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

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.