A reassessment of the Japanese clinical diagnostic criteria of familial hypercholesterolemia in a hospital-based cohort using comprehensive genetic analysis.

Achilles tendon thickness Familial hypercholesterolemia Low-density lipoprotein receptor Proprotein convertase subtilisin/kexin type 9

Journal

Practical laboratory medicine
ISSN: 2352-5517
Titre abrégé: Pract Lab Med
Pays: Netherlands
ID NLM: 101690848

Informations de publication

Date de publication:
Nov 2020
Historique:
received: 02 03 2020
accepted: 15 10 2020
entrez: 2 11 2020
pubmed: 3 11 2020
medline: 3 11 2020
Statut: epublish

Résumé

Clinical diagnostic criteria of familial hypercholesterolemia (FH) in Japan include LDL cholesterol ​≥ ​180 ​mg/dL, Achilles tendon thickness ​≥ ​9.0 ​mm, and family history. However, few data exist regarding its validation. A series of 680 participants, with a mean LDL cholesterol of 175 ​mg/dL were enrolled at Kanazawa University Hospital between 2006 and 2018. All had full assessments of, LDL cholesterol, Achilles tendon X-rays, family history records, and genetic analysis of FH-associated genes ( The optimal cutoff values predicting the presence of an FH-associated mutation were 181 ​mg/dL for LDL cholesterol and ≥7.0 ​mm for Achilles tendon thickness. AUCs predicting FH mutations were 0.827 for Achilles tendon thickness ≥9.0 ​mm, 0.889 for LDL cholesterol ≥180 ​mg/dL, and 0.906 for family history. If Achilles tendon thickness ≥7.0 ​mm was used as a clinical criterion, then 41 participants (6%) were newly diagnosed with FH and 86 (12%) were newly misclassified as FH. Current clinical diagnostic criteria of FH were validated in this cohort. We recommend considering a tentative diagnosis of "potential FH" if the Achilles tendon thickness is ​≥ ​7.0 ​mm and <9.0 ​mm rather than dismissing a diagnosis of FH.

Sections du résumé

BACKGROUND BACKGROUND
Clinical diagnostic criteria of familial hypercholesterolemia (FH) in Japan include LDL cholesterol ​≥ ​180 ​mg/dL, Achilles tendon thickness ​≥ ​9.0 ​mm, and family history. However, few data exist regarding its validation.
DESIGN AND METHODS METHODS
A series of 680 participants, with a mean LDL cholesterol of 175 ​mg/dL were enrolled at Kanazawa University Hospital between 2006 and 2018. All had full assessments of, LDL cholesterol, Achilles tendon X-rays, family history records, and genetic analysis of FH-associated genes (
RESULTS RESULTS
The optimal cutoff values predicting the presence of an FH-associated mutation were 181 ​mg/dL for LDL cholesterol and ≥7.0 ​mm for Achilles tendon thickness. AUCs predicting FH mutations were 0.827 for Achilles tendon thickness ≥9.0 ​mm, 0.889 for LDL cholesterol ≥180 ​mg/dL, and 0.906 for family history. If Achilles tendon thickness ≥7.0 ​mm was used as a clinical criterion, then 41 participants (6%) were newly diagnosed with FH and 86 (12%) were newly misclassified as FH.
CONCLUSIONS CONCLUSIONS
Current clinical diagnostic criteria of FH were validated in this cohort. We recommend considering a tentative diagnosis of "potential FH" if the Achilles tendon thickness is ​≥ ​7.0 ​mm and <9.0 ​mm rather than dismissing a diagnosis of FH.

Identifiants

pubmed: 33134466
doi: 10.1016/j.plabm.2020.e00180
pii: S2352-5517(20)30143-8
pmc: PMC7585136
doi:

Types de publication

Journal Article

Langues

eng

Pagination

e00180

Informations de copyright

© 2020 The Author(s).

Déclaration de conflit d'intérêts

None.

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Auteurs

Hayato Tada (H)

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

Hirofumi Okada (H)

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

Akihiro Nomura (A)

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

Atsushi Nohara (A)

Department of Genetics, Ishikawa Prefectural Central Hospital, Kanazawa, Japan.

Soichiro Usui (S)

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

Kenji Sakata (K)

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

Masayuki Takamura (M)

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

Masa-Aki Kawashiri (MA)

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

Classifications MeSH