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Achievement of target LDL particle number leads to fewer CV events

Issue: September 2014

ByJames A. Underberg, MS, MD, FACP, FACPM, FNLA

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For decades, clinicians have relied on cholesterol-based measures of LDL to predict and manage their patients’ risk for cardiovascular disease. This practice has continued for historical reasons despite the emergence of new, real-world data suggesting that an alternative measure of LDL — LDL particle number or LDL-P — provides a more clinically reliable measurement of risk, based on significant reductions in CVD events.

Physicians should therefore examine the evidence and reconsider the way they evaluate LDL in light of patient adherence or response to therapy, as well as for managing CVD risk as a means to optimize clinical outcomes in high-risk patients.

LDL particles are vehicles that carry cholesterol in the blood. The amount of LDL cholesterol (LDL-C) content per LDL particle can be highly variable, resulting in a phenomenon called discordance, whereby LDL-C and LDL-P values disagree. Such discordance occurs in as much as half of the general population, and in 75% of those with type 2 diabetes or metabolic syndrome. Due to this variability, when LDL-P and LDL-C are discordant, CVD risk tracks more closely with LDL-P than with LDL-C.

Real-world data

The real-world data demonstrating the reliability of LDL-P in managing CVD risk were presented in a poster session at the 2014 American College of Cardiology Scientific Sessions in Washington, D.C., and published in the August issue of the journal Atherosclerosis. The findings, derived from a sample of more than 4,000 high-risk patients selected from the HealthCore Integrated Research Database, showed that for patients achieving a target LDL-P of <1,000 nm/l as  measured by nuclear magnetic resonance (nmr) there was a significan reduction in cv event rates over 3-year period vs. those who attained ldl-c targets of <100 mg/dL.

James A. Underberg

The relative risk of a CV event in the HealthCore study was 22% to 25% lower in the LDL-P target group than in the LDL-C target group over 1 to 3 years of follow-up. In addition, patients managed to LDL-P goals were more likely to be treated with higher-intensity statin doses and more likely to be treated with non-statin lipid-lowering medications.

These data have important implications for high-risk patients, particularly those with insulin resistance, type 2 diabetes and/or metabolic syndrome, as well as those who are treated with lipid-lowering therapies. In the presence of discordance, which occurs frequently among these types of patients, LDL-P appears to be a more clinically reliable measure of LDL and a better predictor of clinical outcomes than LDL-C.

Optimizing patient management

Given that the HealthCore findings are derived from a real-world sample, over a normal course of treatment, the results appear to provide additional validation for NMR-measured LDL-P, in conjunction with other lipid measurements, as a CV risk-management tool. At the very least, these data add to the ongoing discussion of how best to optimize individual patient management. Indeed, a growing number of experts and organizations, including the American Association of Clinical Endocrinologists, the National Lipid Association, and the American Association for Clinical Chemistry, recommend using LDL-P as a target of therapy in managing at-risk patients.

LDL management decisions based on LDL-C alone can result in under- or overestimation of the need for LDL-lowering therapy. As a result, many patients are not treated aggressively enough to optimally manage their LDL-related CVD risk, while many others receive unnecessary LDL-lowering treatment.

For patients presenting with signs and symptoms of insulin resistance, type 2 diabetes or metabolic syndrome, including those on optimized statin therapy, the CVD risk-management plan should not be based solely on one diagnostic measure of LDL. Rather, optimizing patient care for many patients should include measuring and treating to LDL-P, a more clinically reliable measure of LDL.