Clinicians should consider age before dismissing the possibility of obstructive coronary artery disease (CAD) in patients with a zero coronary artery calcium score (CAC), cardiologists suggest, after finding the system could miss a “sizeable proportion” of young adults with CAD.
A Danish study of 23,759 patients with symptomatic cardiovascular disease showed a null CAC score’s diagnostic value changes with age and least reliably rules out obstructive CAD in patients aged 18–40.
Over half (58%) the patients under 40 with obstructive CAD scored 0 for CAC, while 34%, 18%, 9% and 5% of patients aged 40–49, 50–59, 60–69 and 70+ had the same outcome, respectively.
Study authors Dr Martin Mortensen and his team at Aarhus University Hospital noted that obstructive CAD was relatively uncommon, however, prevalent in just 3% of patients under 40 years to 8% of those over 70.
The CAC score’s ability to rule out obstructive CAD beyond clinical variables decreased with younger age, with mean diagnostic likelihood ratio being 0.68 in the youngest group and 0.18 in the eldest.
“The explanation for this apparent paradox is that early atherosclerotic lesions are usually non-calcified,” they wrote in JAMA Cardiology.
“Thus, a strategy that uses a CAC score of 0 to rule out obstructive CAD in all symptomatic patients will likely miss a sizeable proportion of younger patients … with obstructive CAD.”
Patients under 60 with CAC-less obstructive CAD had a higher risk of myocardial infarction (adjusted hazard ratio [HR]: 1.51) and all-cause death (HR: 1.80) versus non-obstructive CAD, the authors found.
The results should “give pause to efforts to broaden the use of a CAC score of 0 to de-escalate or defer therapy in all individuals”, Northwestern University and University of Texas-based cardiologists, Associate Professors Sadiya Khan and Ann Marie Navar wrote in an accompanying editorial.
Current Australian and American Heart Association/American College of Cardiology guidelines recommend that clinicians consider avoiding statins in patients with low CAC and no other clinical risk factors such as family history, smoking status and diabetes.
“Beyond this recommendation, however, some investigators have called for even more aggressive de-risking of patients with a CAC score of 0, suggesting that even those with familial hypercholesterolaemia and a CAC score of 0 may not need statins,” Associate Professors Khan and Novar noted.
Although statins have not been evaluated in clinical trials of young adults with non-calcified coronary plaques, other studies have supported “the use of statins early in life to prevent atherosclerosis” in children and young adults with familial hypercholesterolaemia, they countered.
While a CAC score of 0 should be interpreted with caution, CAC is “still a useful tool for identifying those at high risk for atherosclerotic heart disease”, they wrote.
The presence of CAC in young adults “should be a red flag for a high-risk patient” and “aggressive primary prevention, including statin therapy, blood pressure control and intensive lifestyle modification should be prioritised”.
However, similar measures should extend to those without CAC, Associate Professors Khan and Novar suggested.
“The goal of primary prevention should be to prevent the atherosclerotic lesions that lead to CAC, not to wait for CAC to develop before initiating risk-lowering therapy,” they wrote.
“Emphasising true primary prevention of atherosclerosis before evidence of subclinical atherosclerosis emerges is of paramount importance to improve population-level cardiovascular health and to mitigate the growing burden of cardiovascular disease morbidity and mortality,” they concluded.