Discordance between non-HDL-cholesterol and LDL-particle measurements: Results from the Multi-Ethnic Study of Atherosclerosis

Abstract

Background Cardiovascular risk assessment incorporates measurement of atherogenic lipids such as non-HDL cholesterol (non-HDL-C). It remains uncertain under which circumstances atherogenic lipoprotein enumeration such as LDL particle number (LDL-P) differs from simultaneously acquired non-HDL-C. Methods Participants of the Multi-Ethnic Study of Atherosclerosis (MESA) were deemed LDL-P>non-HDL-C discordant if they exhibited higher LDL-P than expected for simultaneously measured non-HDL-C, given the observed distribution of both in MESA. Conversely, a lower LDL-P than would be suggested from non-HDL-C characterized LDL-P<non-HDL-C discordance. Regression models were used to estimate associations of demographics and comorbidities with discordance and of discordance with carotid intima-media thickness (CIMT) and detectable coronary artery calcium (CAC). Results Discordance was observed among 44% of subjects. LDL-P>non-HDL-C compared to LDL-P<non-HDL-C discordance was more common among Hispanics and smokers; among subjects with lower HDL-C, lower triglycerides, or greater insulin resistance by homeostatic model assessment of insulin resistance (HOMA-IR); and among subjects on lipid-lowering therapy, anti-hypertensive therapy, or hormone replacement therapy. In the setting of discordance, LDL-P exhibited a modestly greater association with CIMT than did non-HDL-C (+0.024−0.025 mm vs +0.018−0.021 mm per SD increase). In the presence of LDL-P<non-HDL-C discordance, LDL-P demonstrated a modestly greater association with detectable CAC than did non-HDL-C (OR 1.51 vs 1.46 per SD increase). Conclusions Our results demonstrated that disagreement between LDL-P and non-HDL-C was common and significantly associated with several clinical characteristics. In the setting of discordance, LDL-P was more closely associated with CIMT and CAC than non-HDL-C, though observed differences were small.

Patient-Level Discordance in Population Percentiles of the Total Cholesterol to High-Density Lipoprotein Cholesterol Ratio in Comparison With Low-Density Lipoprotein Cholesterol and Non–High-Density Lipoprotein Cholesterol

“…Two studies have examined discordance between particle-based measures such as LDL-P and apoB vs. non-HDL-C in this way. 23,39 In these studies, discordance was sizeable and cardiovascular outcomes, including events, coronary artery calcium and carotid intimal medial thickness, tracked more closely with LDL-P and apoB. However, there is no conclusive outcome data to suggest that an advantage lies in the direction of the TC/HDL-C ratio in instances of discordance; thus, additional clinical studies using the patient-level discordance approach are warranted.…”

NMR measurement of LDL particle number using the Vantera® Clinical Analyzer

“…As a result, discordance is frequently noted between LDL-C levels and nuclear magnetic resonance (NMR) measurements of LDL particle number (LDL-P) [5][6][7][8]. As a CVD risk management tool, LDL-C values indicate which patients have lowered their risk to acceptable levels (as inferred from their treatment goal having been reached) and which have not (indicating a need for more aggressive treatment).…”

Description of Discordance Between LDL Cholesterol, Non-HDL Cholesterol, and LDL Particle Number Among Patients of a Lipid Clinic

“…16,17 Non-HDL-C and LDL-P percentiles correlate to the LDL-C thresholds and population percentiles outlined in the Framingham Offspring Cohort (Table 1). 16,17 Discordance was identified if LDL-P, non-HDL-C, or LDL-C fell into a different population percentile. For example, if LDL-C and non-HDL-C fell between the 20 th and 50 th percentile, but LDL-P fell between the 50 th and 80 th percentile the patient had discordant values.…”

“…ATP III's 2004 update or physician specified targets were used to individualize patient LDL-C and non-HDL-C. 3 LDL-P goals were determined by assessing LDL-C and non-HDL-C goals and obtaining corresponding LDL-P goals based on an equivalent percentile. [16][17][18] ASCVD events, diagnosis of new onset diabetes mellitus, and death from any cause and death due to cardiovascular disease were also collected. The time a patient was followed in the study was recorded as well due variable follow-up periods.…”