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About half of middle-aged adults in the community without cardiovascular (CV) symptoms have coronary atherosclerosis by CT angiography (CTA) that puts them at substantial risk for myocardial infarction (MI), suggests a prospective cohort study.

The 10% of participants who had subclinical disease considered obstructive at CTA showed a ninefold increased risk for MI over several years. Obstructive disease seemed to elevate risk more than subclinical disease that wasn’t obstructive but still considered extensive within the coronary arteries.

The findings, based on a Copenhagen General Population Study cohort, are new for CTA but consistent with research based on coronary artery calcium (CAC) scores and other ways to assess CV risk, prevacid gluten free say researchers.

Although all participants underwent CTA, such imaging isn’t used in the general population for atherosclerosis screening. But the findings may have implications for “opportunistic screening” for subclinical coronary disease at CTA conducted for other reasons, notes the study’s report, published online March 27 in the Annals of Internal Medicine.

“Identification of luminal obstructive or extensive subclinical coronary atherosclerosis” could potentially provide “clinically relevant, incremental risk assessment” in nonischemic patients who undergo cardiac CT or electrocardiogram-gated chest CT before procedures such as arrhythmia ablation or valve repair, it states.

Such patients found with subclinical coronary atherosclerosis might potentially “benefit from referral to intensified cardiovascular primary prevention therapy,” write the authors, led by Andreas Fuchs, MD, PhD, Copenhagen University Hospital-Rigshospitalet, Denmark.

The group acknowledges the findings may not entirely apply to a non-Danish population.

A Screening Role for CTA?

Whether CTA has a role to play in adults without symptoms “is a big, open question in the field right now,” observed Ron Blankstein, MD, not associated with the current analysis, for theheart.org | Medscape Cardiology.

Most population studies of CV risk prediction, such as MESA, have looked at CAC scores, not CTA, and have shown that “the more plaque individuals have, the higher the risk.” The current findings are similar but novel in coming from coronary CTA in a large asymptomatic community population, said Blankstein, who is director of cardiac CT at Brigham and Women’s Hospital, Boston.

“It’s possible that patients who have obstructive plaque in general tend to have a larger amount of plaque as well,” he said. So, while the study suggests that “the more plaque individuals have, the worse their overall risk,” it also shows that the risk “is enhanced even more if they have obstructive disease.”

The Danish cohort analysis “provides a unique opportunity to study the contemporary natural history of coronary artery disease in the absence of intervention,” notes an accompanying editorial.

For example, both patients and clinicians were blinded to CTA results, and CV preventive therapies weren’t common, observe Michael McDermott, MBChB, and David E. Newby, DM, PhD, of the BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom.

The analysis suggests that subclinical coronary disease that is obstructive predicts MI risk more strongly than extensive coronary disease, they note, and may be present in two thirds of MI patients. “This contrasts with symptomatic populations, where nonobstructive disease accounts for most future myocardial infarctions, presumably from plaque rupture.”

It also points to “strong associations between nonobstructive extensive disease and adverse plaque characteristics,” write McDermott and Newby. “This underscores the major importance of plaque burden” for the prediction of coronary events.

Graded Risk

The analysis included 9533 persons aged 40 and older without known ischemic heart disease or symptoms with available CTA assessments.

Obstructive disease, defined as presence of a luminal stenosis of at least 50%, was seen in 10% and nonobstructive disease in 36% of the total cohort, the report states.

Disease occupying more than one third of the coronary tree was considered extensive and less than one third of the coronaries nonextensive, occurring in 10.5% and 35.8% of the cohort, respectively.

There were 71 MIs and 193 deaths over a median of 3.5 years. The adjusted relative risk (RR) for MI compared to those without coronary atherosclerosis was:

  • 7.65 (95% CI, 3.53 – 16.57) overall in patients with extensive disease

  • 8.28 (95% CI, 3.75 – 18.32) in those with obstructive but non-extensive disease

  • 9.19 (95% CI, 4.49 – 18.82) overall in those with obstructive disease

  • 12.48 (95% CI, 5.50 – 28.12) in those with or obstructive and extensive disease

The adjusted RR for the composite of death or MI was also elevated in persons with extensive disease:  

  • 2.70 (95% CI, 1.72 – 4.25) in those with extensive but nonobstructive disease

  • 3.15 (95% CI, 2.05 – 4.83) in those with extensive and obstructive disease

“It’s one thing to show that the more plaque, the higher the risk,” Blankstein said. But “does the information ultimately lead to better outcomes? Do patients have fewer MIs or fewer deaths?” Several ongoing randomized trials are exploring these questions.

They include DANE-HEART (Computed Tomography Coronary Angiography for Primary Prevention), projected to enroll about ,000 participants from the Copenhagen General Population Study cohort who have at least one CV risk factor. And SCOT-HEART 2 (second Computed Tomography Coronary Angiography for the Prevention of Myocardial Infarction), enrolling a similar cohort in Scotland.

The study was supported by grants from AP Møller og Hustru Chastine Mc-Kinney Møllers Fond, the Research Council of Rigshospitalet, and Danish Heart Foundation. Fuchs reports no relevant financial relationships. Disclosures for the other authors can be found here. Blankstein recently disclosed serving as a consultant to Amgen, Caristo Diagnostics, Novartis, and Silence Therapeutics. Disclosures for McDermott and Newby, who are SCOT-HEART-2 investigators, can be found here.

Ann Intern Med. Published online March 28, 2023. Abstract, Editorial.

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