Kati Miettinen

Prognostic role of pro- and anti-inflammatory cytokines and their polymorphisms in acute decompensated heart failure

Cytokines play an important role in chronic heart failure (HF), but little is known about their involvement in acute decompensated heart failure (ADHF).

Utility of plasma apelin and other indices of cardiac dysfunction in the clinical assessment of patients with dilated cardiomyopathy.

Apelin is a recently discovered peptide ligand reported to be involved in the regulation of cardiovascular homeostasis. The exact role of apelin in the pathophysiology of congestive heart failure has remained obscure, and the reported circulating levels of apelin in patients with heart failure have been contradictory. To establish the role of apelin in the assessment of cardiac dysfunction we measured plasma apelin levels in 65 patients with congestive heart failure caused by idiopathic dilated cardiomyopathy (IDC) and 14 healthy volunteers by specific radioimmunoassay. IDC patients were carefully examined including echocardiography, both-sided cardiac catheterization and cardiopulmonary exercise test. In addition, plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), N-terminal pro-atrial natriuretic peptide (NT-proANP), interleukin (IL)-6, tumor necrosis factor alpha (TNF-alpha), epinephrine and norepinephrine were determined. Plasma apelin levels were similar in IDC patients (median 26.5 pg/ml, range<3.40-97.6 pg/ml) and in control subjects (median 24.1 pg/ml, range 19.0-28.7 pg/ml; p=NS). Unlike the levels of NT-proBNP, IL-6, TNF-alpha, and norepinephrine, plasma apelin levels did not reflect the severity of heart failure. Our study demonstrates that although disturbed apelin-APJ signalling in heart may play a role in the pathophysiology of heart failure, circulating apelin levels cannot be applied in the clinical assessment of patients with chronic left ventricular dysfunction.

The activation of the inflammatory cytokines in overweight patients with mild obstructive sleep apnoea

It is widely accepted that obstructive sleep apnoea (OSA) is linked with cardiovascular diseases. The relationship is complex and remains still poorly understood. The presence of chronic systemic inflammation has been connected with pathogenesis of both OSA and cardiovascular diseases. While atherogenesis is believed to be a process of many years, little is known about the potential impact of the largest OSA subgroup, mild OSA, on the development of cardiovascular diseases. The aim of the present study was to assess whether untreated mild OSA is associated with an activation of inflammatory cytokine system. The adult study population consisted of two groups: 84 patients with mild OSA [apnoea–hypopnoea index (AHI) 5–15 h−1] and 40 controls (AHI <5 h−1). Serum concentrations of pro‐ and anti‐inflammatory cytokines were measured before any interventions. After adjustments for age, sex, body mass index, fat percentage, most important cardiometabolic and inflammatory diseases, and non‐steroidal anti‐inflammatory medication, the mean level of tumour necrosis factor‐α was significantly elevated (1.54 versus 1.17 pg mL−1, P = 0.004), whereas the level of interleukin‐1β (IL‐1β) was reduced (0.19 versus 0.23 pg mL−1, P = 0.004) in patients with mild OSA compared with controls. The concentrations of the protective anti‐inflammatory cytokines, interleukin‐10 (1.28 versus 0.70 pg mL−1, P < 0.001) and interleukin‐1 receptor antagonist (478 versus 330 pg mL−1, P = 0.003) were elevated in the OSA group. The concentrations of C‐reactive protein increased, but IL‐1β decreased along with the increase of AHI. Mild OSA was found to be associated not only with the activation of the pro‐inflammatory, but also with the anti‐inflammatory systems.

Idiopathic dilated cardiomyopathy and chronic atrial fibrillation

Atrial fibrillation (AF) is common in idiopathic dilated cardiomyopathy (IDC). We explored the clinical characteristics of IDC patients with chronic AF compared with those with sinus rhythm (SR).

Prognostic role of NT-proXNP, a novel virtual analyte, in acute heart failure

function, whereas free fatty acids (FFA) may compromise contractile function. It is unknown whether short-term modulation of myocardial substrate supply affects risk markers of HF severity. Methods: We studied 8 patients with ischemic heart disease and chronic HF and 8 healthy controls. Each patient was subjected to a 3-h infusion of 1) saline (SAL), 2) insulin–glucose (INS) (high insulin, low FFA), and 3) somatostatin–heparin (HEP) (low insulin, high FFA). Measurements were made at baseline and during the last 15 min of each study period. Results: Hemodynamics remained unaltered. NT-proBNP, OPG and ADI were increased in patients compared to controls [NT-proBNP (pg/ml): 169±46 (patients) vs. 8±2 (controls), pb0.01]; [OPG (ng/ml): 1.8±0.3 (patients) vs. 1.2±0.1 (controls), pb0.05]; [ADI (mg/L): 13.7±2.1 (patients) vs. 10.0±1.4 (controls), p=0.07]. Expressed as percentage change from fasting baseline values, INS caused a significant decrease in NT-proBNP [(%): 98±5 (SAL); 90±3 (INS); 103±4 (HEP), pb0.05] and a near significant decrease in ADI [(%): 97±1 (SAL); 94±1 (INS); 97±1 (HEP), p=0.096]. OPG tended to be decreased during INS [(%): 119± 12 (SAL); 97±5 (INS); 111±11 (HEP), p=0.25]. Conclusions: In HF patients short-term metabolic modulation with insulin has a favourable effect on risk markers in spite of unaltered hemodynamics. Metabolic status must be considered when interpreting NT-proBNP, OPG, and ADI levels.