【論文摘要】Familial Hypercholesterolaemia among Patients with Coronary Angiogram-proven Premature Coronary Artery Disease

Background/Synopsis: Familial hypercholesterolaemia (FH) is a hereditary disorder, primarily caused by mutation of low-density lipoprotein receptor gene, resulting in severely elevated serum low-density lipoprotein cholesterol (LDL-C), leading to premature coronary artery disease (PCAD). In Malaysia, the prevalence of FH among PCAD and their coronary risk factors (CRFs) is still unclear. Objectives/Purpose: To determine the prevalence of clinically diagnosed FH among PCAD patients and to evaluate their CRFs. Methods/Results: Male(＜55 years) and female(＜60 years) Malaysians were screened for PCAD from Institut Jantung Negara and UiTM Specialist Clinics(Cardiology and Lipid Clinics). Those with previous history of an abnormal coronary angiogram with ≥50% stenosis or underwent percutaneous coronary intervention to at least one major epicardial coronary artery were recruited. FH was clinically diagnosed using modified Dutch Lipid Clinic Criteria where they were categorised into Definite, Probable, or Possible FH. Assessment for diabetes mellitus, hypertension, dyslipidaemia, obesity and smoking were done through standard validated questionnaires, clinical history, physical examination and laboratory analyses. Obesity was defined as body mass index(BMI≥30) and central obesity was assessed by measuring waist circumference (males ≥90cm; females ≥80cm). Written informed consents were obtained from all subjects before recruitment.Out of 264 angiogram-proven PCAD patients, 81.4%(215/264) were males(mean+SD age = 57.2 ± 9.3 years) and 75.8%(200/264) were Malays, followed by Indian(12.5%; 33/264), Chinese(10.9%; 29/264) and other races(0.8%; 2/264). A total of 91 (34.5%; 91/264) PCAD patients were clinically diagnosed as FH [males = 87.9%(80/91), mean+SD age = 55.4 ± 9.6 years]. Nearly 40%(36/91) of FH patients were Potential FH(Definite and Probable FH). FH patients' mean+SD of LDL-C, TC and HDL were 5.5 ± 1.5, 5.2 ± 1.8 and 1.2 ± 0.8 (mmol/L) respectively. The median(IQR) level of TG was 1.6(0.9) mmol/L. Among FH, 21.9%(20/91) were current smokers, 62.6%(57/91) have hypertension, 42.9%(39/91) were diabetic, 40.6%(37/91) have family history of PCAD, 26.4%(24/91) were obese and 71.4%(65/91) were centrally obese. FH categories were significantly associated with LDL-C(p＜0.001), TC(p＜0.001), hypertension(p＜0.009), and family history PCAD(p＜0.001). However, there were no association between FH categories and current smokers, diabetes mellitus, obesity and central obesity. Conclusion: Clinically diagnosed FH is common and detected in over one-third of the angiogram-proven PCAD patients. Thus, molecular and genetic characterisation is important to capture a more accurate FH prevalence. Results suggested that central obesity was the highest CRF in PCAD patients with FH in Malaysian cohort. Future research may be warranted to provide more information on the association and relationship between FH and CRFs among PCAD patients.