SCAPIS: CTA Finds Silent CAD in 42% of Middle-aged Adults

A Swedish initiative with the ambitious vision of “reducing the risk of cardiovascular and respiratory diseases for generations to come” has turned up some grim numbers: among more than 25,000 middle-aged men and women screened by cardiac CT angiography (CTA), four in 10 had coronary artery disease, with one in 20 having severe CAD. None of those screened had a history of cardiovascular disease.

Importantly, however, a home-based questionnaire could identify most of those with silent CAD, potentially paving the way for better preventive treatments, while singling out patients who should proceed to imaging confirmation, according to Göran Bergström, MD, PhD (Gothenburg University, Sweden).

Bergström presented this analysis from the Swedish CardioPulmonary BioImage Study (SCAPIS) today during a late-breaking clinical trial session of the virtual American Heart Association (AHA) 2020 Scientific Sessions.

SCAPIS, funded by the Swedish Heart-Lung Foundation, enrolled more than 30,000 men and women age 50 to 64 from the general population, of whom 25,182 with no known coronary disease were imaged using coronary CT angiography. Imaging was performed at six different universities, with each doing approximately 5,000 CT angiograms. Of note, the examination protocol for SCAPIS is also collecting carotid ultrasounds, body measurements, blood samples, lung function tests, accelerometry, ECGs, and blood pressures.

In all, 42.1% of subjects were found to have some degree of coronary disease, with both prevalence and disease severity increasing with age. Severe coronary disease, defined as any obstruction greater than 50% was seen in 5.2% of patients. Coronary disease prevalence and severity was higher in men than in women. When the Framingham and the European SCORE risk tools were applied to the patient population, they predicted the prevalence of both CAD and severe CAD.

SCAPIS investigators then used an AI algorithm based on machine learning for 120 different risk factors to develop “clinical” and “home” risk models capable of predicting four or more diseased arterial segments. As Bergström showed today, the home model demonstrated “good” accuracy, identifying two-thirds of study participants “with widespread atherosclerosis.”

During a morning press conference, he clarified that the home-based tool yielded an area under the curve of 0.8, compared with the Framingham tool’s 0.75. Of note, he said, Framingham is intended for predicting cardiovascular events, not presence of coronary artery disease.

“Interestingly to us, the home model was equally effective as the clinical model in discriminating widespread coronary artery disease,” he said during the press conference. Applied to a screening situation “it means that if we image 30% of the population at highest risk according to the home model, we can identify around two-thirds of the participants with widespread atherosclerosis and that could potentially direct preventive efforts.”

He concluded: “Using a home-based test we can with reasonable precision identify individuals [and] predict who has wide-spread coronary artery disease without requiring healthcare resources. We hope these findings can be developed into a future screening strategy. This strategy could involve simple home-based tests to first select individuals with a high likelihood of having silent CAD and then define this risk further using CT imaging. This would lead to early detection of coronary artery disease and may provide preventive treatment to those at the highest risk and decrease the risk of future heart attacks.”

Defining Anatomical Risk

Commenting on the SCAPIS results for the press, Pamela Douglas, MD (Duke University, Durham, NC), called it a “very interesting study with important implications for prevention.”

A fundamental question underpinning this whole area of research, though, remains the best way of pinpointing clinically relevant coronary atherosclerosis, she said. “This may seem very elementary but it’s critical to understand this, and SCAPIS has already provided novel data on the prevalence of CAD in the general population and will address many important clinical questions like this one over the long term.”

SCAPIS, Douglas continued, is testing a tiered testing proposal that predicts risk by a definition of anatomic risk based on the presence of any coronary disease in four or more segments. “The rationale for choosing this cut point is unclear as clinical risk/mortality is higher in all nonobstructive CAD than no CAD, starting at one vessel involvement,” she explained. Other studies have defined clinical risk using fewer segments, any segment, or other findings on CTA.

What’s more, in SCAPIS the risk algorithm “failed to detect one-third of patients with a [segment involvement score] of 4 or greater and may not identify those with the greatest event burden,” she noted. Other trials, after all, have shown that “most MACE events occur in the very large population with nonobstructive CAD group and not the tiny minority with stenosis.”

Speaking with TCTMD today, Douglas pointed out that SCAPIS was presented at AHA alongside TIPS-3, a trial testing a low-cost, low-risk, and population-wide polypill approach. SCAPIS aims to do the opposite: namely, to identify patients who can be best targeted with preventive therapy. The choice by the AHA program committee to present these two trials side-by-side was likely intentional, Douglas said.

“The juxtaposition of a precision strategy and a treat-everyone, polypill strategy is very important because of the expense, feasibility, and potential side effects with the polypill strategy versus the same questions with a more precision strategy,” she stressed. “So the very first step is to see whether there is disease in the population. And there have been a lot of epidemiologic studies with calcium score but very few with CT angiography, per se, looking at plaque, and that’s the gold standard.”

Whether a segment score is the best component to focus on is unclear. Other trials have used the Leaman score, number of involved vessels, or plaque characteristics including so-called vulnerable plaque. “So it's not clear yet which is the most important anatomic feature that you want to predict with your clinical score, but they had to choose something,” said Douglas.

SCAPIS, however, is well-positioned to answer questions like this one over the next 5 to 10 years, she added.

Then there’s the question of whether, working backward from CT findings, a machine-learning-derived score could provide anything over and above what’s currently available for predicting the presence of disease and its downstream risks. For example, asked during the session today how the SCAPIS home-based risk score or other AI-derived scores might compare with coronary calcium, Bergström called the question “very relevant.”

“The answer is, we don’t know,” he said. “Yet.” The SCAPIS investigators are also collecting coronary calcium, Bergström said, but prospective data will ultimately be needed to see if CTA offers additive value.

As for whether a polypill approach or a targeted CTA approach might be better for primary prevention, Anushka Patel, MBBS, PhD (The George Institute for Global Health, Sydney, Australia), speaking in the main session, observed that it’s not necessarily a scenario of one approach versus the other. TIPS-3 and other polypill approaches, she pointed out, also stratified the population according to predicted risk by using different methods.

“We’re talking about a continuum,” she said. “And then of course, pragmatism and cost become a major factor. So I think these are definitely not mutually exclusive, and I think in different contexts, different populations, and different combinations, with risk stratification, the use of the polypill could be anticipated.”

Douglas, too, pointed out that to date no one knows how to best treat people with very mild amounts of coronary plaque. “We have some observational data from CONFIRM and other studies that those who get statins do better than those who do not, but it may well be that for somebody with very mild plaque, a polypill is actually the best preventive therapy, she said. “So I can see these [approaches] intersecting.”