Serum Serine and the Risk of All-Cause Mortality: A Nested Case-Control Study From the China Stroke Primary Prevention Trial (CSPPT)

Qiangqiang He; Nan Zhang; Qiongyue Liang; Zhuo Wang; Ping Chen; Yun Song; Ziyi Zhou; Yaping Wei; Yong Duan; Binyan Wang; Peiwu Qin; Xianhui Qin; Xiping Xu

doi:10.3389/fnut.2022.946277

Serum Serine and the Risk of All-Cause Mortality: A Nested Case-Control Study From the China Stroke Primary Prevention Trial (CSPPT)

Front Nutr. 2022 Jul 12:9:946277. doi: 10.3389/fnut.2022.946277. eCollection 2022.

Authors

Qiangqiang He^{1

2}, Nan Zhang³, Qiongyue Liang⁴, Zhuo Wang⁵, Ping Chen⁶, Yun Song^{7

8}, Ziyi Zhou^{1

2}, Yaping Wei⁵, Yong Duan^{9

10}, Binyan Wang^{2

11}, Peiwu Qin¹², Xianhui Qin¹¹, Xiping Xu^{5

11}

Affiliations

¹ Graduate School at Shenzhen, Tsinghua University, Shenzhen, China.
² Shenzhen Evergreen Medical Institute, Shenzhen, China.
³ Department of Cardiology, Peking University First Hospital, Beijing, China.
⁴ State Key Laboratory of Natural Medicines, Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, China.
⁵ Key Laboratory of Precision Nutrition and Food Quality, Ministry of Education, Department of Nutrition and Health, College of Food Sciences and Nutritional Engineering, China Agricultural University, Beijing, China.
⁶ College of Pharmacy, Jinan University, Guangzhou, China.
⁷ AUSA Research Institute, Shenzhen AUSA Pharmed Co. Ltd., Shenzhen, China.
⁸ Institute of Biomedicine, Anhui Medical University, Hefei, China.
⁹ Yunnan Key Laboratory of Laboratory Medicine, Kunming, China.
¹⁰ Department of Clinical Laboratory, the First Affiliated Hospital of Kunming Medical University, Kunming, China.
¹¹ National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health, Guangdong Laboratory, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
¹² Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.

Abstract

Background: Serine plays a key role in numerous cellular processes, the levels and metabolism is therefore of critical importance. However, few data are available to illustrate the association of serine with long-term health effects, especially, the predictive value for long-term mortality.

Objective: This study was conducted to evaluate the relationship between serum serine levels and all-cause mortality in general hypertensive patients in a longitudinal cohort, and to examine the potential effect modifiers.

Methods: A nested case-control (NCC) study was conducted utilizing 20702 hypertensive participants from the China Stroke Primary Prevention Trial (CSPPT), a randomized, double-blind, actively controlled trial conducted from May 2008 to August 2013 in China. The current study included 291 cases of all-cause mortality and 291 controls matched on age (≤ 1 year), sex and treatment group. All-cause mortality was the main outcome in this analysis, which included death due to any reason.

Results: With the increase in serum serine levels, the risk of all-cause mortality first increased before flattening. After adjusting for related variables, the risk of mortality increased significantly with the increase of serum serine levels. Compared with group Q1, the mortality risk of group Q2, Q3 and Q4 were significantly increased [ORs, 95% CI: Q2: 2.32, (1.32-4.07); Q3: 2.59, (1.48-4.54); and Q4: 1.85, (1.07-3.22)]. In the exploratory analysis, we observed three effect modifiers, total homocysteine, 5-Methyltetrahydrofolate, and estimated glomerular filtration rate significantly modified the serum serine and all-cause mortality association.

Conclusion: Serum serine levels were significantly associated with an increased risk of all-cause mortality in hypertensive patients. Our results and findings, if confirmed further, suggest that serum serine should be considered as a marker for screening risk factors of mortality.

Clinical trial registration: [https://www.clinicaltrials.gov/ct2/show/study/NCT00794885.], identifier [CSPPT, NCT00794885].

Keywords: all-cause mortality; hypertension; longitudinal cohort; nutrition; serum serine.

Associated data

ClinicalTrials.gov/NCT00794885