Determinants and Outcomes of Accelerated Arteriosclerosis: Major Impact of Circulating Antibodies.

Abstract

RATIONALE:

The role of circulating antibodies in addition to traditional cardiovascular risk factors in the development of accelerated arteriosclerosis and their long-term clinical consequences have not been demonstrated.

OBJECTIVE:

We investigated the role of circulating antibodies in accelerated arteriosclerosis and the role of immune-associated arteriosclerosis in graft and patient survival and the occurrence of major adverse cardiovascular events.

METHODS AND RESULTS:

This was an observational prospective cohort study that included 1065 kidney transplant patients (principal cohort, n=744; validation cohort, n=321) between 2004 and 2010. Participants were assessed for traditional cardiovascular risk factors and circulating anti-human leukocyte antigen (HLA) antibodies. All patients underwent allograft biopsies to assess arteriosclerotic lesions and endothelial activation, endarteritis, and complement deposition. In the principal cohort, 250 (33.6%) patients had severe arteriosclerosis (luminal narrowing >25% via fibrointimal arterial thickening). Circulating donor-specific anti-HLA antibodies were significantly associated with severe allograft arteriosclerosis (hazard ratio, 2.9; P<0.0001), independently of traditional risk factors. Patients with severe arteriosclerosis and anti-HLA antibodies (n=91, 12.2%) demonstrated allograft endothelial activation, endarteritis, and complement deposition. High levels of anti-HLA antibodies and their complement binding capacity were associated with increased severity of arteriosclerosis. Patients with antibody-associated severe arteriosclerosis had decreased allograft survival and increased mortality (P<0.0001); they exhibited a 2.5- and 4.1-fold increased risk of major adverse cardiovascular events compared with patients who had severe arteriosclerosis without antibodies and patients with minimal arteriosclerosis, respectively (P<0.0005). Circulating donor-specific anti-HLA antibodies were significantly associated with occurrence of major adverse cardiovascular events (hazard ratio, 2.4; P=0.0004), independently of traditional risk factors.

CONCLUSIONS:

Circulating antibodies are major determinants of severe arteriosclerosis and major adverse cardiovascular events, independent of traditional cardiovascular risk factors.

• Authors: Alexandre Loupy, Dewi Vernerey, Denis Viglietti, Olivier Aubert, Jean-Paul Duong Van Huyen, Jean-Philippe Empana, Patrick Bruneval, Denis Glotz, Christophe Legendre, Xavier Jouven, Carmen Lefaucheur
• Journal: Circulation research (Circ Res) Vol. 117 Issue 5 Pg. 470-82 (Aug 14 2015) ISSN: 1524-4571 [Electronic] United States
• PMID: 26056252 (Publication Type: Journal Article, Observational Study)
• Copyright: © 2015 American Heart Association, Inc.

Chemical References

• Autoantibodies
• HLA Antigens

Topics

• Adult
• Aged
• Arteriosclerosis (blood, diagnosis, surgery)
• Autoantibodies (blood)
• Cohort Studies
• Female
• Follow-Up Studies
• Graft Rejection (blood, diagnosis)
• Graft Survival (physiology)
• HLA Antigens (blood)
• Humans
• Kidney Transplantation (trends)
• Male
• Middle Aged
• Prospective Studies
• Transplantation, Homologous (trends)
• Treatment Outcome