Abstract

Background and aims: To examine the clinical profile and associated clinical characteristics of heterozygous Familial Hypercholesterolemia clinical phenotype (FH) in adults attended in primary care in a large health area of the Community of Madrid, Spain. Methods: Cross-sectional, multicenter study including 156,082 adults (≥18 years) from 69 health centers with at least one lipid profile between 2018 and 2021, using electronic health records (EHR). Severe hypercholesterolemia (SH) was defined as total cholesterol ≥300 mg/dL or LDL-cholesterol≥220 mg/dL and FH phenotype was defined as LDL-C ≥240 mg/dL (≥90th percentile within our study sample) or ≥160 mg/dL under lipid-lowering therapy (LLT), with triglycerides <200 mg/dL and normal TSH levels. Multivariate logistic regression was used to assess clinical associations. Results: SH was present in 6187 individuals (3.96 %), and FH phenotype in 1600 (1.03 %; mean age 60.7 years; 72.7 % women). Compared with non-FH individuals, those with FH were more often female, on LLT (97.6 % vs. 79.0 %), and had lower prevalence of diabetes, hypertension, and obesity (all p < 0.005). Women with FH were more frequently treated but less often with high/very-high intensity LLT than men (25.3 % vs. 36.6 %; p < 0.001). All treated FH patients had LDL-C >130 mg/dL (vs. 60.4 % in non-FH), with higher levels in men (178.7 vs. 170.9 mg/dL; p = 0.0015). Female sex and LLT were independently associated with FH phenotype, while age, diabetes, hypertension, and obesity were inversely associated (all p < 0.05). Conclusions: FH phenotype was identified in 1.03 %, of primary care patients. Women were more often treated but less likely to receive high-intensity or combined therapy compared to men. LDL-C levels were higher in men and intensive therapy reduced sex differences. LDL-C targets were largely unmet. EHR may aid early identification and improve preventive strategies. © 2025 Elsevier B.V.