Marlene Busko

July 20, 2015

LAS VEGAS, NV — In patients with suspected coronary artery disease (CAD) but without modifiable traditional risk factors—hypertension, diabetes, hypercholesterolemia, or current smoking—those with CAD identified by coronary CT angiography (CCTA) had an increased risk of major adverse cardiac events (MACE) or death within 5 years, according to a new analysis[1].

The results, based on data from the Coronary CT Angiography Evaluation for Clinical Outcomes International Multicenter registry (CONFIRM), were presented this week at the Society of Cardiovascular Computed Tomography (SCCT) 2015 Annual Scientific Meeting. "This is the first prospective, large study to link CCTA-diagnosed CAD in individuals with no modifiable risk factors to long-term (>5-year) mortality," reported lead investigator Dr Chaitu Cheruvu (St Paul's Hospital, Vancouver, BC).

Following the SCCT presentation, session moderator Dr Martin Hadamitzky (University of Duisburg–Essen, Germany) asked: "What's the rationale for looking at patients with no modifiable risk factors?" Cheruvu clarified that these patients all had a clinically indicated CT scan; for example, they had chest pain and suspected CAD or they lacked symptoms but had a strong family history of CAD.

To heartwire from Medscape, Cheruvu said that patients who present with chest pain but without any of these traditional modifiable risk factors for cardiac disease are "difficult to categorize in terms of risk of a coronary event or of coronary disease itself." Moreover, if such patients are assessed with other noninvasive imaging tests, such as stress echo or nuclear testing, there is only a slim chance that atherosclerosis would be detected, he added. Thus, this study shows "the value of a CT scan in a group that is otherwise difficult to assess."

Suspected CAD, No Risk Factors

In a previous analysis of the CONFIRM registry, researchers showed that CCTA could identify patients at higher risk of early MACE in those with suspected CAD. The current study extends this work and looks at longer-term outcomes.

Cheruvu and colleagues identified 1884 patients in CONFIRM with suspected CAD, no prior CAD, none of the four modifiable risk factors, or complete data. Patients underwent CCTA and were classified into three groups: no CAD (0% stenosis), nonobstructive CAD (1%–49% stenosis), or obstructive CAD (>50% stenosis).

During a mean follow-up of 5.6 years, 7.7% of patients died and 11.8% had a major cardiac event (death, nonfatal MI, unstable angina, or late target vessel revascularization beyond 90 days).

Importantly, researchers note that patients without CCTA-detected CAD had a low rate of incident death (annualized death rate 0.69%; 95% CI 0.50–0.95).

Compared with patients without CCTA-detected CAD, the risk of dying during follow-up was significantly higher in those with more than one segment of nonobstructive CAD (HR 1.73, 95% CI 1.07–2.79) or one- and two-vessel obstructive CAD (HR 1.70, 95% CI 1.08–2.71), and the risk was even higher in patients with three-vessel or left-main CAD (HR 2.87, 95% CI 1.57–5.23), all after adjustment for age and sex.

The prevalence of MACE increased from 5.6% in patients with no CAD, to 13.2% in patients with nonobstructive CAD, to 36.3% in patients with obstructive CAD (P<0.001 for trend).

Patients with obstructive CAD were three times more likely to have a major cardiac event than those with nonobstructive CAD (HR 6.63, 95% CI 3.91–11.26 vs HR 2.20, 95% CI 1.31–3.67, respectively), after adjustment for age, sex, and family history.

Cheruvu acknowledged that study limitations included a lack of information about patient treatments, cause of death, and plaque characteristics. Nevertheless, it revealed that among individuals without modifiable CAD risk factors, obstructive CAD was associated with higher all-cause mortality at 5 years, and "interestingly, even nonobstructive disease was associated with a signal for a heightened risk of death," he said.

In reply to a question from the audience, Cheruvu clarified that in CONFIRM, hypercholesterolemia was defined as total cholesterol of 200 mg/dL or higher. He agreed that "nonmodifiable" was a bit of a misnomer for the risk factor, as recent studies have shown that patients with CAD can benefit from lowering their cholesterol further, even if it is already below this cutoff.

Clinically speaking, Cheruvu said that based on these findings, "If I have a patient with no risk factors but demonstrated [coronary artery] disease, I would start [therapy] with at least a statin, not aspirin, just a statin for the moment."

Cheruvu reported no relevant financial relationships.

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