High-Density Lipoprotein Particle Number (HDL-P)

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The idea that HDL cholesterol is cardioprotective is well accepted.

What is not as well appreciated is that, similar to the discordant relationship between the level of LDLC and number of low density lipoprotein particles in patients with residual CHD risk, the amount of cholesterol carried within high density lipoprotein particles may also vary significantly between individuals who have the same level of HDLC.1,2

For this reason, HDLC levels may not be a good indicator of the number of circulating HDL particles present and the amount of cardioprotection they confer.

CHD risk is impacted by the interaction of lipoproteins within the arterial wall. Lowdensity lipoprotein particles promote atherosclerosis by penetrating the artery wall and subsequently becoming oxidized and ingested by macrophages. These macrophages become cholesterolrich foam cells that then deposit their lipid contents into the vessel wall and initiate development of atherosclerotic plaque.

HDL particles antagonize the atherosclerotic process by facilitating reverse cholesterol transport back to the liver, by inhibiting oxidation of LDL and blocking the deposition of lipids into the arterial wall, stimulating vasodilatation, inhibiting platelet aggregation and inhibiting endothelial cell apoptosis.

Therefore, the overall risk of CHD is greatly dependent upon the balance of these atherogenic and antiatherogenic processes.2,3

EPIC-Norfolk Study

Dr. Karim El Harchaoui and his colleagues performed a nested casecontrol study of 822 apparently healthy men and women within the EPICNorfolk cohort to determine the relationship of HDL particle size and number to risk of future CHD events. They observed that both HDL size and number were independently associated with other CHD risk factors and CHD risk.

Upon correction for metabolic syndrome markers, the HDL size was no longer associated with risk of future CHD events while the relationship of HDL particle number (HDLP) to CHD risk was not affected by adjustment for these same parameters. These data suggest that the association of HDL particle size is confounded by metabolic dysregulation, but that HDLP is an independent predictor of CHD even after correction for metabolic parameters.4


An earlier publication by Dr. James Otvos and his colleagues report data from a prospective, nested casecontrol study of 364 men with a new CHD event to determine if lowdensity lipoprotein particle number (LDLP) and HDLP provide additional information relative to CHD risk reduction at baseline and after 7 months of treatment with gemfibrozil or placebo.

On gemfibrozil treatment, HDLC increased by 6% while total HDLP increased by 10%. HDLC was not a significant predictor of CHD risk either at baseline or on–trial. HDLP was a strong, independent predictor of a new CHD event both at baseline and ontrial. This relationship was preserved even after adjustment for LDLC, HDLC and triglycerides.5

How To Increase HDL-P

Until work is published containing management guidelines for HDLP, physicians are likely to be guided by the National Cholesterol Education Program – ATP III Guidelines that recommend treatment of low HDLC (< 40 mg/dL) after LDLC goals have been reached and triglycerides are < 200 mg/dL. Intensive weight management and increased physical activity are recommended as well as consideration of prescribing niacin or fibrates to increase HDLC.


Multiple studies support the relationship of HDLP to CHD outcomes and work continues to address the role HDLP plays at the molecular level and to measure the potential benefit of managing to HDLP targets. Since cardioprotection is a function of HDL particles themselves and is not a function of the cholesterol carried within them, it is possible that HDLP, may be a better indicator of cardioprotection than HDLC and may be a suitable target for CVD management.


  1. Cromwell WC, Otvos JD, et al. LDL Particle number and risk of future cardiovascular disease in the Framingham Offspring Study – implications for LDL management. J Clin Lipidol 2007;1:583592.
  2. Cromwell WC. Highdensity lipoprotein associations with coronary heart disease: Does measurement of cholesterol content give the best result? J Clin Lipidol 2007;1:5764.
  3. Assmann G, Nofer J. Atheroprotective effects of highdensity lipoproteins. Annu Rev Med 2003;54:32141.
  4. El Harchaoui K, Arsenault BJ, Franssen R. High density lipoprotein particle size and concentration and coronary risk. Ann Intern Med 2009;1508493.
  5. Otvos JD, Collins D, Freedman DS, et al. Lowdensity lipoprotein and highdensity lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy in the Veteran’s Affairs HighDensity Lipoprotein Intervention Trial. Circulation 2006;113:15561563.
  6. ATP III Guidelines AtAGlance Quick Desk Reference. NHLBI. U.S. Department of Health and Human Services, NIH Publication No. 01330.
  7. Cromwell WC, Dayspring T, Richman M. Lipid and Lipoprotein Disorders: Current Clinical Solutions. Pocket Guide. International Guidelines Center. 2009.