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

Abstract

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.

The Ratio of High‐Density Lipoprotein Cholesterol to Apolipoprotein A‐I Predicts Myocardial Injury Following Elective Percutaneous Coronary Intervention

“…After adjustment for factors that independently correlated to postprocedural cTnI, the U‐shaped association between HDL‐C/apoA‐I ratio and postprocedural cTnI elevation still existed (Figure , all P values for quadratic term were <0.05). Metabolic markers, such as diabetes, metabolic syndrome/insulin resistance, or triglycerides, may confound the link of HDL parameters to cardiovascular risk . We then additionally adjusted for diabetes, body mass index, and triglycerides in the adjusted model.…”

“…Metabolic markers, such as diabetes, metabolic syndrome/insulin resistance, or triglycerides, may confound the link of HDL parameters to cardiovascular risk. 11 We then additionally adjusted for diabetes, body mass index, and triglycerides in the adjusted model. The relationships of HDL-C, apoA-I, and HDL-C/apoA-I ratio with myocardial injury did not change (see Supporting Information, Table S2, in the online version of this article).…”

Association of Lipoprotein Subfractions and Coronary Artery Calcium In Patient at Intermediate Cardiovascular Risk

“…28 The inverse association between HDL 2 and CAC was limited to those with normal lipid levels. Previous reports have already suggested that HDL fails to predict CAC in dyslipemic states such as diabetes, 29 likely because lipid derangements, such as hypercholesterolemia 30 and, especially, the dyslipidemia of the metabolic syndrome, 31,32 tend to shift metabolic maturation of HDL from HDL 2 toward HDL 3 . The HDL subtype might therefore be an indicator of a highly atherogenic metabolic turnover rather than an independent predictor of coronary atherosclerosis in its own right.…”

Plasma Lipoprotein(a) Levels Are Associated with Mild Renal Impairment in Type 2 Diabetics Independent of Albuminuria

“…Plasma insulin levels were measured at the core laboratory of the Penn Diabetes Center by radioimmunoassay (Linco Research, St. Charles, MO). Total cholesterol (TC), TG, HDL-C, and VLDL-C were measured enzymatically, while LDL-C was measured directly, after ultracentrifugation (β-centrifugation technique) in a Centers for Disease Control (CDC) certified lipid laboratory [42] , [43] , [45] . Lp(a) and apolipoproteins were measured by immunoturbidimetric assay (Wako Chemicals, U.S.A. Inc., Richmond, VA) on a Hitachi 912 autoanalyzer (Roche Diagnostics, Basel, Switzerland).…”