Comparison of High-Density Lipoprotein Cholesterol to Apolipoprotein A-I and A-II to Predict Coronary Calcium and the Effect of Insulin Resistance

Martin, Seth S.; Qasim, Atif N.; Wolfe, Megan; St. Clair, Caitlin; Schwartz, Stanley; Iqbal, Nayyar; Schutta, Mark; Bagheri, Roshanak; Mehta, Nehal N.; Rader, Daniel J.; Reilly, Muredach P.

doi:10.1016/j.amjcard.2010.09.033

« Previous Next »American Journal of Cardiology
Volume 107, Issue 3 , Pages 393-398, 1 February 2011

Comparison of High-Density Lipoprotein Cholesterol to Apolipoprotein A-I and A-II to Predict Coronary Calcium and the Effect of Insulin Resistance

Seth S. Martin, MD
- Cardiovascular Institute, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
- Duke University Medical Center, Durham, North Carolina
- Drs. Martin and Qasim contributed equally to this study.
Atif N. Qasim, MD
- Cardiovascular Institute, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
- Drs. Martin and Qasim contributed equally to this study.
Megan Wolfe, BS
- Cardiovascular Institute, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
Caitlin St. Clair, BS
- Cardiovascular Institute, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
Stanley Schwartz, MD
- Institute of Diabetes, Obesity, and Metabolism, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
Nayyar Iqbal, MD
- Institute of Diabetes, Obesity, and Metabolism, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
Mark Schutta, MD
- Institute of Diabetes, Obesity, and Metabolism, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
Roshanak Bagheri, MD
- University of Connecticut Health Center, Farmington, Connecticut
Nehal N. Mehta, MD
- Cardiovascular Institute, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
Daniel J. Rader, MD
- Cardiovascular Institute, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
- Institute of Diabetes, Obesity, and Metabolism, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
- Institute for Translational Medicine and Therapeutics, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
Muredach P. Reilly, MB, MSCE
- Cardiovascular Institute, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
- Institute of Diabetes, Obesity, and Metabolism, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
- Institute for Translational Medicine and Therapeutics, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
- Corresponding author: Tel: 215-573-1214; fax: 215-573-9004

Received 4 July 2010; received in revised form 18 September 2010; accepted 18 September 2010.

High-density lipoprotein (HDL) cholesterol and its apolipoproteins each capture unique lipid and cardiometabolic information important to risk quantification. It was hypothesized that metabolic factors, including insulin resistance and type 2 diabetes, would confound the association of HDL cholesterol with coronary artery calcification (CAC) and that apolipoprotein A-I (apoA-I) and/or apolipoprotein A-II (apoA-II) would add to HDL cholesterol in predicting CAC. Two community-based cross-sectional studies of white subjects were analyzed: the Penn Diabetes Heart Study (PDHS; n = 611 subjects with type 2 diabetes, 71.4% men) and the Study of Inherited Risk of Coronary Atherosclerosis (SIRCA; n = 803 subjects without diabetes, 52.8% men) using multivariable analysis of apoA-I, apoA-II, and HDL cholesterol stratified by diabetes status. HDL cholesterol was inversely associated with CAC after adjusting for age and gender in whites with type 2 diabetes (tobit ratio for a 1-SD increase in HDL cholesterol 0.58, 95% confidence interval [CI] 0.44 to 0.77, p <0.001) as well as those without diabetes (tobit ratio 0.72, 95% CI 0.59 to 0.88, p = 0.001). In contrast, apoA-I was a weaker predictor in subjects with (tobit ratio 0.64, 95% CI 0.45 to 0.90, p = 0.010) and without (tobit ratio 0.79, 95% CI 0.66 to 0.94, p = 0.010) diabetes, while apoA-II had no association with CAC. Control for metabolic variables, including triglycerides, waist circumference, and homeostasis model assessment of insulin resistance, attenuated these relations, particularly in subjects without diabetes. In likelihood ratio test analyses, HDL cholesterol added to apoA-I, apoA-II, and atherogenic apolipoprotein B lipoproteins but improved CAC prediction over metabolic factors only in subjects with diabetes. In conclusion, HDL cholesterol outperformed apoA-I and apoA-II in CAC prediction, but its association with CAC was attenuated by measures of insulin resistance.