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. 2022 Dec 31;21(1):293.
doi: 10.1186/s12933-022-01726-y.

High-density lipoprotein subclasses and cardiovascular disease and mortality in type 2 diabetes: analysis from the Hong Kong Diabetes Biobank

Qiao Jin  1 , Eric S H Lau  1   2 , Andrea O Luk  1   2   3 , Claudia H T Tam  1   2   3   4 , Risa Ozaki  1   2 , Cadmon K P Lim  1   2   3   4 , Hongjiang Wu  1   2 , Elaine Y K Chow  1   2   3 , Alice P S Kong  1   2   3 , Heung Man Lee  1 , Baoqi Fan  1   2   3   4 , Alex C W Ng  1 , Guozhi Jiang  5 , Ka Fai Lee  6 , Shing Chung Siu  7 , Grace Hui  7 , Chiu Chi Tsang  8 , Kam Piu Lau  9 , Jenny Y Leung  10 , Man-Wo Tsang  11 , Elaine Y N Cheung  11 , Grace Kam  11 , Ip Tim Lau  12 , June K Li  13 , Vincent T Yeung  14 , Emmy Lau  15 , Stanley Lo  15 , Samuel Fung  16 , Yuk Lun Cheng  17 , Chun Chung Chow  1 , Weichuan Yu  18 , Stephen K W Tsui  19 , Yu Huang  19   20 , Hui-Yao Lan  1   3 , Cheuk Chun Szeto  1   3 , Wing Yee So  1   2   3 , Alicia J Jenkins  1   21 , Juliana C N Chan  1   2   3   4 , Ronald C W Ma  22   23   24   25 ; Hong Kong Diabetes Biobank Study Group
Affiliations

High-density lipoprotein subclasses and cardiovascular disease and mortality in type 2 diabetes: analysis from the Hong Kong Diabetes Biobank

Qiao Jin et al. Cardiovasc Diabetol. .

Abstract

Objective: High-density lipoproteins (HDL) comprise particles of different size, density and composition and their vasoprotective functions may differ. Diabetes modifies the composition and function of HDL. We assessed associations of HDL size-based subclasses with incident cardiovascular disease (CVD) and mortality and their prognostic utility.

Research design and methods: HDL subclasses by nuclear magnetic resonance spectroscopy were determined in sera from 1991 fasted adults with type 2 diabetes (T2D) consecutively recruited from March 2014 to February 2015 in Hong Kong. HDL was divided into small, medium, large and very large subclasses. Associations (per SD increment) with outcomes were evaluated using multivariate Cox proportional hazards models. C-statistic, integrated discrimination index (IDI), and categorial and continuous net reclassification improvement (NRI) were used to assess predictive value.

Results: Over median (IQR) 5.2 (5.0-5.4) years, 125 participants developed incident CVD and 90 participants died. Small HDL particles (HDL-P) were inversely associated with incident CVD [hazard ratio (HR) 0.65 (95% CI 0.52, 0.81)] and all-cause mortality [0.47 (0.38, 0.59)] (false discovery rate < 0.05). Very large HDL-P were positively associated with all-cause mortality [1.75 (1.19, 2.58)]. Small HDL-P improved prediction of mortality [C-statistic 0.034 (0.013, 0.055), IDI 0.052 (0.014, 0.103), categorical NRI 0.156 (0.006, 0.252), and continuous NRI 0.571 (0.246, 0.851)] and CVD [IDI 0.017 (0.003, 0.038) and continuous NRI 0.282 (0.088, 0.486)] over the RECODe model.

Conclusion: Small HDL-P were inversely associated with incident CVD and all-cause mortality and improved risk stratification for adverse outcomes in people with T2D. HDL-P may be used as markers for residual risk in people with T2D.

Keywords: Cardiovascular disease; High-density lipoprotein particles; High-density lipoprotein subclasses; Mortality; Prognostic marker; Residual risk; Risk stratification; Type 2 diabetes.

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Conflict of interest statement

JCNC received consultancy fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Celltrion, MSD, Pfizer, Servier and Viatris Pharmaceutical, speaker fees from Astra Zeneca, Bayer, Boehringer Ingelheim, MSD, Merck, Sanofi and Servier and research grants through her institutions from Applied Therapeutics, Astra Zeneca, Hua Medicine, Lee Powder, Lilly, Merck and Servier. APSK received research grants from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli-Lilly, Kyowa Kirin, and Merck Serono, and honoraria for consultancy or giving lectures from Nestle, Novo Nordisk, Pfizer, and Sanofi. EYKC received speaker fees from Sanofi and Novartis, and institutional research funding from Sanofi, Medtronic Diabetes, and Powder Pharmaceuticals Inc. RCWM received research funding from AstraZeneca, Bayer, Merck Sharp & Dohme, Novo Nordisk, Pfizer, Roche Diagnostics and Tricida Inc. for carrying out clinical trials or studies, and from AstraZeneca, Bayer and Boehringer Ingelheim for speaker honoraria or consultancy in advisory boards. All proceeds have been donated to the Chinese University of Hong Kong to support diabetes research. The remaining authors declare that they have no relevant financial interests.

Figures

Fig. 1
Fig. 1
Kaplan-Meier plots for cumulative incidence of incident CVD and all-cause mortality according to tertiles of HDL-P measurements. Adjusted for age, sex, smoking, diabetes duration, systolic blood pressure, body mass index, glycated hemoglobin, estimated glomerular filtration rate, ln (urinary albumin-creatinine ratio), ln (triglycerides), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, glycoprotein acetyls, oral antihyperglycemic drugs, insulin use, renin-angiotensin system blockers, antihypertensive drugs, lipid-lowering drugs, and history of cardiovascular disease (for all-cause mortality). P value was obtained by the log-rank test
Fig. 2
Fig. 2
Adjusted restricted cubic spline analysis for the associations between HDL-P measurements and incident CVD and all-cause mortality. The solid lines are the adjusted log hazard ratios, and the shaded areas are 95% CIs derived from corresponding restricted cubic spline regressions. A knot was located at 10th, 50th (reference value), 90th percentiles for each of the HDL-P measurements. Analyses were adjusted for age, sex, smoking, diabetes duration, systolic blood pressure, body mass index, glycated hemoglobin, estimated glomerular filtration rate, ln (urinary albumin-creatinine ratio), ln (triglycerides), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, glycoprotein acetyls, oral anti-hyperglycemic drugs, insulin use, renin-angiotensin system blockers, anti-hypertensive drugs, lipid-lowering drugs, and history of cardiovascular disease (for all-cause mortality)
See this image and copyright information in PMC

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