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. 2024 Dec 18;22(1):586.
doi: 10.1186/s12916-024-03810-4.

The association of HDL-cholesterol levels with incident major adverse cardiovascular events and mortality in 0.6 million individuals with type 2 diabetes: a population-based retrospective cohort study

David Tak Wai Lui #  1   2 , Lanlan Li #  1 , Xiaodong Liu  3   4 , Xi Xiong  4   5   6 , Eric Ho Man Tang  4   7 , Chi Ho Lee  1   2 , Yu Cho Woo  1 , Brian Hung Hin Lang  3 , Carlos King Ho Wong  8   9   10 , Kathryn Choon Beng Tan  11
Affiliations

The association of HDL-cholesterol levels with incident major adverse cardiovascular events and mortality in 0.6 million individuals with type 2 diabetes: a population-based retrospective cohort study

David Tak Wai Lui et al. BMC Med. .

Abstract

Background: High levels of high-density lipoprotein cholesterol (HDL-C) are previously considered protective against cardiovascular diseases (CVD), but recent studies suggest an increased risk of adverse events at very high HDL-C levels in the general population. It remains to be elucidated such a relationship in diabetes, a condition with high cardiovascular risks. We examined the association of HDL-C levels with the risk of major adverse cardiovascular events (MACE) and mortality in type 2 diabetes.

Methods: This retrospective cohort study identified individuals with type 2 diabetes who had HDL-C records (2008-2020) from the electronic health record database of the Hong Kong Hospital Authority. They were classified into three groups based on their first-recorded HDL-C levels following diabetes diagnosis: low (≤ 40 mg/dL), medium (> 40 and ≤ 80 mg/dL) and high HDL-C (> 80 mg/dL) groups. The primary outcome was incident MACE (composite of myocardial infarction, stroke, heart failure, and cardiovascular mortality). Cox regression model and restricted cubic spline analysis were employed to assess the relationship between HDL-C and adverse outcomes.

Results: Among 596,943 individuals with type 2 diabetes included, 168,931 (28.30%), 412,863 (69.16%), and 15,149 (2.54%) were classified as low HDL-C, medium HDL-C, and high HDL-C groups, respectively. Over a median follow-up of 79.5 months, both low and high HDL-C groups had higher risk of incident MACE compared to the medium HDL-C group (HR 1.24, 95% CI 1.23-1.26, P < 0.001; HR 1.09, 95% CI 1.04-1.13, P < 0.001). The spline curves revealed a U-shaped association between HDL-C levels and incident MACE (non-linear p < 0.001). Similar U-shaped relationship was observed for all-cause and non-cardiovascular mortality.

Conclusions: Our study demonstrated a U-shaped association between HDL-C levels and incident MACEs and all-cause and non-cardiovascular mortality in individuals with type 2 diabetes, highlighting the need for mechanistic studies on the adverse outcomes seen at high HDL-C levels in type 2 diabetes.

Keywords: Cardiovascular; Dyslipidemia; HDL cholesterol; Mortality; Type 2 diabetes.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Ethical approval was obtained from the Institutional Review Board of the Hong Kong Hospital Authority (Ref No. UW 21–320). Informed consent was not required for the use of anonymous patient data in this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of Individuals with Type 2 Diabetes Included and Excluded for this Analysis. HDL-C = High-density lipoprotein cholesterol; ESKD = End-stage kidney disease. The index date was defined as the date of the first HDL-C measurement available after the diagnosis of type 2 diabetes
Fig. 2
Fig. 2
Association between Continuous HDL-C levels and Incident MACEs Estimated by Restricted Cubic Splines Models. a without adjustment (Model 1), and (b) with adjustment for age, sex, and index year (Model 2); MACEs = Major adverse cardiovascular events; HDL-C = High-density lipoprotein cholesterol; CI = Confidence interval; The reference point was set at the HDL-C level of 60 mg/dL
Fig. 3
Fig. 3
Association between Continuous HDL-C Levels and Incident Secondary Outcomes Estimated by Restricted Cubic Spline Models. HDL-C = High-density lipoprotein cholesterol; CI = Confidence interval. The reference point was set at the HDL-C level of 60 mg/dL
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