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Walldius G, de Faire U, Alfredsson L, et al. Long-term risk of a major cardiovascular event by apoB, apoA-1, and the apoB/apoA-1 ratio-Experience from the Swedish AMORIS cohort: A cohort study. PLoS Med. 2021;18(12):e1003853doi: 10.1371/journal.pmed.1003853.
Walldius, G., de Faire, U., Alfredsson, L., Leander, K., Westerholm, P., Malmström, H., Ivert, T., & Hammar, N. (2021). Long-term risk of a major cardiovascular event by apoB, apoA-1, and the apoB/apoA-1 ratio-Experience from the Swedish AMORIS cohort: A cohort study. PLoS medicine, 18(12), e1003853. https://doi.org/10.1371/journal.pmed.1003853
Walldius, Göran, et al. "Long-term risk of a major cardiovascular event by apoB, apoA-1, and the apoB/apoA-1 ratio-Experience from the Swedish AMORIS cohort: A cohort study." PLoS medicine vol. 18,12 (2021): e1003853. doi: https://doi.org/10.1371/journal.pmed.1003853
Walldius G, de Faire U, Alfredsson L, Leander K, Westerholm P, Malmström H, Ivert T, Hammar N. Long-term risk of a major cardiovascular event by apoB, apoA-1, and the apoB/apoA-1 ratio-Experience from the Swedish AMORIS cohort: A cohort study. PLoS Med. 2021 Dec 01;18(12):e1003853. doi: 10.1371/journal.pmed.1003853. eCollection 2021 Dec. PMID: 34851955; PMCID: PMC8635349.
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PLoS Med. 2021 Dec 01;18(12):e1003853. doi: 10.1371/journal.pmed.1003853. eCollection 2021 Dec.

Long-term risk of a major cardiovascular event by apoB, apoA-1, and the apoB/apoA-1 ratio-Experience from the Swedish AMORIS cohort: A cohort study.

PLoS medicine

Göran Walldius, Ulf de Faire, Lars Alfredsson, Karin Leander, Peter Westerholm, Håkan Malmström, Torbjörn Ivert, Niklas Hammar

Affiliations

  1. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  2. Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  3. Research & Development, Swedish Orphan Biovitrum, Stockholm, Sweden.
  4. Department of Cardiothoracic Surgery, Karolinska University Hospital, Stockholm, Sweden.
  5. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

PMID: 34851955 PMCID: PMC8635349 DOI: 10.1371/journal.pmed.1003853

Abstract

BACKGROUND: Elevated apolipoprotein B (apoB) and elevated apoB/apoA-1 ratio increase the risk of myocardial infarction (MI) and stroke, whereas high apoA-1 is protective. We study how these apolipoproteins are associated with major adverse cardiovascular events (MACEs), whether apoA-1 contributes to this association, and whether abnormal values occur decades before such events develop.

METHODS AND FINDINGS: In the Swedish AMORIS (Apolipoprotein-related MOrtality RISk) cohort study, 137,100 men and women aged 25-84 years were followed an average 17.8 years. ApoB, apoA-1, and the apoB/apoA-1 ratio were analysed in relation to MACEs (non-fatal MI, stroke, and cardiovascular [CV] mortality), yielding 22,473 events. Hazard ratios (HRs) were estimated using Cox regression. Kaplan-Meier estimates were used to investigate the relationship of MACEs with increasing quintiles of the apoB/apoA-1 ratio in all age groups for both sexes. In nested case-control analyses, cases were randomly matched to age- and sex-matched controls, yielding population trajectories for apolipoproteins. Increased level of apoB and increased apoB/apoA-1 ratio were associated with risk of MACE and all clinical sub-components in both men and women across all ages (10th versus first decile in both sexes combined: HR 1.7 for MACE and 2.7 for non-fatal MI). Decreased values of apoA-1 potentiated the impact of apoB at all levels of apoB (on average across apoB range: 40% increase in HR for MACE and 72% increase in HR for non-fatal MI), indicating that the apoB/apoA-1 ratio covers a broader range of persons with dyslipidaemia at risk than apoB alone. In both men and women, MACEs occurred earlier on average for each increasing quintile of the apoB/apoA-1 ratio. Individuals with the highest levels of apoB/apoA-1 ratio experienced CV events on average several years earlier than those with lower ratios. Higher apoB/apoA-1 ratio in cases of MACE versus controls was seen already about 20 years before the event. A limitation of this study was that adjustment for tobacco smoking and hypertension was only possible in a small validation study.

CONCLUSIONS: An imbalance between apoB and apoA-1 resulting in an increased apoB/apoA-1 ratio is strongly associated with the outcome MACE and its sub-components, in both men and women of all ages. An increased apoB/apoA-1 ratio already 2 decades before events calls for early recognition and primary prevention. Simple evidence-based cut values should be considered in future cardiovascular guidelines.

Conflict of interest statement

No authors have competing interests.

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