Bojan Miletić

Obesity dilemma in the global burden of cardiovascular diseases

Obesity is a well‐known risk factor in the cardiovascular disease continuum. However, its clinical effects are multimodal, perplexed and non‐unanimously understood. Our aim was to assess the prevalence and effects of obesity on the cardiometabolic risk factors and systolic function of left ventricle ejection fraction (LVEF) in patients scheduled for cardiovascular rehabilitation.

Granulysin Expression in Lymphocytes that Populate the Peripheral Blood and the Myocardium after an Acute Coronary Event

We aimed to analyse granulysin (GNLY)‐mediated cytotoxicity in the peripheral blood of patients with non‐ST‐segment elevation myocardial infarction (NSTEMI) treated with anti‐ischaemic drug therapy. Thirty‐nine NSTEMI patients with a median age of 70 years and 28 age‐matched healthy subjects were enrolled in this study. On day 7 after MI, the number of GNLY+ lymphocytes in the peripheral blood increased approximately six‐fold of that in the healthy subjects, measured by flow cytometry. On day 14, the number of GNLY+ cells significantly decreased in T, NKT, and both CD56+dim and CD56+bright NK subsets. GNLY+ CD3+ and GNLY+ CD56+ cells infiltrated central zone of myocardial infarction (MI). In persons who died in the first week after MI, GNLY+ cells were found within accumulation of apoptotic leucocytes and reached the apoptotic cardiomyocytes in border MI zones probably due to the influence of interleukin‐15 in peri‐necrotic cardiomyocytes, as it is was shown by immunohistology. By day 28, the percentage of GNLY+ lymphocytes in peripheral blood returned to the levels similar to that of the healthy subjects. Anti‐GNLY mAb decreased apoptosis of K562 targets using peripheral blood NK cells from days 7 and 28 after MI, while in assays using cells from days 1 and 21, both anti‐GNLY and anti‐perforin mAbs were required to significantly decrease apoptosis. Using NK cells from day 14, K562 apoptosis was nearly absent. In conclusion, it seems that GNLY+ lymphocytes, probably attracted by IL‐15, not only participate partially in myocardial cell apoptosis, but also hasten resolution of cardiac leucocyte infiltration in patients with NSTEMI.

Perforin‐Mediated Cytotoxicity in non‐ST Elevation Myocardial Infarction

The aim of this investigation was to examine the role of perforin (P)‐mediated cytotoxicity in the dynamics of tissue damage in patients with non‐ST‐segment elevation myocardial infarction (NSTEMI) treated with anti‐ischaemic drugs. We enrolled 48 patients with NSTEMI in this study [age, 71.5 years; 61.5/76 (median, 25th/75th percentiles)]. The percentage of total peripheral blood P+ lymphocytes was elevated owing to the increased frequency of P+ cells within natural killer (NK) subsets, T and NKT cells in patients on day 1 after NSTEMI when compared with healthy controls. Positive correlations were found between cardiac troponin I plasma concentrations and the frequency of P+ cells, P+ T cells, P+ NK cells and their CD56+dim and CD56+bright subsets during the first week after the NSTEMI. The expression of P in NK cells was accompanied by P‐mediated cytotoxicity against K‐562 targets at all days examined, except day 21, when an anti‐perforin monoclonal antibody did not completely abolish the killing. The percentage of P+ T cells, P+ NKT cells and P+ NK subsets was the highest on the day 1 after NSTEMI and decreased in the post‐infarction period. CD56+ lymphocytes were found in damaged myocardium, suggesting their tissue recruitment. In conclusion, patients with NSTEMI have a strong and prolonged P‐mediated systemic inflammatory reaction, which may sustain autoaggressive reactions towards myocardial tissue during the development of myocardial infarction.

Left ventricle diastolic dysfunction in obese patients with newly diagnosed arterial hypertension.

