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Four in 10 middle-aged individuals without a history of heart disease have silent coronary atherosclerosis and 1 in 20 have significant stenosis on coronary CT angiography (CCTA), Swedish researchers report.

“What’s important is that we actually looked at the atherosclerosis of the vessel wall with angiography and now have data on the extent and the severity of atherosclerosis in the general population,” lead author Göran Bergström, MD, lasix sulfa allergy PhD, University of Gothenburg, Sweden, told theheart.org | Medscape Cardiology.

This baseline population-level information is a prerequisite for developing successful screening strategies in high-risk individuals, he said. Recent US guidelines suggest that a coronary artery calcium (CAC) score can be used to improve classification of adults at intermediate risk based on the pooled cohort equation (PCE), with a CAC score of 0 indicating lower risk and not favoring statin therapy.

CAC testing, however, doesn’t provide information on the degree of stenosis or the presence of noncalcified plaques, he noted. Significant atherosclerosis is also possible in the absence of CAC.

Indeed, among the 60% of participants with a 0 CAC score, 5.5% (4.3% of women and 7.3% of men) had CCTA-verified atherosclerosis, according to the study, published September 21 in the journal Circulation.

Defining the true prevalence of atherosclerosis in the general population is an essential first step to guide future prevention strategies, but prior estimates have been based on post-mortem evidence or small, selected populations or relied on CAC, Kuan Ken Lee, MBChB, University of Edinburgh, Scotland, and colleagues observe in an accompanying editorial.

“It is in this context that the findings of the Swedish CArdioPulmonary bioImage Study (SCAPIS) are particularly important,” the editorialists write.

The nationwide, multicenter SCAPIS study recruited 30,154 randomly invited adults aged 50-64 years without known coronary disease who underwent CCTA and CAC imaging based on previously detailed protocols between 2013 and 2018. The present analysis included 25,182 participants (50.6% women). The median age was 57.4, median effective radiation dose was 0.34 mSv from CAC and 1.33 mSv from CCTA imaging, and the median CAC score was 35.

In all, 42.1% of participants had any atherosclerosis on coronary CTA; 5.2% had significant (at least 50%) stenosis; 1.9% had severe disease involving the left main, proximal left anterior descending (LAD) artery, or all three vessels; and 8.3% had noncalcified plaques.

Atherosclerosis was most commonly found in the proximal LAD and was more prevalent in older individuals. As previously observed, the onset of disease averaged about 10 years later in women than in men, Bergström said.

All participants with CAC scores of more than 400 had coronary CTA-verified atherosclerosis, nearly half (45.7%) had at least 50% stenosis, and 20.3% had severe disease. “So there was a very strong association between high calcium scores and obstructive disease on CT,” he said.

CCTA detected atherosclerosis in 5.5% of participants with CAC score of 0 and in 89.1% with ultra-low CAC scores (1 to 10). Significant stenosis was present in 0.4% and 2%, respectively, and severe disease in 0.2% and 0.5%, respectively.

In the subset with CAC scores of 0, CCTA detected atherosclerosis in 6% of those with a strong family history of myocardial infarction, 6.8% of current smokers, and 8.1% who had diabetes.

There was a good correlation between the prevalence of atherosclerosis and risk categories using the PCE and the Systemic Coronary Risk Estimation (SCORE), with a 2.9-fold and 2.1-fold higher prevalence in participants classified as high vs low risk by both scores.

“Interestingly, in those classified as low risk by both scores, as many as 1 in 3 men and 1 in 4 women were found to have coronary atherosclerosis,” Lee and colleagues point out. “Furthermore, in women the prevalence of coronary atherosclerosis was similar whether they were classified as moderate or high risk by SCORE, suggesting that discrimination in those who are higher risk could also be improved.”

Notably, 9.2% of those with a CAC score of 0 and at intermediate risk on the PCE had CCTA-verified atherosclerosis, and thus, would have been misclassified as having a lower risk based on current guidelines, noted Bergström. “In the future, the guidelines may need to account for the noncalcified plaque as well.”

He suggested that the results are generalizable to Western countries, including the United States. The study, however, suffered from a relatively high exclusion rate because of strict safety protocols, and readings of CCTA and CAC data were not independent, as the readers had access to both contrast and noncontrast image sets.

“The high prevalence of subclinical coronary atherosclerosis raises the question as to whether CCTA could help identify persons more precisely who would benefit from early initiation of preventative therapies to treat the underlying atherosclerotic disease process and reduce their lifetime risk of coronary events,” Lee and colleagues write.

CCTA, however, is not uniformly available and, even where testing is available, capacity would have to be significantly expanded to establish high-risk population screening programs, they point out.

Novel bioimaging markers could help identify those most likely to have subclinical coronary atherosclerosis but, “ultimately, evidence from randomized controlled trials will be needed to determine whether targeting preventative therapy using CCTA is superior to our current practice of estimating risk using probabilistic risk scores,” the editorialists suggest.

That question, they note, is currently being addressed in individuals with one or more cardiovascular risk factors in the SCOT-HEART 2 trial, which will determine whether screening with CCTA or the ASSIGN score is superior with regard to cardiac death or myocardial infarction at 5 years. The primary completion date is set for October 2023.

The study received funding from the Swedish Heart-Lung Foundation, Knut and Alice Wallenberg Foundation, Swedish Research Council and Vinnova, University of Gothenburg and Sahlgrenska University Hospital, Karolinska Institutet and Stockholm county council, Linkoping University and University Hospital, Lund University and Skane University Hospital, Umea University and University Hospital, and Uppsala University and University Hospital. Bergström and Lee have disclosed no relevant financial relationships.

Circulation. Published online September 20, 2021. Full text, Editorial 

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