Higher frequency of coronary atherosclerotic plaques in patients with genetically confirmed FH

An age-matched computed tomography angiographic study of coronary atherosclerotic plaques in patients with familial hypercholesterolaemia

Literature - Pang J, Abraham A, Vargas-García C et al., - Atherosclerosis. 2020. doi:10.1016/j.atherosclerosis.2020.03.001.

Introduction and methods

Familial hypercholesterolemia (FH) is characterized by elevated LDL-c levels and a high risk of premature coronary artery disease (CAD) [1]. There is, however, a wide variation of CAD prevalence in FH patients [2,3]. Coronary events in FH patients could potentially be predicted by coronary artery stenoses and coronary artery calcium (CAC) scoring on cardiac computed tomography angiography (CCTA) [4,5]. CCTA and CAC scoring may therefore play a role in risk assessment in FH patients [2, 6-8]. The present study investigated the frequency and distribution of coronary artery plaques in asymptomatic adult patients with a presumptive phenotypic FH diagnosis with and without genetically confirmed heterozygous FH.

Patients with asymptomatic phenotypic FH (Dutch Lipid Clinic Network [DLCN] category score of at least 3) were included in this aged-matched case-control study. Patients were managed according to expert guidelines [9], consented to genetic testing, and underwent CCTA and CAC scoring. From the total group of patients, 104 patients with genetically confirmed heterozygous FH (mutation-positive cases, M+) were randomly aged-matched 1:1 with 104 patients without a FH-causing mutation (mutation-negative controls, M-). Mean age was 49.9±10.4 years and 45.2% were male. The Society of Cardiovascular Computed Tomography guidelines were used to define calcific, non-calcific and mixed plaques [10]. CAC scores were semi-automatically calculated by the Agatston method [11]. The segment stenosis score (SSS) was calculated as the sum of scores attributed to each of the 19 coronary segments (0: no stenosis, 1: mild stenosis [<50%], 2: moderate stenosis [50-70%], 3: severe stenosis [>70%]) [12].

Main results

  • Pre-treatment LDL-c levels and phenotypic DLCN score were significantly higher in the M+ group compared to the M- group (LDL-c [mean±SD]: 7.8±2.1 vs 6.2±1.2 mmol/L, P<0.001 [adjusted for correlations within family clusters]; DLCN score: 11.2±4.5 vs 7.4±2.7, P<0.001).
  • A greater proportion of patients in the M+ group had mixed or calcified coronary plaques, compared to patients in the M- group (66.4% vs 50.0%, adjusted P-value=0.018 [adjusted for correlations within family clusters, age, gender, pre-treatment LDL-c levels, LP(a)>0.5 g/L and statin use]).
  • A higher proportion of patients with no plaques was observed in the M- group (23.1%) compared with the M+ group (10.6%; adjusted P-value=0.046).
  • Median CAC score and mean SSS were significantly higher in the M+ group, compared to the M- group (CAC score [median and IQR]: 33 [IQR 124] vs 0.25 [IQR 36], adjusted P-value=0.001; SSS [mean±SD]: 3.8±4.3 vs. 2.8±3.3, adjusted P-value=0.023).
  • There was a higher proportion of patients with calcification in the right coronary artery (RAD), Left main (LM) and left anterior descending (LAD) in the M+ group compared to the M- group (RAD: 39.4% vs 23.1%, adjusted P-value=0.015; LM: 27.9% vs 7.7%, adjusted P-value=0.001; LAD: 65.4% vs 40.4%, adjusted P-value=0.015). No significant differences between the two groups in the proportion of patients with calcification in other coronary artery segments were observed.
  • A higher proportion of patients in the M+ group had calcification in ≥2 vessels or ≥3 vessels, compared with the M- group (calcification in ≥2 vessels: 51.0% vs 36.5%, adjusted P-value=0.036; calcification in ≥3 vessels: 31.7% vs 16.4%, adjusted P-value=0.034).


Among asymptomatic adult patients with a presumptive phenotypic FH diagnosis, patients with a genetically confirmed diagnosis of FH had a higher frequency and severity of coronary atherosclerotic plaques, compared to patients without a FH-causing mutation.


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