Table 1 Inflammatory, cell stress and apoptosis specific proteins included in the CVD II panel and used in the study

Interleukin-6 (IL-6)

IL-6 is a cytokine involved in the acute phase response to tissue injury or to an inflammatory stimulus. It acts both locally and systemically and it has its peak concentration a few hours after the end of ECC and gradually decreases within the following 24 h [7].

Interleukin-18 (IL-18)

IL-18 has a central role in the inflammatory cascade and it is widely expressed by monocytes/macrophages. High circulating levels have been associated with cardiovascular diseases, ranging from coronary artery disease to heart failure. In particular, a strong association between increased IL-18 levels and atrial fibrillation has been seen [8].

Serine/threonine-protein Kinase 4 (STK4)

STK4, also known as MST1, is a cytoplasmic kinase. It is a critical component of the Hippo pathway and a key regulator of organ size and regeneration. It acts by inducing autophagy [9], apoptosis and inhibition of cell proliferation. Recently it was shown that STK4 plays an important role in regulating stress response and apoptosis in myocardial injury [10].

Protease-activated receptor 1 (PAR-1)

PAR-1 is a G-protein coupled receptor, activated by the coagulation protease thrombin, as well as other proteases. In the heart, it is expressed by cardiomyocytes and cardiac fibroblasts. PAR-1 plays an important role in cardiac remodeling after myocardial infarction. Elevated PAR-1 expression in human heart failure contributes to pathological cardiac remodeling (cardiac fibrosis) and hypertrophy [11].

Heat shock protein 27 (HSP27)

Heat shock proteins are a ubiquitous family of chaperones. They represent the key players within cellular stress responses by stabilizing protein folding of newly synthesized proteins. With a molecular weight of 27 kDa in humans, HSP27 has a dual role, depending on its intracellular or extracellular location [12]. The intracellular overexpression protects cardiac myocytes against ischemic injury. When located in the extracellular spaces HSP27 contributes to the mechanism underlying post ischemic myocardial inflammatory response and cardiac functional injury [13, 14].

TNF-related apoptosis inducing ligand- receptor 2 (TRAIL-R2)

TRAIL-R2 is a cell surface receptor for TNF-related apoptosis- inducing ligand with the capacity to induce apoptotic signaling cascades leading to cell death High TRAIL-R2 levels were recently shown to be a predictor of long term mortality in patients with acute myocardial infarction [15].