Calcium level may yield more accurate risk score in FH patients
CHICAGO – Adjusting the Framingham risk score to reflect the atherosclerotic burden for patients with familial hypercholesterolemia may more accurately identify patients at high risk and better guide treatment, according to results presented at the American Heart Association Scientific Sessions.
“If they are treated with statin and ezetimibe, most patients with FH have a very low risk and wouldn’t need to be treated with PCSK9 inhibitors, so we could target the more expensive, lower value therapy to the real high-risk patients that can be identified with just a clinical risk score plus calcium,” said Marcio S. Bittencourt, MD, MPH, PhD, from the University of Sao Paolo in Brazil.
Bittencourt and colleagues studied 206 patients older than 18 years with molecularly confirmed FH. All patients were asymptomatic for atherosclerotic CVD and were being treated based on AHA/ACC guidelines, with 98% receiving statins, 80% receiving high-dose statins and 65% receiving ezetimibe. The average age of patients was 45 years and 36.4% of patients were male. Baseline LDL was 269 mg/dL and on-therapy LDL was 150 mg/dL. Patients underwent coronary artery calcium (CAC) measurement; CAC was present in 105 (51%).
Framingham scores were calculated from baseline LDL levels using both the patient’s biological age and an imputed vascular age based on the Mesa formula for determining vascular age, which incorporates the level of CAC.
The annualized rate of atherosclerotic CVD events – fatal or nonfatal myocardial infarctions, fatal and nonfatal strokes, unstable angina requiring revascularization and elective myocardial revascularization due to angina pectoris or positive myocardial stress testing – was calculated for both biological and vascular ages. Among patients with a <10% risk Framingham risk score based on biological age, there were 8.45 events per year. Among patients with a 10% to 20% Framingham risk score, there were 23.28 events per year; in patients with a Framingham risk score >20%, the annualized rate was 28.13. No events occurred in patients with a Framingham risk score <20% based on vascular age, but the annualized rate among patients with a risk score >20% was 50.37.
Patients with a higher Framingham risk score would be most likely to benefit from treatment with a PCSK9 inhibitor, the researchers explained.
“This identified that two-thirds of the FH population really has no risk and only one-third has very high risk – 50% over 10 years – which is a huge risk,” Bittencourt said. “This represents a significant improvement in risk stratification. What we are suggesting is that an adjusted score based on vascular age may be more appropriate in this population than risk scores we have used previously for patients with FH.”
The analysis of CAC in patients with FH also introduces other interesting questions, according to the researchers. Despite having a significant atherosclerotic burden for an extended period, all the patients in this study were asymptomatic.
“These patients have been exposed to high LDL for 40 to 50 years. The question is: Why didn’t they develop atherosclerosis?” said Khurrum Masir, MD, MPH, MSc, associate professor of medicine at Yale University. “Is there a gain or loss of function? We need to understand this is not an entirely homogeneous group. It’s pretty heterogeneous; 40% have no calcium. The good news is that if you follow them up to 7 years, or a mean of 4.5 years, you will see zero events. That doesn’t mean they have zero risk, but you can really reassure patients that they have very low risk. This $100 test can help guide treatment for a $5,000 per year PCSK9 treatment to patients who are more likely to benefit.” – by Chris Rosenberg
Miname M, et al. Abstract Sa1075. Presented at American Heart Association Scientific Sessions 2018; Nov. 10, 2018; Chicago.
Disclosure: Santos reports consulting fees/honoraria from Amgen, Akcea, Astra-Zeneca, Biolab, Esperion, Kowa, Merck, Novo-Nordisk, Pfizer and Sanofi/Regeneron. Bittencourt reports research grant from Sanofi and speakers fees from Boston Scientific. Nasir reports no relevant financial disclosures.