Subclinical Atherosclerosis Common in General Population, Even Those With Zero CAC

The study is the first population-based sample to confirm that having no calcium does not mean no disease, one expert notes.

Subclinical Atherosclerosis Common in General Population, Even Those With Zero CAC

Silent coronary atherosclerosis is present in more than 40% of the general population, with significant lesions identified in 5%, according to a large Swedish coronary computed tomography angiography (CTA) data set. The findings, seen among 25,000 randomly recruited middle-age volunteers with no history of CVD, have important implications for more-broadly predicting future cardiovascular risk, authors say.

So far, coronary artery calcium (CAC) scoring has emerged as the most-reliable way to estimate cardiovascular risk, but the test yields no information on total plaque burden or specific plaque characteristics, which may be just as useful—and indeed more precise—for predicting future events.

The Swedish Cardiopulmonary Bioimage Study (SCAPIS), published in the September 21, 2021, issue of Circulation, “lays the foundation for developing and designing successful high-risk screening strategies,” write lead author Göran Bergström, MD, PhD (University of Gothenburg, Sweden), and colleagues. “Although there is a strong association between high CAC score and significant stenosis, atherosclerosis is not excluded in those with zero CAC, especially in those at high baseline risk.”

This paper represents “the best and probably the first population-based sample where we can get a real-time look at what's the true burden of plaque in the arteries,” Parag Joshi, MD (UT Southwestern Medical Center, Dallas, TX), who was not involved in the research, told TCTMD. Prior data from MESA and the Dallas Heart Study have shown good estimates of plaque burden and frequency, he said, “but there's always been this question that if you don't have coronary calcium you could still have plaque. Calcification happens later in the plaque process so the noncalcified plaque that develops first, what's the true prevalence of that? And how reassured can you be if you have no coronary calcium on a calcium score?”

SCAPIS Findings

For SCAPIS, researchers included more than 25,000 Swedish adults (50.6% women) ages 50 to 64 years without known coronary disease who underwent coronary CTA and CAC imaging using dedicated dual-source CT scanners between 2013 and 2018. In total, 42.1% of the population were found to have any atherosclerosis on coronary CTA, with 5.2% having significant (≥ 50%) lesions; 1.9% having left main, proximal LAD artery, or three-vessel disease; and 8.3% showing noncalcified plaques.

Women tended to develop atherosclerosis an average of 10 years later than men. Overall, plaques were more prevalent in older patients and were most often found in the proximal LAD.

All patients with CAC scores of more than 400 had atherosclerosis, with 45.7% of this subset having significant lesions. On the other hand, plaques were identified in 5.5% of those with CAC scores of zero, with 0.4% having significant stenoses. Coronary CTA verified atherosclerosis in 9.2% of patients with zero CAC and an intermediate 10-year risk of atherosclerotic CVD according to the pooled cohort equation.

Coronary CTA and CAC Scoring

So far, no comprehensive tool has emerged to delineate the amount of plaque that “really matters” in terms of risk prediction, “but probably our best way of getting to that is a coronary calcium score,” Joshi said. “But the absence of coronary calcium also plays a big role in decision-making with our patients, and to see now the truth, which is this coronary CTA where you can see all the plaque and not just the calcified plaque, really puts all of that into context nicely.”

For Joshi, one of the most-interesting findings from the study was the burden of plaque shown in patients with zero CAC scores. “Generally, we use that calcium score as a test to help us decide on how aggressive we're going to be,” he said. “And if there's no coronary calcium, we're going to potentially withhold some therapies. But depending on their risk factor burden, their age, there's up to maybe a one in 10 chance or maybe even a little higher if they have a lot of risk factors that they still have some plaque.”

This could also help a clinician decide whether to repeat a CAC scan a few years later to gauge any progression, he said.

According to the study authors, the biggest contribution of this study is that it can be generalized to the population at large, as compared with prior research mostly done based on autopsy studies in small or selected populations.

As far as generalizability, Joshi estimated that the US population may have a slightly higher burden of disease compared with the Swedish patients included here. Still, this is “really meaningful information,” he said.

In an accompanying editorial, Kuan Ken Lee, MBChB (University of Edinburgh, Scotland), and colleagues write that the study demonstrates the advantages of using coronary CTA to understand the broader implications of atherosclerosis beyond coronary calcium. “The prevalence identified by coronary CTA in SCAPIS was slightly higher than prior estimates that have relied on CAC alone, as is to be expected given that coronary CTA provides a more-detailed assessment,” they say.

The sex differences identified in the data support long-established observations, the editorialists write, in that the findings lend “further support for the theory that coronary atherosclerosis is the same in women and men but presents at a later stage in women. The reasons for this are poorly understood but are likely to reflect the protective or harmful effects of sex hormones on atherosclerosis or other yet unknown factors.”

As for the future of coronary CTA in predicting risk in the general population, they argue it will be a good complement to CAC scoring in those who use the latter clinically, even for those with low or zero CAC. “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.

Long-term analyses of the SCAPIS data should give more answers as to whether coronary CTA findings will prove better at predicting coronary events above and beyond CAC. Future analyses, they write, “should evaluate alternative measures of coronary atherosclerosis burden including functional measurements of stenosis severity and quantification of plaque characteristics which have been shown to identify those at high risk in those with symptoms.”

Joshi added that he, too, would like to see the SCAPIS population followed for future events. “That'll take time, but if you can see what happens to the people—if you can nicely show that here are the event rates across the burden of plaque—[then] that'll really guide us a little more into if there is a clinical utility to coronary CTA in asymptomatic patients. We would need to know that for sure to be able to weigh that as a test.”

  • This 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, Linköping University and University Hospital, Lund University and Skåne University Hospital, Umeå University and University Hospital, and Uppsala University and University Hospital.
  • Bergström and Joshi report no relevant conflicts of interest.