ZusammenfassungHINTERGRUND: Arterielle Hypertonie und Adipositas sind als unabhängige Risikofaktoren der linksventrikulären diastolischen Dysfunktion schon lange bekannt; ebenso bekannt ist die häufige Koexistenz von arterieller Hypertonie und Adipositas. Daten über die linksventrikuläre diastolische Dysfunktion bei adipösen Patienten mit neu diagnostizierter arterieller Hypertonie gibt es allerdings bisher nur wenige. Diese Studie wurde durchgeführt, um die Prävalenz der linksventrikulären diastolischen Dysfunktion bei adipösen Patienten mit neu diagnostizierter arterieller Hypertonie zu erheben. METHODEN: 125 adipöse Patienten wurden in unsere Studie einbezogen, davon 65 mit neu diagnostizierter arterieller Hypertonie. Alter, Geschlecht und Body Mass Index der Hypertoniker waren mit der Gruppe der 60 adipösen Nicht-Hypertoniker vergleichbar. Die linksventrikuläre diastolische Funktion wurde mittels Doppler-Echokardiographie durch Messung folgender Parameter erhoben: Geschwindigkeit des Mitral-Influx (E- und A-Welle), E-Wellen-Dezelerationszeit, isovolumetrische Relaxationszeit, linksatriale und linksventrikuläre Diameter, intraventrikuläre Septumdicke und linksventrikuläre Herzmasse. Ein E/A-Verhältnis <1 wurde als diastolische Dysfunktion aufgefasst. ERGEBNISSE: Bei neu diagnostizierten adipösen Hypertonikern wurden signifikant höhere A-Wellen, signifikant niedrigere E/A Verhältnisse, signifikant längere E-Wellen-Dezelerationszeiten und signifikant größere linke Vorhöfe gefunden. Die Spitzengeschwindigkeit der E-wellen unterschied sich nicht signifikant. Auch in der Prävalenz der linksventrikulären Hypertrophie und der linksventrikulären Herzmasse wurde kein signifikanter Unterschied gefunden. Die Prävalenz der diastolischen Dysfunktion war bei den adipösen Patienten mit neu diagnostizierter arterieller Hypertonie signifikant häufiger. KONKLUSION: Die Studie weist auf einen signifikanten Beitrag der neu diagnostizierten arteriellen Hypertonie zur Verschlechterung der diastolischen Funktion des linken Ventrikels bei adipösen Patienten – noch vor dem Nachweis struktureller Änderungen – hin.SummaryBACKGROUND: The frequent coexistence of obesity and arterial hypertension is well known. Although both conditions have been identified as independent risk factors for impaired left ventricular diastolic function, there is a paucity of data on the dysfunction among obese patients with newly diagnosed arterial hypertension. The study was performed to determine the prevalence of diastolic dysfunction in obese individuals with newly diagnosed arterial hypertension and to compare it with the prevalence in normotensive obese persons. METHODS: We enrolled 125 obese patients: 65 with newly diagnosed hypertension and 60 normotensive patients matched for age, sex and body mass index. Left ventricular diastolic function was assessed from the following Doppler-echocardiographic measurements: mitral inflow velocities (E and A wave), E wave deceleration time, isovolumetric relaxation time, left atrial and left ventricular diameters, left ventricular wall thickness and left ventricular heart mass index. Diastolic dysfunction was considered when the E/A ratio was <1. RESULTS: We found significantly higher A wave, lower E/A ratio, longer E deceleration time and a bigger left atrium in obese patients with newly diagnosed arterial hypertension. We did not find significant differences in E wave peak velocities between the two groups. Although there was no difference in left ventricle heart mass or the prevalence of left ventricle hypertrophy, the prevalence of diastolic dysfunction was higher in the group with newly diagnosed arterial hypertension. CONCLUSION: This study suggests that newly diagnosed arterial hypertension significantly contributes to impairment of left ventricular diastolic function in obese patients before development of structural aberrations detectable on echocardiography.