Vascular alterations in apolipoprotein A-I amyloidosis (Leu75Pro). A case-control study

Among hereditary amyloidoses, apolipoprotein A-I (APO A-I) amyloidosis (Leu75Pro) is a rare, autosomal dominant condition in which renal, hepatic, and testicular involvement has been demonstrated.

To investigate vascular structural as well as functional alterations.

In 131 carriers of the amyloidogenic Leu75Pro APO A-I mutation (mean age 52 + 16 years, 56 women) and in 131 subjects matched for age, sex, body mass index and clinic blood pressure (BP), arterial stiffness (pulse wave velocity, PWV) and carotid intima-media thickness (IMT) were measured.

By definition no differences for age, sex, body mass index, and BP were observed. Meanmax IMT (Mmax-IMT) in the common (CC), bifurcation (BIF) and internal (ICA) carotid artery were comparable in the two groups. After adjustment for high-density lipoprotein cholesterol and renal function differences between the two groups, a lower meanmax-IMT was observed in APO A-I Leu75Pro mutation carriers than in controls (CC Mmax-IMT 0.87 ± 0.21 versus 0.93 ± 0.2 mm, p = 0.07; BIF Mmax-IMT 1.19 ± 0.48 versus 1.36 ± 0.46 mm, p = 0.025; ICA Mmax-IMT 0.9 ± 0.37 versus 1.02 ± 0.35 mm, p = 0.028). On the other hand, aortic stiffness was significantly greater in patients with APO A-I amyloidosis than controls (PWV 11.5 ± 2.9 and 10.7 ± 2.3 m/s, p < 0.05), even after adjusting for confounders.

In carriers of the amyloidogenic Leu75Pro APO A-I mutation, a significant increase in arterial stiffness is observed; on the contrary, carotid artery IMT is comparable to that of control subjects. These results may add significant information to the clinical features of this rare genetic disorder.