Association of platelet to highdensity lipoprotein cholesterol ratio (PHR) with stroke and its subtypes: a large prospective cohort study

The platelet to highdensity lipoprotein cholesterol ratio (PHR) is an emerging indicator reflecting the balance between thrombogenesis and lipid metabolism inflammation. This study aimed to investigate the relationship between PHR and stroke and its subtypes (ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage). This study included 400,318 participants without prior stroke history in the UK Biobank. Participants were grouped according to PHR tertiles. Cox proportional hazards regression models were employed to assess the association between PHR and stroke occurrence and subtypes, progressively adjusting for demographic, lifestyle, and metabolic covariates. Restricted cubic spline (RCS) analysis examined nonlinear relationships, while the Fine and Gray competing risks model evaluated cumulative incidence of stroke across PHR groups. The receiver operating characteristic (ROC) curves were performed to explored the additional predictive value of PHR. A total of 16,169 stroke events occurred during follow-up. After multivariable adjustment, PHR showed no significant association with stroke [1.02 (0.97, 1.07)]. However, subtype analysis indicated a positive association of PHR with ischemic stroke [1.10 (1.03, 1.18)] and inversely with intracerebral hemorrhage [0.77 (0.66, 0.90)]. RCS analysis revealed significant nonlinear associations between PHR and stroke risk: U-shaped for overall stroke, J-shaped for ischemic stroke, and L-shaped for intracerebral hemorrhage. The ROC curves indicated that the inclusion of PHR significantly improved the model’s predictive performance. A non-linear association exists between PHR and stroke risk, with opposing directions for ischemic stroke and intracerebral hemorrhage. PHR may serve as a potential marker reflecting the balance between platelet activation and lipid metabolism inflammation, offering novel insights for stroke risk assessment and prevention strategies.