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Association Between HDL2-C and HDL3-C with Cardiovascular Disease: A Nested Case-Control Study in an Iranian
Abdolreza Chary1,2, Maryam Tohidi2, Mitra Hasheminia2
1Department of Biology, Payame Noor University, Tehran, Iran.
Insights
High-density lipoprotein cholesterol (HDL-C) subclass HDL3-C, not HDL2-C, significantly reduces cardiovascular disease (CVD) and coronary heart disease (CHD) risk in Iranian adults. This finding clarifies HDL-C
Area of Science:
- Cardiovascular Medicine
- Lipid Metabolism
- Preventive Cardiology
Background:
- The role of high-density lipoprotein cholesterol (HDL-C) subclasses in cardiovascular disease (CVD) and coronary heart disease (CHD) risk is debated.
- Understanding these associations is crucial, especially in populations with high rates of dyslipidemia and CVD.
Purpose of the Study:
- To investigate the specific contributions of HDL-C, HDL2-C, and HDL3-C to incident CVD and CHD.
- To analyze these associations in a population characterized by high dyslipidemia and CVD prevalence.
Main Methods:
- A nested case-control study involving 370 matched subjects.
- Multivariable-adjusted conditional logistic regression was used to assess associations.
- Models were adjusted for numerous confounders including BMI, smoking, diabetes, and lipid-lowering drug use.
Main Results:
- Increased HDL-C and HDL3-C levels were associated with reduced CVD and CHD risk (ORs < 1).
- Higher quartiles of HDL-C and HDL3-C showed significantly lower incident CVD and CHD.
- The HDL2-C/HDL3-C ratio paradoxically correlated with increased CHD risk.
Conclusions:
- HDL3-C, not HDL2-C, appears to be the primary HDL-C subclass conferring protection against CVD and CHD.
- Findings are specific to the studied population of Iranian adults.
- This research clarifies the differential impact of HDL-C subclasses on cardiovascular risk.
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.
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