Plasma levels of sRANKL and OPG are associated with atherogenic cytokines in patients with intermediate cardiovascular risk.

Osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) are regulators of bone remodeling, but are also considered to play important roles in coronary artery disease (CAD). This study evaluated potential associations of soluble (s) RANKL and OPG with atherosclerosis-relevant cytokines. Blood was collected from 414 individuals who presented to our hospital with intermediate likelihood for CAD for further examination. Plasma concentrations of total sRANKL, OPG, and 20 cytokines were measured using sandwich-type enzyme-linked immunoassays (ELISAs; OPG and sRANKL) and Luminex laser-based fluorescence analysis and correlated with each other. The plasma levels of interferon-γ (IFN-γ) and the T-helper cell 2 cytokines interleukin-4 (IL-4) and IL-13 showed a positive correlation with sRANKL. The association with sRANKL levels was negative for IFN-γ-induced protein-10 (IP-10) and monocyte chemotactic protein-1 (MCP-1). The strongest independent association with sRANKL in multivariable analyses was found for IFN-γ (positive) and IP-10 (negative), while IL-13 showed a positive and independent association with OPG plasma levels. OPG and sRANKL plasma levels correlate strongly and independently with specific circulating atherosclerosis-related cytokines in patients with intermediate cardiovascular risk.

Differences of inflammatory cytokine profile in patients with vulnerable plaque: A coronary CTA study.

BACKGROUND AND AIMS: Various pro- and anti-inflammatory biomarkers are involved in the process of atherosclerosis. We analyzed the association of different biomarkers with coronary plaque volume and vulnerable plaque subcomponents. METHODS: In 301 patients undergoing coronary CT angiography (CTA), total coronary plaque volume (TPV) and subcomponents including non-calcified plaque volume (NCPV) and vulnerable plaque burden were quantified using semi-automated software. Serum was analyzed for various cytokines. RESULTS: Out of 301 patients, 207 (69%) were male. The mean age was 59 ± 10 years. Patients were divided using the median of TPV, NCPV and vulnerable plaque burden. In univariable analysis, patients with high TPV, high NCPV and high vulnerable plaque burden showed significant higher serum levels for IFNƔ, IL-1a, -2, -4, -10 and -17 and significant lower levels for IL-8 and MCP-1 (all p < 0.05). Multivariable analysis showed positive associations between high vulnerable plaque burden, IL-1a (OR 2.60, p = 0.001) and Eotaxin (OR 1.89, p = 0.020), and inverse association to MCP-1 (OR 0.33, p < 0.001), independent of age, gender and CVRF. In exploratory subanalyses, patients with presence of atherosclerosis (n = 247; 82%) showed significantly higher levels of IL-17 in all subgroups with high vulnerable plaque burden, irrespective of overall plaque volume (all p < 0.001). CONCLUSIONS: The cytokine profile significantly differs between patients with high and low coronary plaque volume. IL-1a and IL-17 seem to play a major proatherogenic role in vulnerable plaque formation, whereas MCP-1 paradoxically portends protective effects. Longitudinal studies with serial cytokine testing are needed to identify potential targets for therapeutic interventions.

Pericoronary adipose tissue CT attenuation and its association with serum levels of atherosclerosis-relevant inflammatory mediators, coronary calcification and major adverse cardiac events.

BACKGROUND: Increased attenuation of pericoronary adipose tissue (PCAT) around the right coronary artery (RCA) derived from coronary CTA might detect coronary inflammation. We investigated a potential association between RCA PCAT attenuation and serum levels of atherosclerosis-relevant cytokines and MACE (coronary revascularization, myocardial infarction and/or cardiac death). METHODS: Blood samples of 293 clinically stable individuals (59.0 â€‹± â€‹9.8 years, 69% males) were analyzed for atherosclerosis-relevant cytokines including interleukin (IL)-2, IL- 4, IL-6, IL-7, IL-8, IL-10, IL-13, IL-15, IL-17, TNF-a, IP-10, CRP, MCP-1, MIP-1a, Eotaxin and GM-CSF. Subjects also underwent coronary calcium scoring (CCS) followed by CTA. PCAT CT attenuation was measured around the RCA using semi-automated software. Increased RCA PCAT attenuation was defined as PCAT attenuation above the 75th percentile (>-73.5 HU). To assess MACE, 232 individuals were followed for a mean duration of 9.6 â€‹± â€‹2.1 years. RESULTS: In patients with increased RCA PCAT attenuation the serum levels of MCP-1 were increased (p â€‹< â€‹0.01), whereas levels of anti-inflammatory mediators IL-4 and -13 were significantly reduced (each p â€‹< â€‹0.05). Adipocytokine MCP-1 (r â€‹= â€‹0.23, p â€‹< â€‹0.01) and pro-inflammatory mediator IL-7 (r â€‹= â€‹0.12, p â€‹= â€‹0.04) showed a mild positive correlation with RCA PCAT attenuation, whereas anti-inflammatory mediators Il-4, -10 and -13 correlated inversely (each r < -0.12, each p â€‹< â€‹0.05). 40/232 patients experienced MACE during follow-up. In multivariable Cox regression analysis increased RCA PCAT attenuation was shown to be an independent predictor of MACE (HR 2.01, p â€‹= â€‹0.044). CONCLUSIONS: Increased RCA PCAT CT attenuation shows a weak association with serum levels of selected atherosclerosis-relevant inflammatory biomarkers. Increased RCA PCAT attenuation is an independent predictor of MACE and may potentially guide future prevention strategies in stable patients.