Abstract 551: HDL Particle Concentration and Incident Ischemic Stroke in Type 1 Diabetes

Recently, we showed that HDL particle concentration (HDL-P) and cholesterol efflux capacity (CEC) predict coronary artery disease (CAD) better than HDL-C in people with type 1 diabetes (T1D). Cardiovascular risk factors have been shown to associate with different cardiovascular outcomes differently. We therefore investigated the association of HDL-P and CEC with ischemic stroke (IS) incidence in people with T1D. We quantified HDL-P using calibrated differential ion mobility and total and ABCA1-specific HDL CEC in 549 participants with childhood-onset (<17 years) T1D from the Epidemiology of Diabetes Complications study using the first available blood sample. The participants were free of cerebrovascular disease at baseline (mean age 27.8 years, T1D duration 19.6 years, 49% women). Stroke incidence/type was determined by self-report of physician diagnosis and confirmed by medical record review. During the follow-up (median 25 years), there were 35 (6.5%) incident IS events. Participants with IS were more likely to be older, have a longer T1D duration, have hypertension, a history of smoking, and a worse lipid, inflammatory and renal markers’ profile at baseline; HDL-C, HDL-P, and CEC did not differ between participants with and without IS. While HDL-C, total HDL-P, and CEC were not associated with IS risk, extra-small HDL-P (xsHDL-P, ~7.8nm) subspecies were strongly associated with incident IS (HR=4.49, 95% CI: 1.72-11.74), even after adjustment for IS risk factors (including smoking, diabetes duration, hypertension as well as HDL-C), in multivariable Cox proportional hazards regression analyses. When all stroke events including hemorrhagic stroke were considered the association was weaker (n=47 events, HR=2.5, 95% CI: 0.97-6.47) suggesting specificity in the association of xsHDL-P with ischemic stroke.In contrast to a strong protective association of total HDL-P and CEC against CAD in the same T1D population, these HDL metrics were not associated with IS. However, the xsHDL-P subspecies were specifically associated with increased IS risk. These striking findings require further investigation and suggest a differential association of HDL particle metrics with CAD and IS.