Advanced Lipid Testing Uncovers Hidden Cardiovascular Disease Risk: A Case Control Analysis

Abstract

Lead Author’s Financial Disclosures: None Study Funding: This study was funded by Boston Heart Diagnostics on a contract and approved protocol with the Cardiovascular Research Institute, University of California, San Francisco, CA. All analyses were run in a blinded fashion. Background/Synopsis: Recommended standard lipid testing includes total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), and calculated low density lipoprotein cholesterol (LDL-C), which many healthcare providers view as providing insufficient information about cardiovascular disease (CVD) risk. Objective/Purpose: To compare standard lipid profile testing with advanced lipid and inflammatory marker analysis in a CVD case-control study. Methods: In addition to standard methods, we measured serum direct LDL-C, small dense LDL-C (sdLDL-C), very low density lipoprotein cholesterol (VLDL-C), apolipoprotein (apo) B, apoA-I, lipoprotein(a) or Lp(a), HDL particles by gel electrophoresis and apoA-I immunoblotting, high sensitivity C reactive protein (hsCRP), and serum amyloid A (SAA) in 298 documented CVD cases (mean age 68.4 years, 54% male, 46% female) and 609 age and gender matched controls. All subjects were off lipid altering medications. All cases were sampled more than 4 weeks after any CVD event. All subjects had blood drawn after an overnight fast. Results: In male and female cases, median TC levels were 1% and 3% higher, TG levels 19% and 29% higher, direct LDL-C 2% and 17% higher, sdLDL-C 46% and 46% higher, VLDL-C 22% and 4% higher, apoB 6% and 17% higher, and Lp(a) 26% and 70% higher, respectively, than in matched controls. In male and female cases, median HDL-C levels were 25% and 26% lower, apoA-I 9% and 7% lower, while apoA-I values in HDL particles were 30% and 26% lower in very large a-1 HDL, 9% and 11% lower in large a-2 HDL, 4% and 4% lower in medium a-3 HDL, 13% and 6% lower in small a-4 HDL, and 16% and 15% higher in very small preb-1 HDL as compared to matched controls. In male and female cases, median hsCRP levels were 113% and 178% higher, and SAA levels were 41% and 43% higher than in matched controls. Values for sdLDL-C, Lp(a), apoA-I in preb-1 HDL and a-1 HDL, hsCRP, and SAA were all significantly different (p,0.001) in male and female cases versus controls. Conclusions: Our results indicate that advanced lipid and inflammatory marker testing provides significantly more information distinguishing CVD cases from controls than does standard lipid testing. Our data supports the use of advanced testing in CVD prevention, especially in CVD patients being considered for proprotein convertase subtilisin/kexin type 9 inhibitor therapy.