Xiangyi Kong1, Xiao Huang2, Min Zhao3, Benjamin Xu4, Richard Xu5, Yun Song6, Yaren Yu7, Wenbin Yang8, Jingping Zhang8, Lishun Liu6, Yan Zhang9, Genfu Tang8, Binyan Wang7, Fan Fan Hou7, Ping Li2, Xiaoshu Cheng2, Shuiping Zhao10, Xiaobin Wang11, Xianhui Qin7, Jianping Li9, Yong Huo12. 1. Department of Cardiology, Peking University First Hospital, Beijing, China; Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. 2. Department of Cardiology, Second Affiliated Hospital, Nanchang University, Nanchang, China. 3. Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. 4. Department of Cardiology, Peking University First Hospital, Beijing, China; Trinity College of Arts and Sciences, Duke University, Durham, North Carolina. 5. Department of Cardiology, Peking University First Hospital, Beijing, China; Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland. 6. Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Laboratory for Food Quality and Safety, and Key Laboratory for Functional Dairy, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing, China. 7. National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China. 8. School of Health Administration, Anhui University, Hefei, China. 9. Department of Cardiology, Peking University First Hospital, Beijing, China. 10. Department of Cardiology, Second Xiangya Hospital, Central South University, Changsha, China. 11. Department of Population, Family, and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland. 12. Department of Cardiology, Peking University First Hospital, Beijing, China. Electronic address: huoyong@263.net.cn.
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).
RCT Entities:
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).
Authors: Mahmoud H Elbatreek; Sepideh Sadegh; Elisa Anastasi; Emre Guney; Cristian Nogales; Tim Kacprowski; Ahmed A Hassan; Andreas Teubner; Po-Hsun Huang; Chien-Yi Hsu; Paul M H Schiffers; Ger M Janssen; Pamela W M Kleikers; Anil Wipat; Jan Baumbach; Jo G R De Mey; Harald H H W Schmidt Journal: PLoS Biol Date: 2020-11-10 Impact factor: 8.029