association between hdl2-c and hdl3-c with cardiovascular disease: a nested case-control study in an iranian population

Background: the contribution of high-density lipoprotein cholesterol (hdl-c) subclasses to incident cardiovascular disease (cvd) and coronary heart disease (chd) remains a subject of debate. objectives: the objective of this study was to investigate these associations in a population with a high prevalence of dyslipidemia and cvd. methods: in a nested case-control study, hdl-c and its subclasses (hdl2-c and hdl3-c) in 370 age and gender-matched case and control subjects were determined. this study employed multivariable-adjusted conditional logistic regression to calculate the odds ratios (ors) for the associations between hdl-c, hdl2-c, hdl3-c, and hdl2-c/hdl3-c (both as continuous and categorical variables) with incident cvd and chd. the present study models were adjusted for a comprehensive set of confounders, including body mass index, current smoking, hypertension, type 2 diabetes mellitus, use of lipid-lowering drugs, family history of premature cvd, non-hdl-c, and triglycerides. results: in multivariate analysis, when considering lipoprotein parameters as continuous variables, a 1-unit increase in hdl-c and hdl3-c was associated with a reduced risk of incident cvd and chd. for cvd, the ors (95% confidence intervals [ci]) were 0.95 (0.92 - 0.98) and 0.95 (0.93 - 0.98) for hdl-c and hdl3-c, respectively. the corresponding values for chd were 0.94 (0.91 - 0.97) and 0.94 (0.91 - 0.97). in the categorical approach to lipoprotein parameters, higher quartiles of hdl-c and hdl3-c, compared to the first quartile, were significantly associated with a lower risk of incident cvd and chd. the ors (95% ci) for the fourth quartiles were 0.43 (0.25 - 0.74, p for trend = 0.003) and 0.46 (0.27 - 0.78, p for trend = 0.005) for hdl-c and hdl3-c regarding cvd and 0.32 (0.17 - 0.59) and 0.32 (0.18 - 0.59) (all p for trend = 0.001) regarding chd, respectively. paradoxically, across quartiles of hdl2-c/hdl3-c, this lipid ratio was associated with a higher risk of chd (92% higher risk in the fourth quartile). conclusions: the results showed that hdl3-c, but not hdl2-c, was primarily responsible for the protective effect of hdl-c against cvd, particularly chd, in iranian adults.