High-density lipoprotein-cholesterol and risk of stroke and carotid atherosclerosis: A systematic review

Background and purpose Epidemiological studies have found no relationship between total cholesterol and stroke risk, but little attention has been paid to high-density lipoprotein-cholesterol (HDL-C). Methods We performed a systematic PubMed literature search for epidemiological studies that examined the association between HDL-C level and stroke or carotid intima-media thickness (IMT). Results We identified 18 studies on the relationship between HDL-C and stroke risk and 37 on HDL-C and carotid IMT. Eight of ten prospective cohort studies (n = 238 739) and three of eight case–control studies (n = 3604 cases, 8220 controls) supported an association between elevated HDL-C level and decreased risk of stroke. Prospective cohort studies reporting on relative risk per unit increase in HDL-C showed an 11–15% decreased stroke risk per 10-mg/dl increase in HDL-C. Of 37 studies on carotid IMT, 31 reported cross-sectional, one longitudinal, and five both cross-sectional and longitudinal associations between HDL-C level and carotid IMT. Of 36 cross-sectional studies (n = 51 288), 20 showed an inverse association between HDL-C level and carotid IMT. Of six longitudinal studies (n = 20 065), three showed no association, one showed a weak association in a subgroup of white women and two showed a significant inverse relationship between HDL-C level and carotid IMT. Pooled estimates could not be calculated because of the variation in study designs and analysis. Conclusions The weight of evidence in the literature supports an inverse association between HDL-C level and stroke or carotid atherosclerosis, but more data are needed to firmly establish this protective effect.