#343 Less is More Unless it’s Sleep or Toilet Paper: Non-traditional lipoproteins for cardiovascular risk
CLINICAL QUESTION
In patients without established cardiovascular disease (CVD), can lipoprotein(a) or apolipoprotein B meaningfully improve standard CVD risk estimation?
BOTTOM LINE
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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EVIDENCE
- 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.
- UK adults (n=340,339) without CVD not on statins, follow-up 8.9 years.4
- Systematic review of 24 prospective studies (n=133,502, mean follow-up 10.6 years).3
- 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.
- UK adults (346,686) without CVD not on statins, follow-up 8.9 years.6
- Other cohorts found similar results.8-9
- Systematic review of 26 prospective studies (n=139,581, mean follow-up 10.5 years).3
- 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.
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Interesting
This article supports my clinical practice.
Grateful for this simplified guideline & study, as based on CCS recommendation, I had started to add Lp(a) to first assessement
Informative has not had a number of questions about these tets