Coronary artery calcium as a measure of biologic age☆
Introduction
With increasing age, the absolute cardiovascular mortality risk increases significantly due to the progressive accumulation of atherosclerosis [1]. Although advancing age is one of the strongest prognostic factors for cardiovascular disease, chronologic age can be confounded by the presence of other traditional and conditional risk factors as well as comorbid conditions. Calcium is a common component of atherosclerotic plaque and is not present in the normal vessel wall [2]. Furthermore, calcium is an accurate index of atherosclerotic disease burden and directly relates to the risk of adverse outcomes as has been noted in several prior reports [2], [3], [4]. The prevalence of coronary artery calcium increases with age ranging from 5% in a middle-aged cohort to more than 50% in an elderly cohort [5], [6]. Previous reports have examined the importance of age- and sex-specific calcium score percentiles to predict the occurrence of a cardiovascular event in subjects with a similar risk profile [3], [7]. The implication of those studies was that a high calcium score, as reflective of the chronic disease process that may be accelerated or diminished based upon a patient's lifestyle and concurrent risk factor profile, indicates an age that has progressed beyond one's chronological age. The purpose of the present study was to calculate the added and/or lost years of life for a varying extent of calcium in asymptomatic subjects with cardiac risk factors using mortality data accrued in a large cohort of asymptomatic individuals submitted to electron beam tomography (EBT) screening. Although one may propose to include calcification as an additional risk factor in the Framingham risk score, the alteration of age has appeal for ease of patient understanding, it allows for the current risk scoring system to remain in place, and it does not require re-weighting of other risk factors in a multivariable or global scoring system (e.g., Framingham risk score).
Section snippets
Inclusion criteria
We included a prospectively collected cohort of 10,377 asymptomatic individuals referred by their primary care physician for coronary artery calcium screening with EBT, as a marker for subclinical disease. Patients with symptomatic coronary heart disease or a prior history of coronary disease (including acute coronary syndromes, angiographically-defined coronary artery disease or coronary revascularization) were excluded. Overall prognosis in this series was previously published [6].
Data collection
Upon
Clinical characteristics by age group (Table 1)
Of the 10,377 asymptomatic individuals referred for evaluation of cardiac risk using EBT, 8, 30, 35, 19, 7, and 1% were <40, 40–49, 50–59, 60–69, 70–79, and ≥80 years of age, respectively. With advancing age, there was a greater frequency of women, hypertension, diabetes mellitus and coronary artery calcification (all p < 0.0001). Average calcium scores ranged from 10 to 686 for patients <40 to ≥80 years of age (p < 0.0001). A high risk calcium score (score > 400) [12] occurred in <1% in subjects <40
Discussion
Global risk scores are increasingly recommended for the initial evaluation of cardiovascular risk. However, prior reports have noted a substantial detection gap when risk scores, such as the Framingham risk estimates, are applied to individuals and to low risk population cohorts [13]. Although the prevalence of cardiovascular disease increases dramatically with age, the presence and clustering of additional factors has a synergistic effect on increasing the relative risk for major adverse
Conclusion
The current analysis confirms prior findings that the prevalence of coronary calcification increases with age [2]. We did evaluate a unique method whereby measures of the extent of coronary calcium may be used to adjust a patient's age. Our data reveal that for elderly patients with low risk calcium scores, survival is equivalent to patients 1–10 years younger. Conversely, for younger patients with moderate–high risk calcium scores, survival is equivalent to patients approximately 20 years
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Preliminary results of this analysis were presented at the 2002 Scientific Sessions of the American Heart Association, Chicago, Illinois, November 2002.