Global registry study shows that FH is diagnosed late and poorly managed
Global perspective of familial hypercholesterolemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)
Introduction and methods
In contemporary studies, it has been estimated that familial hypercholesterolemia (FH) is twice as common as previously assumed, affecting >25 million people in the world . However, estimations are that <5% of FH patients have been diagnosed [2,3].
Lack of an integrated approach has hampered efforts for a global registry on FH. The European Atherosclerosis Society (EAS) Familial Hypercholesterolemia Studies Collaboration (FHSC)  therefore created a global registry of patients with FH using a network of investigators (currently from 66 countries) by harmonizing and pooling regional and national data. The aim was to provide insights on detection and management of FH globally. The registry of the FHSC consists of adults and children with a clinical or genetic diagnosis of homozygous or heterozygous FH. At March 16, 2021, the registry included 61600 participants from 56 countries.
In this study, the detection and management of the adult population with probably or definite heterozygous FH (n=42167) was described in a cross-sectional assessment at the time they were entered in the registries. Those with untreated LDL-c ≥12.9 mmol/L were excluded because of likelihood of homozygous FH. Because the Netherlands contributed a large percentage of cases, separate analyses for the Netherlands and the European region excluding the Netherlands were made.
Most individuals (75.4%) were diagnosed with the DLCN criteria, the remaining with Simon-Broome criteria, MEDPED, with genetic criteria alone, or with other diagnostic systems. Most came from the Europe (82.4%) including 46.3% from the Netherlands. In the African region, 99.4% were from South Africa.
- Median age of participants at entry was 46.2 years (IQR 34.3-58.0) and 53.6% were women. Age of FH diagnosis was a median of 44. 4 years (32.5-56.5 years).
- Prevalence of premature CAD (in men <55 years and in women <60 years) was 11.3%. Prevalence of CAD increased with increasing concentrations of untreated LDL-c (P <0.0001).
- The Dutch cohort had lower prevalences of CAD and stroke than overall and in Europe excluding the Netherlands.
- Women were ~2.5 years older than men at time of diagnosis, with 38.4% of women diagnosed before 40 years vs. 42.3% of men. Prevalence of CAD was ~2-fold lower in women than in men (P<0.0001). There was no difference by sex in prevalence of stroke or PAD.
- At time of entry, 59.5% patients were taking LLT; 81.1% took statins with or without other LLT. 21.2% Of patients were on combination therapy with 2 or 3 drugs.
- In those ≥50 years, LDL-c among those not on LLT were higher in women compared with men (P<0.0001). No differences in LDL-c by sex were found in those <50 years.
- Among patients on statins, ezetimibe or PCSK9i, 2.7% had LDL-c <1.8 mmol/L at entry, with 2.0% in women and 3.4% in men.
- Use of combination therapy was associated with a higher proportion and greater odds of having LDL-c <1.8 mmol/L (especially with combination of 3 drugs and with use of PCSK9i).
- Non-index cases were younger at diagnosis, with lower prevalence of hypertension and diabetes, lower BMI, more frequent smokers than index cases. Untreated LDL-c was lower (P<0.0001), and prevalence of CAD or PAD was lower (P<0.0001) in non-index cases, with no difference in stroke. The Netherlands accounted for most of the non-index case cohort.
Findings from registry study of the FHSC in adults showed that detection of FH occurs late in life and management is poor with a high proportion of patients having LDL-c levels not below guideline-recommended targets.
The authors write: “More systematic detection of FH and greater use of combination therapy will be required to improve FH care globally.”