The associations of fetuin-A with subclinical cardiovascular disease in community-dwelling persons: the Rancho Bernardo Study

Objectives: The aim of this study was to determine the association of fetuin-A with subclinical cardiovascular disease (CVD) in community-living individuals.

Background: Fetuin-A is a hepatic secretory protein that inhibits arterial calcium deposition in vitro. Lower fetuin-A levels are associated with arterial calcification and death in end-stage renal disease populations. The association of fetuin-A with subclinical CVD in the general population is unknown.

Methods: Among 1,375 community-living individuals without prevalent clinical CVD, we measured plasma fetuin-A concentrations. Peripheral arterial disease (PAD) was defined by ankle brachial index <0.90, coronary artery calcification (CAC) was measured by computed tomography, and common and internal intima-media thickness (cIMT) were measured by carotid ultrasound. PAD was measured concurrent with fetuin-A, and CAC and cIMT were measured 4.6 years (mean) later.

Results: Mean age was 70 ± 11 years, and 64% were women. Fetuin-A levels were inversely associated with CAC severity. When evaluated as CAC categories (0, 1 to 100, 101 to 300, >300) with ordinal logistic regression, each SD higher fetuin-A was associated with 31% lower odds of CAC severity (proportional odds ratio: 0.69; 95% confidence interval: 0.46 to 0.92; p = 0.008) in models adjusted for demographic data, lifestyle factors, traditional CVD risk factors, and kidney function. In contrast, no association of fetuin-A was observed with PAD or high common or internal cIMT in adjusted models.

Conclusions: Lower fetuin-A levels are independently associated with greater CAC severity but not PAD or cIMT. If confirmed, fetuin-A might mark calcium deposition within the vasculature but not atherosclerosis per se.