More Questions About Who Is at Risk for Coronary Disease

Reed Miller

November 28, 2011

November 24, 2011 (Orlando, Florida) — The Coronary CT Angiography Evaluation For Clinical Outcomes International Multicenter (CONFIRM) registry continues to yield new information about the diagnostic power of coronary computed tomography angiography (CCTA) and the different risks of coronary events faced by disparate patient subgroups.

Results presented last week at the American Heart Association 2011 Scientific Sessions showed that patients whose CCTA scans revealed high-risk coronary disease had a survival benefit from revascularization. Lead author Dr James Min (Cedars Sinai Medical Center, Los Angeles, CA) told heartwire that this finding may cause some controversy because it appears to contradict the findings of the COURAGE and BARI 2D trials: that patients with stable coronary disease who have undergone revascularization do not live longer.

The study examined 15 223 patients with CCTA who were followed for an average of 2.2 years, during which there were 185 (1.2%) deaths. The adjusted mortality hazard ratio for patients with nonhigh-risk coronary disease compared with no coronary disease was 1.82 (p=0.0048). Patients with high-risk coronary disease (two or more vessels with at least 70% stenosis and proximal left-anterior descending artery involvement, three-vessel obstructive disease, or left main obstructive stenosis over 50%) were 3.11-times as likely to die as patients with no coronary disease (p<0.0001).

Of patients with nonhigh-risk coronary disease, 7.2% underwent revascularization, while 51.3% with high-risk coronary disease were revascularized. Multivariable Cox models, including a propensity score analysis, showed that revascularization almost doubled the survival chances of patients with high-risk coronary disease, made no difference for patients with nonhigh-risk coronary disease, and dramatically increased the mortality risk for patients with no coronary disease (HR 14, p<0.0001).

Women's Outcomes Are Worse Independent of Disease

In another AHA presentation, Dr Fay Lin (Weill Cornell Medical Center, New York, NY) discussed data from 15 215 consecutive patients in the CONFIRM registry without known coronary artery disease. Every patient underwent CCTA to determine the extent and severity of coronary disease, rated as none, nonobstructive (1–49% stenosis), or obstructive (>50% stenosis). For the purposes of the study, stenosis >50% in the left main coronary was considered equivalent to three-vessel obstructive disease. Researchers also compared 6191 women matched to 6191 men with similar coronary disease patterns. "The point of our propensity [matched] analysis was to really separate the [gender differences] from the results of the procedure," Lin told heartwire .

The women in the matched analysis tended to be older than the men (59.1 vs 53.6 years); had more coronary disease risk factors; and had a higher rate of typical angina (11.6% vs 8.8%) and dyspnea (32.1% vs 19.7%). After adjustment for age, risk factors, coronary disease, and revascularization rates, young women showed a similar risk of coronary events as men; however, for every decade of older age among women, their odds of having a major adverse event increased compared with the risk in men (HR 1.04, p=0.04 for interaction).

Women were just as likely as men to be referred for invasive angiography and only slightly less likely to undergo revascularization (5.2% vs 5.9%, p=0.06), but women were significantly more likely to suffer a major adverse event (2.6% vs 2.0%, p=0.02).

Women who underwent invasive angiography were less likely than matched male subjects to have been categorized based on CCTA as high risk (9.3% vs 14.3%, p=0.0003) or have severely obstructive coronary disease (44.9% vs 50.8%, p=0.004).

Women were just as likely as men to undergo invasive angiography, but they were less likely to undergo early revascularization (24% vs 27%, p=0.004), defined as bypass surgery or percutaneous intervention within three months of a CCTA scan, because they were less likely to have severe or high-risk coronary disease. Despite women's lower rate of severe or high-risk disease, women who had early revascularization were more likely than their male counterparts to die or suffer a myocardial infarction (HR 1.9, p=0.006), independent of other risk factors or disease severity. Lin said that this finding confirms what most interventionalists have observed in the cath lab.

Lin and colleagues concluded that although women and men are referred for revascularization and/or invasive angiography at similar rates, older women are still at greater risk for an adverse event than either men or younger women, suggesting that older women with coronary disease may need more intensive management. "Above and beyond their tendency to go to earlier revascularization, there is something about older women that make them do worse," Lin said. One possibility worthy of further study could be that women's overall size puts them at higher risk for worse outcomes, because the study did not control for body mass, Lin said.

CAC Score of Zero Doesn't Completely Rule Out Coronary Disease

The prognostic value of a zero coronary artery calcification (CAC) score has been the subject of much controversy since a Coronary Evaluation Using Multidetector Spiral Computed Tomography Angiography Using 64 Detectors (CORE 64) substudy showed that the absence of coronary calcification did not always exclude the possibility of obstructive coronary disease in symptomatic patients.

Dr Todd Villines (Walter Reed Hospital, Washington, DC) and colleagues examined the value of a zero CAC score in a CONFIRM study published earlier this month in the Journal of the American College of Cardiology [1]. Villines et al analyzed data from 10 037 symptomatic patients without known coronary artery disease who underwent concomitant CCTA and CAC scoring. Among the 51% of patients with a CAC score of zero, 84% also had no coronary disease on the CCTA scan. Of the patients with coronary disease, 13% had nonobstructive stenosis, and 3.5% had stenosis of at least 50%, including 1.4% with >70% stenosis.

A CAC score of greater than zero had a sensitivity of 89% and a specificity of 59% for detecting stenosis over 50%; the negative predictive value was 96% and the positive predictive value was 29%. Over a median follow-up of 2.1 years, there was no difference in mortality among the patients with a CAC score of zero, regardless of how much coronary disease they had.

Of patients followed for at least 90 days after the CCTA, 3.9% of those with a CAC score of zero but at least one stenosis >50% experienced an adverse event, compared with only 0.8% of patients with a zero CAC score and no apparent coronary artery disease.

For the composite end point of mortality, myocardial infarction, and late coronary revascularization, CAC score did not add incremental prognostic information to the CCTA coronary artery disease findings, the authors explain.

"The finding of increased rates of late coronary revascularizations among patients with a CAC score of zero and >50% stenosis on CCTA but no difference in mortality is not surprising," Villines et al explain. "The majority of patients with a CAC score of zero and obstructive disease had single-vessel disease, a cohort in which coronary revascularization has not been shown to improve survival." The authors also point out that the pre-test risk for this population was low to intermediate, so longer follow-up may be needed to fully understand the prognostic value of nonobstructive coronary disease.

CCTA-Predicted Risk Varies Across Ethnicities

Finally, a study of 14 320 patients in CONFIRM by Dr Edward Hulten (Walter Reed Hospital), also presented at the AHA conference, compared adverse event rates by ethnicity. Almost two-thirds of study subjects were white and 30% were East Asian. Another 5% were African and only 0.2% were Latin.

Over a median follow-up of two years, the annualized incidence of death or myocardial infarction in patients with obstructive disease and nonobstructive disease, respectively, was 2.6% vs 0.7% among whites, so obstructive disease increased the chances of death or myocardial infarction by 2.71-times that for nonobstructive disease (p<0.001). In Africans, the adjusted HR was 4.06 (4.7% vs 1.1%, p=0.02).

In East Asians, the absolute event rates for both nonobstructive and obstructive disease were low--0.1% vs 0.9%--but the difference in adverse outcome rates between the two groups was greater than for the other ethnic groups (HR 6.80, p<0.001). The study was underpowered to evaluate the differences in outcomes among Latin patients or those of other ethnicities.

Min reported research grants, speaking fees, and consulting arrangements from GE Healthcare. Villines has received speaker honoraria from Boehringer-Ingelheim.


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