Research Blog
Optimal Takeaways
Measurement of low-density lipoprotein particle number (LDL-P) is a better tool for assessing cardiovascular risk and a better indicator of subclinical disease than just measuring LDL cholesterol. Even if LDL-C is decreased, the depleted LDL particles can still be atherogenic. Increased LDL-P is associated with other CVD risk factors as well, including inflammation, insulin resistance, hypertriglyceridemia, and increased coronary artery calcium score. A low LDL-P may not be clinically relevant.
Standard Range: 592.00 – 2404.00 nmol/L (NMR)
The ODX Range: 0.00 – 935.00 nmol/L (NMR)
Low LDL-P number may not be clinically relevant unless associated with malnutrition or other disease state.
High LDL-P number is associated with increased cardiovascular disease risk, inflammation, insulin resistance, small LDL particle size (Feingold 2023), unhealthy diet, and increased trans-fat intake (Garshick 2014).
Overview
The LDL particle number (LDL-P) is a direct measurement of how many LDL particles are in circulation at a given time. An increasing number of LDL particles is a sign of increased cardiovascular risk, even if the amount of cholesterol carried on LDL is low. Research suggests that atherosclerotic cardiovascular disease (ASCVD), carotid intima-media thickness, and coronary artery calcium may be more closely associated with LDL particle number than LDL-cholesterol or non-HDL cholesterol (Feingold 2023).
Higher LDL-P numbers are associated with other cardiovascular risk factors as well, including systemic inflammation, insulin resistance, and small LDL particle size. An elevated LDL-P may identify CVD risk better than LDL-C, HDL-C, or apoB. Elevated LDL-P detected CVD risk even when apoB was optimal, i.e., below 69 mg/dL. However, when LDL-P was favorable and below 1073 nmol/L, as measured by NMR, apoB was a better indicator of residual CVD risk. Elevated LDL-P may also identify “hidden” CVD risk in those with low LDL-C, including those on statin drugs. In such cases, LDL may be depleted of cholesterol but still, be atherogenic. Researchers note that the reduction of LDL-C by statins reduces the risk of a cardiovascular event by less than 30% (Varvel 2015), and a relative risk reduction of 25% translates into an absolute risk reduction of only 3.4% (Superko 2022).
The denser LDL particles with less cholesterol are cleared less efficiently, leading to an increase in LDL particle number and increased CVD risk (Langlois 2018). Guidelines of the Association of Clinical Endocrinologists note that LDL particle number is superior to LDL particle size and sdLDL for predicting adverse cardiovascular events (Talebi 2020).
Data from 3,066 individuals enrolled in the Framingham Offspring Study revealed that LDL-P was the strongest predictor of future CVD events. The risk of a CVD event was lowest when both LDL-P and LDL-C were low. However, if LDL-C was low but LDL-P was elevated, the CVD event rate increased. It is possible that lowering LDL-C alone may mask CVD risk that can be picked up by measuring LDL-P and that a low LDL-P is a better indicator of low CVD risk than a low LDL-C is. The NMR LDL-P value associated with CVD events in the study was 1641 nmol/L in men and 1628 nmol/L in women (Cromwell 2007).
Increased NMR LDL-P above 1,001 nmol/L identified residual cardiac risk in type 2 diabetics despite having very low LDL-C below 50 mg/dL (1.29 mmol/L) and a non-HDL-C below 80 mg/dL (2.07 mmol/L). The phenomenon is considered “discordance” when LDL-P and LDL-C are not in agreement. Researchers also note that triglyceride levels increased as LDL-P increased, further indicating cardiometabolic dysfunction (Malave 2012).
A healthy diet low in trans-fats and saturated fats, maintenance of a healthy weight, and regular exercise can help reduce LDL particle number. For every 1% decrease in trans-fat intake, NMR LDL-P was found to decrease by 27 nmol/L (Garshick 2014). Natural products and foods, including avocadoes, phytosterols, plant stanols, and omega-3 DHA, were also associated with a significant reduction in LDL particle number (Talebi 2020).
References
Cromwell, William C et al. “LDL Particle Number and Risk of Future Cardiovascular Disease in the Framingham Offspring Study - Implications for LDL Management.” Journal of clinical lipidology vol. 1,6 (2007): 583-92. doi:10.1016/j.jacl.2007.10.001
Feingold, Kenneth R. “Utility of Advanced Lipoprotein Testing in Clinical Practice.” Endotext, edited by Kenneth R Feingold et. al., MDText.com, Inc., 3 January 2023.
Garshick, M et al. “Reduction in dietary trans fat intake is associated with decreased LDL particle number in a primary prevention population.” Nutrition, metabolism, and cardiovascular diseases : NMCD vol. 24,1 (2014): 100-6. doi:10.1016/j.numecd.2013.06.003
Langlois, Michel R et al. “Quantifying Atherogenic Lipoproteins: Current and Future Challenges in the Era of Personalized Medicine and Very Low Concentrations of LDL Cholesterol. A Consensus Statement from EAS and EFLM.” Clinical chemistry vol. 64,7 (2018): 1006-1033. doi:10.1373/clinchem.2018.287037
Malave, Hector et al. “Evaluation of low-density lipoprotein particle number distribution in patients with type 2 diabetes mellitus with low-density lipoprotein cholesterol <50 mg/dl and non-high-density lipoprotein cholesterol <80 mg/dl.” The American journal of cardiology vol. 110,5 (2012): 662-5. doi:10.1016/j.amjcard.2012.04.046
Superko, Harold, and Brenda Garrett. “Small Dense LDL: Scientific Background, Clinical Relevance, and Recent Evidence Still a Risk Even with 'Normal' LDL-C Levels.” Biomedicines vol. 10,4 829. 1 Apr. 2022, doi:10.3390/biomedicines10040829
Talebi, Sepide et al. “The beneficial effects of nutraceuticals and natural products on small dense LDL levels, LDL particle number and LDL particle size: a clinical review.” Lipids in health and disease vol. 19,1 66. 11 Apr. 2020, doi:10.1186/s12944-020-01250-6
Varvel, Stephen A et al. “Discordance between apolipoprotein B and low-density lipoprotein particle number is associated with insulin resistance in clinical practice.” Journal of clinical lipidology vol. 9,2 (2015): 247-55. doi:10.1016/j.jacl.2014.11.005
