Introduction: Heterozygous familial hypercholesterolemia (hFH) is the most common genetic disease and leading cause of premature cardiovascular disease (CVD). hFH is caused by mutations of FH genes such as LDL-receptor (LDLR), apolipoprotein B-100 (APOB), proprotein convertase subtilisin / kexin type 9 (PCSK9), or low-density lipoprotein receptor adapter protein 1 (LDLRAP1). On the other hand, aortic valve calcification (AVC) is associated with an elevated risk of cardiovascular events.
Objectives: To investigate the association between AVC and coronary plaque morphology related with gene mutation.
Methods: We enrolled 39 patients with clinical hFH, diagnosed according to FH guidelines of Japanese Atherosclerosis Society (median age, 57.2±2.0 years; men 64%) and 32 patients with DL (median age, 64.8±2.2 years; men 63%). We evaluated all patients underwent 320-slice coronary CT, AVC score, ABI and PWV for the assessment of atherosclerosis. The genotypes of 44 patients were analyzed using an Illumina Mi-seq sequencer.
Results: AVC was detected more frequently in patients with hFH than in patients with DL (76% and 56%, p<0.05). AVC score was higher in FH patients than in DL patients (280±61 and 124±68, p<0.05). AVC score was significantly associated with the coronary artery plaque score (p<0.01). In hFH patients, 27 patients (61.3%) had gene mutations. The LDLR mutation was observed in 7 patients (16.0%); APOB, 6 (13%); PCSK9, 8 (18.2%). The double gene mutation of LDLR and PCSK-9 was observed (4.5%). hFH patients with LDLR mutation or PCSK9 mutation had higher AVC score (P<0.05) and coronary plaque score (P<0.05). In addition, the gene mutation of ABCG5 (6.8%), ABCG8 (4.5%), and APOA5 (11.3%) were found in FH with related gene mutation. The FH patients with polygenetic gene mutation were developed atherosclerosis more than without polygenetic gene mutation.
Conclusions: The AVC is developed in hFH patients, and the AVC is related to coronary plaque morphology. hFH patients with LDLR mutation or PCSK9 mutation had higher AVC. The genetic diagnosis is important to assess coronary plaque morphology and to prevent the future CVD incidence in FH patients.