Prognostic role of lipoprotein(a) in atherosclerotic cardiovascular disease risk from a perspective on current risk stratification

Abstract

Lipoprotein(a) [Lp(a)] is an emerging predictor for atherosclerotic cardiovascular disease (ASCVD) but the association from a perspective on current risk stratification was unknown. A cohort of 9944 Chinese patients with ASCVD was recruited and refined into very-high-risk (VHR) and non-VHR subgroups according to current guideline. Lp(a) plasma levels were divided by its concentration (<30, 30–50, 50–75, and ≥75 mg/dL) and percentile zones (<25th, 25–50th, 50–75th, 75–90th, ≥90th). Cardiovascular events (CVEs) occurred during an average of 38.5 months’ follow-up were recorded. We found that Lp(a) was increased with risk stratification of ASCVD increasing. Prevalence of CVEs had a significantly increasing trend with gradients of Lp(a) elevation in VHR but not in non-VHR subgroup. The adjusted HRs (95%CIs) for CVEs were 1.75(1.25–2.46) in the highest group of Lp(a) ≥75 mg/dL compared with the group of Lp(a) <30 mg/dL as the reference in overall patients, 2.18(1.32–3.58) in VHR subgroup and 1.43(0.93–2.18) in non-VHR subgroup, respectively. The adjusted HRs (95%CIs) at the highest grade of Lp(a) levels (≥90th) were 1.72(1.19–2.50) in overall population, 2.83(1.53–5.24) in VHR subgroup and 1.38(0.86–2.12) in non-VHR subgroup, respectively. These findings suggested that Lp(a) might contribute more to CVEs risk in VHR subgroup of ASCVD.

Keywords

atherosclerotic cardiovascular disease / Chinese / lipoprotein(a) / risk stratification

References

[1] Gencer B, Kronenberg F, Stroes ES, Mach F. Lipoprotein(a): the revenant. Eur Heart J. 2017; 38(20): 1553-1560.

[2] Sandholzer C, Saha N, Kark JD, et al. Apo(a) isoforms predict risk for coronary heart disease. A study in six populations. Arterioscler Thromb. 1992; 12(10): 1214-1226.

[3] Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009; 301(22): 2331-2339.

[4] Tsimikas S. A Test in Context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2017; 69(6): 692-711.

[5] Ruscica M, Sirtori CR, Corsini A, et al. Lipoprotein(a): knowns, unknowns and uncertainties. Pharmacol Res. 2021; 173: 105812.

[6] Kamstrup PR. Lipoprotein(a) and cardiovascular disease. Clin Chem. 2021; 67(1): 154-166.

[7] Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010; 31(23): 2844-2853.

[8] Kronenberg F, Mora S, Stroes ESG, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J. 2022; 43(39): 3925-3946.

[9] Reyes-Soffer G, Ginsberg HN, Berglund L, et al. Lipoprotein(a): a genetically determined, causal, and prevalent risk factor for atherosclerotic cardiovascular disease: a scientific statement from the. Arterioscler Thromb Vasc Biol. 2022; 42(1): e48-e60. American Heart Association..

[10] Li JJ, Ma CS, Zhao D, et al. Lipoprotein(a) and cardiovascular disease in Chinese population: a Beijing heart society expert scientific statement. JACC:Asia. 2022; 2(6): 653-665.

[11] Rosenblit PD. Extreme atherosclerotic cardiovascular disease (ASCVD) risk recognition. Curr Diabetes Rep. 2019; 19(8): 61.

[12] Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol. 2019; 73(24): e285-e350.

[13] Mach F, Baigent C, Catapano AL, et al. ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020; 41(1): 111-188.

[14] Wong ND. Identifying the very-high-risk atherosclerotic cardiovascular disease patient: does it really matter. J Am Coll Cardiol. 2019; 74(20): 2508-2510.

[15] Figtree GA, Broadfoot K, Casadei B, et al. A call to action for new global approaches to cardiovascular disease drug solutions. Eur Heart J. 2021; 42(15): 1464-1475.

[16] Arnett DK, Blumenthal RS, Albert MA, et al. ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019; 140(11): e596-e646.

[17] Khera AV, Everett BM, Caulfield MP, et al. Lipoprotein(a) concentrations, rosuvastatin therapy, and residual vascular risk: an analysis from the JUPITER Trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin). Circulation. 2014; 129: 635-642.

[18] Mehta A, Vasquez N, Ayers CR, et al. Independent association of Lipoprotein(a) and coronary artery calcification with atherosclerotic cardiovascular risk. J Am Coll Cardiol. 2022; 79(8): 757-768.

[19] Kaiser Y, Daghem M, Tzolos E, et al. Association of lipoprotein(a) with atherosclerotic plaque progression. J Am Coll Cardiol. 2022; 79(3): 223-233.

[20] Nissen SE, Wolski K, Cho L, et al. Lipoprotein(a) levels in a global population with established atherosclerotic cardiovascular disease. Open Heart. 2022; 9(2): e002060.

[21] Schmidt K, Noureen A, Kronenberg F, Utermann G. Structure, function, and genetics of lipoprotein(a). J Lipid Res. 2016; 57(8): 1339-1359.

[22] Trinder M, Uddin MM, Finneran P, et al. Clinical utility of lipoprotein(a) and LPA genetic risk score in risk prediction of incident atherosclerotic cardiovascular disease. JAMA Cardiol. 2021; 6(3): 1-9.

[23] Cobbaert C, Jukema JW, Zwinderman AH, et al. Modulation of lipoprotein(a) atherogenicity by high density lipoprotein cholesterol levels in middle-aged men with symptomatic coronary artery disease and normal to moderately elevated serum cholesterol. Regression Growth Evaluation Statin Study (REGRESS) Study Group. J Am Coll Cardiol. 1997; 30: 1491-1499.

[24] Willeit P, Ridker PM, Nestel PJ, et al. Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials. Lancet. 2018; 392(10155): 1311-1320.

[25] Li S, Liu HH, Guo YL, et al. Improvement of evaluation in Chinese patients with atherosclerotic cardiovascular disease using the very-high-risk refinement: a population-based study. Lancet Reg Health West Pac. 2021; 17: 100286.

[26] Li S, Liu HH, Guo YL, et al. Current guideline risk stratification and cardiovascular outcomes in Chinese patients suffered from atherosclerotic cardiovascular disease. Front Endocrinol (Lausanne). 2022; 13: 860698.

RIGHTS & PERMISSIONS

2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.