Detection rate and diagnostic accuracy of familial hypercholesterolaemia tools (FAMCAT,SB, DLCC) vs. genetic diagnosis in the Malaysian primary care setting

Familial hypercholesterolemia (FH) is an autosomal dominant disorder that increases low-density lipoprotein cholesterol (LDL-c) levels, raising the risk of premature coronary artery disease. This study aimed to assess the detection rate and diagnostic accuracy of the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT), Simon Broome (SB) criteria, and Dutch Lipid Clinic Criteria (DLCC) against genetic diagnosis in the Malaysian primary care settings. The study was conducted at 11 public primary care clinics in Klang Valley from September 2020 to December 2022, involving 3085 patients aged ≥18 years with LDL-c ≥4.0 mmol/L. Of these, 429 (13.9%) were eligible, and 310 (72.3%) met criteria for genetic testing. Of this, 86 patients were genetically confirmed to have FH. Detection rates for SB criteria, DLCC and FAMCAT were 25.2%, 21.6%, and 16.8%, respectively. FAMCAT demonstrated a high specificity (57.6%) among the tools. Its positive predictive value (PPV) was also the highest at 35.4%, indicating that it is effective in identifying patients with FH who are more likely to have the condition. The area under the curve (AUC) for FAMCAT was 0.59, showing decent overall performance. In comparison, SB criteria had the highest sensitivity (90.7%) but lower specificity (18.8%), while DLCC had moderate sensitivity (77.9%) and specificity (40.2%). Additionally, FAMCAT exhibited the highest overall diagnostic accuracy at 58.4%, outperforming both DLCC (50.6%) and SB criteria (38.7%), further validating its utility for FH screening in primary care. In conclusion, FAMCAT’s high specificity, PPV and the overall diagnostic accuracy makes it a valuable screening tool for FH in primary care. Those who are identified to have high probability of FH using FAMCAT should then be assessed with the clinical diagnostic criteria (SB and DLCC). Patients who are clinically diagnosed can then be referred for genetic testing if it is available.