Clinical cardiology
Coronary calcium better than carotid IMT for predicting CVD risk, MESA analysis shows
June 23, 2008 | Shelley Wood

Minneapolis, MN - 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 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 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 rations 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

To download table as a slide, click on slide logo above

The authors propose that the "modestly better" ability of IMT to predict stroke and the "clearly better" prediction of CHD 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 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."

Source
  1. 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.



Your comments
Coronary calcium better than carotid IMT for predicting CVD risk, MESA analysis shows
# 1 of 8
June 23, 2008 06:14 (EDT)
Michael Cobble, M.D.
Pretty impressive
The title perhaps is a little dramatic and the full article paints the total picture better.

As rec by ACC expert consensus 2000 and 2007, AHA 2006, SHAPE 2006. Looks like more evidence to support noninvasive imaging in moderate risk patients (or perhaps all pts over 44).

This is a great read in Archives of Int Medicine June 23 2008.. MESA - multi ethnic study of athero 6698 people (3200 men, 3700 women) age 45-84 'free' of cvdz (baltimore, maryland, chicago, north carolina, los angeles, st paul) 38% caucasian, 28% aa, 22% hisp, 12% chinese amer - median follow up 3.9 years.

Both tests improved AUC for risk detection beyond the usual risk predictors.

quintiles:
Max cimt 0.4-0.74 mm 22 events HR 1
Max cimt 0.74-0.84 mm 37 events almost dbl HR 2.1
Max cimt 0.84-0.97 mm 61 events almost trpl HR 2.1
Max cimt 0.97-2.45 mm 102 events 5x HR 4.9

quintiles:
CACS zero 33 events HR 1
CACS 1-88 53 events almost dbl HR 3.3
CACS 88-6315 141 events 5x HR 9.5

CACS above 90 should raise concern in this population/this age, 'free' of cvdz. Max CIMT > 0.74 mm should do the same.

17% of people with 'high' CACS were referred for risk mgmt. only 1% with 'high' CIMT were referred for risk mgmt.

Hopefully the publication of these results will impact medical care.
# 2 of 8
June 24, 2008 12:56 (EDT)
Sergio Stagnaro
Paramount Role of CAD Inherited Real Risk
In this website at URL I've described earlier once again the importance of recognizing since birth Inherited Real Risk of CAD, upon which ALL known CAD environmental risk factors (about 300!) can act.
# 3 of 8
June 24, 2008 12:57 (EDT)
Sergio Stagnaro
Paramount Role of CAD Inherited Real Risk
In this website at URL I've described earlier once again the importance of recognizing since birth Inherited Real Risk of CAD, upon which ALL known CAD environmental risk factors (about 300!) can act.
# 4 of 8
June 25, 2008 04:03 (EDT)
Wiliam Blanchet
Lessons from MESA, one of many!
Stroke screening and MI screening are not the same thing. I conclude from this DATA that to appropriately screen patients, we should do both an EBT-CAC as well as a carotid screening ultrasound. If you are to do one only, do EBT as heart attacks are much more common that strokes.

Michael I think your analysis understates the difference in predictive value of IMT vs EBT for CAD. For every standard deviation increase of IMT you see a 20% increase in coronary events. For every standard deviation increase of EBT you see a 140% increase incidence of events. Your analysis suggests EBT to be twice as powerful; my reading of the statistics is that EBT is 7 times more predictive than IMT.

Is there a statistician in the house?
# 5 of 8
June 25, 2008 06:08 (EDT)
Michael Cobble, M.D.
both or independent
I don't think one can make any conclusion other than both tests predict HR's better than conventional risk analysis. Both tests increase AUC.

What was most powerful to me was that the highest EBT quintile was 89-over6000
the highest CIMT quintile was > 0.97 mm.

I think any EBT over 100 is not good. (over 10 is quite concerning) every 100-200 above this even worse per rise.
Any CIMT over 0.76 mm (above 0.6 mm concern depending on age) is not good and rise > 0.1 mm above this also not good.

Both tests are better than not and the dilemma is not so much which to choose, but rather will insurance allow them, will clinicians order them or understand them or even do anything about them if abnl. Will people demand them, etc... They are complementeray rather than competitive, but I certainly think one can treat disease quite well with either and follow them longitudinally. It's just great to see more RCT and EBM which support these noninvasive imaging studies... (really shows that AHA, ACC, SHAPE know what they are talking about) motivating change as we have seen in other threads is really difficult and makes people VERY worried and even angry/defensive. I have made a habit of questioning my mistakes, learning from my mistakes and trying to improve upon them. Continuously doing this. When I went through training (evidence based medicine - EBM) wasn't even in our vocabulary. Medicine is exciting to see interventions show statistical benefit whether it be wt loss, nutrition change, exercise, etc.... great stuff
# 6 of 8
June 30, 2008 11:01 (EDT)
Bradley Bale
carotid plaque is a strong predictor
We have been using CIMT clinically for seven years now. We have never predicted short term risk on the basis of IMT unless it reaches a value defined as plaque (for us 1.3mm or >). IMT values less than that are not synonimous with atherosclerosis. Why would anyone believe a thickened intima without plaque would predict CV events? I would love to see the MESA data re-analysed using carotid plaque as a predictor of CV events. A positive CACS score proves there is plaque in the coronaries and that should be associated with increased risk for a CV event.
# 7 of 8
July 1, 2008 12:15 (EDT)
Michael Cobble, M.D.
Brad, great to hear from you.
I hope practice is going well. Circulation Jan 2007 showed CIMT independently predicted events based on either tertile of IMT thickening or tertile evidence of plaque. I think MESA was interesting how few events there were and the tertiles that were broken out as outlined in post and article. mike

Disclaimer - again vascular imaging is recognized by aha, acc, shape concensus and may be a consideration for moderate risk individuals or used in clinical practice for risk mgmt. This post is not intended to encourage it's use only to outline evidence which may be supportive or contradictive.
# 8 of 8
July 1, 2008 01:59 (EDT)
D Hackam
Carotid plaque imaging
We use carotid plaque area quantitation rather than IMT.

Doing so, affords the following advantages:

1) Measurement of plaque area throughout the entire carotid tree, on both sides, rather than at merely one or two points only. IMT is highly dependent on where you measure. You might completely miss the plaque in an eccentric stenosis for instance, given you a falsely normal or near normal reading.

2) The range of values goes from 0 to up to 10.0 cm2 or more. This is a much broader range than IMT.

3) Plaque spreads circumferentially along the artery faster and earlier than it grows in thickness.

4) IMT is a one-dimensional measurement, plaque area is two dimensional. This is critical in sample size calculation for RCTs of plaque regression (need a much larger sample for IMT than for plaque area - by an order of magnitude).

5) IMT reflects hypertensive vascular hypertrophy much more closely than it reflects atheroma - therefore, it is a better marker of hypertensive end organ damage than the cumulative burden of age, diabetes, smoking, dyslipidemia, etc. Plaque area sums all these risk factors. Thus IMT strongly predicts stroke but not CHD, whereas plaque area predicts both.

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