Identifying CVD Risk in Women and Minorities: The Role of Advanced Lipid Testing

Watson, Karol E., MD, PhD
Professor of Medicine/Cardiology
Co-director, UCLA Program in Preventive Cardiology
Director, UCLA Barbra Streisand Women’s Heart Health Program
Also by this Author 

Standard risk assessment may underestimate cardiovascular disease (CVD) risk in women and minorities, compounding the challenge of identifying risk in these populations. Dr. Karol Watson, Professor of Medicine/Division of Cardiology, Co-director, UCLA Program in Preventive Cardiology, discusses approaches to identifying risk in these groups and how advanced lipid testing can help assess and manage risk.

Recognizing Hidden Risks in Sub-Populations

“Because minority populations like South Asians and African Americans have much higher age-adjusted coronary heart disease and stroke rates, we always have to pay particular attention to those populations,” says Dr. Watson. Among the various minority population groups in the United States, African American men have the highest overall death rate from CVD. They have among the highest rates of hypertension in the world but exhibit lower levels of blood pressure control than whites in the U.S. This group has a higher overall prevalence of risk factors that are unrecognized and therefore not treated, which places these individuals at a greater likelihood of experiencing adverse outcomes and therefore potentially higher morbidity and mortality.1-5  

“While these populations do exhibit some dominant risk factors, such as smoking or obesity, in many of them there are also hidden risks, which physicians do not necessarily think about,” notes Dr. Watson. “We need to ensure we identify and control all the risk factors to decrease the overall risk.”

For women, there may be an even greater chance of underestimating CVD risk, as women may be more likely to have  “hidden” risk factors like insulin resistance. “In these patients classic risk factors may look unimpressive,” continues Dr. Watson. “For instance women typically have around the same LDL level but higher HDL levels than men, so they have a falsely reassuring lipid panel.6 Based on this physicians often decide not to treat. But if advanced lipid testing shows that a patient with a LDL of 120 mg/dL and HDL of 80 mg/dL also has a LDL particle number of 2000 their assessment of risk would be completely changed.”

Advanced Lipid Testing with Ion Mobility Fractionation

Advanced lipid testing, which goes beyond standard lipid panel, is enabled by Ion Mobility lipoprotein fractionation. This is a technology that separates unmodified lipoproteins on the basis of size and precisely quantifies lipoprotein fractions across the entire lipoprotein spectrum.  Measurements reported are those that significantly correlate with CVD events in a cohort of men and women from the prospective Malmo Diet and Cancer Study.7 These are:

  • Small, medium, and total LDL particle numbers
  • LDL peak size and the associated LDL pattern
  • Large HDL particle number

The focus on these measurements is consistent with identification of the “atherogenic lipoprotein phenotype (ALP)”.8-9 ALP is characterized by a predominance of small LDL particles and associated with elevations of triglycerides and reductions in HDL cholesterol and large HDL particles.Further, the particle diameter of the major LDL peak could be used in the majority of individuals to discriminate carriers of this higher-risk phenotype from noncarriers.

An elevated total LDL particle number is associated with a 1.4-fold increase in CVD risk.9 Similarly, elevated small and medium LDL particle numbers have been associated with a 1.3 to 1.4-fold increase in risk.7 Ion mobility identifies two main subclasses of HDL: large HDL and small HDL. Large HDL may help protect the arterial wall due to its antioxidant properties. A decreased large HDL subclass suggests increased CVD risk.

Sub-Particle Measurement

Using Ion Mobility to analyze the composition of a patient’s LDL allows a physician to identify and measure lipoproteins which may confer CVD risk. At higher levels, apolipoproteinB (ApoB),the predominant apoprotein attached to LDL, may signify increased coronary disease risk, even when LDL-C is not in the high-risk range.  Prospective epidemiologic studies support the benefit of tracking ApoB in identifying CVD progression, response to therapy and risk for CVD events.10-12

Another sub-particle of interest is lipoprotein(a) (Lp(a)), a LDL particle with an inherited apoprotein (a) variant attached, which has been linked to the promotion of both early and advanced stage atherosclerosis.13 Elevated Lp(a) is associated with increased coagulation and a three to five-fold increased incidence of cardiovascular disease (CVD). An elevated level of Lp(a) is an independent risk factor for CVD.14 In combination with other abnormal disease markers, the associated risk increases further.

When to Go Beyond Standard Risk Assessment

“In many cases it is obvious what a drives a patient’s risk,” says Dr. Watson, “but if a physician believes a patient may have hidden risk, other factors can be considered. ‘Hidden’ risks may exist in patients with atherosclerosis out of proportion to risk factors, in patients with a very strong family history out of proportion to risk factors, or in patients who continue to have cardiovascular events despite having apparent control of risk factors. With such patients, physicians should consider evaluating additional modifiable factors. In some cases, advanced lipid testing might be considered as results from these tests may help tailor an estimation of risk and determine whether or not to initiate statin treatment and at what intensity.”



  1. Kurian AK, Cardarelli KM. Racial and ethnic differences in cardiovascular disease risk factors: a systematic review. Ethn Dis. 2007;17(1):143–152.
  2. Bonow RO, Grant AO, Jacobs AK. The cardiovascular state of the union: confronting healthcare disparities. Circulation. 2005;111(10):1205–1207.
  3. Mensah GA, Mokdad AH, Ford ES, Greenlund KJ, Croft JB. State of disparities in cardiovascular health in the United States. Circulation. 2005;111(10):1233–1241.
  4. Graham G. Population-based approaches to understanding disparities in cardiovascular disease risk in the United States. International Journal of General Medicine. 2014;7:393-400. doi:10.2147/IJGM.S65528.
  5. Redmond N, Baer HJ, Hicks LS. Health behaviors and racial disparity in blood pressure control in the national health and nutrition examination survey. Hypertension. 2011;57(3):383–389.
  6. American Heart Association. Women and Cholesterol. Accessed 27 October, 2015.
  7. Musunuru K,  Orho-Melander M, Caulfield MP, et al. Ion mobility analysis of lipoprotein subfractions identifies three independent axes of cardiovascular risk. Arterioscler Thromb Vasc Biol. 2009;29:1975-1980.
  8. Austin MA, King MC, Vranizan KM, Krauss RM. Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk. Circulation. 1990;82:495-506.
  9. Superko HR. Advanced lipoprotein testing and subfractionation are clinically useful. Circulation 2009;119:2383-2395.
  10. St-Pierre AC, Cantin B, Dagenais GR et al. Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Quebec Cardiovascular Study. Arterioscler Thromb Vasc Biol 2005 March;25(3):553-9.                                                                               
  11. Lamarche B, Moorjani S, Lupien PJ et al. Apolipoprotein A-I and B levels and the risk of ischemic heart disease during a five-year follow-up of men in the Quebec cardiovascular study. Circulation 1996 August 1;94(3):273-8
  12. Moss AJ, Goldstein RE, Marder VJ et al. Thrombogenic Factors and Recurrent Coronary Events. Circulation 1999 May 18;99(19):2517-22.
  13. Assmann G, Schulte, H, von Eckardstein. Hypertriglyceridemia and elevated lipoprotein (a) are risk factors for major coronary events in middle-aged men. J Am Coll Cardiol 1996;77(14).
  14. Hokanson JE, Austin M. Plasma Triglyceride Level is a Risk Factor for Cardiovascular Disease Independent of High-Density Lipoprotein Cholesterol Level: A Metaanalysis of Population-Based ProspectiveStudies. Eur J Prev Cardiol.1996; 3(2) 

Released on Monday, December 21, 2015