Review Article | Published:

Temporal shifts in clinical presentation and underlying mechanisms of atherosclerotic disease

Nature Reviews Cardiology volume 14, pages 2129 (2017) | Download Citation


The concept of the 'vulnerable plaque' originated from pathological observations in patients who died from acute coronary syndrome. This recognition spawned a generation of research that led to greater understanding of how complicated atherosclerotic plaques form and precipitate thrombotic events. In current practice, an increasing number of patients who survive their first event present with non-ST-segment elevation myocardial infarction (NSTEMI) rather than myocardial infarction (MI) with ST-segment elevation (STEMI). The culprit lesions that provide the pathological substrate for NSTEMI can vary considerably from the so-called 'vulnerable plaque'. The shift in clinical presentation of MI and stroke corresponds temporally to a progressive change in the characteristics of human plaques away from the supposed characteristics of vulnerability. These alterations in the structure and function of human atherosclerotic lesions might mirror the modifications that are produced in experimental plaques by lipid lowering, inspired by the vulnerable plaque construct. The shift in the clinical presentations of the acute coronary syndromes mandates a critical reassessment of the underlying mechanisms, proposed risk scores, the results and interpretation of preclinical experiments, as well as recognition of the limitations of the use of population data and samples collected before the application of current preventive interventions.

Key points

  • An increasing number of patients presenting with myocardial infarction (MI) are diagnosed with non-ST-segment elevation myocardial infarction rather than an MI with ST-segment elevation, and consequently survive their first event

  • The shift in the clinical presentation of acute coronary syndrome mandates a critical reassessment of the underlying mechanisms and the concept of the vulnerable plaque

  • This change in clinical presentation warrants re-assessment of currently applied cardiovascular risk scores, preclinical experiments, and the validity of population data collected before the application of current preventive interventions

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  1. Laboratory of Experimental Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, Netherlands.

    • Gerard Pasterkamp
    •  & Hester M. den Ruijter
  2. Laboratory of Clinical Chemistry, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, Netherlands.

    • Gerard Pasterkamp
  3. Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB 741G Boston, Massachusetts 02115, USA.

    • Peter Libby


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G.P. and P.L. researched data for the article. All authors contributed substantially to discussion of content, and wrote, reviewed, and edited the manuscript before submission.

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Correspondence to Gerard Pasterkamp.

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