To discuss the heterogeneity of atherosclerotic cardiovascular disease (ASCVD) risk in heterozygous familial hypercholesterolemia and evidence and limitations of clinical risk scores and subclinical coronary atherosclerosis (SCA) imaging to evaluate risk.
Risk evaluation in contemporary familial hypercholesterolemia cohorts needs to consider the cause of the familial hypercholesterolemia phenotype, for example the presence of autosomal molecular defects that impart a greater ASCVD risk than in polygenic hypercholesterolemia, prospective follow-up and the impact of statin treatment. As atherosclerosis is multifactorial, clinical scores like the Montreal familial hypercholesterolemia score and SAFEHEART risk equation have been proposed to stratify ASCVD in statin-treated, molecularly defined familial hypercholesterolemia individuals. However, these scores need further validation. SCA distribution in familial hypercholesterolemia individuals undergoing conventional lipid-lowering treatment is heterogeneous, with 45–50% of individuals not presenting any coronary artery calcification (CAC). One study suggests that the absence of CAC associates with no ASCVD events in asymptomatic familial hypercholesterolemia individuals undergoing statin therapy despite elevated residual LDL-cholesterol levels. In contrast, the presence of CAC was independently associated with ASCVD events.
ASCVD risk is heterogeneous in statin-treated familial hypercholesterolemia individuals. Further studies are necessary to determine how risk stratification, especially with SCA detection, impacts on prescription of proprotein convertase subtilisin kexin type 9 inhibitors within a cost-constrained environment.
aHeart Institute (InCor) University of Sao Paulo Medical School Hospital
bHospital Israelita Albert Einstein
cSchool of Medicine, Faculdade Israelita de Cie[Combining Circumflex Accent]ncia da Sau[Combining Acute Accent]de Albert Einstein
dCenter for Clinical and Epidemiological Research, University Hospital and Sa[Combining Tilde]o Paulo State Cancer Institute, University of Sa[Combining Tilde]o Paulo, Sa[Combining Tilde]o Paulo, Brazil
eCenter for Outcomes Research and Evaluation and Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut, USA
Correspondence to Raul D. Santos, MD, MSc, PhD, Unidade Clinica de Lipides InCor-HCFMUSP, Av. Dr Eneas C. Aguiar, 44 CEP, 05403–900 São Paulo, Brazil. E-mail: firstname.lastname@example.org