2025-11-21 国立循環器病研究センター
<関連情報>
- https://www.ncvc.go.jp/hospital/topics/topics_36383/
- https://www.sciencedirect.com/science/article/abs/pii/S1933287425003502
家族性高コレステロール血症における角膜輪とアキレス腱の厚さは循環リポタンパク質(a)レベルを反映する:将来の心血管イベント予測への示唆 Corneal arcus and Achilles tendon thickness reflect circulating lipoprotein(a) levels in familial hypercholesterolemia: Implication for predicting future cardiovascular events
Kota Murai MD, PhD, Yu Kataoka MD, PhD, Kausik K. Ray MB ChB, MD, MPhil, Sayaka Funabashi MD, PhD, Mika Hori PhD, Masatsune Ogura MD, PhD, Takahito Doi MD, PhD, Hisashi Makino MD, PhD, Teruo Noguchi MD, PhD, Mariko Harada-Shiba MD, PhD
Journal of Clinical Lipidology Available online: 20 November 2025
DOi:https://doi.org/10.1016/j.jacl.2025.07.010
Graphical Abstract
Association of FH-related physical features with Lp(a) levels and their impact on cardiovascular outcomes In Japanese clinically diagnosed FH subjects, more frequent elevated Lp(a) levels were observed in those showing CA, ATT ≥14 mm, and both. The concomitance of these physical features with Lp(a) ≥30 mg/dL was associated with poor cardiovascular prognosis. Abbreviations: ACS, acute coronary syndrome; ATT, Achilles tendon thickness; CA, corneal arcus; FH, familial hypercholesterolemia; Lp(a), lipoprotein(a); MACE, major adverse cardiovascular event
Highlights
- The presence of corneal arcus (CA) and Achilles tendon thickness (ATT) ≥14 mm was associated with lipoprotein(a) (Lp[a]) levels ≥30 mg/dL, and 56.0% of familial hypercholesterolemia subjects with both these 2 physical features exhibited Lp(a) levels ≥30 mg/dL.
- During an observational period of up to 15 years, the presence of physical features was not associated with higher cardiovascular risk in those with Lp(a) <30 mg/dL.
- Cardiovascular outcomes were higher among those with Lp(a) ≥30 mg/dL and were substantially worse when both CA and ATT ≥14 mm were present.
BACKGROUND
Familial hypercholesterolemia (FH) causes corneal arcus (CA) and xanthomas via lipid particle deposition. Lipoprotein(a) [Lp(a)] consists of an apolipoproteinB100 and apolipoprotein(a). As apolipoprotein(a) accumulates within extracellular connective tissues, it may associate with CA and tendon xanthoma.
OBJECTIVES
To elucidate the association between elevated Lp(a) and FH-related physical features and evaluate their independent and joint prognostic utility on cardiovascular risk.
METHODS
We retrospectively analyzed 484 clinically diagnosed FH patients, evaluating both Lp(a) and physical features. Physical features were compared in individuals with and without Lp(a) ≥ 30 mg/dL. The occurrence of major adverse cardiovascular events (MACE = cardiovascular death + acute coronary syndrome + ischemic stroke) was compared in those stratified according to Lp(a) ≥ 30 mg/dL and physical features.
RESULTS
The median value of Lp(a) was 18.4 mg/dL; subjects with Lp(a) ≥ 30 mg/dL were more likely to exhibit CA and greater Achilles tendon thickness (ATT). Receiver operating characteristic analysis suggested 14.0 mm as an optimal cut-off value of ATT predicting Lp(a) ≥ 30 mg/dL (C-statistic = 0.58). Even after adjusting for age, sex, untreated low-density lipoprotein cholesterol level, and FH-related pathogenic variants, the co-existence of CA and ATT ≥ 14.0 mm was independently associated with Lp(a) ≥30 mg/dL (odds ratio = 2.31; 95% CI = 1.22-4.38; P = .010). During a 15-year observational period (median = 1835 days), MACE occurred more frequently in subjects with Lp(a) ≥ 30 mg/dL (log-rank P = .026). This Lp(a)-associated cardiovascular risk was further elevated among those with both CA and ATT ≥ 14.0 mm (log-rank P = .042), whereas the presence of physical stigmata did not worsen cardiovascular outcome when Lp(a) was < 30 mg/dL.
CONCLUSIONS
Assessment of CA and ATT in FH identifies those more likely to have higher Lp(a) levels. The presence of these triads is associated with the highest risk of MACE and potentially guides intensification of antiatherosclerotic therapies.
