[Association Between Surrogate Markers of Insulin Resistance and Incident Cardiovascular Disease in a Population With Stages 0-3 Cardiovascular-Kidney-Metabolic Syndrome: A Prospective Cohort Study]

Abstract

Objective: To investigate the association between 8 insulin resistance (IR) surrogate markers and incident atherosclerotic cardiovascular disease (ASCVD) in population with cardiovascular-kidney-metabolic syndrome (CKM) of stages 0-3, and to identify the surrogate marker with the best predictive performance.

Methods: A study was conducted on 20121 community residents classified as CKM stages 0-3 from the Chengdu cohort of the China Multi-Ethic Cohort. A Cox proportional hazards model was used to calculate hazard ratios (HRs) between each IR surrogate marker and incident ASCVD. Cubic spline regression was employed to explore the dose-response relationships between these markers and incident ASCVD. The relative relationships between different markers and incident ASCVD were examined through the ratio of HRs (RHRs). Time-dependent area under the receiver operating characteristic curve (TDAUC) and Uno's C-statistic were calculated to compare the predictive performance of each marker for incident ASCVD. Based on the PREVENT equation components and the 8 surrogate markers under analysis, random forest feature selection was used to determine the contribution of each marker to accurate prediction.

Results: During a follow-up period of 82741.93 person-years, 1447 incident cases of ASCVD were recorded, with an incidence density of 17.49 per 1000 person-years. Association analyses indicated that the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL) and the TyG/(TG/HDL) index were not associated with incident ASCVD (P > 0.05). The TyG index combined with obesity measurement parameters emerged as a reliable predictor of ASCVD incidence. The most promising indicator, TyG index with waist-to-height ratio (TyG_WHtR), exhibited an inverted J-shaped association with incident ASCVD (P for nonlinearity = 0.045; TDAUC = 0.640; C = 0.634), while the TyG index with body mass index (TyG_BMI), waist circumference (TyG_WC), and waist-to-hip ratio (TyG_WHR) showed positive linear associations (all P for trend < 0.05), with relatively lower predictive performance (C = 0.564, 0.588, and 0.598, respectively). Although both the TyG index and the metabolic score for insulin resistance (METS-IR) were associated with increased ASCVD risk (TyG: Q2 vs. Q1, HR = 1.23 and Q4 vs. Q1, HR = 1.24; METS-IR: P for non-linearity = 0.045), they exhibited poor predictive performance for incident ASCVD.

Conclusion: The TyG index combined with obesity measurement parameters is an ideal IR surrogate marker for predicting incident ASCVD in populations with stages 0-3 CKM. Monitoring these markers will facilitate the prevention and control of cardiovascular diseases in CKM populations.

Keywords: Cardiovascular disease; Cardiovascular-kidney-metabolic syndrome; Insulin resistance; Triglyceride-glucose index.

图 1

Restricted cubic spline (RCS) analyses between IR surrogate markers and incident ASCVD in populations with stages 0-3 CKM CKM 0-3期人群中IR替代指标与新发ASCVD间的限制性立方样条分析 HR: hazard ratio; the other abbreviations are explained in the note to Table 1. The model is adjusted for age, sex, income, education, marital status, smoking, drinking, sleep disorders, and physical activity.

图 2

Ratios of hazard ratios (RHRs) between IR surrogate markers and incident ASCVD in population with stages 0-3 CKM CKM 0-3期人群中各IR替代指标与新发ASCVD间的风险比之比 The abbreviations are explained in the note to Table 1. The model is adjusted for age, sex, income, education, marital status, smoking, drinking, sleep disorders, and physical activity. The data represent the ratio of risk ratio (RHR) between the x-axis and y-axis markers. The markers are treated as continuous variables, with the hazard ratio (HR) calculated as the change in ASCVD risk corresponding to an increase of one standard deviation in the IR surrogate markers. RHR > 1 indicates that association of the x-axis marker with the incident ASCVD is stronger than that of the y-axis marker. ^* P < 0.05 indicates that the associations of the two markers with the outcome are significantly different.

图 3

Predictive performance of IR surrogate markers for incident ASCVD in populations with stages 0-3 CKM CKM 0-3期人群中IR替代指标对新发ASCVD的预测性能 TDAUC: time-dependent area under receiver operating characteristic curve; the other abbreviations are explained in the note toTable 1.

图 4

Random forest feature selection based on PREVENT equation components and 8 IR surrogate markers 基于PREVENT等式成分和8个IR替代指标的随机森林特征选择 DM: diabetes mellitus; BP: blood pressure; HLP: hyperlipidemia; MDI: mean decrease in impurity, which measures the contribution of each feature to accurate predictions; the other abbreviations are explained in the note to Table 1. A higher MDI value indicates that the variable is more important.