Abstract

Atherosclerosis has been defined as an inflammatory disease. Three decades of research have pointed to a pivotal role of interleukin 6 for many aspects of cardiovascular disease, not the least of which is atherosclerosis. In this review, experimental and clinical studies are reported on a timeline, exploring mechanisms and possible explanations that form the basis of current knowledge. Some successful clinical trials were proof of concept studies, showing that not only inflammatory biomarkers are related to cardiovascular outcomes, but also that decreasing inflammation can reduce cardiovascular events. Great advances have been made in the management of residual cardiovascular risk due to cholesterol, thrombosis, and metabolic diseases, but the next frontier now seems to be targeting inflammation. In the upcoming years, the importance of inflammation will be evaluated in high-risk patients with chronic kidney disease, after acute coronary heart disease or heart failure with preserved ejection fraction. Inflammation seems to precede the development of cardiovascular risk factors. Moreover, counseling for a heathy lifestyle and, when necessary, the use of cardiometabolic therapies capable of decreasing inflammation, might be important.

Acute coronary syndromes are among the most common diagnoses in the emergency department (ED). It has been estimated that 300,000 to 400,000 cases are seen each year in Brazil. The diagnosis of acute myocardial infarction (AMI) is made on the basis of symptoms, electrocardiogram, and biological markers of myocardial necrosis. Troponins are the most specific cardiac markers, and in the era of highly sensitive assays, they have been shown to make the exclusion of AMI in the ED more rapid, being particularly helpful in patients with atypical presentations.

Cardiotrophin-1 (CT-1) is a member of the interleukin-6 superfamily of proinflammatory cytokines. It is expressed in many tissues, including heart and vessels. CT-1 is upregulated in cardiac fibroblasts and cardiomyocytes in response to mechanical, humoral, metabolic, and hypoxic stress (). It is elevated in the myocardium and plasma of heart failure (HF) patients and has also been associated with hypertension, diabetes, cardiac hypertrophy, and fibrosis, both in patients and experimental studies., CT-1 is expressed after an AMI and seems to be involved in the healing and remodeling process that occurs after myocardial infarction., In the study by Freed et al., CT-1 was able to initiate each of the processes related to scar formation, including fibroblast migration and proliferation, and collagen synthesis.

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OBJECTIVE: The association between cytokines and troponin-I with cardiac function after cardiac surgery with cardiopulmonary bypass remains a topic of continued investigation. METHODS: Serial measurements, within 24h following surgery, of tumor necrosis factor-alpha, its soluble receptors, and troponin-I were performed in patients with normal ejection fraction undergoing coronary artery bypass grafting. Ejection fraction was measured by radioisotopic ventriculography preoperatively, at 24h and at day 7 postoperatively. RESULTS: Of 19 patients studied (59±8.5 years), 10 (group 1) showed no changes in ejection fraction, 53±8% to 55±7%, and 9 (group 2) had a decrease in ejection fraction, 60±11% to 47±11% (p=0.015) before and 24h after coronary artery bypass grafting, respectively. All immunological variables, except tumor necrosis factor-alpha soluble receptor I at 3h postoperation (5.5± 0.5 in group 1 versus 5.9±0.2 pg/ml in group 2; p=0.048), were similar between groups. Postoperative troponin-I had an inverse correlation with ejection fraction at 24h (r= -0.44). CONCLUSIONS: Inflammatory activity, assessed based on tumor necrosis factor-alpha and its receptors, appears to play a minor role in cardiac dysfunction after cardiac surgery. Troponin I levels are inversely associated with early postoperative ejection fraction.