There were no adverse events related to atherosclerotic cardiovascular disease (ASCVD) during a median 3.7 years of follow-up for 101 patients with familial hypercholesterolemia but a coronary artery calcium (CAC) score of zero, according to a study published Nov. 14 in JACC: Cardiovascular Imaging.
Meanwhile, each one-log increase in CAC score was associated with more than triple the odds of suffering an ASCVD event for the other 105 individuals in the Brazilian study—further driving home that this CT-based imaging technique is a useful tool for short-term risk stratification. ASCVD events were defined as MI, stroke, unstable angina requiring revascularization and elective myocardial revascularization, reported lead author Marcio H. Miname, MD, PhD, and colleagues.
The study included asymptomatic patients with confirmed familial hypercholesterolemia (FH), most of whom were on standard lipid-lowering therapies. They were 45 years old on average and 63.6 percent women.
For the 49 percent of patients without CAC, there were no adverse events during follow-up. For patients with CAC between 1 and 100, the annualized event rate was 26.4 per 1,000 patients, while a CAC score above 100 was linked to 44.1 events per 1,000 people each year.
“Apart from highlighting that similar to the general population, subclinical coronary atherosclerosis is heterogeneously distributed among subjects with FH, to the best of our knowledge this is the first study to assess the value of CAC presence and burden to predict ASCVD events in primary prevention asymptomatic FH patients receiving standard guideline recommended lipid-lowering therapy,” Miname and coauthors wrote.
The study was published soon after the new U.S. cholesterol guidelines proposed a larger role for CAC testing to guide statin treatment decisions among patients at intermediate risk of cardiovascular disease. However, this paper suggests patients with FH could also benefit from CAC testing to determine whether additional lipid-lowering therapies beyond statins are necessary and cost-effective.
“Even with a CAC score of zero, most subjects with FH should still receive a recommendation to continue their statin (and possibly ezetimibe) to lower their LDL-C levels,” Michael D. Shapiro, DO, and Ron Blankstein, MD, wrote in a related editorial. “However, when it comes to the use of more expensive therapies (e.g., PCSK9 inhibitors), the data from Miname et al. suggest that patients without evidence of CAC may safely defer such therapies, at least in the short term.”
Miname and colleagues said assuming PCSK9 inhibitors were associated with a relative risk reduction of 20 percent for ASCVD events, 38 patients with CAC scores between 1 and 100 would need to be treated to prevent one event at five years. The number drops to 23 patients to prevent one event for CAC scores above 100.
“At the patient level, CAC assessment may help further ‘personalize’ risk to weigh expected benefits and costs of PCSK9 inhibitor treatment, whereas at the population level, CAC assessment as an ‘interventional prevention’ tool may help prioritize decisions about PCSK9 inhibitors where their use may produce the highest yield, especially in cost-constrained health care systems,” Miname et al. wrote.
Blankstein and Shapiro said CAC scoring represents a way to combine both known and unknown patient factors—along with risk-mitigating characteristics—into a “single, reproducible, and actionable measure of risk.”
The study was limited by its relatively small sample size, along with eight of the 15 ASCVD events being the “soft” endpoint of elective revascularization. However, the authors noted most of those events were driven by symptoms and positive ischemia upon stress testing.