CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Matthew J. Budoff, MD* and
Khurram Nasir, MD, MPH
* Los Angeles Biomedical Research Institute at Harbor, University of California, Los Angeles, 1124 West Carson Street, RB2, Torrance, California 90502 (Email: Budoff{at}ucla.edu).
We completely agree with Dr. Brundage's supposition that a more important marker for treatment targets may be lifetime risk. Data suggest that 67% of men and 50% of women over 40 years of age will develop chronic heart disease (1). The concept of lifetime risk was highlighted in the National Cholesterol Education Program Adult Treatment Panel III guidelines (2) and is especially important for individuals who are young to middle-aged.
However, most data with risk factors, C-reactive protein, and coronary artery calcium (CAC) have shorter-term follow-up and enable clinicians to match intensity of therapy to intensity of risk for near-term events. Lifetime lipid treatment or other antiatherosclerotic therapies may start shifting cost benefits and possibly even risk benefits away from treatment strategies.
Dr. Brundage correctly points out that while absolute scores are better short-term predictors, we cannot completely forgo percentile scores. From our standpoint, presence of "any" CAC, irrespective of percentile, especially in younger individuals is an indicator of significant intermediate-term and lifelong risk. The issues with using "only" percentiles for risk assessment pose problems at 2 levels. First, at each age group, women presenting with the same level of CAC scores as men are less likely to be considered as high risk and, thus, to be treated. Second, another risk of using the percentile scores is underestimation of risk, and, thus, there is potential for undertreatment of those persons with higher scores. Persons with scores as high as 1,500 may be deemed "normal" by age and sex cutpoints, but clearly have at least a 20-fold increased risk of future cardiovascular events (3). As participants with baseline calcium scores are followed up to 12 years, risk continues to diverge based upon baseline score, supporting the concept that CAC is a good predictor of lifetime risk (4).
One limitation of the MESA (Multi-Ethnic Study of Atherosclerosis) study is that there were no persons under age 45 years, so really assessing younger patients with advanced atherosclerosis is outside the scope of our study. Younger patients especially need to rely more heavily on percentile scores, as they rarely achieve scores >100, yet may be at increased risk. Taylor et al. (5) prospectively followed 2,000 persons (mean age 43 years) for 3 years, and the presence of any plaque was associated with an 11.8-fold increased risk of a cardiovascular event (5). Using a percentile to give patients a relative place compared with their age, sex, and ethnic/racial peers allows physicians to treat patients who are "ahead of the curve" with increased vascular age. By emphasizing both absolute and percentile scores, we can identify those at higher risk of lifelong cardiovascular disease by acknowledging presence of any CAC as a marker of subclinical disease.
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Footnotes
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Please note: This research was supported by R01 HL071739 and contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org.
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References
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1. American Heart Association Heart Disease and Stroke StatisticsDallas, TX: American Heart Association; 2008.[Abstract/Free Full Text]2. National Cholesterol Education Program Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report Circulation 2002;106:3143-3421.[Free Full Text] 3. Budoff MJ, Nasir K, McClelland RL, et al. Coronary calcium predicts events better with absolute calcium scores than age-sex-race/ethnicity percentiles: MESA (Multi-Ethnic Study of Atherosclerosis) J Am Coll Cardiol 2009;53:345-352.[Abstract/Free Full Text] 4. Budoff MJ, Shaw LJ, Liu ST, et al. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients J Am Coll Cardiol 2007;49:1860-1870.[Abstract/Free Full Text] 5. Taylor AJ, Bindeman J, Feuerstein I, Cao F, Brazaitis M, O'Malley PG. Coronary calcium independently predicts incident premature coronary heart disease over measured cardiovascular risk factors J Am Coll Cardiol 2005;46:807-814.[Abstract/Free Full Text]
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