Author + information
- Received January 22, 2018
- Revision received February 23, 2018
- Accepted February 26, 2018
- Published online May 7, 2018.
- Xiangyi Kong, MDa,b,
- Xiao Huang, MDc,
- Min Zhao, MDd,
- Benjamin Xua,e,
- Richard Xua,f,
- Yun Song, MDg,
- Yaren Yu, MDh,
- Wenbin Yang, MSi,
- Jingping Zhang, MSi,
- Lishun Liu, MSg,
- Yan Zhang, MDa,
- Genfu Tang, PhDi,
- Binyan Wang, MD, PhDh,
- Fan Fan Hou, MD, PhDh,
- Ping Li, PhDc,
- Xiaoshu Cheng, MDc,
- Shuiping Zhao, MDj,
- Xiaobin Wang, MD, ScDk,
- Xianhui Qin, PhDh,
- Jianping Li, MD, PhDa and
- Yong Huo, MDa,∗ ()
- aDepartment of Cardiology, Peking University First Hospital, Beijing, China
- bDepartment of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- cDepartment of Cardiology, Second Affiliated Hospital, Nanchang University, Nanchang, China
- dDepartment of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
- eTrinity College of Arts and Sciences, Duke University, Durham, North Carolina
- fWhiting School of Engineering, Johns Hopkins University, Baltimore, Maryland
- gBeijing 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
- hNational Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China
- iSchool of Health Administration, Anhui University, Hefei, China
- jDepartment of Cardiology, Second Xiangya Hospital, Central South University, Changsha, China
- kDepartment of Population, Family, and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
- ↵∗Address for correspondence:
Dr. Yong Huo, Department of Cardiology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China.
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)
The study was supported by the National Science and Technology Major Projects Specialized for “Major New Drugs Innovation and Development” during the 12th Five-Year Plan Period: China Stroke Primary Prevention Trial (grant zx09101105 to Dr. Binyan Wang); the National Key Research and Development Program (2016YFC0903101, 2016YFE0205400 to Dr. Huo); the Projects of the National Natural Science Foundation of China (81402735 to Dr. Qin); the Science and Technology Planning Project of Guangzhou (201707020010 to Dr. Binyan Wang); and the Science, Technology and Innovation Committee of Shenzhen (KQCX20120816105958775, JSGG20160229173428526, JSGG20170412155639040, GJHS20170314114526143, KC2014JSCX0071A to Dr. Binyan Wang). Dr. Qin has received consulting fees from AUSA Research Institute, Shenzhen AUSA. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. This work was presented in part as an abstract by Dr. Xiangyi Kong at the 2017 American College of Cardiology Scientific Session in Washington, DC.
- Received January 22, 2018.
- Revision received February 23, 2018.
- Accepted February 26, 2018.
- 2018 American College of Cardiology Foundation
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