Both low and high high-density lipoprotein cholesterol levels were linked to increased risks of major adverse cardiovascular events, demonstrating a U-shaped relationship in nearly 600,000 participants with type 2 diabetes, according to a recent study.
Researchers conducted a large-scale population-based retrospective cohort study to investigate the relationship between high-density lipoprotein cholesterol (HDL-C) levels and the risk of major adverse cardiovascular events (MACE) and mortality in participants with type 2 diabetes (T2D). The study, published in BMC Medicine, analyzed data from 596,943 participants with T2D recorded in the Hong Kong Hospital Authority’s electronic health records between 2008 and 2020.
Participants were stratified into three groups based on their first-recorded HDL-C levels after diabetes diagnosis: low HDL-C (≤40 mg/dL), medium HDL-C (>40 and ≤80 mg/dL), and high HDL-C (>80 mg/dL). The primary outcome was incident MACE, including myocardial infarction, stroke, heart failure, and cardiovascular mortality. Cox proportional hazards models and restricted cubic spline analyses were employed to assess the associations.
Over a median follow-up of 79.5 months, 81,592 MACEs occurred, with an overall incidence rate of 2.08 events per 100 person-years. Compared to the medium HDL-C group, participants in the low HDL-C group had a significantly higher risk of MACE (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.23–1.26; P<0.001). Similarly, the high HDL-C group demonstrated an elevated MACE risk (HR 1.09, 95% CI 1.04–1.13; P<0.001). The study highlighted that low HDL-C levels were associated with a higher hazard ratio for major adverse cardiovascular events compared to high HDL-C levels, emphasizing the asymmetry in the observed U-shaped relationship. The study found that the association between high HDL-C levels and major adverse cardiovascular events was more pronounced in males, while it was less significant in participants aged 60 years or younger. The analysis also revealed a U-shaped relationship between HDL-C levels and MACE, with both low and high levels associated with adverse outcomes.
The researchers, led by David Tak Wai Lui, further noted increased risks of all-cause and non-cardiovascular mortality in the low and high HDL-C groups compared to the medium group. Secondary analyses highlighted a stronger association between high HDL-C levels and MACE in males, with a less pronounced effect in participants aged 60 years or younger. Sensitivity analyses confirmed the consistency of these findings across subgroups and after excluding participants with preexisting cardiovascular disease.
The study acknowledges certain limitations, including the potential influence of unmeasured confounding factors such as lifestyle variables and the lack of a control group without diabetes. Additionally, the findings are specific to a predominantly Chinese population with T2D, limiting their generalizability to other ethnicities and to individuals with type 1 diabetes, and the observational design precludes establishing causal relationships.
The results indicate that very high levels of HDL-C may be associated with adverse outcomes in T2D. Further research is required to understand the biological mechanisms underlying these risks and to evaluate their potential implications for cardiovascular risk prediction models.
Full disclosures can be found in the published study.
