Coronary artery calcium (CAC) scores are better than carotid intima media thickness (IMT) at predicting risk of subsequent cardiovascular disease events, a new analysis from the Multi-Ethnic Study of Atherosclerosis (MESA) suggests [1]. While CAC was best at predicting risk of all cardiovascular disease or coronary heart disease specifically, carotid IMT was modestly better than CAC at predicting the risk of stroke, the research showed.
"Although previous consensus statements indicated that CAC score and IMT are global atherosclerosis measures and either might be used clinically for refinement of CVD [cardiovascular disease] risk assessment, our data suggest that in asymptomatic 45- to 84-year-old US adults, CAC score may be the better choice over IMT," Dr Aaron R Folsom (University of Minnesota, Minneapolis) et al write.
Their study appears in the June 23, 2008 issue of Archives of Internal Medicine.
In an interview with heartwire, Folsom explained that he and his colleagues were interested in comparing the two imaging tests, in part due to recommendations like those of the Screening for Heart Attack Prevention and Education (SHAPE) task force, which advocate blanket screening for atherosclerosis and risk prediction, using either test.
"The SHAPE taskforce didn't discriminate between which test should be offered," Folsom explained. "In practice, people are not necessarily picking one test or the other, they're just going with their favorite. If a person is particularly interested in coronary disease, they'd probably pick CAC scanning if it's available to them. Carotid IMT is another option and, given the SHAPE guidelines, we thought it was worthwhile to see which one might actually be better."
Coronary vs carotid scans in MESA cohort
Folsom and colleagues included 6698 MESA study participants between 2000 and 2004, all of whom underwent baseline CAC and carotid IMT screening, then were followed for a maximum of five years for coronary heart disease, stroke, or fatal CVD events. In all, 222 subjects experienced a CVD event over this period.
They found that for every increase (by one standard deviation) of CAC score, risk of CVD increased 2.1-fold. By contrast, for every increase in maximal carotid IMT, CVD risk increased just 1.3-fold. Similar increases were seen proportionally when coronary heart disease was used as an end point, although for stroke end points, IMT was the better predictor. Multivariable-adjusted analyses produced results very similar to the age-, race-, and sex-adjusted analysis.
Hazard ratios related to a one-standard-deviation increment of maximal carotid IMT or CAC score
End point: test Carotid IMT: Hazard ratio p CAC: Hazard ratio p
CVD: Carotid IMT 1.3 < 0.001 2.1 < 0.001
CHD: Carotid IMT 1.2 0.01 2.5 < 0.001
Stroke: Carotid IMT 1.4 0.001 1.1 0.41
The authors propose that the "modestly better" ability of IMT to predict stroke and the "clearly better" prediction of CHD [coronary heart disease] by CAC score speaks to the different "vascular territories" scanned by the two tests.
This is something clinicians may want to take into account, the authors suggest: IMT, for example, may be a better choice in families with a history of stroke. "There, you're actually looking at the vessel that might be most relevant to stroke, whereas if someone has a strong history of coronary disease, a CAC test might be more relevant," Folsom commented.
Age and ethnic differences may also play a factor in choice of screening tool. CAC scores in MESA were particularly high in whites, while IMT scores were highest in African Americans; there are also hints that IMT may become a more predictive test in older patients.
Folsom was also careful to point out, however, that the value of screening tests is still disputed: no study has yet shown that identification of atherosclerosis will alter patient management in a way that meaningfully changes patient outcomes.
"I would say that if a physician feels a test is warranted to help understand how to treat or prevent CVD, particularly in that intermediate-risk group, the CAC test seems to be better than the carotid IMT for middle-aged persons." But, he continued, "Whether to do any test is unclear. I'm an epidemiologist, not a clinician, and I tend to gravitate toward the recommendation that any test should be done only if it is unclear what to do next, and particularly in the intermediate-risk group of patients. People who are already low risk don't need it, and those who are at high risk don't need it. It's probably just in the intermediate group where physicians are uncertain that this might be warranted. But it shouldn't be up to the patient, or up to the people who want to do mass screening, or up to the companies that are advertising, 'Come and get your carotid scanned.'"
"Hard" end-point studies warranted
Dr Amit Khera (UT Southwestern, Dallas), who was not involved in the study, also commented on the findings for heartwire.
He called it "an interesting manuscript" that addresses a relevant clinical question. "Several consensus panels and position statements have suggested that both of these modalities are options as an adjunct to CV risk assessment, but neither one has been recommended over the other," he said. "Clinicians are left with some uncertainty of the relative value of these two tests."
But Khera also pointed to several limitations of Folsom et al's study that make it difficult to draw solid conclusions from the findings. For one, angina made up one-third of the events tracked in the study, which, he points out, is of lesser clinical importance than other CVD end points and more prone to bias.
