• David Tak Wai Lui, Lanlan Li, Xiaodong Liu, Xi Xiong, Eric Ho Man Tang, Chi Ho Lee, Yu Cho Woo, LangBrian Hung HinBHH0000-0002-9362-0086Department of Surgery, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China., WongCarlos King HoCKH0000-0002-6895-6071Laboratory of Data Discovery for Health (D24H), Hong Kong SAR, China. carlosho@hku.hk.Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of H, and TanKathryn Choon BengKCB0000-0001-9037-0416Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. kcbtan@hku.hk..
• Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
• Bmc Med. 2024 Dec 18; 22 (1): 586586.

BackgroundHigh 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.MethodsThis 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.ResultsAmong 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.ConclusionsOur 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.© 2024. The Author(s).

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