Diagnostic performance of various familial hypercholesterolaemia diagnostic criteria compared to Dutch lipid clinic criteria in an Asian population.

BACKGROUND: Familial hypercholesterolaemia (FH) is a genetic disorder with a high risk of developing premature coronary artery disease that should be diagnosed as early as possible. Several clinical diagnostic criteria for FH are available, with the Dutch Lipid Clinic Criteria (DLCC) being widely used. Information regarding diagnostic performances of the other criteria against the DLCC is scarce. We aimed to examine the diagnostic performance of the Simon-Broom (SB) Register criteria, the US Make Early Diagnosis to Prevent Early Deaths (US MEDPED) and the Japanese FH Management Criteria (JFHMC) compared to the DLCC. METHODS: Seven hundered fifty five individuals from specialist clinics and community health screenings with LDL-c level ≥ 4.0 mmol/L were selected and diagnosed as FH using the DLCC, the SB Register criteria, the US MEDPED and the JFHMC. The sensitivity, specificity, efficiency, positive and negative predictive values of individuals screened with the SB register criteria, US MEDPED and JFHMC were assessed against the DLCC. RESULTS: We found the SB register criteria identified more individuals with FH compared to the US MEDPED and the JFHMC (212 vs. 105 vs. 195; p < 0.001) when assessed against the DLCC. The SB Register criteria, the US MEDPED and the JFHMC had low sensitivity (51.1% vs. 25.3% vs. 47.0% respectively). The SB Register criteria showed better diagnostic performance than the other criteria with 98.8% specificity, 28.6% efficiency value, 98.1% and 62.3% for positive and negative predictive values respectively. CONCLUSION: The SB Register criteria appears to be more useful in identifying positive cases leading to genetic testing compared to the JFHMC and US MEDPED in this Asian population. However, further research looking into a suitable diagnosis criterion with high likelihood of positive genetic findings is required in the Asian population including in Malaysia.

Enhanced status of inflammation and endothelial activation in subjects with familial hypercholesterolaemia and their related unaffected family members: a case control study.

BACKGROUND: Familial hypercholesterolaemia (FH) leads to premature coronary artery diseases (CAD) which pathophysiologically can be measured by inflammation, endothelial activation and oxidative stress status. However, the status of these biomarkers among related unaffected relatives of FH cases and whether FH is an independent predictor of these biomarkers have not been well established. Thus, this study aims to (1) compare the biomarkers of inflammation, endothelial activation and oxidative stress between patients with FH, their related unaffected relatives (RUC) and normolipaemic subjects (NC) (2)determine whether FH is an independent predictor of these biomarkers. METHODS: One hundred thirty-one FH patients, 68 RUC and 214 matched NC were recruited. Fasting lipid profile, biomarkers of inflammation (hsCRP), endothelial activation (sICAM-1 and E-selectin) and oxidative stress [oxidized LDL (oxLDL), malondialdehyde (MDA) and F2-isoprostanes (ISP)] were analyzed and independent predictor was determined using binary logistic regression analysis. RESULTS: hsCRP was higher in FH and RUC compared to NC (mean ± SD = 1.53 ± 1.24 mg/L and mean ± SD = 2.54 ± 2.30 vs 1.10 ± 0.89 mg/L, p < 0.05). sICAM-1 and E-selectin were higher in FH compared to NC (mean ± SD = 947 ± 742 vs 655 ± 191 ng/mL, p < 0.001 and 175 ± 131 vs 21.6 ± 10.7 ng/mL, p < 0.001 respectively) while sICAM-1 concentration was higher in RUC compared to NC (mean ± SD = 945 ± 379 vs 655 ± 191 ng/mL, p < 0.01). Biomarkers of oxidation (ox-LDL, MDA and ISP) were elevated in FH compared to NC [mean ± SD = (48.2 ± 26.8 vs 27.3 ± 13.2 mU/L, p < 0.001), (2.57 ± 1.3 vs 1.20 ± 0.30 nmol/mL, p < 0.001) and (645 ± 396 vs 398 ± 20.5 pg/L, p < 0.001) respectively], but no significant differences were observed between RUC and NC (p > 0.05). FH was an independent predictor for sICAM-1 (p = 0.007), ox-LDL (p < 0.001) and MDA (p < 0.001) while RUC independently predicted for sICAM-1 (p < 0.001). CONCLUSION: The screening for FH is vital as all biomarkers associated with atherogenesis are higher in these subjects and FH also independently predict biomarkers of endothelial activation and oxidative stress. Furthermore, despite not fulfilling the diagnostic criteria for FH, related unaffected family members that may not phenotypically express the mutation may still be at risk of developing CAD as reflected from the enhanced inflammatory and endothelial activation status observed in this group. This highlights the need to not only conduct family tracing in indexed FH cases, but also assess the coronary risk among family members that do not fulfil the FH diagnostic criteria.