Corneal arcus and thick Achilles tendons flag elevated Lp(a) and higher MACE risk in 484 patients with familial hypercholesterolaemia (J Clin Lipidol 2025)

Original title: Corneal arcus and Achilles tendon thickness reflect circulating lipoprotein(a) levels in familial hypercholesterolemia: Implication for predicting future cardiovascular events

J Clin Lipidol · 1 January 2025 · 6

Murai K, Kataoka Y, Ray KK, Funabashi S, Hori M, Ogura M, Doi T, Makino H, Noguchi T, Harada-Shiba M

In a retrospective analysis of 484 patients with clinically diagnosed familial hypercholesterolaemia (median Lp(a) 18.4 mg/dL), those with Lp(a) at or above 30 mg/dL were more likely to have corneal arcus and greater Achilles tendon thickness (ATT), with 14.0 mm identified as the optimal ATT cut-off for predicting elevated Lp(a) (C-statistic 0.58). After adjusting for age, sex, untreated LDL-C and FH-causing variants, the combination of corneal arcus and ATT 14.0 mm or greater remained independently associated with Lp(a) at or above 30 mg/dL (odds ratio 2.31, 95% CI 1.22-4.38, P = .010). Over a 15-year observation period, major adverse cardiovascular events occurred more often with Lp(a) at or above 30 mg/dL (log-rank P = .026), and risk was highest when both physical signs were also present (log-rank P = .042); the physical signs added no risk when Lp(a) was below 30 mg/dL. Simple physical examination for corneal arcus and Achilles tendon thickness could help flag FH patients most likely to have high Lp(a) and the greatest cardiovascular risk.

Original abstract

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.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.