Background: Hypertension (HTN) progression is linked to insulin resistance (IR), yet the association between Metabolic Score for Insulin Resistance (METS-IR) and HTN remains underexplored. Methods: This study included 4,051 individuals without a history of HTN from the China Health and Retirement Longitudinal Study (CHARLS). Participants were stratified into four groups according to their baseline METS-IR values. It was the development of incident HTN that was the primary outcome. We used Cox regression to assess this association, conducted subgroup and sensitivity analyses, and evaluated METS-IR’s incremental predictive value over conventional risk factors (age, sex, systolic blood pressure) using C-statistic, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). Results: Over the 9-year follow-up, 1,572 participants (38.81%) experienced their first incident of HTN. Participants were categorized into quartiles (Q1-Q4) based on their METS-IR levels. After full adjustment for confounders, the hazard ratio (HR) with a 95% confidence interval (CI) for incident HTN demonstrated a progressive increase across ascending METS-IR quartiles, with Q1 as reference: Q2, 0.99 (0.85–1.15); Q3, 1.17 (1.01–1.36); Q4, 1.31 (1.13–1.52). The restricted cubic spline (RCS) model revealed a linear dose-response relationship between METS-IR and the incidence of HTN ( P for overall trend < 0.001; P for nonlinear = 0.310). Adding METS-IR to a base model (age/sex/systolic blood pressure) improved HTN prediction (C-statistic Δ= + 0.004; NRI = 16.58%, IDI = 0.75%; all P < 0.001). DCA confirmed greater net benefit across risk thresholds. Subgroup and sensitivity analyses consistently supported the primary findings. Conclusion: Elevated METS-IR independently predicts HTN risk in Chinese adults, suggesting METS-IR as a potential indicator.

Epidemiological studies have yielded inconsistent findings regarding the relationship between conventional low-density lipoprotein cholesterol (LDL-C) and stroke, revealing limitations in its utility as a predictive biomarker. Small dense LDL-C (sdLDL-C), a highly atherogenic lipoprotein subclass, may better capture residual cardiovascular risk; however, direct measurement of sdLDL-C is restricted by limited assay standardization, and large prospective evidence for estimated sdLDL-C (esdLDL-C)—a practical surrogate derivable from standard lipid profiles—remains limited. This prospective analysis included 7,503 participants from the China Health and Retirement Longitudinal Study. esdLDL-C was calculated from standard lipid parameters using Sampson’s equation. Three analytical strategies were employed—percentile-based differences (≥ 15 percentile), cohort-derived and guideline-based clinical thresholds, and continuous model-based residual and percentage-threshold analyses—to evaluate the independent association of esdLDL-C with stroke risk relative to conventional LDL-C. The analysis was further extended to incorporate high-sensitivity C-reactive protein (hsCRP) for comprehensive risk stratification. Subgroup and sensitivity analyses validated the strength of the findings. Incremental predictive performance was assessed using C-statistics, integrated discrimination improvement, and net reclassification index (NRI). Over a median follow-up of 9.0 years, during which 860 incident stroke cases occurred, elevated esdLDL-C was modestly but significantly associated with an increase in stroke risk after full adjustment (hazard ratio [HR] per standard deviation increment: 1.26, 95% confidence interval [CI]: 1.05–1.50), with risk estimates exceeding those of other lipid parameters. Discordance analyses—percentile-based (HR: 1.40, 95% CI: 1.14–1.73), clinical threshold-based (HR: 1.46 at LDL-C < 130 mg/dL; HR: 1.06 at LDL-C < 100 mg/dL), and continuous model-based—generally demonstrated elevated stroke risk associated with high esdLDL-C relative to LDL-C, with graded risk observed across 2%–30% discordance (HRs: 1.23–1.40), although the association was not statistically significant at the more stringent LDL-C < 100 mg/dL threshold. Among individuals with optimal LDL-C (< 130 mg/dL) and low hsCRP (< 2 mg/L), high esdLDL-C (≥ 36 mg/dL) remained significantly associated with stroke risk (HR: 1.53, 95% CI: 1.23–1.89). Incorporation of esdLDL-C significantly enhanced risk reclassification (NRI: 0.1503; P < 0.001). esdLDL-C may confer incremental prognostic value for stroke risk beyond conventional LDL-C and hsCRP in Chinese adults. Derivable from routine lipid panels, it represents a practical adjunct marker for population-level risk assessment, pending external validation and head-to-head comparisons with directly measured sdLDL-C and apolipoprotein B.