Elevated plasma levels of TNF-alpha and Interleukin-6 in patients with diastolic dysfunction and glucose metabolism disorders

Abstract

BackgroundDiabetes mellitus (DM) has reached epidemic proportions and is an important risk factor for heart failure (HF). Left ventricular diastolic dysfunction (LVDD) is recognized as the earliest manifestation of DM-induced LV dysfunction, but its pathophysiology remains incompletely understood. We sought to evaluate the relationship between proinflammatory cytokine levels (TNF-alpha, IL-6) and tissue Doppler derived indices of LVDD in patients with stable coronary artery disease.MethodsWe enrolled 41 consecutive patients (mean age 65+/-10 years) submitted for coronary angiography. Echocardiographic assessment was performed in all patients. Pulsed tissue Doppler imaging was performed at the mitral annulus and was characterized by the diastolic early relaxation velocity Em. Conventional transmitral flow was measured with pw-doppler. Early (E) transmitral flow velocity was measured. LVDD was defined as E/Em ratio ≥ 15, E/Em 8-14 was classified as borderline. Plasma levels of TNF-alpha and IL-6 were determined in all patients. A standardized oral glucose tolerance test was performed in subjects without diabetes.ResultsPatients with E/Em ratio ≥ 15, classified as LVDD and those with E/Em ratio 8-14 (classified as borderline) had significantly higher IL-6 (P = 0,001), TNF-alpha (P < 0,001) and NT-pro- BNP (P = 0,001) plasma levels compared to those with normal diastolic function. TNF-alpha and IL-6 levels remains significantly elevated after adjustment for sex, age, left ventricular ejection function, body mass index, coronary heart disease, smoking, hypertension and diabetes mellitus with linear regression analysis. Furthermore, in subjects LVDD or borderline LV diastolic function, 75% had diabetes or IGT, respectively. When subjects without diabetes were excluded, both IL-6 (P = 0,006) and TNF-alpha (P = 0,002) remained significantly elevated in subjects with E/Em ratio ≥ 15.ConclusionThis study reveals that increased plasma levels of IL-6 and TNF-alpha were associated with LVDD. These findings suggest a link between low-grade inflammation and the presence of LVDD. An active proinflammatory process may be of importance in the pathogenesis of diastolic dysfunction.

Biochemical markers of psoriasis as a metabolic disease

“…A positive correlation between TNF-alpha and BMI has also been reported [137]. Recently, it was reported that elevated plasma levels of TNF-alpha are associated with left ventricular diastolic dysfunction, which is one of the earliest manifestations of left ventricular dysfunction due to diabetes mellitus [138], while administration of TNF-alpha inhibitors leads to an increase of HDL levels [39]. It has been stressed that TNF-alpha is involved in the pathogenesis of metabolic syndrome [1,46].…”

Biochemical aspects of gender differences in response to cardiac resynchronization therapy

“…При отсут-ствии различий базовых уровней ИЛ-6 в группах его динамика была более выражена во II группе. С гиперпро-дукцией ИЛ-6 ассоциируется развитие диастолической дисфункции ЛЖ [39]. В исследованиях снижение уровня ИЛ-6, ФНО-α было описано только у респондеров [24,31].…”

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