Editorial
Impact of Familial Hypercholesterolemia Diagnosis in Real-World Data
2023 Volume 30 Issue 10 Pages 1303-1304
Details
2023 Volume 30 Issue 10 Pages 1303-1304
See article vol. 30: 1317-1326
Familial hypercholesterolemia (FH) is a genetic disease that shows high prevalence of atherosclerotic cardiovascular diseases (ASCVD) due to high levels of low-density cholesterol (LDL-C) from the birth1, 2). Because high accumulation of LDL-C from the childhood is considered to cause premature ASCVD, early initiation and intensive lipid lowering therapy is recommended. Statins have been the mainstream of the treatment of FH. Awareness-raising activities have been underway around the world, which enabled many FH patients to be diagnosed and treated.
There are several strategies to survey the real-world situation of FH, including a registry study, retrospective-observational study, and so on. A registry study uses a cohort to register information on a patient population under certain inclusion criteria. Usually, the attending physician registers the patients according to the criteria, so that a diagnosis that meets the criteria is made by the attending physician. On the other hand, in case of a retrospective-observational study, the data of patients who meet certain criteria are extracted mechanically in a certain database; therefore, correct diagnosis is not always been made. In the analysis of diagnosis rate or therapeutic situation, there may be some discrepancies between these studies.
Recently, European Atherosclerosis Society (EAS) Familial Hypercholesterolemia Studies Collaboration (FHSC) global registry has provided the global surveillance of FH through harmonization and pooling of multinational data3). In this registry, 61,612 individuals were included which is the largest cohort of FH that ever performed. The registry consists of patients that clinical diagnoses must conform with accepted clinical criteria (or modified criteria thereof), such as the Dutch Lipid Clinic Network (DLCN) criteria4), Make Early Diagnosis to Prevent Early Deaths (MEDPED)5), Simon–Broome criteria6), Canadian definition of familial hypercholesterolemia7), or Japanese Atherosclerosis Society (JAS)8) familial hypercholesterolemia criteria. The patients included in these kinds of registries were diagnosed and treated as FH according to the guidelines, which means the attending doctor made the diagnosis of FH and gave treatment as FH. In the EAS-FHSC registry, age averaged 46.2 y.o., 59.5% were on lipid lowering drugs and 17.4% had coronary artery diseases. Among the patients with lipid lowering drugs, 81.1%, 24.6%, 2.1%, and 3.0% were on statins, ezetimibe, fibrates, and PCSK9i, respectively. Among patients with statins, ezetimibe, PCSK9i, or in combination, 1.2% had LDL-C levels lower than 1.4 mmol/L and 2.7% lower than 1.8%.
In the present paper, the candidate subjects were screened among Malaysian patients with hypercholesterolemia registered in the National Heart Institute, Universiti Teknologi MARA Cardiology Clinic, and UiTM specialist Lipid Clinic database9). After excluding secondary hypercholesterolemia and the patients with LDL-C ＜4.0 mmol/L, total of 206 FH patients were divided into 3 groups: definite, probable, and possible FH based on the DLCN criteria. Target LDL-C of ＜1.4 and ＜1.8 mmol/L was achieved 2.9% and 7.8% in all the patients, 1.5% and 11.9% in the definite FH group, 1.8% and 7.3% in the probable FH group, and 4.8% and 13.1% in the possible FH group, respectively. The authors concluded that only a small fraction achieved the therapeutic target LDL-C levels. As the patients were not diagnosed as FH by attending doctors, there could be some possibility that the doctors and/or patients did not know that they are FH and did not know their target LDL-C levels.
Teramoto T et al reported a retrospective-observational study of FH using the Medical Data Vision database, an electronic hospital-based administrative claims database10). The paper is similar to the present paper, which used hospital-based database. However, the study population was divided into two groups, patients with existing diagnosis of FH (FH-D)(N=193) and patients with suspected FH (FH-S)(N=3,339). High intensity statin was used in 19.2% of FH-D and mean LDL-C level was 119.2±45.2 mg/dL while it was used in 2.3% of FH-S and LDL-C level of 147.6±46.5 mg/dL. In FH-D, 9.3% patients reached LDL-C ＜1.8 mmol/L while only 2.5% reached in FH-S group. These results suggest that patients diagnosed as FH show more strictly controlled in LDL-C levels than those without diagnosis, and that making diagnosis gives significant impact on treatment intensity.
Several surveys as the present paper have been conducted and reported to determine the actual treatment status of FH in the present clinical settings. In this and many other papers, the DLCN is used to classify the patients into definite, probable, and possible FH. However, it is important to analyze separately whether FH is diagnosed by an attending doctor, because the target LDL-C levels and treatment methods differ depending on whether the patient is FH or not. In addition, because FH has an earlier onset and development of atherosclerosis; screening, follow-up, and earlier therapeutic intervention for atherosclerotic cardiovascular disease is important. The effort in making the diagnosis of FH should be more evaluated, which contains measurement of LDL-C levels, interviewing family history, and measurement of the Achilles tendon to improve their prognosis.
The author has stock of Liid Pharma, received honoraria from Amgen and MEDPACE.
