Abstract 19283: Low Density Lipoprotein Cholesterol is Associated with the Extent of Noncalcified and Soft Lipid Rich Coronary Plaque but Not Coronary Calcium in Apparently Healthy Individuals from High Risk Families

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Background: Low density lipoprotein cholesterol (LDL-C) is strongly associated with CAD events. Calcified coronary plaque (CCP) is a proxy of overall plaque burden but the relationship between LDL-C and CCP has been inconsistent. LDL-C likely plays a more putative role in the early stages of atherogenesis including the formation and progression of noncalcified coronary plaque (NCP), especially lipid rich plaque (LRP), than later processes of vascular remodeling with CCP. Thus, we examined the association of LDL-C levels with the extent and relative volumes of NCP in apparently healthy individuals from families with premature CAD. Methods: Participants in GeneSTAR (N=561; mean age 51±10 years; 58% female, 37% AA) were screened for CAD risk factors and for coronary plaque using 256 multidetector dual-source CT angiography. Segmental CCP volumes (mm3) were measured using standard techniques and volumes of NCP and LRP defined as <30 HU were quantified (mm3) using an automated well-validated method. All plaque volumes were log transformed as log(plaque+0.05). Controlling for age, sex, and race, multivariate GEE regression analyses for the association of CAD risk factors, including LDL-C, hypertension, diabetes, and smoking, as well as statin medication use, were performed separately for transformed NCP, CCP, and LRP. Results: The prevalence of any coronary plaque was 45.6%. Multivariate regression demonstrated that LDL-C was significantly associated with the volume of NCP (p=0.02) and LRP (p=0.01) but not CCP (p=0.23). All other risk factors and statin use were significantly associated with all three plaque volumes. Additionally LDL-C was the only risk factor associated with the relative ratio of noncalcified to calcified plaque volume (p=0.02), consistent with a more putative role of LDL-C in earlier stages of plaque development and progression. Conclusion: This is the first study to show that LDL-C is more strongly associated with noncalcified and lipid-rich coronary plaque volumes than with the extent of coronary calcification in high-risk apparently healthy individuals. These findings suggest that early preventive therapies to lower LDL-C may have the greatest benefit prior to the detection of significant CCP.