For years, the traditional lipid panel has been the standard of care for risk assessment and monitoring cardiovascular disease (CVD) or dyslipidemia, with low-density lipoprotein cholesterol (LDL-C) levels being the main target of treatment. However, while a traditional lipid panel measures the amount of cholesterol and triglycerides within lipoprotein particles, additional diagnostic tests can help identify other risk factors, including the number of atherogenic particles and the size of these particles.
In other words, not only does the amount and density of lipids matter, but so do the number and size of the lipoprotein particles that carry them.
How do you obtain these lipoprotein measurements, and what might they tell you? Advanced lipid testing, which includes lipoprotein subfractionation and apolipoprotein measurements, can help you assess whether your patient has a hidden lipid problem.
What advanced lipid testing can tell you
Lipoprotein subfractionation identifies individual lipoprotein subclasses that contribute to CVD risk and provides precise particle counts for each lipoprotein type and subclass. This advanced lipid testing, called Ion Mobility, provides an LDL particle number (LDL-P) and identifies small and medium LDL subclasses. LDL-P measurement quantifies the actual number of LDL particles in circulation. It has been shown that the measurement of LDL-P can help identify intermediate-risk patients at risk for CVD events, supporting LDL-P as a main target of therapy to reduce CVD risk.1 Small and medium LDL subclasses are highly atherogenic. There is a 1.3x increased CVD risk associated with the small LDL trait and a 1.4x increased risk with the medium LDL trait.1-3
Subfractionation also identifies the large HDL subclass, historically thought to be the most efficient cholesterol-reabsorbing HDL particle, and the one that best reflects the efficacy of the reverse cholesterol transport system and cholesterol clearance by the liver. Low levels of large HDL are correlated with a 1.8x increased CVD risk.2
Apolipoprotein measurements assess levels of proteins that bind lipids to form lipoproteins and transport the lipids through the lymphatic and circulatory systems. Elevated levels of the following apolipoproteins indicate CVD risk.
ApoB is the predominant apoprotein attached to LDL, intermediate-density lipoproteins (IDL), and very low-density lipoproteins (VLDL). Several decades of scientific literature supports the measurement of ApoB for monitoring response to statin therapy. Elevated ApoB is associated with a 2.0-2.5x increased CVD risk.4
Lp(a), or lipoprotein (a), is an LDL-like particle with an attached apolipoprotein (a). The amount of Lp(a) in circulation is genetically determined and has been linked to both early- and advanced-stage atherosclerosis. Elevated Lp(a) is associated with increased coagulation and a 1.5-5.3x increased risk of CVD.5 When the measurement of Lp(a) is combined with other abnormal CVD risk markers, the associated risk increases further.
Advanced lipid testing in practice
Your patient, Luis, is a slightly overweight 47-year-old owner of a convenience store who also has diabetes mellitus. His diabetes is generally well-managed. However, blood work after his most recent visit showed a slightly elevated LDL-C of 120 mg/dL—a moderate risk in a healthy individual, but because of Luis’s diabetes, weight, sedentary lifestyle, and family history of CVD, you’re concerned. Is Luis at risk?
A patient fitting Luis’s profile could benefit from advanced lipid testing. Advanced lipid testing is indicated for many patients, including those with established diabetes and for patients with two or more risk factors for coronary heart disease (CHD). Luis has at least four risk factors—diabetes, overweight, lack of physical activity, and family history of heart disease.
What would advanced lipid testing tell you? In this hypothetical case, it shows a high LDL-P (number of LDL particles), moderate risk level of small LDL particles, and normal large HDL levels. ApoB and Lp(a) are also elevated. Luis is at higher risk for CVD than indicated by his original traditional lipid panel result.
The point is that a patient presenting with moderate LDL-C may have a higher risk of CVD than is indicated by standard lipid testing. You now know that Luis may be at greater risk, and you can treat and counsel accordingly—all with greater confidence that you’re choosing the best course.
Other advanced cardio testing
Above is just one example of how advanced lipid testing can provide essential insight into your patient’s risk profile and aid your clinical decision-making. In fact, Luis’s results indicate that he could benefit from other advanced cardio testing, such as inflammatory biomarker testing. To learn more about inflammation’s role in CVD development and progression, see our previous post.
Know your patient’s true CVD risk, beyond LDL-C
Advanced lipid testing gives you more precise tools in assessing your patients’ risk of CVD. Quest Diagnostics offers a complete menu for CVD risk assessment that includes advanced lipid testing, inflammatory marker testing, metabolic markers, and innovative gut microbiome testing. Learn more today. The more you know, the more you can do to prevent disease progression and keep your patients well.
Next: A closer look at how advanced cardio testing can help your practice as well as your patients. For this and other upcoming articles on what’s new in diagnostics, subscribe to Primary Insights.
1. Melander O, Shiffman D, Caulfield MP, et al. Low-density lipoprotein particle number is associated with cardiovascular events among those not classified into statin benefit groups. J Am Coll Cardiol. 2015;65(23):2571-2573.
2. Musunuru K, Orho-Melander M, Caulfield MP, et al. Ion mobility analysis of lipoprotein subfractions identifies three independent axes of cardiovascular risk. Arterioscler Thromb Vac Biol. 2009;29:1975-1980.
3. Mora S, Caulfield MP, Wohlgemuth J, et al. Atherogenic lipoprotein subfractions determined by ion mobility and first cardiovascular events after random allocation to high-intensity statin or placebo: the justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin (JUPITER) trial. 2015;132:2220-2229.
4. Sniderman AD, Williams K, Contois JH, et al. A meta-analysis of low density lipoprotein cholesterol, nonhigh-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes. 2011;4:337-345.
5. Nordesgaard B, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31:2844-2853.