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Human susceptibility to coronary artery disease: lessons from chimpanzee resilience

Nature Reviews Cardiology volume 19, pages 497–498 (2022)Cite this article

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Important lessons about human susceptibility to coronary atherosclerosis can be learned from the relative resilience of chimpanzees to coronary artery disease (CAD), despite their higher baseline plasma levels of LDL cholesterol and lipoprotein(a) than in humans. Evolutionary pressure and hyper-reactive T cells might have a role in the unique susceptibility of humans to CAD.

Coronary artery disease (CAD) is one of the leading causes of death among adults globally. Although CAD is associated with well-known standard modifiable risk factors, such as hypercholesterolaemia, diabetes mellitus, hypertension and smoking, these risk factors are absent in a substantial proportion of patients with CAD. Indeed, at our centre (the Royal North Shore Hospital in Sydney, Australia), the proportion of patients presenting with first-time ST-segment-elevation myocardial infarction (STEMI) without standard modifiable risk factors increased from 14% to 27% over the past decade1. The importance of understanding the mechanisms associated with increased susceptibility to CAD in this group was highlighted by our unexpected finding from the SWEDEHEART registry (n = 62,048 patients with STEMI) that early mortality (<30 days) was ~50% higher in patients with no standard modifiable risk factors than in those with at least one modifiable risk factor2. Why is human susceptibility to atherosclerotic CAD so variable?

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Fig. 1: Differences in susceptibility to and underlying factors driving CAD between humans and chimpanzees.

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Acknowledgements

G.A.F. is grateful for grant support from the National Health and Medical Research Council (Australia), Heart Research Australia and the NSW Office of Health and Medical Research. J.C.K. acknowledges research support from the US National Institutes of Health (R01HL148167), a New South Wales government health grant (RG194194), the Bourne Foundation and Agilent. H.M.M. is supported by the International Society for the Advancement of Cytometry Marylou Ingram Scholars programme.

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Authors and Affiliations

  1. Kolling Institute of Medical Research, Sydney, New South Wales, Australia

    Gemma A. Figtree

  2. Department of Cardiology, Royal North Shore Hospital, Northern Sydney Local Health District, Sydney, New South Wales, Australia

    Gemma A. Figtree

  3. Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia

    Gemma A. Figtree & Helen M. McGuire

  4. Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia

    Jason C. Kovacic

  5. St. Vincent’s Clinical School, University of NSW, Sydney, New South Wales, Australia

    Jason C. Kovacic

  6. Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Jason C. Kovacic

Authors
  1. Gemma A. Figtree
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  3. Helen M. McGuire
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Correspondence to Gemma A. Figtree.

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Competing interests

G.A.F. reports personal fees from AstraZeneca, CSL and Janssen; grants from Abbott Diagnostic; and a patent (Biomarkers and Oxidative Stress; US9638699B2) issued to the Northern Sydney Local Health District. J.C.K. is the recipient of an Agilent Thought Leader Award, which includes funding for research that is unrelated to the current manuscript.

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Nature Reviews Cardiology thanks Renu Virmani and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Figtree, G.A., Kovacic, J.C. & McGuire, H.M. Human susceptibility to coronary artery disease: lessons from chimpanzee resilience. Nat Rev Cardiol 19, 497–498 (2022). https://doi.org/10.1038/s41569-022-00738-1

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