Original research article
Prognostic significance of zero coronary calcium scores on cardiac computed tomography

https://doi.org/10.1016/j.jcct.2007.10.001Get rights and content

Abstract

Background

Most unexpected cardiovascular events occur in persons at intermediate risk of coronary artery disease (10%–20% 10-year risk). Coronary artery calcium (CAC) has been shown to be highly specific for atherosclerosis, occurring only in the intima of the coronary arteries. Evidence shows that elevated coronary calcium scores (CCSs) are predictive of future cardiovascular events, both independently of and incrementally to conventional cardiovascular risk factors. Several studies reported event rates of zero for those persons without CAC by cardiac computed tomography (CT).

Objectives

We sought to evaluate the event rates in persons with negative calcium scores from the reported literature to establish whether these patients may be considered at low risk for hard cardiovascular events (myocardial infarction and death).

Methods

English-language studies from January 1, 1975, through February 1, 2007, were retrieved using MEDLINE and Current Contents databases, bibliographies, and expert consultation.

Results

Summary data show that in a total follow-up of 35,765 asymptomatic persons, 16,106 (45%) had scores of zero. Pooled sensitivity for CAC to detect a cardiovascular event was 98.1% [95% confidence interval (CI), 95.1%–99.9%], and negative predictive value was 99.9% (95% CI, 98.9%–100%). There were 48 hard events in this population, with an annual event rate of 0.027%.

Conclusion

These large observational cohorts show that the absence of CAC by cardiac CT is associated with a low adverse event risk and therefore could be used as a tool to counsel patients about their risk of such events.

Introduction

The principal cause of morbidity and mortality in all industrialized nations is coronary artery disease (CAD).1 In approximately half of the persons, the initial presentation of CAD is either myocardial infarction (MI) or death.2 Unfortunately, conventional risk factor assessment predicts only 60%–65% of cardiovascular risk, leaving many persons to have cardiovascular events in the absence of traditional risk factors for atherosclerosis.3 One study showed that only 25% of younger patients who had presented with a MI would have qualified for pharmacotherapy with a statin, based on their Framingham risk profile before the occurrence of MI.4 It is extremely disturbing to note that most cardiac events occur in the intermediate-risk population, and it is the same group in which aggressive risk-factor modification is most often applied haphazardly. Many physicians tend to overtreat patients in this intermediate-risk population, because of uncertainty about future cardiovascular risk. In the Anglo-Scandinavian Cardiac Outcomes Trial, in which hypertensive persons with 3 risk factors were randomly assigned to a statin or placebo, the number needed to treat was 93, indicating 93 persons had to be treated for 3.3 years to prevent one cardiac event.5 Treating all intermediate-risk persons will be highly cost-inefficient, and these patients tend to have poor long-term compliance with therapy.6, 7

The presence of calcium in coronary arteries is pathognomonic of atherosclerosis, as confirmed by prior histopathology and intravascular ultrasound studies. Coronary artery calcium (CAC) detected and quantified represents an anatomic measure of plaque burden. Available outcome data for CAC scoring in almost every study have shown CAC to be an independent and incremental predictor of future events and coronary heart disease (CHD) over conventional risk factors.8, 9 Coronary calcium score (CCS) was also shown to add incremental value to newer studied risk factors, including C-reactive protein.7 Because treatment in this intermediate-risk population is most uncertain, CAC can theoretically direct the treatment of a high score, suggesting intensive treatment, and a zero score, suggesting lifestyle changes with no or minimal drug therapy.10 We sought to evaluate whether the event rates in persons with negative calcium scores may be considered low risk for hard cardiovascular events, providing physicians with some comfort in not treating this portion of the population with aggressive lipid-lowering therapies.

Section snippets

Methods

We used established methods for systematic review. A broad search of the literature in all languages was performed, incorporating both electronic and manual components. The electronic search was performed using PubMed, which includes MEDLINE, OLDMEDLINE, OVID, and the Cochrane Library database. PubMed was searched from 1975 (before electron beam CT was developed) to February 2007. Search terms were as follows: spiral CT/spiral computed tomography matched with coronary artery, coronary artery

Results

Thirteen coronary calcium studies with cardiac outcomes reported as MI or cardiovascular death were included. These encompassed 35,765 asymptomatic subjects, with weighted mean follow-up of 4.7 years. Summary data showed that in a total follow-up of 35,765 persons, 16,106 (45%) had CCSs of zero. There were 48 hard events in this population, with an annual event rate of 0.027%, or an estimated 10-year event rate of 0.3% (Table 1). Pooled sensitivity for CAC to detect a cardiovascular event was

Discussion

Recent guidelines have suggested that the use of a CCS derived from noncontrast cardiac CT can refine the traditional risk factor stratification such as the Framingham risk score (FRS).13, 14 Specifically, low scores are associated with a low adverse event risk and high scores are associated with a worse event-free survival. Current data support the recommendation to measure atherosclerosis burden in clinically selected intermediate-risk patients with CAD (such as 10%–20% 10-year risk estimate

References (31)

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Conflict of interest: The authors report no conflict of interest.

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