Fetuin-A Is Inversely Associated with Coronary Artery Calcification in Community-Living Persons: The Multi-Ethnic Study of Atherosclerosis

Abstract

BACKGROUND Fetuin-A is a hepatic secretory protein that inhibits arterial calcification in vitro. The association of fetuin-A with coronary arterial calcification (CAC) in the general population is uncertain. METHODS Among 2457 community-living individuals without cardiovascular disease (CVD), we measured serum fetuin-A concentrations by ELISA and evaluated the cross-sectional association of fetuin-A with CAC prevalence (any vs none) and severity; on follow-up 3.2 years (median) later, we evaluated the association of fetuin-A with CAC incidence and progression. RESULTS The mean age was 62 (SD 10) years, and the mean fetuin-A concentration was 0.48 (0.10) g/L. At baseline, 1200 individuals (49%) had CAC, and 272 individuals developed CAC during follow-up. At baseline, there was a threshold effect at the lowest fetuin-A quartile with CAC prevalence. In models adjusted for demographics, traditional cardiovascular disease (CVD) risk factors and kidney function, the lowest fetuin-A quartile had 7% (95% CI 1%–13%; P = 0.04) greater CAC prevalence compared with quartiles 2–4. Similar associations were observed with CAC severity at baseline, but the association was more linear. Each SD (0.10 g/L) lower fetuin-A was associated with a 12% (95% CI 3%–21%; P = 0.01) greater CAC severity in adjusted models. There was no significant association of fetuin-A with CAC incidence or progression. CONCLUSIONS Fetuin-A is inversely associated with CAC severity among community-living individuals without CVD. Whether fetuin-A concentrations are associated with incident CVD event in the general population requires future study.

Fetuin-A (AHSG) and its usefulness in clinical practice. Review of the literature

“…On the other hand, some clinical studies have indicated the opposite trends-a decrease in fetuin-A levels have been associated with the presence of PAD in diabetics, an increased arterial stiffness, atherosclerotic plaque calcification and progression of cardiovascular disease 14,48 . Contrary to some reports, many previous studies indicate that fetuin-A concentrations are decreased in patients with stable angina and acute myocardial infarction, this glycoprotein may be independent predictor of death after ST-elevation myocardial infarction and low levels of fetuin-A are correlated to the severity of coronary arterial calcification 49,50,51 . It should be mentioned that the renal function has influence on cardiovascular risk due to accelerated vascular calcifications aggravated by hyperphosphataemia and hypercalcaemia.…”

Biomarkers of Key Biological Pathways in CVD

“…Similarly, higher serum FGF-23 concentration was associated with left ventricular hypertrophy, heart failure events, and incident atrial fibrillation[17]. These findings suggested that PTH, FGF-23, and underlying phosphorus excess, may increase risk of heart failure and related clinical outcomes by reducing vascular compliance or promoting myocardial hypertrophy.…”

“…In humans, fetuin-A circulates at relatively high concentrations and may be a marker of arterial calcification. In a subset of MESA participants, fetuin-A levels were inversely associated with CAC severity, independent of traditional cardiovascular risk factors and kidney function[17]. …”

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

“…Additionally, low fetuin-A levels were associated in these patients with cardiovascular and all-cause mortality [18]. By contrast, studies in patients with normal renal function have yielded ambiguous results, with either higher or lower fetuin-A concentrations in vascular disease [37,38]. Furthermore, atherosclerosis of different vascular beds may not be uniformly associated with altered fetuin-A levels, since peripheral artery disease or carotid intima-media thickness -as opposed to coronary artery calcification -have not been shown to be associated with fetuin-A levels [39].…”