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BACKGROUND Diagnostic tools for familial hypercholesterolemia (FH) rely on estimation of LDL cholesterol concentration. However, routine measurement or calculation of LDL cholesterol concentration using the Friedewald equation contains a cholesterol contribution from lipoprotein(a) [Lp(a)]. We investigated whether Lp(a) influences the phenotypic diagnosis of FH by commonly used clinical criteria. METHODS A cohort of 907 adult index patients attending a clinic were studied. The Dutch Lipid Clinic Network (DLCN) and Simon Broome (SB) diagnostic criteria were estimated before and after adjusting LDL cholesterol concentration for the cholesterol content (30%) of Lp(a). Diagnostic reclassification rates and area under the ROC (AUROC) curves in predicting an FH mutation were also compared. RESULTS Seventy-four patients defined by DLCN criteria (8.2%) and 207 patients defined by SB criteria (22.8%) were reclassified to “unlikely” FH after adjusting LDL cholesterol for Lp(a) cholesterol. The proportion of FH patients defined by DLCN (probable/definite) and SB (possible/definite) criteria decreased significantly in patients with increased Lp(a) (&amp;gt;0.5 g/L; n = 330) after Lp(a) cholesterol adjustment (P &amp;lt; 0.01). The overall reclassification rate was significantly higher in patients with Lp(a) concentration &amp;gt;1.0 g/L (P &amp;lt; 0.001). The AUROC curve for LDL cholesterol concentration ≥191 mg/dL (≥5.0 mmol/L), DLCN criteria, and SB criteria in predicting an FH mutation increased significantly after adjustment (P &amp;lt; 0.001). There was no significant difference in AUROC curve before and after Lp(a) cholesterol adjustment at an LDL cholesterol concentration ≥251 mg/dL (≥6.5 mmol/L). CONCLUSIONS Adjusting LDL cholesterol concentration for Lp(a) cholesterol improves the diagnostic accuracy of DLCN and SB criteria, especially with Lp(a) &amp;gt;1.0 g/L and LDL cholesterol &amp;lt;251 mg/dL (&amp;lt;6.5 mmol/L). Lp(a) should be measured in all patients suspected of having FH.

Effect of Lipoprotein(a) on the Diagnosis of Familial Hypercholesterolemia: Does It Make a Difference in the Clinic?