Familial hypercholesterolaemia (FH) patients have elevated levels of low-density lipoprotein cholesterol, rendering them at high risk of premature coronary artery disease (PCAD). However, the FH prevalence among angiogram-proven PCAD (AP-PCAD) patients and their status of coronary risk factors (CRFs) have not been reported in the Asian population. This study aimed to (1) determine the prevalence of clinically diagnosed FH among AP-PCAD patients, (2) compare CRFs between AP-PCAD patients with control groups, and (3) identify the independent predictors of PCAD. AP-PCAD patients and FH patients without PCAD were recruited from Cardiology and Specialist Lipid Clinics. Subjects were divided into AP-CAD with FH (G1), AP-PCAD without FH (G2), FH without PCAD (G3) and normal controls (G4). Medical records were collected from the clinic database and standardised questionnaires. FH was clinically diagnosed using Dutch Lipid Clinic Network Criteria. A total of 572 subjects were recruited (males:86.4%; mean±SD age: 55.6±8.5years). The prevalence of Potential and All FH among AP-PCAD patients were 16.0% (51/319) and 45.5% (145/319), respectively. G1 had higher central obesity, family history of PCAD and family history of hypercholesterolaemia compared to other groups. Among all subjects, diabetes [OR(95% CI): 4.7(2.9,7.7)], hypertension [OR(95% CI): 14.1(7.8,25.6)], FH [OR(95% CI): 2.9(1.5,5.5)] and Potential (Definite and Probable) FH [OR(95% CI): 4.5(2.1,9.6)] were independent predictors for PCAD. Among FH patients, family history of PCAD [OR(95% CI): 3.0(1.4,6.3)] and Definite FH [OR(95% CI): 7.1(1.9,27.4)] were independent predictors for PCAD. In conclusion, potential FH is common among AP-PCAD patients and contributes greatly to the AP-PCAD. FH-PCAD subjects have greater proportions of various risk factors compared to other groups. Presence of FH, diabetes, hypertension, obesity and family history of PCAD are independent predictors of PCAD. FH with CAD are in very-high-risk category, hence, early management of modifiable CRFs in these patients are warranted.In Malaysia, coronary artery disease (CAD) is the leading cause of morbidity and mortality. CAD prevalence among young Malaysians is increasing rapidly, accounting for 10-15% of acute coronary syndrome, 16% of percutaneous coronary intervention, with younger age of onset. Hence, identifying the cause and reducing premature CAD is a key national priority. Familial Hypercholesterolemia (FH), the most common and serious, but potentially treatable form of inherited hyperlipidaemia, is an important cause of premature CAD. FH results from genetic mutation causing severe hypercholesterolaemia, leading to premature CAD, which is preventable with early detection and treatment with low cost lipid-lowering therapies. FH mutations are linked to several candidate genes such as LDLR, APOB100 and PCSK9. FH has been reported to increase CAD risk by 20-fold, but for any given LDL-c concentration, presence of a FH gene mutation increases CAD risk if untreated due to lifelong exposure to hypercholesterolaemia. The community prevalence of FH varies between 1:200-1:500. Globally, majority of FH individuals remain undiagnosed, resulting in lost opportunities for preventing premature CAD. In Malaysia, the prevalence of FH is not well established. With an estimated Malaysian population of 31 million, it is projected that 62,000 individuals are affected, majority of whom are predicted to be undiagnosed and inadequately treated. DNA testing is expensive and not commonly available, particularly in primary care. The diagnostic thresholds for untreated LDL-C for use in clinical practice have not been defined in relation to their ability in prediction of pathogenic FH mutation. Therefore, this study aims to screen for FH using the DLCC and determine the prevalence of FH in the community and amongst premature CAD patients.

This was a comparative cross-sectional study where subjects were recruited from the National Heart Institute (IJN) and Specialist Clinics (Cardiology and Lipid Clinics) and community health screening programmes from the year 2018 to 2019. The inclusion criteria were male and female Malaysians aged ≥18 years, with AP-PCAD and voluntarily consented to participate in this study. PCAD patients (Age of onset <55 years in males and <60 years in females) were enrolled into this study. Patients were diagnosed as having AP-PCAD based on significant angiogram results, or previous history of CABG and/or PCI procedures. FH was clinically diagnosed using the Dutch Lipid Clinic Network criteria (DLCC). The exclusion criteria were non-Malaysians, pregnancy, and those with secondary hypercholesterolaemia (such as hypothyroidism, nephrotic syndrome, cholelithiasis and chronic renal disease). Personal and family medical history, smoking status, body mass index (BMI), waist circumference (WC) and lipid-lowering therapy (types and dosage) were collected from the clinics’ database and by on-site measurement. Data for the normal control subjects were obtained through standard questionnaire, assisted by trained research assistants and physician on-site. A total of 572 individuals were recruited for the study. Subjects were divided into four groups: G1 (Group 1 - PCAD with FH), G2 (Group 2 - PCAD without FH), G3 (Group 3 - Non-PCAD with FH) and G4 (Group 4 - normal controls, without PCAD nor FH).