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Cervantes-Gracia et al. Vessel Plus 2020;4:27 I http://dx.doi.org/10.20517/2574-1209.2020.22 Page 9 of 19
[92]
of increased risk of developing CIN: the study published by Yuan et al. in 2017 found in 1,061 patients
that white blood cell count, neutrophil count, neutrophil lymphocyte ratio, CRP level, and big ET-1 level
were all associated with an increased risk of CIN development. It is important to mention that all of the
patients in this study went through emergency PCI.

Regarding the assessment of multiple markers to predict the development of CIN, different studies have
reported combinations between proteins that can be measured in human serum. The study performed by
[141]
Satilmis et al. , presented an assessment of the ratio between 2 inflammatory markers, CRP and albumin.
205 patients with non-ST-elevation myocardial infarction that underwent PCI were subsequently assessed
for development of CIN. The prevalence of CIN in this study was 10.2%. Multivariate logistic regression
analysis showed significant association between CRP: albumin ratio and the development of CIN; advanced
age, diabetes, dyslipidemia and left ventricular ejection fraction were also associated with the condition.

Animal models have also been used in the search for the potential role of inflammation in the development
[29]
of CIN. Demirtas et al. evaluated the role of IL-33 in the pathogenesis of CIN in diabetic rats. 30 male
Sprague-Dawley rats were divided into 3 groups (healthy, diabetic and diabetic with CIN). Significantly
increased presence of IL-33 was found in the kidney tissue of the diabetic group after induction of CIN
when compared with the healthy and diabetic groups. Serum levels of IL-33, IL-6, and IL-1β were also
significantly increased in the diabetic + CIN group when compared to the healthy and diabetic groups
[Figure 3].

Prophylactic use of carotenoids has been studied in animal models to assess the relation between oxidative
stress induced inflammation and CIN development. The studies presented by Buyuklu et al. [142,143] aimed
to investigate the effects of lycopene and curcumin as protection against the development of CIN in rats.
28 male Wistar albino rats were divided into 4 groups, they included a normal control group, CIN group,
CIN + lycopene and CIN + curcumin groups. Significant increase in urea, creatinine and malondialdehyde
were observed in the CIN group when compared with the control group. Additionally, histological tests
showed significant increase of infiltrated inflammatory cells and necrotic degenerative changes in the CIN
group when compared against the control [142,143] .

[14]
The role of the inflammatory state in CVD was addressed in an extensive literature . The search for
markers has two principal aims: to look into the understanding of the mechanisms of disease and to
identify molecules that can be detected more accurately to predict the risk of cardiovascular events.
The role of inflammation in CVD development has been assessed throughout different populations and
experimental models, critical importance has been given to events such as acute myocardial infarction
(AMI) and atherosclerosis due to their high incidence and mortality rates [144] . Inflammation in CVD
includes a vast number of processes which can occur at the site of disease, in the bloodstream and at
sites far from the disease [145] . Immune response takes the spotlight when addressing inflammation and
CVD. In AMI a signaling cascade induces the expression and recruitment of proinflammatory molecules,
accelerating both damage and further repair of injured cardiac tissue. Elevated levels of high-sensitivity
[146]
CRP and IL-6 in plasma have been found correlated with unfavorable outcomes in patients [Figure 3] .

Rajendran et al. [147] assessed both IL-6 and hs-CRP in a Chennai based population. 93 patients with
AMI and 102 healthy subjects as a control group were analyzed. Both IL-6 and hs-CRP were found to be
significantly increased when compared with the control group. Pro-inflammatory cytokines IL-6, IL-10,
IL-18 and TNF-a were evaluated in a study published in 2019 including 120 patients with acute coronary
syndrome (ACS) and 60 healthy controls. Serum levels of IL-6, IL-18 and TNF-a were significantly higher
in the ACS group when compared to the healthy group [Figure 3]. No significant difference in serum
[148]
levels of IL-10 was found . Additionally, TNF-a has been found to promote the release proinflammatory