Elsevier

Atherosclerosis

Volume 188, Issue 1, September 2006, Pages 112-119
Atherosclerosis

Coronary artery calcium as a measure of biologic age

https://doi.org/10.1016/j.atherosclerosis.2005.10.010Get rights and content

Abstract

Background

Age is assigned a heavy weight in the calculation of the total cardiovascular risk score but often the atherosclerotic disease burden varies from a patient's chronological age.

Methods

We used measures of coronary artery calcium to estimate the number of life years lost (calcium-adjusted age) in 10,377 asymptomatic individuals referred for electron beam tomography (EBT) screening and followed for 5 years for all-cause mortality. Linear regression was used to calculate predicted age and time to death was estimated via a Cox proportional hazard model.

Results

There was a direct relationship between coronary artery calcium and observed age (r = 0.32, p < 0.0001). In linear prediction models, a calcium score <10 resulted in a reduction in observed age by 10 years in subjects older than 70 years, while a calcium score >400 added as much as 30 years of age to younger patients. Calcium-adjusted age was a better predictor of mortality (model χ2 = 373, p < 0.0001) than observed age (model χ2 = 355, p < 0.0001).

Detectable calcium was noted in 16% of men and 12% of women with an unadjusted low risk Framingham score (p < 0.0001). For those with an intermediate Framingham risk score, calcium scores >10 were noted in 31 and 43% of men and women (p < 0.0001). Using calcium-adjustments to age, 55% of previously low risk Framingham scores to intermediate risk (p < 0.0001). Similarly, 45% of the unadjusted intermediate Framingham risk scores were re-classified as high risk based upon calcium-adjusted ages (p < 0.0001).

Conclusions

Measures of coronary artery calcium are related to survival and can be used to assess an individual's biological age. Undetected risk based upon current calculations of the Framingham risk may be improved based upon determination of a re-adjustment of a patient's age using the extent of coronary calcification.

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.

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