Tools for Practice


#122 Lipoproteins: The risk of (over)interpreting these risk factors?


CLINICAL QUESTION
Does lipoprotein testing (like apolipoprotein B) provide meaningful cardiovascular disease (CVD) risk assessment or management information? (For this article, “lipoproteins” do not include LDL or HDL).

BOTTOM LINE
Lipoproteins (like apolipoprotein B) are associated with CVD but so are ~300 other risk factors. Lipoproteins do not add meaningfully to risk estimation before treatment or prediction of benefit with treatment. Assess risk with CVD risk calculators and treat with proven therapies. 


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EVIDENCE
Primarily systematic reviews of cohort studies examining apolipoprotein B, AI, B/AI ratio, lipoprotein(a) and lipoprotein-associated phospholipase A2. 
  • Are lipoproteins associated with CVD? Yes. 
    • Five systematic reviews1-5 with 23-40 studies: All lipoproteins are associated with CVD.  
      • Example: Higher apolipoprotein B, relative risk 1.99 (1.65-2.39).1  
  • Do lipoproteins add to risk prediction models? No. 
    • Systematic review6 with 37 studies. Taking standard risk prediction tools and: 
      • Replacing total cholesterol/HDL with any lipoprotein made prediction worse.   
      • Adding any lipoprotein improved overall risk prediction by ≤0.0018 (from 0.7244 area-under-the-curve), a clinically meaningless value.  
        • For comparison, leukocyte count improves prediction by 0.0036.7 
    • Reclassification: Limiting lipoprotein testing to patients at moderate (10%-<20%) 10-year CVD risk and treating those reclassified as high risk would require testing 801-4,541 to prevent one CVD event in 10 years.6   
  • Do changes in lipoproteins predict benefit? No. 
    • One randomized controlled trial of 15,828 CVD patients demonstrated that using darapladib (lipoprotein-associated phospholipase A2 inhibitor) did not change CVD outcomes.8  
    • Two systematic reviews9,10 with 8-25 studies: Apolipoprotein B changes did not predict benefit better than LDL and maybe worse than non-HDL cholesterol.   
      • Regardless, monitoring is not required to predict statin benefit.   
  Context:   
  • There are ~300 CVD risk factors.11  
  • Many drugs (ezetimibe,12 torcetrapib,13 niacin,14 aleglitazar,15 rosiglitazone,16 darapladib,8 etc.) improve biomarkers but do not change or worsen CVD.    
  • 2012 Canadian guidelines recommend apolipoprotein B as an alternate biomarker for CVD risk and for treatment target.17 New US Guidelines do not.18   
September 29, 2014

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Author(s):

  • G. Michael Allan MD CCFP
  • Grenvil Gracias MSc MD

1. Thompson A, Danesh J. J Intern Med 2006; 259:481-92.

2. Emerging Risk Factors Collaboration, Di Angelantonio E, Sarwar N, et al. JAMA. 2009; 302:1993-2000.

3. Erqou S, Thompson A, Di Angelantonio E, et al. J Am Coll Cardiol. 2010; 55:2160-7.

4. Danesh J, Collins R, Peto R, et al. Circulation. 2000; 102:1082-5.

5. Lp-PLA(2) Studies Collaboration, Thompson A, Gao P, et al. Lancet. 2010 May 1; 375(9725):1536-44.

6. Emerging Risk Factors Collaboration, Di Angelantonio E, Gao P, et al. JAMA. 2012; 307:2499-506.

7. Emerging Risk Factors Collaboration, Kaptoge S, Di Angelantonio E, et al. N Engl J Med. 2012; 367:1310-20.

8. STABILITY Investigators, White HD, Held C, et al. N Engl J Med. 2014; 370:1702-11.

9. Robinson JG, Wang S, Jacobson TA. Am J Cardiol. 2012; 110:1468-76.

10. Boekholdt SM, Arsenault BJ, Mora S, et al. JAMA. 2012; 307(12):1302-9.

11. Vinereanu D. Herz. 2006; 31 Suppl 3:5-24.

12. Allan GM, Zarnke KB. Tools for Practice. http://www.acfp.ca/wp-content/uploads/tools-for-practice/1397763523_20131212_022029.pdf.

13. Barter PJ, Caulfield M, Eriksson M, et al. N Engl J Med. 2007;357:2109-22.

14. Kolber MR, Allan GM. Tools for Practice. http://www.acfp.ca/wp-content/uploads/tools-for-practice/1397837860_20120502_095745.pdf.

15. Lincoff AM, Tardif JC, Schwartz GG, et al. JAMA. 2014;311:1515-25.

16. Korownyk C, Allan GM. Tools for Practice. http://www.acfp.ca/wp-content/uploads/tools-for-practice/1397764848_20140408_114420.pdf.

17. Anderson TJ, Grégoire J, Hegele RA, et al. Can J Cardiol. 2013; 29(2):151-67.

18. Stone NJ, Robinson JG, Lichtenstein AH, et al. Circulation. 2014; 129(25 Suppl 2):S1-45

Authors do not have any conflicts of interest to declare.