The association of the platelet/high-density lipoprotein cholesterol ratio with self-reported stroke and cardiovascular mortality: a population-based observational study.

BACKGROUND: Previous studies have shown that the relationship between high-density lipoprotein cholesterol (HDL-C) and stroke is controversial, and the association between the platelet/high-density lipoprotein cholesterol ratio (PHR), a novel marker for inflammation and hypercoagulability states, and stroke has not been established.

METHODS: This study presents an analysis of cross-sectional data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES). Stroke history, HDL-C levels, and platelet counts were obtained during cross-sectional surveys. The PHR was calculated as the ratio of the number of platelets to HDL-C concentration. Weighted logistic regression was used to assess the associations of HDL-C and the PHR with stroke. Nonlinearity of this relationship was determined through restricted cubic splines (RCSs) and two-piecewise linear regression for identifying inflection points. Furthermore, Cox regression was utilized to prospectively analyze the associations of the PHR and HDL-C concentration with cardiovascular disease (CVD) mortality in stroke survivors.

RESULTS: A total of 27,301 eligible participants were included in the study; mean age, 47.28 years and 50.57% were female, among whom 1,040 had a history of stroke. After full adjustment, the odds ratio (OR) of stroke associated with a per standard deviation (SD) increase in the PHR was estimated at 1.13 (95% confidence interval (CI): 1.03 - 1.24, P = 0.01), and the OR of stroke associated with a per SD increase in HDL-C was 0.95 (95% CI: 0.86-1.05, P = 0.30). The RCS indicated a nonlinear relationship for both variables (PPHR  = 0.018 and PHDL-C  = 0.003), and further piecewise linear regression identified inflection points at PHR = 223.684 and HDL-C = 1.4 mmol/L. Segmental regression indicated that in the PHR ≥ 223.684 segment, the estimated OR of stroke associated with a per-SD increase in the PHR was 1.20 (95% CI: 1.09 - 1.31, P < 0.001), while the association of stroke with HDL-C was not significant before or after the inflection point (P > 0.05). Furthermore, Cox regression and RCS showed that a per-SD increase in the PHR was linearly associated with a greater risk of CVD mortality among stroke survivors (HR: 1.14, 95% CI: 1.06 - 1.22, P < 0.001; nonlinear, P = 0.956), while HDL-C was not significantly associated with CVD mortality.

CONCLUSION: The association between the PHR and stroke incidence exhibited a significant threshold effect, with an inflection point at 223.684. A PHR exceeding 223.684 was positively associated with stroke, while the association between HDL-C and stroke was not significant. Additionally, the PHR was positively and linearly associated with CVD mortality among stroke survivors.