In the Journals

Scoring system helps diagnose patients with obstructive CAD

A new clinical and biomarker scoring system can help providers diagnose obstructive CAD, according to findings published in the Journal of the American College of Cardiology.

“Advantages of such a reliable clinical and biomarker score include the fact such a technology can be widely disseminated in a cost-effective manner, is easily interpreted and might be associated with a well-defined sequence of therapeutic steps to reduce risk for CAD-related complications, such as antiplatelet or lipid-lowering therapy,” James L. Januzzi Jr., MD, cardiologist at Massachusetts General Hospital and professor of medicine at Harvard Medical School, and colleagues wrote.

Researchers analyzed data from 927 patients who were undergoing peripheral and coronary angiography at Massachusetts General Hospital between 2008 and 2011. Patients were then split into two groups: training set (n = 649; 70%) and validation set (n = 278; 30%). Within the training group, 428 patients (mean age, 67 years; 79% men) had significant coronary stenosis ( 70% luminal obstruction) in at least one major coronary artery vs. 221 patients who did not (mean age, 64 years; 58% men).

James L. Januzzi

Blood was drawn before and after angiography and was examined for 109 biomarkers. The researchers identified four biomarkers that predicted 70% stenosis: midkine, adiponectin, apolipoprotein C-I and kidney injury molecule-1. They were included in the score along with two clinical factors: male sex and previous PCI.

The scoring system diagnosed severe CAD in all patients in the training group (OR = 9.74; 95% CI, 6.05-16.1), as well as in men (OR = 7.88; 95% CI, 4.31-14.9), women (OR = 24.8; 95% CI, 7.11-111.6) and patients with no history of CAD (OR = 8.67; 95% CI, 4.38-17.9).

Researchers noted that women benefited from this scoring system, especially since they often face diagnostic difficulties. “These are exciting data, given the fact women patients may present with unique symptoms and signs when they have coronary disease, and as a consequence, women are more likely to have the diagnosis of coronary disease missed when compared to men,” Januzzi told Cardiology Today.

The CAD algorithm throughout various scores was analyzed. For patients with severe CAD, researchers found that its sensitivity was 77%, specificity was 84%, positive predictive value was 90% and the negative predictive value was 67%. Sensitivity was 84% and specificity was 66% in patients with prior CAD, whereas sensitivity was 78% and specificity was 80% in patients with no prior CAD.

The biomarker scoring system was more accurate at predicting severe CAD than traditional diagnostics methods such as nuclear stress tests and exercise stress tests (P < .001 for difference in area under the curve).

After mean follow-up of 3.6 years, the scoring system predicted incident subsequent acute MI in score- and age-adjusted models (HR = 2.23; 95% CI, 1.53-3.25).

“It is interesting that none of the four biomarkers identified is a marker of inflammation, as would be expected if the goal had been determining unstable disease,” Robert A. Vogel, MD, a preventive cardiologist at the University of Colorado Denver, wrote in a related editorial.

Robert A. Vogel

“Both C-reactive protein and interleukin-6 did not make the cut for our panel,” Januzzi told Cardiology Today. “While we were initially intrigued that traditional inflammatory markers such as [CRP] did not add to the panel we identified, it is worthwhile noting our testing strategy identified anatomic [CAD], whereas testing for CRP has been modestly useful not for predicting anatomic coronary disease, but future [CV] events. This suggests CRP or [interleukin-6] may predict something different than presence of coronary disease.” – by Darlene Dobkowski

For more information:

James L. Januzzi Jr., MD, can be reached at the Division of Cardiology, Massachusetts General Hospital, 32 Fruit St., Yawkey 5984, Boston, MA 02114; email: jjanuzzi@partners.org.

Disclosure : The study was supported by a grant from Prevencio. Januzzi reports receiving research grants from Prevencio, Roche Diagnostics, Siemens Diagnostics and Singulex; consulting for Boehringer Ingelheim, Critical Diagnostics, Merck, Novartis, Philips and Roche Diagnostics; serving as a member of a clinical endpoints committee for Boehringer Ingelheim, Novartis and Pfizer; and serving on a data monitoring committee for Amgen and Pfizer. Please see the full study for the other researchers’ relevant financial disclosures. Vogel reports no relevant financial disclosures.

