Discordance of LDL Cholesterol With Alternative LDL-Related Measures and Future Coronary Events

Study Questions:

What is the prevalence and long-term prognosis of discordant levels of directly measured low-density lipoprotein cholesterol (LDL-C) compared with non-high-density lipoprotein cholesterol (NHDL-C), apolipoprotein B (apoB), and LDL particle number (LDL-P) in apparently healthy women followed long-term?

Methods:

This was an analysis of 27,533 women participating in the Women’s Health Study, an ongoing prospective cohort study. Participants were free of self-reported cardiovascular disease and cancer at study entry. Blood samples were obtained at enrollment. LDL-C was directly measured, NHDL-C was calculated, apoB was measured with immunoassay, and LDL-P was measured with nuclear magnetic resonance spectroscopy. The primary endpoint was incident coronary events. The authors performed a discordance analysis in which participants were categorized according to less than or greater than or equal to median levels of LDL-C (121 mg/dl) and each NHDL-C (154 mg/dl), apoB (100 mg/dl), and LDL-P (1216 nmol/L). Discordance was defined as LDL-C greater than or equal to median and the alternative measures less than median (or vice versa).

Results:

The prevalence of LDL-C discordance with NHDL-C, apoB, and LDL-P was 11.6%, 18.9%, and 24.3%, respectively. Among women with LDL-C less than median and compared to participants with concordant levels, coronary risk was underestimated for women with discordant (greater than or equal to median) N-HDLC (age-adjusted hazard ratio [HR], 2.92; 95% confidence interval, 2.33-3.67), apoB (2.48, 2.01-3.07), or LDL-P (2.32, 1.88-2.85). Among women with LDL-C greater than or equal to median and compared to participants with concordant levels, coronary risk was overestimated for women with discordant (less than 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).

Conclusions:

In apparently healthy women, discordance between LDL-C and the alternative measures of NHDL-C, apoB, and LDL-P is common, and relying on LDL-C alone may be associated with an under- or overestimated risk for incident coronary events.

Perspective:

The authors’ analysis provides useful insight about variations in long-term coronary risk in women with discordance between baseline levels of LDL-C and other LDL-related measures. While the results may support the use of alternative lipid testing when such discordance is present, future studies should clarify this approach, particularly in light of new guidelines, which do not recommend for or against treatment to particular LDL-C and NHDL-C targets.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Lipid Metabolism, Nonstatins

Keywords: Prevalence, Cholesterol, Incidence, Prognosis, Risk, Dyslipidemias, Cardiology, Cardiovascular Diseases, Lipoproteins, Magnetic Resonance Spectroscopy


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