CAUSAL RELATIONSHIP BETWEEN SERUM CYSTATIN C AND HYPERTENSION IN MIDDLE-AGED AND ELDERLY PEOPLE BASED ON NESTED CASE-CONTROL AND MENDELIAN RANDOMIZATION STUDY: A NATIONWIDE COHORT STUDY

Abstract

Objective: Objective: Investigate dose-response and bidirectional causality between Cystatin C and hypertension in a national cohort.

Method: Utilizing data from the China Health and Retirement Longitudinal Survey (CHARLS) spanning 2011 to 2015, a nested case-control sample comprising 2,355 individuals was constructed. Logistic regression and restricted cubic splines were employed to analyze the dose-response relationship. A bidirectional two-sample Mendelian randomization was conducted to determine bidirectional causality.

Result: During the 4-year follow-up, 471 (20%) patients developed hypertension.  For each 1 mg/L Cystatin C, the risk increased by 130% (OR=2.35, 95%CI 1.38-4.01), and there was a linear dose-response relationship, with Q4 being 59% higher than Q1, and the effect was stronger in <60 years old.  MR: Cystatin C→ hypertension IVW OR=1.13 (p=0.005), adjusted OR=1.02 (p=0.89);  Hypertension →Cystatin C IVW OR=1.08 (p<0.001), with no heterogeneity or pleiotropy, and the results were robust.

Conclusion: In the middle-aged and elderly population in China, elevated hypertension is a definitive cause of increased Cystatin C levels, whereas elevated Cystatin C does not exert a significant causal effect on hypertension. Cystatin C should be utilized as a real-time biomarker for assessing blood pressure-related renal filtration stress and can aid in the early evaluation, prevention, and monitoring of hypertension in middle-aged individuals.