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

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.

Conflict of interest statement

YS was employed by Shenzhen AUSA Pharmed Co Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 He, Zhang, Liang, Wang, Chen, Song, Zhou, Wei, Duan, Wang, Qin, Qin and Xu.

Figures

Figure 1

Flow chart of the study participants.

Figure 2

The relationship of serum serine with the risk of all-cause mortality1. 1Adjusted for age, sex, body mass index (BMI), treatment group, MTHFR C677T genotypes, smoking, alcohol drinking, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR) at baseline, folate, total homocysteine (tHcy), vitamin B12 as well as mean SBP and DBP during the treatment period.