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Accelerated coronary atherosclerosis not explained by traditional risk factors in 13% of young individuals - 20/02/19

Doi : 10.1016/j.ahj.2018.11.005 
Trajen Head, PhD a, 1, Lisa Henn, PhD b, 1, Victor P. Andreev, PhD, DSc b, Edward E. Herderick c, Sapna K. Deo, PhD a, Sylvia Daunert, PhD a, Pascal J. Goldschmidt-Clermont, MD d,
a Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA 
b Arbor Research Collaborative for Health, Ann Arbor, MI, USA 
c Eehscience, LLC, Pickerington, OH, USA 
d Cardiology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA 

Reprint requests: Pascal J. Goldschmidt-Clermont, M.D, Cardiology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA.Cardiology, Department of Medicine, University of Miami Miller School of MedicineMiamiFL33136USA

Abstract

Importance

Most individuals who die of sudden cardiac death (SCD) display very advanced lesions of atherosclerosis in their coronary arteries. Thus, we sought to identify and characterize a putative subpopulation of young individuals exhibiting accelerated coronary artery atherosclerosis.

Objective

Our analysis of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study—which examined 2651 individuals, obtaining quantitative measurements of traditional risk factors for coronary heart disease (CHD)—aimed to identify individuals with advanced coronary artery lesions, and to determine whether risk factors could account for such rapid disease progression, or not.

Design

Using the cross-sectional PDAY study data, an exploratory de facto analysis stratified the population by age and observed number of coronary raised lesions and examined these groups via Poisson regression modeling. A separate de novo approach utilized Poisson mixture modeling to generate low- and high-growth groups based on measurements of traditional risk factors, and identified factors contributing to disease progression.

Participants

Participants, n = 2651 individuals aged 15–34, who had died of non-cardiac death, were recruited post mortem. Tissues and other samples were harvested for analysis (details in previously published PDAY studies).

Main Outcome(s) and Measure(s).

Using quantitative measurements of raised coronary lesions and traditional risk factors of CHD, we sought to identify which risk factors account for disease progression.

Results

A group of ~13% of the PDAY population exhibits accelerated coronary atherosclerosis despite their young age. Several traditional risk factors were associated with increased odds of inclusion in this subgroup, reflecting current understanding of these markers of disease. However, only age was a significant contributing factor to the observed coronary lesion burden.

Conclusions

While a range of traditional risk factors contribute to an individual's inclusion to the identified subgroup with accelerated atherosclerosis, these factors, with the exceptions of age, are not able to predict an individual's lesion burden. Moreover, unattributed variances in observations indicate the need to study novel risk factors.

Short summary

Hypothesis

The extent of coronary atherosclerotic disease is limited and homogeneous within youth, and its progression can be accounted for by traditional risk factors in this population.

Findings

A subpopulation (~13%) of the Pathobiological Determinants of Atherosclerosis in Youth cohort exhibited accelerated coronary artery atherosclerosis. While several traditional risk factors contribute to an individual's inclusion in this subgroup, these factors, with the exceptions of age, do not predict accurately an individual's lesions burden. Critically, unattributed variances in observations indicate the need for the identification of novel risk factors.

Meaning

Screening of the general population at a young age for high-risk group membership could provide opportunity for disease prevention and avoidance of the worse complications such as myocardial infarction and sudden cardiac death later in life.

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Vol 208

P. 47-54 - février 2019 Retour au numéro
Article précédent Article précédent
  • Sex differences in management and outcomes of patients with stable symptoms suggestive of coronary artery disease: Insights from the PROMISE trial
  • Neha J. Pagidipati, Adrian Coles, Kshipra Hemal, Kerry L. Lee, Rowena J. Dolor, Patricia A. Pellikka, Daniel B. Mark, Manesh R. Patel, Sheldon E. Litwin, Melissa A. Daubert, Svati H. Shah, Udo Hoffmann, Pamela S. Douglas, PROMISE Investigators
| Article suivant Article suivant
  • Characterization of cardiovascular clinical events and impact of event adjudication on the treatment effect of darapladib versus placebo in patients with stable coronary heart disease: Insights from the STABILITY trial
  • Claes Held, Harvey D. White, Ralph A.H. Stewart, Richard Davies, Shani Sampson, Karen Chiswell, Adam Silverstein, Renato D. Lopes, Ulrika Heldestad, Andrzej Budaj, Kenneth W Mahaffey, Lars Wallentin, on behalf of the STABILITY Investigators

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