Multiplexed apolipoprotein profiling advances the assessment of residual lipid-related cardiovascular risk. (10th June 2022)

• Record Type: Journal Article
• Authors: Schmidt, L; Clarke, R; Von Ende, A; Yin, X; Theofilatos, K; Hopewell, J; Mayr, M
• Is Part Of: Cardiovascular research. Volume 118(2022)Supplement 1
• Publication Date: 2022-06-10
• Subjects: Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Periodicals; 616.1
• DOI: 10.1093/cvr/cvac066.190
• Languages: English
• ISSNs: 0008-6363

Abstract

Abstract: Funding Acknowledgements: Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background and Purpose: Low-density lipoprotein cholesterol (LDL-C) is among the conventional lipid parameters used to predict risk of cardiovascular disease (CVD). Statins lower blood levels of pro-atherogenic LDL-C, but a residual cardiovascular risk remains in some individuals with therapeutically optimised LDL-C levels. Although the metabolism of LDL-C and other lipoprotein particles is governed by a range of different apolipoproteins, only apolipoproteins A-I and B are measured in clinical assays. Using a more comprehensive apolipoprotein panel in a large epidemiological cohort, this study aimed to determine the association of individual apolipoprotein levels with risk of coronary heart disease (CHD). Methods: Bottom-up multiple reaction monitoring–mass spectrometry (MRM–MS) was used in conjunction with stable isotope-labelled peptide standards to quantify plasma levels of 13 apolipoproteins in participants of the Precocious Coronary Artery Disease (PROCARDIS) study (N = 1916; 941 cases of CHD, 975 controls). The relationship between apolipoprotein levels and CHD was assessed after adjusting for established risk factors for CVD and correcting for statin use. Results: The strongest positive associations with CHD in the PROCARDIS study were seen for triglyceride-related apolipoproteins C-I (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.63–3.46), C-III (OR 2.95, 95% CI 1.85–4.71) and E (OR 2.35, 95% CI 1.54–3.58), as well as for apolipoprotein (a) (kringle IV type 2 repeat, OR 2.84, 95% CI 2.04–3.95). Comparing these with associations of apolipoproteins with CVD in the Bruneck study (N = 688) revealed consistency across the two cohorts. Robust inverse associations with CHD were observed for apolipoproteins A-IV (OR 0.45, 95% CI 0.31–0.65) and M (OR 0.29, 95% CI 0.19–0.44). Conclusion: Analysing two large epidemiological cohorts, Bruneck and PROCARDIS, demonstrated that multiplexed apolipoprotein profiling improves the understanding of cardiovascular risk independent of conventional lipid parameters. Most prominently, triglyceride-related apolipoproteins were shown to positively associate with residual cardiovascular risk. The findings of this study support the need for development and implementation of standardised, MRM–MS-based apolipoprotein profiling assays to guide novel lipid-modifying therapies beyond statins.