Interplay between Pro-inflammatory Mediators and Oxidative Stressinvolved Recurrent Chronic Heart Failure in Elderly Patients with Coronary Stents.

Introduction: Inflammation and oxidative stress are related to congestive heart failure in patients with coronary heart disease.

Objective: Chronic congestive heart failure is a serious stage of coronary artery disease and is mainly a disease of elderly people over the age of 65. Elderly heart failure patients are characterized by myocardial ischemia, and post-ischemic myocardial dysfunction. Oxidative Stress, inflammation, and immune response play important roles in the development of heart failure. We tried to examine the mutual triggering of oxidative stress (malondialdehyde), inflammatory cytokines (tumor necrosis factor-α and soluble tumor necrosis factor receptor-1/2), immune response (toll-like receptors 2,3,4), and high sensitivity C-reactive protein expression in elderly patients with recurrent congestive heart failure after coronary stenting and investigated the effect of interplay of these changes on onset and progression of recurrent congestive heart failure in elderly patients underwent coronary stent implantation.

Methods: A total of 726 patients were enrolled in this study. We determined the levels of malondialdehyde (MDA), high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF- α), soluble tumor necrosis factor receptor-1 and 2 (sTNFR-1/2) and toll-like receptor 2,3,4 (TLR2/3/4) in elderly patients with recurrent congestive heart failure after coronary artery stent implantation.

Results: Levels of MDA, hs-CRP, TNF-α, sTNFR-1, sTNFR-2, TLR2, TLR3 and TLR4 were remarkably increased (p<0.01) in elderly patients with recurrent congestive heart failure after coronary artery stenting. The results indicated that these markers were closely correlated to each other and showed that these markers were associated with increased New York Heart Association functional classification and low left ventricular ejection fractions. Further analysis confirmed that the independent clinical risk factors for recurrent congestive heart failure were MDA, hs-CRP, TNF-α, sTNFR-1, sTNFR-2, TLR2, TLR3 and TLR4. The interplay of oxidative stress, inflammatory cytokines and toll-like receptors, and hs-CRP expression levels was an important factor involved in recurrent congestive heart failure of elderly patients after coronary stenting.

Conclusion: High levels of MDA, hs-CRP, TNF-α, sTNFR-1, sTNFR-2, TLR2, TLR3 and TLR4 had an important implication for recurrent heart failure with increased New York Heart Association functional classification and low left ventricular ejection fractions. These eight factors amplified each other's positive effects and this interaction may be a key element of their roles in recurrent heart failure. The eight risk factors were inter-dependent and occurred simultaneously, and exerted detrimental effects forming a vicious circle. MDA may trigger the over-expressions of pro-inflammatory risk factors (hs-CRP, TNF-α, sTNFR-1, sTNFR-2) through the activation of TLRs as risk factors (TLR2, TLR3 and TLR4) contributing to the dysfunction of myocardial mitochondria, cardiomyocyte hypertrophy, maladaptive myocardial remodeling, myocardial interstitial fibrosis, cardiac systolic decrease and recurrent heart failure. These eight risk factors were the basis of the mechanisms of recurrent heart failure. Therefore, the mutual triggering of oxidative stress, inflammatory and toll-like receptor signaling pathways, and hs-CRP expression could play key roles in the development of recurrent congestive heart failure in elderly patients after coronary stenting.