A new clinical and biomarker scoring system can help providers diagnose obstructive CAD, according to findings published in the Journal of the American College of Cardiology.

“Advantages of such a reliable clinical and biomarker score include the fact such a technology can be widely disseminated in a cost-effective manner, is easily interpreted and might be associated with a well-defined sequence of therapeutic steps to reduce risk for CAD-related complications, such as antiplatelet or lipid-lowering therapy,” James L. Januzzi Jr., MD, cardiologist at Massachusetts General Hospital and professor of medicine at Harvard Medical School, and colleagues wrote.

Researchers analyzed data from 927 patients who were undergoing peripheral and coronary angiography at Massachusetts General Hospital between 2008 and 2011. Patients were then split into two groups: training set (n = 649; 70%) and validation set (n = 278; 30%). Within the training group, 428 patients (mean age, 67 years; 79% men) had significant coronary stenosis ( 70% luminal obstruction) in at least one major coronary artery vs. 221 patients who did not (mean age, 64 years; 58% men).

James L. Januzzi

Blood was drawn before and after angiography and was examined for 109 biomarkers. The researchers identified four biomarkers that predicted 70% stenosis: midkine, adiponectin, apolipoprotein C-I and kidney injury molecule-1. They were included in the score along with two clinical factors: male sex and previous PCI.

The scoring system diagnosed severe CAD in all patients in the training group (OR = 9.74; 95% CI, 6.05-16.1), as well as in men (OR = 7.88; 95% CI, 4.31-14.9), women (OR = 24.8; 95% CI, 7.11-111.6) and patients with no history of CAD (OR = 8.67; 95% CI, 4.38-17.9).

Researchers noted that women benefited from this scoring system, especially since they often face diagnostic difficulties. “These are exciting data, given the fact women patients may present with unique symptoms and signs when they have coronary disease, and as a consequence, women are more likely to have the diagnosis of coronary disease missed when compared to men,” Januzzi told Cardiology Today.

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The CAD algorithm throughout various scores was analyzed. For patients with severe CAD, researchers found that its sensitivity was 77%, specificity was 84%, positive predictive value was 90% and the negative predictive value was 67%. Sensitivity was 84% and specificity was 66% in patients with prior CAD, whereas sensitivity was 78% and specificity was 80% in patients with no prior CAD.

The biomarker scoring system was more accurate at predicting severe CAD than traditional diagnostics methods such as nuclear stress tests and exercise stress tests (P < .001 for difference in area under the curve).

After mean follow-up of 3.6 years, the scoring system predicted incident subsequent acute MI in score- and age-adjusted models (HR = 2.23; 95% CI, 1.53-3.25).

“It is interesting that none of the four biomarkers identified is a marker of inflammation, as would be expected if the goal had been determining unstable disease,” Robert A. Vogel, MD, a preventive cardiologist at the University of Colorado Denver, wrote in a related editorial.

Robert A. Vogel

“Both C-reactive protein and interleukin-6 did not make the cut for our panel,” Januzzi told Cardiology Today. “While we were initially intrigued that traditional inflammatory markers such as [CRP] did not add to the panel we identified, it is worthwhile noting our testing strategy identified anatomic [CAD], whereas testing for CRP has been modestly useful not for predicting anatomic coronary disease, but future [CV] events. This suggests CRP or [interleukin-6] may predict something different than presence of coronary disease.” – by Darlene Dobkowski

For more information:

James L. Januzzi Jr., MD, can be reached at the Division of Cardiology, Massachusetts General Hospital, 32 Fruit St., Yawkey 5984, Boston, MA 02114; email: jjanuzzi@partners.org.

Disclosure : The study was supported by a grant from Prevencio. Januzzi reports receiving research grants from Prevencio, Roche Diagnostics, Siemens Diagnostics and Singulex; consulting for Boehringer Ingelheim, Critical Diagnostics, Merck, Novartis, Philips and Roche Diagnostics; serving as a member of a clinical endpoints committee for Boehringer Ingelheim, Novartis and Pfizer; and serving on a data monitoring committee for Amgen and Pfizer. Please see the full study for the other researchers’ relevant financial disclosures. Vogel reports no relevant financial disclosures.