Discordance of LDL Cholesterol with Alternative LDL-Related Measures and Future Coronary Events
Background—LDL cholesterol (LDL-C) is the traditional measure of risk attributable to LDL. Non-HDL-cholesterol (NHDL-C), apolipoprotein B (apoB), and LDL particle number (LDL-P) are alternative measures of LDL-related risk. However, the clinical utility of these measures may only become apparent among individuals for whom levels are inconsistent (discordant) with LDL-C.
Methods and Results—LDL-C was directly measured, NHDL-C was calculated, apoB was measured with immunoassay, and LDL-P with nuclear magnetic resonance spectroscopy among 27,533 healthy women (median follow-up 17.2 years; 1,070 incident coronary events). Participants were grouped by median LDL-C (121 mg/dL) and each of NHDL-C, apoB, and LDL-P. Discordance was defined as LDL-C ≥median and the alternative measure <median, or vice versa. Despite high LDL-C correlations with NHDL-C, apoB, and LDL-P (r=0.910, 0.785, and 0.692, all p<0.0001), prevalence of LDL-C discordance as defined by median cut-points was 11.6%, 18.9%, and 24.3% for NHDL-C, apoB, and LDL-P, respectively. Among women with LDL-C<median, coronary risk was underestimated for women with discordant (≥median) NHDL-C (age-adjusted hazard ratio 2.92, 95% CI 2.33-3.67), apoB (2.48, 2.01-3.07), or LDL-P (2.32, 1.88-2.85), compared to women with concordant levels. Conversely, among women with LDL-C ≥median, risk was overestimated for women with discordant (<median) NHDL-C (0.40, 0.29-0.57), apoB (0.34, 0.26-0.46), or LDL-P (0.42, 0.33-0.53). After multivariable adjustment for potentially mediating factors including HDL cholesterol and triglycerides, coronary risk remained under or overestimated by ≈20-50% for women with discordant levels.
Conclusions—For women with discordant LDL-related measures, coronary risk may be under or overestimated when relying on LDL-C alone.
Clinical Trial Registration Information—ClinicalTrials.gov. Identifier: NCT00000479
- Received August 25, 2013.
- Revision received October 23, 2013.
- Accepted October 23, 2013.