Key result
Primary care screening links suspected HeFH to ~63 mmol/L-years higher cumulative LDL-C burden.
Why the study?
In low-middle Southeast European settings lacking national registries, detection of heterozygous familial hypercholesterolaemia remains limited and relying on single LDL-C measurements may underestimate cumulative atherogenic exposure.
Does systematic ESC/EAS-aligned primary care screening identify previously unrecognized heterozygous familial hypercholesterolaemia and quantify cumulative LDL-C burden in unselected adults in a Southeast European setting?
Cohort (n=1,000)
No
Does systematic ESC/EAS-aligned primary care screening identify previously unrecognized heterozygous familial hypercholesterolaemia and quantify cumulative LDL-C burden in unselected adults in a Southeast European setting?
Systematic ESC/EAS-aligned primary care screening in a Southeast European cohort identified a 1.6% prevalence of unrecognized heterozygous familial hypercholesterolaemia with an average diagnostic delay of 13.8 years and a 2.6-fold greater cumulative LDL-C exposure compared to non-FH individuals with similar single LDL-C thresholds.
Low yield cautions against broad screening; leaves open optimized detection strategies in research.
Background Heterozygous familial hypercholesterolaemia (HeFH) causes lifelong low-density lipoprotein cholesterol (LDL-C) elevation and markedly increased premature atherosclerotic cardiovascular disease (ASCVD) risk. In low-middle Southeast European settings lacking national registries, detection remains limited and reliance on single LDL-C measurements may underestimate cumulative atherogenic exposure. Purpose To determine the diagnostic yield of systematic ESC/EAS-aligned primary care screening for previously unrecognized HeFH and quantify cumulative LDL-C burden prior to diagnosis. Methods In a prospective single-centre, consecutive cohort (2024–2025), 1,000 unselected adults (mean age 52.8±13 years) were screened. Individuals with untreated or highest documented pre-treatment LDL-C ≥4.9 mmol/L underwent structured phenotypic assessment after exclusion of secondary causes. HeFH suspicion was defined using Dutch Lipid Clinic Network criteria (possible 3–5; probable 6–8). Serial LDL-C values were used to calculate cumulative LDL-C burden (mmol/L-years) by trapezoidal integration. Time-weighted average (TWA) LDL-C was derived as burden divided by exposure duration. Results Fifty-one individuals (5.1%) had LDL-C ≥4.9 mmol/L. Sixteen (1.6%, 95% CI 0.8–2.4%) fulfilled criteria for suspected HeFH, including seven probable cases (1 in 143 screened). None had prior structured FH evaluation. Diagnostic delay averaged 13.8±5.3 years, corresponding to a cumulative pre-diagnostic LDL-C burden of 102±37 mmol/L-years and a TWA LDL-C of 6.6±0.9 mmol/L. Pre-treatment LDL-C strongly correlated with diagnostic delay (r=0.80, p<0.001). Despite identical LDL-C thresholds, suspected HeFH individuals (n=16) had markedly greater cumulative LDL-C exposure than non-FH participants (n=35): 102±37 vs 39.5±21 mmol/L-years, (mean difference 62.5 mmol/L-years, 95% CI 42.6–82.4; p<0.0001) with a 2.6-fold higher burden. TWA LDL-C was also higher: 6.6±0.9 vs 4.4±0.5 mmol/L (mean difference 2.2 mmol/L, 95% CI 1.72–2.68; p<0.0001). Conclusions ESC/EAS-aligned screening revealed a higher-than-expected prevalence of previously unrecognized HeFH and prolonged diagnostic delay, resulting in >100 mmol/L-years of cumulative LDL-C exposure. Although this burden was derived from documented measurements and may potentially underestimate true lifetime exposure, structured phenotypic assessment demonstrated marked heterogeneity with suspected HeFH patients showing a 2.6-fold greater cumulative burden. These findings support cumulative LDL-C as a biomarker that more accurately reflects preventable ASCVD risk than single measurements and highlight the importance of integrating cumulative biomarker–based assessment into primary care cardiovascular risk pathways, especially in regions without national FH registries.
No takes yet. Share an insight, caveat, or question.
Leskaroska et al. (2026) conducted a cohort in Heterozygous familial hypercholesterolaemia (HeFH) (n=1,000). Suspected HeFH (Dutch Lipid Clinic Network score 3–8) vs. Non-FH individuals with LDL-C ≥4.9 mmol/L was evaluated on Cumulative pre-diagnostic LDL-C burden (mmol/L-years) (MD 62.5 mmol/L-years, 95% CI 42.6-82.4, p=<0.0001). Systematic primary care screening identified suspected HeFH in 1.6% of adults, who had higher cumulative LDL-C burden than non-FH peers (102 vs 39.5 mmol/L-years; MD 62.5, 95% CI 42.6-82.4; p<0.0001).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: