Winston-Salem, NC - A comparison of multiple risk markers suggests that coronary artery calcium (CAC) provides the most improvement in the assessment of cardiovascular disease risk in patients at intermediate risk for future events . Ankle-brachial index, high-sensitivity C-reactive protein (CRP), family history, and CAC were all independent risk predictors for incident coronary heart disease and cardiovascular disease, but CAC provided superior discrimination and risk reclassification compared with the other risk markers.
"If you go to any cardiologist, all that they're doing while you're sitting in front of them is trying to put you into one of three risk categories," lead investigator Dr Joseph Yeboah (Wake Forest University School of Medicine, Winston-Salem, NC) told heartwire. "We know what we should do for low-risk people. We just emphasize lifestyle changes, and most of the time over 10 years nothing happens to them. We know that in high-risk patients, in addition to lifestyle, certain medications work. What we don't know how to do is treat people who fall into the intermediate group. They're in no-man's land. Yet we know a chunk of the people who have heart attacks are within this group. This tells us that there are people who are wrongly put into this category based on current risk tools."
In an editorial accompanying the study , Dr J Michael Gaziano (Brigham and Women's Hospital, Boston, MA) and Dr Peter Wilson (Atlanta Veteran Affairs Medical Center, GA) agree that a CAC scan might help guide clinical decisions, but radiation exposure and costs remain important considerations. "Coronary artery calcium findings also are somewhat resistant to change even in the face of improvement in risk factors and may be useful as a single measure for assessment, especially when refinement of a risk estimate is important, but might not be useful for tracking risk over time," according to the editorialists.
The study and editorial are published in the August 22, 2012 issue of the Journal of the American Medical Association.
Data from the MESA study
Using data from the Multiethnic Study of Atherosclerosis (MESA), the researchers identified 1330 intermediate-risk patients without diabetes mellitus who had data available for all six of the following cardiovascular risk markers: CAC, carotid intima-media thickness (CIMT), ankle-brachial index (ABI), brachial flow-mediated dilation (FMD), and CRP, as well as family history of coronary heart disease. The purpose of the study, explained Yeboah, was to test the effectiveness of these "top-tier" risk markers for cardiovascular risk stratification when added to conventional risk scores in the same group of patients.
After a median follow-up of 7.6 years, there were 123 cardiovascular events. CAC, ABI, high-sensitivity CRP, and family history of coronary heart disease were independently associated with incident coronary heart disease, defined as a composite of MI, angina followed by revascularization, resuscitated cardiac arrest, and coronary heart disease death.Association of risk markers with incident coronary heart disease*
|Risk marker||Hazard ratio (95% CI)|
|Ankle-brachial index||0.79 (0.66-0.96)|
|Brachial flow-mediated dilation||0.93 (0.74-1.16)|
|Coronary artery calcium||2.60 (1.94-3.50)|
|Carotid intima-media thickness||1.17 (0.96-1.45)|
|Family history||2.18 (1.38-3.42)|
|High-sensitivity CRP||1.28 (1.00-1.64)|
*Adjusted for age, sex, race/ethnicity, systolic blood pressure, total cholesterol, HDL cholesterol, smoking status, body-mass index, use of blood-pressure medication, and use of statins
For coronary and cardiovascular disease events, which included stroke and cardiovascular death, the addition of each of the six markers to the Framingham risk score significantly improved the discrimination of clinical events compared with the Framingham score alone. The area under the curve (AUC) improved for all the risk markers but improved the most with CAC scoring. With the addition of CAC, the AUC improved from 0.623 to 0.784.
Similarly, CAC fared best when assessed by net reclassification improvement (NRI), a measure of the relative improvement in the classification of risk with the additional variable. The researchers note that 25.5% of the events were reclassified correctly to the high-risk category, while 40.4% of nonevents were reclassified into the low-risk group. The NRI for the addition of CAC to the Framingham risk score, plus race/ethnicity, was 0.659, the highest reported NRI of the six risk markers.
CAC fares best, but there are caveats
While CAC performed the best of the six markers, Yeboah said that there are important caveats to the results. Echoing the editorialists, he told heartwire that only CAC scoring exposes patients to a small, but not trivial, amount of radiation. He said the long-term effects of radiation on patients remain unknown and will need to be determined before widespread screening using CAC can be used to help the decision-making process.
There would be no benefit to society if we drastically reduce the number of heart attacks only to find out that everybody is developing cancer.
"There would be no benefit to society if we drastically reduce the number of heart attacks only to find out that everybody is developing cancer," said Yeboah.
In addition, there are no outcome studies showing that adding CAC screening to traditional risk scoring systems in intermediate-risk patients reduces the risk of cardiovascular events. If these caveats are addressed, said Yeboah, then CAC screening should be used for the 28 million US adults who fall within the intermediate-risk category. Currently, the American Heart Association and the European Society of Cardiology say it is "reasonable" to use CAC as a screening method for intermediate-risk patients.
In their editorial, Gaziano and Wilson note that research into general cardiovascular disease prevention is timely, given that the National Cholesterol Education Program (NCEP) Adult Treatment Panel 4 treatment guidelines are expected this year, and the addition of novel risk markers to Framingham or the Reynolds risk score might help physicians make a decision about whether or not to start a patient on lifelong statin therapy.
They note, however, that if a patient is near a boundary for lipid-lowering therapy, the doctor can simply choose to see the patient again in a few months rather than order a costly CAC imaging test. Reassessing vascular risk with a patient visit to repeat tests might improve accuracy and reveal trends that could help guide treatment decisions, according to Gaziano and Wilson. While CAC scores can help augment the risk-assessment process, they have limited utility in tracking a patient's progress, as the test is not likely to be repeated over time.
Read the full article here.