Related Experiment Video
Updated: Mar 13, 2026
Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
Folic Acid Therapy Reduces the First Stroke Risk Associated With Hypercholesterolemia Among Hypertensive Patients
Xianhui Qin1, Jianping Li1, J David Spence1
1From 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., B.W., F.F.H.); Department of Cardiology (J.L., Y.Z., Y. Huo) and Department of Neurology (Y. Huang), Peking University First Hospital, Beijing, China; Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, University of Western Ontario, London, Canada (J.D.S.); Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (X.W.); Department of Cardiology, Peking University People's Hospital, Beijing, China (N.S., H.C.); Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, China (F.C.); Department of Cardiology, Peking University Third Hospital, Beijing, China (J.G.); Department of Cardiology, First People's Hospital, Lianyungang, China (D.Y.); Department of Cardiology, Second People's Hospital, Lianyungang, China (L.S.); Institute for Biomedicine, School of Health Administration (G.T.) and Department of Neurology, First Affiliated Hospital (J.F., X.S.), Anhui Medical University, Hefei, China; Department of Neurology, First People's Hospital, Lianyungang, China (M.H.); Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China (Y.C.); Department of Geriatric Cardiology, the General Hospital of the People's Liberation Army, Beijing, China (P.Y.); Department of Cardiology, Second Xiangya Hospital, Central South University, Changsha, China (S.Z.); Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China (M.C.); Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, China (C.G.); and Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China (X.K.).
Background And Purpose:
We sought to determine whether folic acid supplementation can independently reduce the risk of first stroke associated with elevated total cholesterol levels in a subanalysis using data from the CSPPT (China Stroke Primary Prevention Trial), a double-blind, randomized controlled trial.
Methods:
A total of 20 702 hypertensive adults without a history of major cardiovascular disease were randomly assigned to a double-blind daily treatment of an enalapril 10-mg and a folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. The primary outcome was first stroke.
Results:
The median treatment duration was 4.5 years. For participants not receiving folic acid treatment (enalapril-only group), high total cholesterol (≥200 mg/dL) was an independent predictor of first stroke when compared with low total cholesterol (<200 mg/dL; 4.0% versus 2.6%; hazard ratio, 1.52; 95% confidence interval, 1.18-1.97; P=0.001). Folic acid supplementation significantly reduced the risk of first stroke among participants with high total cholesterol (4.0% in the enalapril-only group versus 2.7% in the enalapril-folic acid group; hazard ratio, 0.69; 95% confidence interval, 0.56-0.84; P<0.001; number needed to treat, 78; 95% confidence interval, 52-158), independent of baseline folate levels and other important covariates. By contrast, among participants with low total cholesterol, the risk of stroke was 2.6% in the enalapril-only group versus 2.5% in the enalapril-folic acid group (hazard ratio, 1.00; 95% confidence interval, 0.75-1.30; P=0.982). The effect was greater among participants with elevated total cholesterol (P for interaction=0.024).
Conclusions:
Elevated total cholesterol levels may modify the benefits of folic acid therapy on first stroke. Folic acid supplementation reduced the risk of first stroke associated with elevated total cholesterol by 31% among hypertensive adults without a history of major cardiovascular diseases.
Clinical Trial Registration:
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.
Insights
Folic acid supplementation significantly reduced stroke risk in hypertensive adults with high total cholesterol. This benefit was observed in a subanalysis of the China Stroke Primary Prevention Trial (CSPPT).
Area of Science:
- Cardiovascular Medicine
- Nutritional Science
- Preventive Cardiology
Background:
- Elevated total cholesterol is a known risk factor for stroke.
- Folic acid supplementation is investigated for its potential cardiovascular benefits.
- The China Stroke Primary Prevention Trial (CSPPT) provides data on stroke prevention in hypertensive adults.
Purpose of the Study:
- To determine if folic acid supplementation independently reduces the risk of first stroke.
- To investigate the effect of folic acid on stroke risk in relation to total cholesterol levels.
- To analyze data from a sub-study of the CSPPT.
Main Methods:
- A subanalysis of the double-blind, randomized CSPPT was conducted.
- 20,702 hypertensive adults without prior cardiovascular disease were included.
- Participants received either enalapril with folic acid or enalapril alone.
Main Results:
- High total cholesterol (≥200 mg/dL) independently predicted first stroke in the enalapril-only group (HR, 1.52).
- Folic acid supplementation significantly reduced stroke risk in participants with high total cholesterol (HR, 0.69; P<0.001).
- No significant stroke risk reduction was observed in participants with low total cholesterol (HR, 1.00; P=0.982).
Conclusions:
- Elevated total cholesterol levels may modify the benefits of folic acid therapy on first stroke.
- Folic acid supplementation demonstrated a 31% reduction in first stroke risk associated with elevated total cholesterol.
- These findings suggest a targeted benefit of folic acid in hypertensive individuals with high cholesterol.
Related Concept Videos
01:26Atherosclerosis III: Management
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
01:23Atherosclerosis IV: Nursing Management
01:28Hypertension IV: Drug Therapy and Lifestyle Modifications
01:26Coronary Artery Disease IV: Preventive Measures
01:27Peripheral Artery Disease III: Interprofessional Care