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Published on: September 15, 2018
Prognostic impact of cascade screening for familial hypercholesterolemia on cardiovascular events
Hayato Tada1, Hirofumi Okada1, Akihiro Nomura1
1Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Insights
Cascade screening for familial hypercholesterolemia (FH) identifies younger patients with fewer risk factors. Early FH detection through cascade screening improves patient prognosis and reduces major adverse cardiac events.
Area of Science:
- Cardiology
- Genetics
- Public Health
Background:
- Familial hypercholesterolemia (FH) is an inherited condition causing high LDL cholesterol.
- FH significantly increases the risk of premature atherosclerotic cardiovascular disease (ASCVD).
- Genetic mutations in LDL receptor pathways are primary causes of FH.
Purpose of the Study:
- To evaluate the prognostic impact of cascade screening for FH.
- To assess if cascade screening improves outcomes for FH patients.
- To compare MACE rates between probands and relatives identified via cascade screening.
Main Methods:
- Retrospective analysis of 1050 clinically diagnosed FH patients and their relatives.
- Utilized Cox models adjusted for ASCVD risk factors to analyze MACE.
- Follow-up period for MACE was a median of 12.3 years.
Main Results:
- Patients identified via cascade screening were significantly younger (mean age 38.7 vs 57.0 years) and had fewer ASCVD risk factors.
- Cascade screening identified FH patients at an 18-year younger age compared to probands.
- Patients identified through cascade screening showed a reduced risk of MACE (HR=0.67, P=0.0044) even after risk factor adjustment.
Conclusions:
- Cascade screening for FH appears to lead to a better patient prognosis.
- Early identification of FH through cascade screening is associated with improved cardiovascular outcomes.
- This strategy aids in managing FH and mitigating ASCVD risk.
Background:
Familial hypercholesterolemia (FH) is an autosomal dominant disorder mainly caused by mutations in the low-density lipoprotein (LDL) receptor or associated genes, resulting in elevated serum cholesterol levels and an increased risk of premature atherosclerotic cardiovascular disease (ASCVD).
Objective:
We aimed to evaluate the prognostic impact of cascade screening for FH.
Methods:
We retrospectively investigated the health records of 1050 patients with clinically diagnosed FH, including probands and their relatives who were cascade-screened, who were referred to our institute. We used Cox models that were adjusted for established ASCVD risk factors to assess the association between cascade screening and major adverse cardiac events (MACE). The median period of follow-up evaluating MACE was 12.3 years (interquartile ranges [IQR] = 9.1-17.5 years), and MACE included death associated with ASCVD, or acute coronary syndrome.
Results:
During the observation period, 113 participants experienced MACE. The mean age of patients identified through cascade screening was 18-years younger than that of the probands (38.7 yr vs. 57.0 yr, P < 0.0001), with a lower proportion of ASCVD risk factors. Interestingly, patients identified through cascade screening under milder lipid-lowering therapies were at reduced risk for MACE (hazard ratio [HR] = 0.67; 95%CI = 0.44 to 0.90; P = 0.0044) when compared with the probands, even after adjusting for those known risk factors, including age, and prior ASCVD.
Conclusions:
The identification of patients with FH via cascade screening appeared to result in better prognosis.
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