Qualitative evaluation of coronary atherosclerosis in a large cohort of young and middle-aged Dutch tissue donors implies that coronary thrombo-embolic manifestations are stochastic

PLoS One. 2018 Nov 27;13(11):e0207943. doi: 10.1371/journal.pone.0207943. eCollection 2018.

Abstract

Background and aims: With the intention to gain support for the hypothesis that incident ischemic complications of atherosclerotic disease involve a stochastic aspect, we performed a histological, qualitative evaluation of the epidemiology of coronary atherosclerotic disease in a cohort of aortic valve donors.

Patients and methods: Donors (n = 695, median age 54, range 11-65 years) were dichotomized into a non-cardiovascular (non-CVD) and a cardiovascular disease death (CVD) group. Consecutive 5 mm proximal left coronary artery segments were Movat stained, and the atherosclerotic burden for each segment was graded (revised AHA-classification).

Results: Non-CVD and CVD groups showed steep increase of atherosclerosis severity beyond the age of 40, resulting in an endemic presence of advanced atherosclerosis in men over 40 and women over 50 years. In fact, only 19% of the non-CVD and 6% of the CVD donors over 40 years were classified with a normal LCA or a so called non-progressive lesion type. Fibrous calcified plaques (FCP), the consolidated remnants of earlier ruptured lesions, dominated in both non-CVD and CVD donors. Estimates of the atherosclerosis burden (i.e. average lesion grade, proportion of FCPs, and average number of FCPs per cross-section) were all higher in the CVD group (p<1.10-16, p<0.0001, and p<0.05, respectively).

Conclusions: Dominance of consolidated FCP lesions in males over 40 and females over 50 years, show that plaque ruptures in the left coronary artery are common. However, the majority of these ruptures remain asymptomatic. This implies that the atherosclerotic process is repetitive. A relative difference in disease burden between CVD and non-CVD donors supports the concept that complications of atherosclerotic disease involve a stochastic element.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aortic Valve / transplantation
  • Child
  • Cohort Studies
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / pathology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Netherlands
  • Plaque, Atherosclerotic / mortality
  • Plaque, Atherosclerotic / parasitology*
  • Plaque, Atherosclerotic / pathology
  • Stochastic Processes
  • Thromboembolism / mortality
  • Thromboembolism / pathology*
  • Tissue Donors
  • Young Adult

Grants and funding

This study was funded by the European Commission (Cartardis, FP7 HEALTH.2013.2.4.2-1). The funders had no role in the study design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. There was no additional external funding received for this study.