Key result
Correcting LDL-C for Lp(a) reclassifies ~20% of suspected FH patients to a lower DLCN category.
Why the study?
Standard LDL-C measurements include cholesterol carried by Lp(a), which may influence the clinical classification of familial hypercholesterolemia, motivating a systematic estimate of diagnostic reclassification after correcting LDL-C for Lp(a)-cholesterol.
Does correction of LDL-C for estimated Lp(a)-cholesterol reclassify clinical diagnostic categories in adults with suspected familial hypercholesterolemia?
Meta-Analysis (n=2,970)
Yes
Does correction of LDL-C for estimated Lp(a)-cholesterol reclassify clinical diagnostic categories in adults with suspected familial hypercholesterolemia?
Adjusting LDL-C for estimated Lp(a)-cholesterol reclassifies approximately one in five adults with suspected familial hypercholesterolemia to a lower diagnostic category, highlighting the impact of Lp(a) on clinical FH diagnosis.
Answers are grounded in this paper and cite their sources.
Lp(a) adjustment of LDL-C may avoid overdiagnosis of familial hypercholesterolemia; extends evidence supporting refined DLCN criteria.
Background/Objectives: Low-density lipoprotein cholesterol (LDL-C) measurements include cholesterol carried by lipoprotein(a) [Lp(a)], which may influence the clinical classification of familial hypercholesterolemia (FH). We aimed to systematically review the available evidence and estimate the pooled proportion of individuals reclassified to a lower FH diagnostic category after correction of LDL-C for estimated Lp(a)-cholesterol. Methods: Embase, PubMed, and Scopus were searched from inception through 9 October 2026. We included observational studies with cross-sectional analyses of adults aged ≥18 years evaluated for suspected FH using the Dutch Lipid Clinic Network (DLCN) criteria before and after LDL-C correction for Lp(a)-cholesterol. Lp(a)-cholesterol was estimated as 30% of Lp(a) mass. The primary endpoint was reclassification to a lower DLCN diagnostic category among participants with possible, probable, or definite FH at baseline. Random-effects models were used to estimate pooled proportions. Risk of bias was assessed using the JBI critical appraisal tool for cross-sectional studies. Results: Four studies comprising 2970 individuals were included. The primary analysis included 2793 participants with possible, probable, or definite FH at baseline. After LDL-C correction for estimated Lp(a)-cholesterol, 19.8% (95% CI, 15.9–24.5) were reclassified to a lower DLCN diagnostic category. Conclusions: Correction of LDL-C for estimated Lp(a)-cholesterol resulted in downward DLCN reclassification in approximately one in five adults with at least possible FH from selected referral populations. The clinical utility of this adjustment, including its consequences for genetic testing and missed FH diagnoses, needs to be investigated.
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Procyk et al. (2026) conducted a meta-analysis in Suspected familial hypercholesterolemia (n=2,970). LDL-C correction for estimated Lp(a)-cholesterol (30% of Lp(a) mass) vs. Uncorrected baseline LDL-C DLCN classification was evaluated on Reclassification to a lower Dutch Lipid Clinic Network (DLCN) diagnostic category among participants with possible, probable, or definite FH at baseline (Pooled proportion 19.8%, 95% CI 15.9-24.5). LDL-C correction for estimated Lp(a)-cholesterol reclassified 19.8% (95% CI, 15.9–24.5) of adults with baseline possible, probable, or definite FH to a lower DLCN diagnostic category.
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