Abstract 3935: Heritability of Lipoprotein Subfractions and Their Correlation with the Severity of Coronary Artery Disease: An Assessment by NMR Spectroscopy
The plasma lipoprotein profile, in particular LDL and HDL cholesterol levels, is a major predictor of coronary artery disease (CAD). The major lipoprotein classes can be further characterized into subfractions by size and density, and there is growing evidence that the profile of these subclasses has a greater prognostic impact than the overall amounts of LDL and HDL cholesterol. So far, it is unclear whether the profile of these subclasses is genetically determined. Therefore, we aimed
to investigate the impact of lipoprotein subclasses on the severity of angiographically derived CAD in siblings with a strong family background of CAD and
to determine the heritability of the entire spectrum of LDL and HDL particle subclasses.
Methods: We used NMR spectroscopy to analyze 16 lipoprotein subfraction classes in more than 1,200 plasma samples of patients with angiographically characterized CAD. Patients were recruited from 590 families of the German myocardial infarction family study. The heritability of the lipoprotein subfractions was estimated by variance component analysis.
Results: Subfractions and mean size of LDL und HDL subclasses showed a highly significant heritability, ranging from 22– 42% (all p<1x10-3) for LDL and 40 – 65% for HDL subclasses (all p<1x10-10). Correlating the lipoprotein subclasses to the severity of CAD, we found after multivariate adjustment that only small LDL particles have a significant association with diffuse CAD (OR 2.70 [1.14–3.41] ) or 3-vessel disease (OR 2.81 [1.10–3.82]), while small HDL particles have a significant protective effect towards diffuse CAD (OR 0.72 [0.65– 0.98]) or 3-vessel disease (OR 0.76[0.66 – 0.99]). In contrast, after adjustment the routine plasma levels of HDL and LDL cholesterol did not show a significant relationship with the severity of CAD.
Conclusion: The lipid subfraction profile has a highly significant heritability and its predictive capability for advanced CAD is greater than that of routine LDL and HDL cholesterol levels. Therefore, analyzing lipid subfractions might markedly improve the risk assessment in patients with CAD and their relatives.