, based on data from a large retrospective study presented by Allison W. Peng at the annual meeting of the American College of Cardiology.
“Our data argues for consideration of CAC 1000 (or more) as a distinct group with CVD mortality greater than that of contemporary secondary prevention trials ... We showed that those with CAC 1000 (or more) have both a higher area and density of calcification, a more dispersed pattern of calcification in their coronary artery tree (the majority with 4-vessel disease), with a markedly more diffuse distribution of extra-coronary calcification compared to the other CAC groups,” Ms. Peng and her colleagues wrote in the study, which was published online in the Journal of the American College of Cardiology.
Future guidelines should address these patients as a distinct risk group that might gain the most benefit from targeted, aggressive preventive therapy, the researchers said.
Current guidelines identify individuals with CAC scores over 400 as the highest risk group. With a mean follow-up time of 12.3 years, the results from 66,636 asymptomatic individuals in the CAC consortium study, which included over 2,800 patients with CAC (Agatston) scores of 1,000 or more, indicate patients with CAC scores of 1000 or more have nearly a 2-fold higher risk of CVD mortality compared to those with CAC scores of 400-999. While the mortality risk levels off slightly in those with scores exceeding 1000, all-cause and cause-specific mortality risk still increases with no apparent upper CAC threshold.
Patients with a CAC score of at least 1000 were 66.3 years old, on average; 86.3% were male, 52.4% had 4-vessel CAC, and they had a larger total CAC area.
Compared to patients with CAC scores of 400-999, those with a CAC score of 1000 or more had a greater risk of cardiovascular disease (HR, 1.71; 95% CI, 1.41-2.08), coronary heart disease (HR, 1.84; 95% CI, 1.43-2.36), cancer (HR, 1.36; 95% CI, 1.07-1.73), and all-cause mortality (HR, 1.51; 95% CI, 1.33-1.70).
Those with CAC scores of 400-999 had a 2.1, 3.6, 2.7, and 9.8 mortality rate per 1000 person-years for CHD, CVD, cancer, and all-cause mortality, respectively. But those with CAC scores of 1000 of more had a 5.1, 8.0, 4.6, and 18.8 mortality rate per 1000 person-years for CHD, CVD, cancer, and all-cause mortality, respectively.
The leading cause of death was CVD; 36.5% in the CAC 400-999 group and 42.6% in the CAC 1000 or more group. CHD mortality, as a subset of CVD mortality, constituted 21.1% of deaths in the CAC 400-999 group and 27.1% of deaths in the CAC 1000 or more group.
“Future randomized controlled trials of aggressive preventative therapies, for example PCSK9-inhibitors and anti-inflammatory drugs, in patients with CAC ≥ 1000, may prove helpful to evaluate the benefits of such treatment in this unique group,” the authors wrote. They also urged updating current guidelines to reflect best practices for these patients.
The study was funded by The National Institutes of Health. The authors have no relevant financial disclosures.
SOURCE: Peng A et al. Journal of the American College of Cardiology.