Evidence mapPaperPMID 40560421Full record

Observational studyDeutsches Arzteblatt international2025

Familial Hypercholesterolemia: Prevalence and Discrepancy between Genotype and Phenotype. Findings of the Population-based Hamburg City Health Study.

Cristian Riccio, Natalie Arnold, Georgios Koliopanos, Vivian Link, Linlin Guo, Raphael O Betschart, Tanja Zeller, Stefan Blankenberg, Andreas Ziegler, Raphael Twerenbold

Registry-linked trialAbstract readObservational Study
In one paragraph

Observational study in Deutsches Arzteblatt international, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03934957 (A Single Center, Prospective, Epidemiologic Cohort Study With Emphasis on Imaging to Improve the Identification of Individuals at Risk for Major Chronic Diseases and to Improve Early Diagnosis and Survival), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03934957 recruitingnot on this map

A Single Center, Prospective, Epidemiologic Cohort Study With Emphasis on Imaging to Improve the Identification of Individuals at Risk for Major Chronic Diseases and to Improve Early Diagnosis and Survival

TypeobservationalSponsorUniversitätsklinikum Hamburg-EppendorfRan2016 to 2028Enrolled45,000ConditionsCoronary Heart Disease, Stroke, Dementia, Cancer
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. In Reply.Deutsches Arzteblatt international · 2026
    Article
  2. Lacking Evidence.Deutsches Arzteblatt international · 2026
    Article
  3. Paradigm Shift.Deutsches Arzteblatt international · 2026
    Article
  4. Important Aspects.Deutsches Arzteblatt international · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Cristian RiccioCardio-CARE, Medizincampus Davos, Davos, Switzerland; University Heart and Vascular Center Hamburg, Department of Cardiology, University Medical Center Hamburg-Eppendorf, Hamburg; German Center for Cardiovascular Research (DZHK), Hamburg/Kiel/Lübeck site; Center for Population Health Innovation (POINT), University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf; Hamburg; Institute for Cardiogenetics, University of Lübeck, Lübeck; School of Mathematics, Statistics, and Computer Science, University of KwaZulu-Natal, Pietermaritzburg, South Africa.
Natalie Arnold
Georgios Koliopanos
Vivian Link
Linlin Guo
Raphael O Betschart
Tanja Zeller
Stefan Blankenberg
Andreas Ziegler
Raphael Twerenbold

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFamilial hypercholesterolemia (FH) is among the more common monogenic diseases, yet population-based data on genetically confirmed FH (genFH) and its association with LDL cholesterol (LDL-C) in Germany are lacking.

methodsIn the Hamburg City Health Study (registration: Clinical Trials.gov, NCT03934957), five FH-associated genes were exam - ined for pathogenic mutations with whole genome sequencing and compared with LDL-C levels that had been corrected for lipidlowering medication. Severe hypercholesterolemia was defined as an LDL-C level of 190 mg/dL or above.

resultsThere were 7373 adult participants (49.1% women; median age 62 years), of whom 23 had FH, corresponding to a prevalence of 0.31% (95% confidence interval [CI]: [0.21; 0.47]), or a prevalence ratio of 1:321 [1:213; 1:476]. All genFH cases were due to mutations in the LDLR gene. The median treatment-adjusted LDL-C level was higher in genFH cases (191 mg/dL) than in persons without genFH (128 mg/dL; p <0.001). Eleven of the participants with genFH had severe hypercholesterolemia. Among the 7253 participants without genFH, 465 had severe hypercholesterolemia. Only 2.3% (n = 11) of the severely hypercholesterolemic participants had genFH. Forty-three people would need to be genetically tested to identify one genFH case if an LDL-C threshold of ≥190 mg/dL is selected, 98 people at ≥160 mg/dL, and 175 people at ≥130 mg/dL.

conclusionThe prevalence of genFH in this German study was 0.31%, which corresponds to the global average. As only half of the persons from our adult cohort identified as having genFH had severe hypercholesterolemia, population-based genetic screening would seem to be of questionable benefit.

Indexed as

Hyperlipoproteinemia Type IIAdultAgedCholesterol, LDLFemaleGenotypeGermanyHumansMaleMiddle AgedMutationPhenotypePrevalenceProspective StudiesReceptors, LDLCholesterol, LDLReceptors, LDL

Identifiers

PMID40560421
PMCPMC12620900

What Socratic holds

Textmetadata
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.