome was a composite of cardiovascular events consisting of cardiovascular death, myocardial infarction, and stroke. The percent decline in tHcy was calculated as [(baseline tHcy - exit tHcy)/baseline tHcy × 100]. RESULTS: Over the median treatment duration of 4.5 years, participants who developed a first stroke had a significantly lower percent decline in tHcy (β = -5.7; 95% confidence interval [CI] -8.8 to -2.6) compared to their counterparts. A 20% tHcy decline was associated with a reduction in stroke risk of 7% (hazard ratio [HR] 0.93; 95% CI 0.90-0.97). When percent decline in tHcy was assessed as tertiles, a significantly lower stroke risk was found in those in tertiles 2-3 (HR 0.79; 95% CI 0.64-0.97) compared with participants in tertile 1. Similar results were observed for the composite of cardiovascular events. The beneficial effect associated with greater tHcy reduction was observed across strata for age, sex, treatment group (with vs without folic acid), MTHFR C677T genotypes, baseline tHcy and serum folate levels, and blood pressure control. CONCLUSIONS: Percent lowering in tHcy was significantly associated with a reduction in first stroke risk in Chinese adults with hypertension, and if further confirmed, may serve as a useful indicator for folic acid treatment efficacy on stroke prevention. CLINICALTRIALSGOV IDENTIFIER: NCT00794885.
OBJECTIVE: To examine whether a change in serum total homocysteine (tHcy) levels is associated with first stroke risk in a post hoc analysis of the China Stroke Primary Prevention Trial (CSPPT). METHODS: We analyzed 16,867 participants of the CSPPT with tHcy measurements at both baseline and exit visits. The primary outcome was first stroke. The secondary outcome was a composite of cardiovascular events consisting of cardiovascular death, myocardial infarction, and stroke. The percent decline in tHcy was calculated as [(baseline tHcy - exit tHcy)/baseline tHcy × 100]. RESULTS: Over the median treatment duration of 4.5 years, participants who developed a first stroke had a significantly lower percent decline in tHcy (β = -5.7; 95% confidence interval [CI] -8.8 to -2.6) compared to their counterparts. A 20% tHcy decline was associated with a reduction in stroke risk of 7% (hazard ratio [HR] 0.93; 95% CI 0.90-0.97). When percent decline in tHcy was assessed as tertiles, a significantly lower stroke risk was found in those in tertiles 2-3 (HR 0.79; 95% CI 0.64-0.97) compared with participants in tertile 1. Similar results were observed for the composite of cardiovascular events. The beneficial effect associated with greater tHcy reduction was observed across strata for age, sex, treatment group (with vs without folic acid), MTHFR C677T genotypes, baseline tHcy and serum folate levels, and blood pressure control. CONCLUSIONS: Percent lowering in tHcy was significantly associated with a reduction in first stroke risk in Chinese adults with hypertension, and if further confirmed, may serve as a useful indicator for folic acid treatment efficacy on stroke prevention. CLINICALTRIALSGOV IDENTIFIER: NCT00794885.