Discussion
Even though MI has been associated with both hsCRP as well as IL-6, albeit to a lesser extent, it has been challenging to establish the direct role of inflammatory cytokines in MI. Nonetheless, a few studies have implicated the IL-6 pathway in the pathogenesis of MI and other heart diseases. According to the present study results, both the IL6 and CRP levels were higher in MI patients than in healthy controls. Additionally, CRP was significantly correlated with BMI and waist circumference. Few studies have also demonstrated that CRP and IL-6 are significantly associated with adverse cardiovascular events.14-16 For example, aChinese study demonstrated a significant correlation between both IL-6 and hsCRP and CVD risk factors and mortality.17 In line with our study, Lai et al. reported that the serum IL-6 concentrations in coronary disease patients were substantially high (p<0.001) in contrast to those in the control group.14 Another study reported that the IL-6 levels were positively correlated to the risk factors for CVD that cause inflammation and plaque formation, and therefore, IL-6 and CRP can be used as indicators of the prognosis of adverse cardiac events.15 In another study, Velásquezet al. reported that CRP and IL-6 had a significant association with hypertension, diabetes, smoking, BMI, and age. The study concluded that elevations in IL-6 levels were associated with the risk of MI.16
In a study on 44 STEMI patients, Wilkowska et al. reported elevated levels of IL-6 in all the patients and observed that the IL-6 levels were higher among depressed MI subjects than among non-depressed MI subjects.18 In another study in the STEMI population, the circulating levels of CRP and IL-6 were found to be increased, especially in patients with a high peak of troponin T.19 Although the biochemical parameters were deranged in MI patients, these parameters were not significantly correlated with IL-6 and CRP.
A study on 73 patients with acute MI (AMI) reported elevated IL-6 levels in CAD patients than in the controls; further, the study concluded that both the IL-6 and CRP levels were associated with AMI and cardiac injury.20 In our MI patients, too, the CRP levels were elevated compared with the controls (p<0.05) and were preceded by an increase in IL-6 levels. Additionally, another study on the association of CRP and IL-6 levels with the risk of death and cardiovascular events in atrial fibrillation patients reported that the IL-6 level was significantly correlated with vascular death, major bleeding, i.e., hemorrhagic stroke, and thromboembolic outcomes, while CRP was significantly associated with MI.21
IL-6 has been reported to be more strongly correlated with the risk of cardiovascular mortality than CRP.22 Elevated IL-6 level is an important biomarker and powerful predictor for long-term assessment of cardiovascular mortality risk in STEMI patients.23 This is because serum IL-6 is the main stimulator for acute phase hepatic response, which is linked with an increase in blood viscosity as well as platelet count and activity. Further, IL-6 slows down lipoprotein lipase activity as well as its levels in plasma, thereby leading to an increase in the uptake of lipid through macrophages.24 In addition to this, circulating IL-6 stimulates the hypothalamic-pituitary-adrenal axis, and the triggering of this axis is significantly correlated with central obesity, insulin resistance, and hypertension, all of which are risk factors for cardiovascular mortality.25 We also observed that age in the control group was negatively correlated with IL6, but there is no specific explanation for this correlation.
The findings discussed in this study support the assumption that IL-6 and CRP levels are involved in the MI, but their correlation with cardiovascular biochemical risk factors is not found. It seems that IL6 and CRP are not involved in AMI’s mechanism via biochemical factors, but these might play a pathogenic role in AMI by some other mechanism.