Natural variability of circulating levels of cytokines and cytokine receptors in patients with heart failure: implications for clinical trials

Dibbs, Ziad; Thornby, John; White, Bill G.; Mann, Douglas L.

doi:10.1016/s0735-1097(99)00130-8

Cited by 117 publications

(72 citation statements)

References 38 publications

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“…A similar difference in intra-individual biological variability could also explain the lack of prognostic value observed for IL-6 in the present study. 38 …”

Section: Tnf-α and LV Reverse Remodeling After Crtmentioning

confidence: 99%

Tumor Necrosis Factor-α Predicts Response to Cardiac Resynchronization Therapy in Patients With Chronic Heart Failure

Rordorf

Savastano

Sanzo

et al. 2014

Circ J

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Background: Pro-inflammatory cytokines contribute to the pathophysiology of heart failure (HF) and are up-regulated in affected patients. We investigated whether pro-inflammatory cytokines might predict the response to cardiac resynchronization therapy (CRT). Methods and Results:Plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-6 were assessed in 91 patients before CRT. Response to CRT was defined as a decrease ≥15% in left ventricular end-systolic volume (LVESV) at 6 months. Baseline TNF-α did correlate with LVESV reduction (P=0.001) after CRT. The subject group was divided according to tertiles of TNF-α. From the lower to the upper tertile LVESV (-31±28%, -17±17%, -9±22%) and LV end-diastolic volume (-23±25%, -14±16%, -4±18%) were progressively less reduced after CRT (P<0.001). The proportion of responders to CRT was 70%, 42% and 33%, according to the lower, intermediate and upper tertile of TNF-α distribution (P=0.01). Serious cardiac events (cardiac death, HF hospitalization or urgent heart transplantation) occurred in 63% of patients in the upper tertile vs. 32% and 17% in the intermediate and lower tertiles, respectively, during a median follow-up of 47 months (P<0.001). Conclusions:Circulating TNF-α predicts the degree of LV reverse remodeling after CRT and may contribute to the early identification of those patients at higher risk of events after device implantation. (Circ J 2014; 78: 2232 -2239

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“…A similar difference in intra-individual biological variability could also explain the lack of prognostic value observed for IL-6 in the present study. 38 …”

Section: Tnf-α and LV Reverse Remodeling After Crtmentioning

confidence: 99%

Tumor Necrosis Factor-α Predicts Response to Cardiac Resynchronization Therapy in Patients With Chronic Heart Failure

Rordorf

Savastano

Sanzo

et al. 2014

Circ J

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“…The term cytokine is applied to a group of relatively small molecular weight protein molecules (generally [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] which are secreted by cells in response to a variety of stimuli. Classically, cytokines are thought to be secreted by ''producer cells'' and act in an autocrine, juxtacrine, or paracrine fashion to influence the biological behavior of neighboring ''target cells'' [8].…”

Section: Overview Of Cytokines Involved In Heart Failurementioning

confidence: 99%

Biomarkers of inflammation in heart failure

2009

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Heart failure (HF) is characterized by the elaboration of a portfolio of pro-inflammatory cytokines and inflammatory mediators that are considered to contribute to disease progression by virtue of the deleterious effects that these molecules exert on the heart and circulation. Recent studies have suggested that these inflammatory mediators may serve as relevant markers of disease severity and HF prognosis. Moreover, there is evidence that changes in the levels of inflammatory biomarkers may prove useful in following the change in patient clinical status following institution of appropriate HF therapy. This review will focus on the emerging role of inflammatory biomarkers, including pro-inflammatory cytokines, C-reactive protein, and erythrocyte sedimentation rate in patients with HF.

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“…Studies of patients with congestive heart failure (CHF) drawn from the general population have shown that high levels of soluble, circulating TNFRs are found in individuals with CHF and are powerful predictors of mortality independently of established markers of CHF severity (17,18). Circulating levels of TNF␣ and interleukin-6 (IL-6) have also been associated with mortality in CHF (17)(18)(19), although the short-term variability in the circulating levels of these cytokines may make them less useful predictors than soluble TNFRs (sTNFR), which maintain more stable levels (20)(21)(22).…”

mentioning

confidence: 99%

Circulating levels of tumor necrosis factor receptors are highly predictive of mortality in patients with rheumatoid arthritis

Mattey

Glossop

Nixon

et al. 2007

Arthritis & Rheumatism

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Objective. To investigate whether circulating levels of soluble tumor necrosis factor receptors (sTNFR) are predictive of mortality in rheumatoid arthritis (RA).Methods. Levels of sTNFRI and sTNFRII at study entry were quantified using enzyme-linked immunosorbent assays in sera from 401 white patients with RA followed up for 13 years. Patients were tracked via the National Health Service Central Register, and the relationship between sTNFR levels and mortality was analyzed using a Cox proportional hazards regression model. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated.Results. At the end of the followup period, 132 (32.9%) of 401 patients had died. Of these, 64 (48.5%) died of cardiovascular disease (CVD). Significant associations between all-cause mortality and baseline levels of sTNFRI and sTNFRII were identified in men (HR 1.7 [95% CI 1.2-2.4] and HR 1.18 [95% CI 1.05-1.32], respectively) and women (HR 1.33 [95% CI 0.99-1.8] and HR 1.14 [95% CI 1.02-1.28], respectively). Analysis including levels of both sTNFRI and sTNFRII indicated that the sTNFRII level was the best overall predictor of mortality. Multivariate analysis also revealed that the sTNFRII level was a predictor of all-cause and CVD mortality independently of age, sex, disease duration, C-reactive protein level, erythrocyte sedimentation rate, rheumatoid factor, nodular disease, modified Health Assessment Questionnaire score, taking CVD drugs, and smoking.Conclusion. Our data indicate that serum levels of sTNFR are powerful predictors of mortality in RA. Elevated levels are particularly associated with mortality due to CVD and may be useful for identifying patients at increased risk of premature death.

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Natural variability of circulating levels of cytokines and cytokine receptors in patients with heart failure: implications for clinical trials

Cited by 117 publications

References 38 publications

Tumor Necrosis Factor-α Predicts Response to Cardiac Resynchronization Therapy in Patients With Chronic Heart Failure

Tumor Necrosis Factor-α Predicts Response to Cardiac Resynchronization Therapy in Patients With Chronic Heart Failure

Biomarkers of inflammation in heart failure

Circulating levels of tumor necrosis factor receptors are highly predictive of mortality in patients with rheumatoid arthritis

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