Angiopoietin-like 3 and subclinical peripheral arterial disease: Evidence from the Brisighella Heart Study

Angiopoietin-like 3 (ANGPTL3) is a 70kDa protein primarily expressed in the liver. The main physiological role is related to the inhibition of lipoprotein and endothelial lipases, thus affecting triglyceride hydrolysis. 1 The role of ANGPTL3 in atherosclerosis has emerged from genetics: carriers of loss of function (LOF) mutations of ANGPTL3, leading to low plasma levels, had a reduced risk of coronary artery disease and a lipid profile characterised by dramatic reductions of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides.2 However, although homozygous or compound heterozygous for ANGPTL3 LOF had a reduced capacity to promote cell cholesterol efflux, no clinical evidence of accelerated atherosclerosis was found.3 ANGPTL3 also influences the endothelial cell adhesion and stimulates the proliferation of haematopoietic stem cells,4 both potentially atherosclerosis associated. As, to date, in a general population no data have been reported on a possible direct involvement of ANGPTL3 with arterial disease, the present retrospective study was aimed to evaluate the relationship between ANGPTL3 plasma levels and extra-coronary arterial health, as assessed by the ankle–brachial blood pressure index (ABI), a validated, non-invasive tool for peripheral artery disease (PAD) screening.5 Moreover, levels of proprotein convertase subtilisn/kexin type 9 (PCSK9), which may play a crucial role in vascular aging, were also evaluated.6 The Brisighella Heart Study is a longitudinal population study on a randomly allocated sample representative of the entire population of Brisighella, a rural northern Italian village. The study, carried out in agreement with the Declaration of Helsinki, was approved by the institutional ethics board of the University Hospital of Bologna