Serum fetuin-A levels and abdominal aortic calcification in healthy men — The STRAMBO study

Abstract

Vascular calcification results from an imbalance between increased extracellular levels of calcium and phosphate, reduced solubility, and low levels of calcification inhibitors in blood or the vascular wall. Fetuin-A is a major circulating calcification inhibitor. Rodent models of fetuin-A deficit indicate its calcification inhibiting potential. Clinical studies suggest its role as a biomarker in vascular disease. This cross-sectional study was performed in a cohort of 974 men aged ≥40years (average 68years) consisting of men holding health insurance cover with Mutuelle des Travailleurs de la Région Lyonnaise. Abdominal aortic calcification (AAC) was assessed semi-quantitatively on lateral dual energy X-ray absorptiometry (DXA) spine scans. Serum fetuin-A was measured by an immunoassay. After adjustment for confounders (age, lifestyle, body composition, health status, treatment, glomerular filtration rate [GFR], hormones, and cytokines), prevalence of severe AAC (AAC score>4) decreased with increasing fetuin-A levels (OR=0.68 per SD increase, 95% CI: 0.54–0.84, p<0.001). After adjustment for confounders, low fetuin-A and hypertension were each associated with higher odds of AAC>4. Coexistence of low serum fetuin-A levels and heavy smoking, elevated fibroblast growth factor 23 levels or low serum dickkopf-1 levels were associated with higher odds of AAC>4. Similar results were obtained for 789 men with GFR>60mL/min/1.73m2. Similar results were obtained when severe AAC was defined as AAC score >3 or AAC>5.Thus, lower serum fetuin-A levels are associated with severe AAC, suggesting that poor calcification inhibitory potential contributes to vascular calcification, independently of renal impairment.