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Published on: September 15, 2018
Predicting genetically defined familial hypercholesterolemia with the FAMCAT algorithm in an Australian tertiary
Ralph K Akyea1, Dick C Chan2, Jing Pang2
1Centre for Academic Primary Care, School of Medicine, University of Nottingham, Nottingham NG7 2RD, UK (Akyea, Iyen, and Qureshi).
Insights
The Dutch Lipid Clinic Network (DLCN) criteria are more effective than the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT) for identifying genetically confirmed familial hypercholesterolemia in Australian lipid clinics. Both tools can aid in prioritizing patients for further testing.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Clinical Diagnostics
Background:
- Familial hypercholesterolemia (FH) is a genetic disorder causing premature coronary artery disease.
- The Dutch Lipid Clinic Network (DLCN) and Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT) are diagnostic aids for FH.
- FAMCAT's accuracy in tertiary care for genetically confirmed FH is not well-established.
Purpose of the Study:
- To evaluate the performance of the FAMCAT tool in identifying patients with genetically confirmed FH.
- To compare FAMCAT's accuracy against the DLCN criteria in an Australian tertiary lipid clinic setting.
Main Methods:
- A cross-sectional study involving 885 adult patients referred for FH genetic testing.
- Calculation of FAMCAT and DLCN scores for each patient.
- Discriminatory ability assessed using receiver operating characteristic (ROC) curve analysis (AUROC).
Main Results:
- 30% of patients (267/885) had genetically confirmed heterozygous FH.
- Both FAMCAT and DLCN scores significantly predicted FH-causing variants (P < .001).
- DLCN demonstrated superior performance with a higher AUROC (0.816) compared to FAMCAT (0.748), and better specificity and positive predictive value.
Conclusions:
- The DLCN criteria are more effective than FAMCAT for identifying FH genetic variants in this Australian tertiary lipid clinic.
- FAMCAT still shows good discriminatory accuracy and can assist in patient prioritization for genetic testing.
- Enhancing family history documentation could improve the diagnostic accuracy of both FH assessment tools.
Background:
Familial hypercholesterolemia (FH) is a monogenic disorder associated with premature coronary artery disease. The Dutch Lipid Clinic Network (DLCN) and Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT) are tools used to identify individuals with possible FH. Although FAMCAT performs well in primary care, its accuracy for genetically confirmed FH in tertiary care settings remains unclear. This study assessed the performance of FAMCAT in an Australian tertiary lipid clinic.
Objective:
This study assessed the performance of FAMCAT in identifying patients with genetically confirmed FH in an Australian tertiary lipid clinic.
Methods:
This cross-sectional study included unrelated adult patients referred for FH genetic testing. FAMCAT and DLCN scores were calculated, and their discriminatory ability was evaluated using area under the receiver operating characteristic curve (AUROC) analysis.
Results:
Of 885 patients, 267 (30%) had genetically confirmed heterozygous FH. In univariate regression analysis, FAMCAT and DLCN scores were significant predictors of an FH-causing variant with an odds ratio of 1.13 (95% CI 1.09-1.17; P < 0.001) and 1.49 (95% CI 1.41-1.58; P < 0.001), respectively. These associations remained significant after adjusting for smoking, hypertension, and obesity. The AUROC for FAMCAT (0.748; 95% CI, 0.712-0.784) was significantly lower than that of DLCN (0.816; 95% CI, 0.784-0.847; P < 0.01). Although FAMCAT and DLCN definite FH category had comparable sensitivity (67.0% vs 65.2%), FAMCAT had a lower specificity (73.3% vs 83.5%), positive predictive value (52.0% vs 63.0%), and Youden index (0.402 vs 0.487).
Conclusions:
The DLCN criteria performed better in identifying FH genetic variants in this Australian lipid clinic. The FAMCAT algorithm showed good discriminatory accuracy and could help prioritize patients referred for specialist review and/or genetic testing. Improved family history documentation may further enhance the diagnostic accuracy of both tools.
