What’s new in dyslipidemia

Dr. Jiri Frohlich (biography and disclosures)

What I did before

The Framingham Study (which started in 1948) introduced the term “risk factors for cardiovascular disease” [1, 2]. Ever since, most physicians including myself have used the Framingham data and tables to assess the patients’ risk [3, 4]. This resulted in a remarkable decline in cardiovascular disease – it is no more the leading cause of death in Canada.   While most of the risk factors can be identified by doing personal and family history of cardiovascular disease (CVD) laboratory data had been used by Framingham and other risk scoring algorithms.

Thus, most of us concentrated on lipid profile, especially LDL-cholesterol which became the focus of treatment [4].  Additional risk factors have also been identified including lipoprotein(a) which is particularly important to measure in individuals with strongly positive family history of CVD and a number of other less important biomarkers [5, 6, 7].

What changed my practice

In 2001, I started collaborating with a Montreal cardiologist, Dr. Allan Sniderman who has been an advocate for using apolipoprotein B for risk assessment [8].  His rationale was that, as there is one molecule of apo B per each LDL particle and the LDL half-life in plasma is much longer than that of the other apo B containing lipoproteins, the concentration of apo B reflects the LDL particle number in plasma. A patient who has, for example, an LDL-cholesterol level of 3.0 mmol/L may have an apo B which is low (say 0.8 g/L if this LDL-cholesterol is carried on large LDL particles) or apo B of 1.6 or higher (if the cholesterol is carried on small dense LDL particles). In addition, several studies established that apo B is a better predictor of risk both at baseline and on treatment than LDL-C [9, 10, 11]. This is due to the fact that small dense LDL particles are much more atherogenic as they easily penetrate the endothelial space.

In patients with triglyceride over 4.5 mmol/L, LDL-C cannot be calculated and thus the measurement of apo B is of additional advantage.  Moreover, numerous studies have shown that LDL-cholesterol goal does not always mean that apo B treatment target has been achieved [12].  Apo B has been shown to be a better predictor of outcomes on treatment, especially in patients with hypertriglyceridemia, such as individuals with diabetes or metabolic syndrome.  The other advantage is that apo B can be measured on a non-fasting specimen.

What I do now

Ideally, I try to obtain with the initial lipid profile also the concentration of patients’ apo B.  This is important for two reasons: first, in patients with hypertriglyceridemia the apo B will help me to differentiate between familial combined hyperlipidemia (these patients have high apo B) and familial hypertriglyceridemia (these patients have normal or low apo B).  After starting treatment in patients where the major problem is hypercholesterolemia, the follow up lab test may be apo B alone.  Again, the advantage here is that it can be done on a non-fasting specimen and is less expensive than repeating the whole lipid profile.

However, two recent papers (both “metaalanyses”) question the superiority of apo B measurement [13, 14].  In the first, the authors suggest that use of non-HDL-cholesterol (total cholesterol-HDL cholesterol) is preferable, although the differences from the results of apo B are only marginal [13].  In the second metaanalysis the authors claim no advantage in measuring of apolipoproteins [14].  Both papers are open to a number of criticism and contradict the results of several previous studies and one contrary metaanalysis in favor of apo B [15].  Thus, the Canadian guidelines continue to recommend the use of apo B as a treatment target [4].

References (Note: Article requests might require a login ID with CPSBC or UBC)

1. Thomas R. Dawber, Gilcin F. Meadors, and Felix E. Moore, Jr. Epidemiological Approaches to Heart Disease: The Framingham Study. Am J Public Health Nations Health. 1951; 41: 279–286. (View article with CPSBC or UBC)
2. Dawber, Thomas R., and Moore, Felix E. (1952), “Longitudinal Study of Heart Disease in Framingham, Massachusetts: An Interim Report,” in Research in Public Health, Papers presented at the 1951 Annual Conference of the Milbank Memorial Fund, 241-247. (View article with CPSBC)
3. O’Donnell CJ, Elosua R.  Cardiovascular risk factors. Insights from Framingham Heart Study. Rev Esp Cardiol. 2008; 61:299-310 (View article with CPSBC or UBC)
4. Genest J, McPherson R, Frohlich J et al. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult- 2009 recommendations. Can J Cardiol 2009; 25: 567-579. (View article)
5. Bostom AG, Gagnon DR, Cupples LA, et al. A prospective investigation of elevated lipoprotein (a) detected by electrophoresis and cardiovascular disease in women. The Framingham Heart Study.Circulation 1994; 90:1688-95. (View article with CPSBC or UBC)
6. Ridker PM, Hennekens CH, Stampfer MJ. A prospective study of lipoprotein(a) and the risk of myocardial infarction. JAMA 1993; 270:2195-9. (View article with CPSBC or UBC)
7. Danesh J, Collins R, Peto R. Lipoprotein(a) and coronary heart disease. Meta-analysis of prospective studies. Circulation 2000; 102:1082-5. (View article with CPSBC or UBC)
8. Sniderman AD, Bergeron J, Frohlich J. Apolipoprotein B versus lipoprotein lipids: vital lessons from the AFCAPS/TexCAPS trial. CMAJ. 2001; 164:44-7. (View article)
9. Lamarche B, Tchernof A, Moorjani S, et al. Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study. Circulation. 1997; 95:69–75. (View article with CPSBC or UBC)
10. 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; 94:273–8 (View article with CPSBC or UBC)
11. Gotto AM Jr, Whitney E, Stein EA, Shapiro DR, Clearfield M, Weis S, Jou JY, Langendörfer A, Beere PA, Watson DJ, Downs JR, de Cani JS. Relation between baseline and on-treatment lipid parameters and first acute major coronary events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Circulation. 2000; 101:477-84. (View article with CPSBC or UBC)
12. Idris I, Tate H, Ahmad A, McCormack T. Concordance between plasma apolipoprotein B levels and cholesterol indices among patients receiving statins and nonstatin treatment: Post-hoc analyses from the UK. InPractice study. J Clin Lipidol. 2011; 5:316-23. (View article with CPSBC or UBC)
13. Boekholdt S. M, Arsenault B, Mora S, Pedersen T, et al. Association of LDL Cholesterol, Non–HDL Cholesterol, and Apolipoprotein B Levels With Risk of Cardiovascular Events Among Patients Treated With Statins.Meta-analysis. JAMA. 2012; 307:1302-09. (View article with CPSBC or UBC)
14. The Emerging Risk Factors Collaboration, Di Angelantonio E, Gao P, et al. Lipid-Related Markers and Cardiovascular Disease Prediction. JAMA. 2012; 307:2499-506. (View article with CPSBC)
15. Sniderman AD, Williams K, Contois JH, et al. A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes. 2011; 4:337-45. (View article with CPSBC or UBC)

Please indicate how this article will change your practice:

What's new in dyslipidemia

• I disagree with this approach
• I will consider changing my practice, but need more information/time
• I will likely change my practice
• I will definitely change my practice (or I already do this)

View Results

 Loading ...