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#343 Less is More Unless it’s Sleep or Toilet Paper: Non-traditional lipoproteins for cardiovascular risk

In patients without established cardiovascular disease (CVD), can lipoprotein(a) or apolipoprotein B meaningfully improve standard CVD risk estimation?

Adding lipoprotein(a) or apolipoprotein B does not meaningfully improve cardiovascular risk prediction above standard risk factors (age, sex, blood pressure, total cholesterol/HDL, diabetes, smoking). Assess risk with CVD risk calculators and offer proven therapies as appropriate.

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  • All evidence from cohort studies and statistically significant unless noted.
  • Search focused on lipoproteins additive value above traditional risk factors on CVD risk estimation. C-statistic measures the predictive accuracy of a statistical model to distinguish between individuals with positive outcomes and those with negative outcomes.1
    • Changes in C-statistic: ≥ 0.1 is large, 0.05-0.1 is moderate, 0.025-0.05 is small and <0.025 is very small.2
  • Lipoprotein(a) [Lp(a)]
    • Systematic review of 24 prospective studies (n=133,502, mean follow-up 10.6 years).3
      • C-statistic improvement=0.0016.
    • Evidence since:
      • UK adults (n=340,339) without CVD not on statins, follow-up 8.9 years.4
        • C-statistic improvement=0.0017.
      • Swiss adults (n=4829), follow-up 9.9 years.5
        • C-statistic improvement=0.004.
  • Apolipoprotein B (apoB)
    • Systematic review of 26 prospective studies (n=139,581, mean follow-up 10.5 years).3
      • C-statistic improvement=0.0001 (not statistically significant).
    • Evidence since:
      • UK adults (346,686) without CVD not on statins, follow-up 8.9 years.6
        • C-statistic improvement=0.0004.
      • Danish adults (8476) without CVD or diabetes, follow-up 18 years.7
        • C-statistic improvement not statistically different.
    • Other cohorts found similar results.8-9
  • Lp(a) and apoB individually are associated with CVD with relative risks of 1.00-2.21 and 1.03-2.87, respectively. Other non-traditional risk markers have similar associations (relative risk for leucocyte count=1.45; albumin=1.55; pro-insulin=2.23) but provide little additional value when combined with traditional risk factors (e.g., additive value of leukocyte count c-statistic=0.0036).10
  • Other measures of diagnostic utility, including Net Reclassification Index, suggest Lp(A) and apo(B) generally provide no meaningful value above traditional risk prediction.3-6
  • Simplified guidelines discourage testing lipoproteins.10
  • Canadian Cardiovascular Society11 recommends measuring:
    • Lp(a) once/lifetime for initial screening.
    • ApoB (or non-HDL-C) as preferred screening parameter if triglycerides>1.5mmol/L.

Vivian Liu June 26, 2023


A Roy Lilly June 26, 2023

This article supports my clinical practice.

Kate Coulson June 27, 2023

Grateful for this simplified guideline & study, as based on CCS recommendation, I had started to add Lp(a) to first assessement

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  • Betsy Thomas BSc. Pharm
  • Jennifer Potter MD CCFP
  • Allison Paige MD CCFP
  • G. Michael Allan MD CCFP

1. Allan GM, Garrison S, McCormack J. Curr Opin Lipidol 2014; 25(4): 254-65.

2. Lin JS, Evans CV, Johnson E, et al. JAMA 2018; 320:281297.

3. Emerging Risk Factors Collaboration; Di Angelantonio E, Gao P, Pennells L, et al. JAMA. 2012 Jun 20; 307(23):2499-506.

4. Welsh P, Welsh C, Celis-Morales CA, et al. Eur J Prev Cardiol. 2022 Feb 9; 28(18):1991-2000.

5. Delabays B, Marques-Vidal P, Kronenberg F, et al. Eur J Prev Cardiol. 2021 Jul 23; 28(8):e18-e20.

6. Welsh C, Celis-Morales CA, Brown R, et al. Circulation. 2019; 140:542-552.

7. Graversen P, Abildstrom SZ, Jespersen L, et al. Eur J Prev Cardiol. 2016; 23(14):1546-1556.

8. Pencina MJ, D’Agostino RB, Zdrojewski T, et al. Eur J Prev Cardiol. 2015; 22(10):1321-1327.

9. Vasquez-Oliva G, Zamora A, Ramos R, et al. Rev Exp Cardiol. 2018; 71(11):910-916.

10. Allan GM, Lindblad AJ, Comeau A, et al. Can Fam Physician. 2015 Oct; 61(10):857-67.

11. Pearson GJ, Thanassoulis G, Anderson TJ, et al. Can J Cardiol. 2021; 37:1129-1150.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.