Congestive Heart Failure
Elevated interleukin-6 levels in patients with asymptomatic left ventricular systolic dysfunction,☆☆

https://doi.org/10.1067/mhj.2001.113078Get rights and content

Abstract

Background Elevated interleukin-6 (IL-6) levels are present in patients with New York Heart Association (NYHA) class III and IV congestive heart failure (CHF) and are associated with a poor prognosis. We sought to determine whether elevated IL-6 levels are also present in patients with left ventricular (LV) dysfunction but without clinical symptoms. Methods Blood samples were obtained from the femoral artery of 58 patients who underwent cardiac catheterization for recognized clinical indications. In a subgroup of 44 patients, samples were also obtained from the femoral vein, the left main coronary artery, and the coronary sinus. Patients with prior coronary artery bypass surgery, recent acute coronary syndrome, or steroid therapy were excluded. All samples were obtained before heparin or contrast administration. IL-6 was measured by enzyme-linked immunosorbent assay and values are expressed in picograms per milliliter. Results Three groups of patients were identified: controls, no CHF, LV ejection fraction ≥0.55 (n = 32); asymptomatic LV systolic dysfunction, no CHF, LV ejection fraction <0.55 (n = 14); and CHF, pulmonary edema (n = 12). IL-6 levels were higher at all sampling sites in both the asymptomatic LV systolic dysfunction and CHF groups compared with controls with the IL-6 levels inversely related to LV ejection fraction. Conclusions Elevated IL-6 levels are present in patients with LV dysfunction even in the absence of the clinical syndrome of CHF. These data suggest that IL-6 may be involved in the progression of subclinical LV dysfunction to clinical CHF. IL-6 may be a marker of patients at risk for progression to clinical CHF or a novel target for therapeutic intervention. (Am Heart J 2001;141:435-8.)

Section snippets

Study population and definitions

We studied 58 patients undergoing cardiac catheterization for a variety of clinical indications. There were no specific inclusion criteria other than a willingness to provide informed consent. The study protocol was approved by the institutional review board of the medical school. The clinical indications for catheterization included chronic stable angina (n = 24), atypical chest pain but an abnormal stress test (n = 20), CHF (n = 12), and evaluation of syncope (n = 2). An LVEF ≥0.55 was

Results

Of the 58 patients analyzed, 32 had no CHF and a normal LVEF (group 1), 14 had no CHF but depressed LVEF (group 2), and 12 had clinical CHF (group 3). Baseline characteristics for these groups are shown in Table I.

. Baseline characteristics for the 3 patient groups

Empty CellGroup 1 (n = 32)Group 2 (n = 14)Group 3 (n = 12)
Age (y)60 ± 2.461.6 ± 3.256.6 ± 5.7
Sex (male)21 (66)11 (79)7 (58)
Race (white)26 (81)9 (64)9 (75)
EF (%)70.1 ± 1.643.1 ± 3.1*30.8 ± 3.8*
Coronary disease17 (53)10 (71)5 (42)
CAD score1.2 ± 0.2

Discussion

Although elevated levels of IL-6 have been reported in patients with symptomatic CHF,3, 4, 5, 6, 7 a relationship between IL-6 and asymptomatic LV dysfunction has not been clearly defined. In our study cohort, we found elevated IL-6 levels in patients with LV systolic dysfunction but without any prior episodes of CHF. The magnitude of these elevations is intermediate between those with normal LV function and the levels reported for patients with CHF, both in this study and in previous reports.3

Acknowledgements

We thank William Boucher for performing the IL-6 measurements at the Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Mass. We also acknowledge the invaluable support of the technical and nursing staff in the cardiac catheterization laboratory.

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    Cardiac IL-6 expression is reported to increase in advanced HF, suggesting a potential role in prognosis.98 In addition, increased IL-6 levels have been associated with left ventricular dysfunction before HF diagnosis, highlighting its potential utility as a risk marker for the onset and progression of HF.99 This prognostic ability has been confirmed in acute HF for prediction of short-term and long-term mortality, both as a sole biomarker and in a multimarker approach when combined with NTproBNP.100

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Supported in part by a young investigator grant from Merck & Co., Inc (Whitehouse Station, NJ) to E. N. D.

☆☆

Reprint requests: Efthymios N. Deliargyris, MD, Cardiac Catheterization Laboratory, Administrative Offices, Room 2227, UNC Hospitals, 101 Manning Dr, Chapel Hill, NC 27514. E-mail: [email protected]

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