"Since the participants and physicians were given the results of the CAC scores, it is probable that physicians were more likely to push patients on the presence of symptoms and to pursue stress testing in those with higher CAC scores, also known as detection bias," he said. "Clinicians are in general less familiar with CIMT [carotid intima media thickness] scores and may not have been as inclined to act on them, especially since they were not directly measuring coronary atherosclerosis."
He also identified "statistical challenges" to comparing one-standard-deviation differences in a population where half of the patients had CAC scores of 0. "So one standard deviation of CAC is not exactly proportional to one standard deviation of CIMT," he explained. "The categorical analyses that were presented are helpful, but CIMT values will have less of a rightward skew than CAC scores, so the CAC scores will have more extreme values that influence the results."
Overall, Khera said, "It's likely that CAC scanning is a better predictor of CV events than CIMT, as demonstrated by the MESA investigators. CIMT by involves precise measurement of very small values, which are more prone to error. This noise in the measurement hampers CIMT testing relative to CAC scanning. As more events accrue, it will be important for the MESA investigators to revisit this question with long-term results and to also examine just hard CV end points."
The National Heart, Lung, and Blood Institute supported this study. One of the study authors serves as a consultant to Sankyo Pharma, sanofi-aventis, GlaxoSmithKline, Eli Lilly, Schering-Plough, Pfizer, AstraZeneca, and Merck and owns stock in Medpace. Another study author has received honoraria for speaking on behalf of General Electric. Six study authors have obtained funding.
Source
Folsom AR, Kronmal RA, Detrano RC, et al. Coronary artery calcification compared with carotid intima-media thickness in the prediction of cardiovascular disease incidence: The Multi-Ethnic Study of Atherosclerosis. Arch Intern Med. 2008;168:1333-1339.
The complete contents of Heartwire, a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.
Clinical Context
The availability of CAC screening has added another means to evaluate patients for cardiovascular risk, but the applicability of this new technology has been an area of controversy. In 2007, the American College of Cardiology Foundation, along with the American Heart Association, published guidelines regarding the use of CAC. These recommendations, which were published in the February 20, 2007, issue of Circulation, suggested that CAC screening was most helpful among patients with an intermediate risk for coronary heart disease (between 10% and 20% chance of a coronary heart disease event in the next 10 years). Among these patients, a higher CAC score could prompt more aggressive treatment of CVD risk factors. However, the authors recommended against the routine use of CAC screening among adults at low or high risk for coronary heart disease events.
Carotid IMT has also been used to estimate the risk for incident CVD. The current study compares CAC score and carotid IMT in estimating the risk for CVD among adults between the ages of 45 and 84 years.
Study Highlights
The MESA enrolled adults who were between the ages of 45 and 84 years from 6 centers in the United States. Adults with a history of CVD were excluded from study participation. All participants underwent an assessment of traditional CVD risk factors at baseline.
CAC was estimated from computed tomography and was reported as the Agatston score, which is a sum of plaque density and area in all coronary arteries.
Carotid IMT was measured at the common and internal carotid arteries and summarized as the average maximal thickness at these 2 sites.
The main outcome of the study was CVD, which included definite and probable myocardial infarction, definite angina, probable angina accompanied by coronary revascularization procedures, resuscitated cardiac arrest, stroke, and CVD death. Outcomes were confirmed with the medical record or death certificate data. Outcomes were adjusted to account for traditional CVD risk factors.
6698 adults were enrolled in the study.
38% of subjects were white, whereas 28% and 22% were African American and Hispanic, respectively, and 12% of subjects were Chinese American.
Half of participants had detectable CAC. The mean maximal common and internal carotid IMTs were 0.87 and 1.07 mm, respectively.
Participants were followed up for a median of 3.9 years. There were 222 incident CVD events reported during this period.
Both carotid IMT and the CAC score were significant independent predictors of an increased risk for CVD. However, the CAC score was a superior risk predictor. After adjustment for the imaging study not being evaluated, each increase of 1 SD in the log-transformed CAC score increased the risk for CVD by a hazard ratio (HR) of 2.1, whereas a similar increase in the maximal carotid IMT was associated with a HR of 1.3.
On examination of individual components of CVD, CAC was associated with a stronger increase in the risk for coronary heart disease outcomes (HR per increase in 1 SD of CAC score vs carotid IMT: 2.5 vs 1.2, respectively).
Carotid IMT, but not the CAC score, was associated with a significant increase in the risk for stroke (HR per increase in 1 SD of CAC score vs carotid IMT: 1.1 vs 1.3, respectively).
The study's main conclusions were similar in a subgroup analysis including only individuals at intermediate risk for incident CVD.
An analysis of receive operating curves also suggested that the CAC score was a better predictor of CVD outcomes vs carotid IMT.
Pearls for Practice
A previous recommendation suggested that CAC may be used to evaluate patients at intermediate risk for coronary heart disease but not patients at low risk or high risk.
The current study suggests that the CAC score is superior to carotid IMT to measure the risk for incident CVD.
Reviewed by Ramaz Mitaishvili, MD
