Subclinical, Asymptomatic Atherosclerosis Linked to 8-Fold Increase in Myocardial Infarction


An analysis of more than 9000 adults aged 40 and older without known cardiovascular disease is shedding new light on the risk of myocardial infarction and mortality associated with subclinical coronary atherosclerosis.

Klaus Fuglsang Kofoed, MD, PhD, DMSc | Courtesy: Rigshospitalet

Klaus Fuglsang Kofoed, MD, PhD, DMSc
Courtesy: Rigshospitalet

Subclinical, obstructive coronary atherosclerosis is associated with a more than 8-fold increase in risk of myocardial infarction among asymptomatic individual without known cardiovascular disease, according to the results of a new study.1

A prospective cohort study of 9533 people aged 40 years or older without known cardiovascular disease, results of the study, which examined subclinical coronary atherosclerosis as assessed with coronary CT angiography, suggest nonextensive obstruction was linked to an 8-fold increase in risk of myocardial infarction while extensive obstruction was associated with a more than 12-fold increase in risk.1

As cardiology’s understanding of the effects of atherosclerotic cardiovascular disease continue to evolve, the community has begun to explore the impact of subclinical atherosclerosis as a means to improve primary prevention. With this in mind, a team from the University of Copenhagen launched a research endeavor aimed at investigating the associations of subclinical atherosclerosis and risk of myocardial infarction within the Copenhagen General Population Study (CGPS).1

A prospective cohort study launched in 2003, the CGPS includes data from more than 100,000 individuals in Denmark. In 2010, the team conducting CGPS introduced a research protocol where participants could opt for a research coronary CT angiography examination. Limiting their analyses to those with a coronary CT aged 40 years or older with normal kidney function, investigators of the current study identified 9533 individuals without known ischemic heart disease for inclusion.1

This cohort had a mean age of 60.2 years, 42.9% were men, and the mean BMI was 25.7 kg/m2. When examining cardiovascular risk factors, investigators found 57% of the cohort had overweight or obesity, 42% had hypertension, 60% had hypercholesterolemia, and 11% were current smokers.1

The primary endpoint of interest for the study was myocardial infarction. The secondary endpoint of interest was a composite of all-cause death or myocardial infarction. For the purpose of analysis, subclinical coronary atherosclerosis was characterized according to luminal obstruction and extent, with extensive defined as one-third or more of the coronary tree.1

Overall, 54% of the cohort had no subclinical coronary atherosclerosis, 36% had non obstructive disease, and 10% had obstructive disease. During a median follow-up of 3.5 (range, 0.1-8.9) years, 71 people experiencing a myocardial infarction and 193 died.1

Upon analysis, results indicated the risk of myocardial infarction was elevated among those with obstructive (Adjusted relative risk [aRR], 9.19 [95% confidence interval [CI], 4.49-18.11]) and extensive (aRR, 7.65 [95% CI, 3.53 to 16.57]) disease. Further analysis suggested the greatest risk for myocardial infarction was observed among a subgroup with obstructive-extensive subclinical coronary atherosclerosis or obstructive-nonextensive (aRR, 8.28 [95% CI, 3.75-18.32]) subclinical coronary atherosclerosis.1

Analysis of the secondary endpoint of interest suggested risk for the composite endpoint was greater among those with extensive disease, regardless of degree of obstruction. Specifically, the aRR for those with nonobstructive-extensive and obstructive-extensive subclinical coronary atherosclerosis were 2.70 (95% CI, 1.72-4.25) and 3.15 (95% CI, 2.05-4.83), respectively.1

In an accompanying editorial, Michael McDermott, MBChB, and David E. Newby, DM, PhD, both of the British Heart Foundation Centre for Cardiovascular Science at the University of Edinburgh, commended study investigators for their work and celebrated the addition of the study results to the contemporary evidence based guiding care.2

“This exceptional and important study now provides a benchmark against which to observe the contemporary natural history of coronary artery disease,” wrote the pair.2 “It also provides invaluable data about event rates and prevalence of asymptomatic coronary artery disease that will inform public health prevention strategies and ongoing clinical trials of targeting preventative therapies in persons screened for occult coronary artery disease, such as the DANE-HEART and SCOT-HEART 2 trials.”


  1. Fuchs A, Kühl JT, Sigvardsen PE, et al. Subclinical coronary atherosclerosis and risk for myocardial infarction in a Danish cohort. Annals of Internal Medicine. March 2023. doi:10.7326/m22-3027
  2. McDermott M, Newby DE. Contemporary natural history of coronary artery disease. Annals of Internal Medicine. March 2023. doi:10.7326/m23-0533
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