Treatment targeting LDL particle numbers results in better clinical outcome than LDL-c levels

Cardiovascular risk in patients achieving low-density lipoprotein cholesterol and particle targets

Literature - Toth et al., Atherosclerosis. 2014

Toth PP, Grabner M, Punekar RS et al.
Atherosclerosis. 2014 Aug;235(2):585-91


A key strategy for reducing the risk of coronary heart disease (CHD) is lowering LDL quantity. LDL-c has served as the principal biomarker for LDL quantity for many years. LDL particle number (LDL-P) is an alternative measure of LDL quantity, which can be determined directly by nuclear magnetic resonance spectroscopy or estimated from apolipoprotein B concentrations [1,2].
LDL-c levels can vary significantly between individuals and in response to drug and lifestyle interventions: thus LDL-c levels may not always accurately reflect a patient’s LDL-related risk [3-5]. This may be specifically true for patients with type 2 diabetes, metabolic syndrome or hypertriglyceridaemia, who often have LDL particles that are cholesterol-depleted, small in size and large in number [4,5]. Particularly in patients whose LDL-P and LDL-c levels are discordant, LDL-P seems to better predict cardiovascular (CV) events than LDL-c levels [6-8]. Several expert panels and guidelines already advocate the use of LDL-P as target of therapy in certain at-risk patients.
This report aimed to provide real world evidence that confirms that clinical management aided by LDL-P information leads to better CV outcomes, using a national sample of commercially insured high-risk patients. Patients who were treated based on LDL-c were compared with patients for whom LDL-P was measured to help guide treatment decisions.

Main results

  • The risk of a CHD event increased with approximately 4% for each 100 nmol/L increase in LDL-P (HR: 1.04, 95%CI: 1.02-1.05, P<0.0001  for those with vs. those without a CHD event).
  • When comparing patients achieving similar pre-specified targets for LDL-c and LDL-P, patients in the LDL-P cohort received higher potency statin therapy than those in the LDL-c cohort.  
  • Patients in the LDL-c cohort had higher levels of LDL-c, total cholesterol, triglycerides and non-HDL-c, and lower levels of HDL-c than those in the LDL-P cohort, both at baseline and at 12 months follow-up.
  • Fewer patients in the LDL-P cohort experienced a CHD event, stroke or combined CHD/stroke events at 12, 24 and 36 months than patients in the LDL-c cohort. Relative risk reduction for the combined CHD/stroke endpoint was about 25% in the LDL-P target cohort, at 12 months (HR: 0.76, 95%CI: 0.61-0.96), 24 months (HR: 0.78; 95% CI: 0.62-0.97), and 36 months (HR: 0.75; 95% CI: 0.58-0.97) of follow-up.

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This is the first time a real-world association is demonstrated between LDL-P levels and CHD/stroke risk. Increases of LDL-P are significantly associated with higher risk of CHD events, after accounting for LDL-c levels. Among high-risk patients who reached similar levels of LDL-P and LDL-c (targets based on the 20th population percentile in the multiethnic study of atherosclerosis), those achieving the LDL-P target of <1000 nmol/L received more aggressive, lipid-lowering treatment and had fewer CHD/stroke events. These results suggest that using LDL-P levels may help to guide treatment decisions, and result in better clinical outcomes.

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2. Cromwell WC, Barringer TA. Low-density lipoprotein and apolipoprotein B: clinical use in patients with coronary heart disease. Curr Cardiol Rep 2009;11:468e75.
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7. Otvos JD, Collins D, Freedman DS, et al. Low-density lipoprotein and high density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy in the Veterans Affairs High- Density Lipoprotein Intervention Trial. Circulation 2006;113:1556e63.
8. Otvos JD, Mora S, Shalaurova I, et al. Clinical implications of discordance between low-density lipoprotein cholesterol and particle number. J Clin Lipidol 2011;5:105e13.

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