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

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.

Circulating metabolomic markers linking diabetic kidney disease and incident cardiovascular disease in type 2 diabetes: analyses from the Hong Kong Diabetes Biobank

“…Furthermore, a recent MR analysis found that medium and small HDL were CVD-protective [ 37 ]. Our observed association of small HDL appeared independent of DKD, which is consistent with findings that small HDL has greater atheroprotective capacities via reverse cholesterol transport, anti-inflammatory, antioxidant and endothelial protection [ 8 , 24 ]. Further studies are warranted to investigate whether detailed HDL composition (proteins, lipids or enzymes) or HDL function may be potential modulators [ 35 ].…”

Periodontitis and the risk of all‐cause and cause‐specific mortality among US adults with diabetes: A population‐based cohort study

“…Area under the curve (AUC), C-statistic, integrated discrimination improvement (IDI) and categorical and continuous net reclassification improvement (NRI) were used to assess the prognostic value of periodontitis (Jin et al, 2022;Mohammedi et al, 2017) between two prognostic models: basic model and basic model plus periodontitis.…”

“…Area under the curve (AUC), C‐statistic, integrated discrimination improvement (IDI) and categorical and continuous net reclassification improvement (NRI) were used to assess the prognostic value of periodontitis (Jin et al, 2022; Mohammedi et al, 2017) between two prognostic models: basic model and basic model plus periodontitis. The basic model refers to previous studies that included the standard risk factors of age, sex, race, BMI, HbA 1c , hyperlipidaemia and hypertension (Basu et al, 2017; Buchan et al, 2021; Mohammedi et al, 2017).…”

Association Between HDL2-C and HDL3-C with Cardiovascular Disease: A Nested Case-Control Study in an Iranian Population

“…Furthermore, findings from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study suggested that high concentrations of total HDL particles were inversely related to cardiovascular mortality, and this relationship was mediated by small HDL particles, with multivariate HRs of 0.55 (0.42 - 0.72) for total HDL and 0.60 (0.46 - 0.77) for small HDL particles ( 33 ). In the Hong Kong Diabetes Biobank (HKDB) prospective cohort study, Jin et al examined the relationship between HDL subclasses and cardiovascular outcomes in patients with T2DM and observed that small HDL particles had an inverse correlation with the development of CVD and all-cause mortality ( 34 ).…”