Negative LDL-C levels with Detectable Apolipoprotein B: Surrogate Markers of Atherosclerotic Disease and Cardiac Event Risk

Background/Synopsis

Serial LDL-C measurements remain the mainstay of targeted therapy for patients on lipid lowering therapy including statins, ezetimibe as well as PCSK9 inhibitors. However, Apolipoprotein (apo) B is the primary lipoprotein that serves as the transport medium for all atherogenic lipid particles: chylomicrons, VLDL, LDL, IDL and also lipoprotein(a). LDL-C is generally measured by way of calculation, however in settings of significantly elevated triglyceride levels or very low LDL-C levels, calculations become inaccurate thereby necessitating direct measurement in those instances.

Objective/Purpose

To demonstrate the importance of apo B levels in determining the risk of future cardiac events compared to LDL-C.

Methods

A 58-year-old male with severe mixed hyperlipidemia presented on fenofibrate and simvastatin. He had initial triglyceride (TG) levels >2000 mg/L, total cholesterol (TC) 300mg/dL, HDL 13 mg/dL with uncalculatable LDL levels. He had an elevated coronary artery calcium score (CAC) of 1600, with predominant disease in the LAD and RCA. Evolocumab was added to his medication regimen, along with icosapent ethyl. He underwent stress testing which subsequently led to cardiac catheterization revealing significant occlusions of the PLA and LCx requiring stent placement, as well as diseased right PDA and mid LAD.

Results

Four months after starting evolocumab and icosapent ethyl therapy, there was a significant decrease in TG levels to 1050, TC 139 mg/dL, LDL-C 28 mg/dL, apo B 47 mg/dL and Lp (a) <10nmol/L. Repeat testing five months later, showed continued improvements in his lipid levels with TG 305 mg/dL, TC 65 mg/dL, LDL-C 23 mg/dL and apo B 30 mg/dL.

Conclusions

Aggressive therapy with PCSK9 inhibitors and statins may lead to significant decreases in LDL-C, to undetectable or calculated negative levels. It is important to note however, that at elevated triglyceride levels usually exceeding 300 mg/dL, calculated LDL levels are grossly inaccurate, and will not serve as a reliable marker of atherosclerotic cardiovascular disease (ASCVD) risk. Sniderman et al. found apo B to be a more reliable marker of the risk of angiographic coronary lesions at any given level of LDL-C and thereby a greater indicator of the risk of future cardiac events. However, at levels less than 40 mg/dL, the risk of a cardiac event should be minimal.