Impact of routine measurement of Lp(a) on CV risk reclassification
Finding very high lipoprotein(a): the need for routine assessment
Literature - Nurmohamed NS, Kaiser Y, Schuitema PCE et al. - Eur J Prev Cardiol 2021, doi: 10.1093/eurjpc/zwab167Introduction and methods
Background
Lp(a) assessment is not included in routine lipid measurement in most hospitals, despite the recommendation to measure Lp(a) at least once in every person’s life in the 2019 ESC/EAS guidelines [1]. Moreover, ASCVD risk algorithms, like SCORE [2] and SMART [3], do not incorporate Lp(a).
In this study, the impact of a single routine measurement of Lp(a) on CV risk reclassification was evaluated.
Study design
During 1 year, Lp(a) levels were routinely measured in 12,437 individuals who underwent clinical lipid profiling in a tertiary hospital setting (Amsterdam UMC, The Netherlands). Cases were defined as those with very high Lp(a) levels >99th percentile (in this study population: 387.8 nmol/L). 119 Cases were matched by age and sex to 119 individuals with low Lp(a) levels (≤20th percentile) from the same sample. 30.7% Of patients had a history of ASCVD. Lp(a) levels were measured by an isoform, independent, second-generation assay (Roche Diagnostics).
Outcomes
The primary outcome was ASCVD prevalence, a composite of prior fatal or non-fatal MI, revascularization therapy, ischemic stroke, and peripheral arterial disease. Prevalence of MI was a key secondary outcome.
Main results
- Median Lp(a) in the very high Lp(a) group was 460 nmol/L (IQR: 418-533) compared to 7 nmol/L (IQR 7-7) in the low Lp(a) group.
- Prevalence of ASCVD was 40.3% in the very high Lp(a) group compared with 21.0% in the low Lp(a) group (OR 2.64, 95%CI: 1.46-4.88, P=0.002).
- Prevalence of MI was also higher in patients with very high Lp(a) levels compared to patients with low Lp(a) levels (22.7% vs. 8.4%) (OR 3.39, 95%CI: 1.56-7.93, P=0.003).
- 70.3% Of patients in the very high Lp(a) group used at least one type of lipid-lowering therapy (LLT), compared with 42.0% of patients with low Lp(a) levels (P<0.001).
- 39.8% Of patients in the very high Lp(a) group treated with LLT reached their recommend LDL-c target vs. 58.0% of patients in the low Lp(a) group (P=0.041).
- Incorporation of Lp(a) into the SCORE algorithm resulted in the very high Lp(a) group to 31% upward reclassification of patients. Incorporation of Lp(a) in the SMART algorithm led to a reclassification of 62.5% of patients with very high Lp(a) levels to a higher risk category.
Conclusion
In this cross-sectional case-control study the risk of ASCVD was 2.6 fold higher in patients with very high Lp(a) levels compared to those with low Lp(a) levels. There is a high impact of the addition of Lp(a) to risk algorithms; reclassification for one-third of individuals with very high Lp(a) in primary prevention and more than 60% of patients with very high Lp(a) in secondary prevention.
The authors conclude: ‘These findings further support routine measurement of Lp(a) as an integral part of cholesterol measurement’.
References
1. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM, Halliday A, Landmesser U, Mihaylova B, Pedersen TR, Riccardi G, Richter DJ, Sabatine MS, Taskinen M-R, Tokgozoglu L, Wiklund O; ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111–188.
2. Conroy RM, Pyo¨ra¨la¨ K, Fitzgerald AP, Sans S, Menotti A, De Backer G, De Bacquer D, Ducimetie`re P, Jousilahti P, Keil U, Njølstad I, Oganov RG, Thomsen T, Tunstall-Pedoe H, Tverdal A, Wedel H, Whincup P, Wilhelmsen L, Graham IM; SCORE Project Group. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J 2003;24:987–1003.
3. Dorresteijn JAN, Visseren FLJ, Wassink AMJ, Gondrie MJA, Steyerberg EW, Ridker PM, Cook NR, van der Graaf Y; on behalf of the SMART Study Group.Development and validation of a prediction rule for recurrent vascular events based on a cohort study of patients with arterial disease: the SMART risk score. Heart 2013;99:866–872
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