Zero CAC Score Confers 15-Year "Warranty" Against CAD

Pam Harrison

July 20, 2015

NEW YORK, NY — A coronary artery calcium (CAC) score of zero confers at least a 15-year "warranty" during which mortality risk from coronary artery disease (CAD) remains under 1% in both men and women, a long-term prospective follow-up study indicates[1].

"Given the 15-year warranty of a CAC equal to zero for individuals at low to intermediate clinical risk irrespective of gender and age—a period only mildly attenuated for older patients 60 years and over—the use of CAC may be instrumental for avoiding unnecessary testing even among individuals generally considered at higher peril for unheralded adverse clinical events," Dr James Min (Weill Cornell Medical College, New York, NY) and colleagues write in their report, published online July 15, 2015 in JACC: Cardiovascular Imaging.

The authors caution, however, that their study findings apply only to the coronary vasculature, not other vascular beds, and do not support stopping or diminishing therapy, as that was beyond the scope of their investigation.

The study cohort consisted of 9715 asymptomatic individuals without CAD at baseline. All were evaluated for CAD and underwent CAC testing with electron beam computed tomography (EBCT). An annual mortality rate below 1% was used to define low-risk individuals. For the purposes of the study, a warranty period was defined as the time an individual remained within the low-risk category.

Of 9715 patients who underwent CAC screening, 4864 had a CAC of zero.

After a mean follow-up of 14.6 years, there were 936 (9.6%) deaths in the study population. Of these, 229 (4.7%) and 707 (14.6%) occurred among individuals with a CAC of or over zero, respectively.

Independent of the Framingham Risk Score (FRS) or National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) III score, a CAC of zero was associated with a favorable prognosis. For example, the risk of all-cause mortality was at least threefold higher among patients with a CAC over zero but at low cardiovascular (CV) risk, as determined by the FRS and NCEP-ATP III score, compared with individuals who had zero coronary calcification but a higher CV risk score.

"The observed duration of the warranty period of a CAC equal to zero was slightly shorter for those 60 years and over and ceased after 14 years of follow-up," investigators observe. "But the low risk associated with a CAC equal to zero persisted to more than 15 years for individuals younger than 60 years and to 14 years for individuals 60 years of age and older, with no apparent disparity among genders."

The warranty period conferred by a CAC of zero was also similar for individuals at low or intermediate clinical risk by the FRS and NCEP-ATP III score. In contrast, patients considered at high CV risk experienced a significantly shorter warranty period of 5 to 6 years than those at low to intermediate risk.

HR Analysis of 15-Year, All-Cause Mortality in Asymptomatic Patients According to CAC Score

 CAC score
Multivariable HR adjusted for FRS (95% CI; P) Multivariable HR adjusted for NCEP-ATP III (95% CI; P)
0 1.00 (ref) 1.00 (ref)
1–99 2.08 (1.74–2.48; <0.001) 2.03 (1.70–2.42; <0.001)
100–399 3.42 (2.83–4.14; <0.001) 3.32 (2.74–4,02; <0.001)
400–999 4.93 (3.98–6.12; <0.001) 4.81 (3.87–5.97; <0.001)
≥1000 6.79 (5.29–8.72; <0.001) 6.99 (5.46–8.95; <0.001)

CAC=coronary artery calcium
FRS=Framingham risk score
NCEP-ATP=National Cholesterol Education Program Adult Treatment Panel

Vascular Age and CAC

Investigators also observed that a CAC of zero was associated with a lower "vascular" age than a patient's chronologic age would suggest. For example, the vascular age of an 80-year-old man was equivalent to the chronologic age of a 50-year-old if he had a CAC of zero.

In contrast, a CAC greater than zero was the strongest predictor of death in the overall population, carrying a nearly threefold increased risk of mortality and conferring more risk than individual CV risk factors and FRS and NCEP-ATP III scores.

"Taken together, these findings indicate the robustness of a CAC equal to zero to identify individuals disposed to a particularly propitious outcome and may be useful as an adjunctive measure to everyday clinical risk assessment," study authors conclude.

This study was supported in part by a grant from the National Institutes of Health and by a gift from the Dalio Institute of Cardiovascular Imaging and Michael Wolk Foundation. Min has served on the medical advisory boards of GE Healthcare, Arineta, AstraZeneca, and Bristol-Myers Squibb; the speaker's bureau of GE Healthcare; has received research support from GE Healthcare, Vital Images, and Phillips Healthcare; and serves as a consultant to Astra Zeneca and HeartFlow. Disclosures for the coauthors are listed in the article. 

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