Introduction: Dyslipidemia plays a paradoxical role in some forms of cerebrovascular disease. Unlike its relationship with ischemic stroke, hypercholesterolemia has been associated with reduced risk of intracerebral hemorrhage (ICH). However, serum lipid levels have wide variation coefficients, and point estimates are likely not representative of long-term exposures. Understanding the temporal trends in serum lipid levels and their association with ICH may improve understanding of the biology of dyslipidemia in ICH. We sought to determine the course of temporal variations in total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG) and high-density lipoprotein (HDL) over 48 months before and after primary ICH.
Methods: We performed a single-center retrospective longitudinal case-control analysis using cases drawn from an ongoing cohort study of primary ICH and controls drawn from a clinical data registry of patients hospitalized for acute non-cerebral events. Piecewise linear mixed-effects models were used to compare the impact of ICH or hospitalization on lipid trends.
Results: 212 ICH cases and 301 control subjects were analyzed. Overall trends in serum TC and LDL levels differed between ICH subjects and non-ICH controls (p<0.0001). ICH subjects experienced significant decline in serum TC and LDL levels during 6 months immediately preceding ICH, compared with levels between 6 to 24 months pre-ICH (TC: -29.25mg/dL, p=0.001; LDL: -21.48mg/dL, p=0.0038), which were not observed in non-ICH controls (TC: -4.32mg/dL, p=0.41; LDL: -1.56mg/dL, p=0.85). Subgroup analysis confirmed that this phenomenon could not be attributed to statin or alcohol exposure. Trends for serum TG and HDL did not differ between groups.
Conclusions: Longitudinal serum TC and LDL levels demonstrate decline within 6 months preceding primary ICH, independent of statin or alcohol use. Subjects hospitalized for non-cerebral events did not exhibit this phenomenon. These temporal trends suggest changes in serum TC and LDL levels herald a generalized process that may precipitate ICH occurrence. Further studies are needed to replicate these results and characterize rate of change in serum lipids as a potential biomarker of impending acute cerebral injury.