Heart rate variability and increased risk for developing type 2 diabetes mellitus.

BACKGROUND/AIM: To our knowledge there are no data about the relationship between elevated risk for developing type 2 diabetes mellitus (DM2) and altered cardiac autonomic function. The aim of this study was to evaluate the association between heart rate variability (HRV) and slightly increased risk for DM2. METHODS: We evaluated 69 subjects (50.0 ± 14.4 years; 30 male) without DM2, coronary artery disease and arrhythmias. The subjects were divided into two groups according to the Finnish Diabetes Risk Score (FINDRISC): group I (n = 39) included subjects with 12 > FINDRISC ≥ 7; group II (n = 30) subjects with FINDRISC < 7. HRV was derived from 24-h electrocardiogram. We used time domain variables and frequency domain analysis performed over the entire 24-h period, during the day (06-22 h) and overnight (22-06 h). RESULTS: Standard deviation of the average normal RR intervals was significantly lower in the group with increased risk for DM2 compared to the group II (127.1 ± 26.6 ms vs 149.6 ± 57.6 ms; p = 0.035). Other time domain measures were similar in both groups. The group I demonstrated significantly reduced frequency domain measures, total power--TP (7.2 ± 0.3 ln/ms2 vs 7.3 ± 0.3 ln/ms2; p = 0.029), and low frequency--LF (5.9 ± 0.4 ln/ms2 vs 6.3 ± 0.6 In/ms2; p = 0.006), over entire 24 h, as well as TP (7.1 ± 0.3 In/ms2 vs 7.3 ± 0.3 In/ms2; p = 0.004), very low frequency (6.2 ± 0.2 In/ms2 vs 6.3 ± 0.2 In/ms2; p = 0.030), LF (5.9 ± 0.4 In/ms2 vs 6.2 ± 0.3 In/ms2; p = 0.000) and high frequency (5.7 ± 0.4 In/ms2 vs 5.9 ± 0.4 In/ms2; p = 0.011) during the daytime compared to the group II. Nocturnal frequency domain analysis was similar between the groups. The low diurnal frequency was independently related to elevated risk for diabetes mellitus (beta = -0,331; p = 0.006). CONCLUSION: The obtained results suggest that even slightly elevated risk for developing diabetes mellitus may be related to impaired HRV.

Impact of acute exercise on antioxidant enzymes activity and lipid status in blood of patients with hypertension.

BACKGROUND/AIM: Many studies support the hypothesis that oxidative stress is involved in the pathogenic process of a variety of diseases including hypertension. In humans, hypertension is also considered a state of oxidative stress that can contribute to the development of arteriosclerosis and other hypertension-induced organ damage. The aim of this study was to evaluate an influence of acute physical exercise on antioxidative enzymes activity and lipid status in patients with hypertension. METHODS: Fourty patients with hypertension and 20 age-matched controls were included in the study. To assess an influence of acute exercise on lipids and antioxidative enzymes activity the following parameters were determined at rest and immediately after the acute cardiopulmonary exercise cycloergometer test: triglycerides (TG), total cholesterol, low density cholesterol (LDL), oxidised LDL cholesterol (OxLDL), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and plasminogen activator inhibitor (PAI). RESULTS: In basal condition, hypertensive patients compared to the control group had increased, but not significantly, level of Ox LDL (88.61 +/- 14.06 vs 79.00 +/- 29.26 mmol/L), PAI (3.06 +/- 0.56 vs 2.6 +/- 0.35 U/mL) and activity of GSH-Px (50.22 +/- 15.20 vs 44.63 +/- 13.73 U/g Hb). After acute exercise test, there was significantly greater level of Ox LDL (79.0 +/- 29.26 vs 89.3 +/- 29.07 mmol/L; p < 0.05) only in the control group. GSH-Px activity was significantly decreased only in hypertensive patients after acute exercise (50.22 +/- 15.2 vs 42.82 +/- 13.42 U/g Hb; p < 0.05), but not in the controls. CONCLUSION: No significantly elevated Ox LDL, GSH-Px and PAI-1 levels were found in hypertensive patients during basal condition in comparison with healthy subjects. Decreased GSH-Px activity was associated with those in acute exercise only in hypertensive patients. It could be an important indicator of deficiency of physiological antioxidative defense mechanism in hypertensive patients during an acute exercise.

Clinical evaluation of oxidative stress in patients with diabetes mellitus type II -- impact of acute exercise.

BACKGROUND/AIM: Exercise is a well recognized model of oxidative stress and, also, an important tool in diabetes management. The aim of our study was to evaluate oxidative stress in patients with diabetes mellitus type 2 and to determine influence of acute exercise training on the investigated parameters. METHODS: To evaluate oxidative stress in the patients, we determinated following parameters: triglycerides (TG), total cholesterol, low density lipoprotein cholesterol (LDL), oxidized LDL cholesterol (Ox LDL), superoxide dismutase (SOD), glutathione peroxidase (GSHPx), plasminogen activator inhibitor (PAI) which were measured at rest and immediately after the acute bout of cardiopulmonary exercise cycle-ergometer test. RESULTS: In basal condition, diabetic patients compared to controls have significant higher values of TG (3.12 +/- 1.09 vs 1.74 +/- 0.9 mmol/L, p < 0.01), Ox LDL (84.73 +/- 16.90 vs 79.00 +/- 29.26 mmol/L, p < 0.05) and SOD enzyme activity (913.38 +/- 120.36 vs 877.14 +/- 153.18 U/g Hb, p < 0.05). During the acute exercise test, there was significant increase of Ox LDL in both the study patients (from 84.73 +/- 16.90 to 92.33 +/- 23.29 mmol/L, p < 0.05) and in the control group (from 79.00 +/- 29.26 to 89.30 +/- 29.07 mmol/L, p < 0.05). SOD activity was significantly increased in both groups during exercise, in diabetic patients from 913.38 +/- 120.36 to 921.50 +/- 130.03 U/gHb, p < 0.05, and in the controls from 877.14 +/- 153.18 to 895.00 +/- 193.49, U/gHb, p < 0.05. GSH-Px activity was significantly increased only in the diabetic patients after the acute exercise (from 45.04 +/- 11.19 to 51.81 +/- 15.07 U/gHb, p < 0.01), but not in the controls (from 44.63 +/- 13.73 to 43.97 +/- 25.97 U/gHb, p = ns). PAI significantly decreased during the exercise test, only in the healthy subjects (from 2.60 +/- 0.35 to 2.22 +/- 0.65, p < 0.05). Type 2 diabetic patients with complications had only significant increase in GSH-Px activity (from 47.10 +/- 7.37 to 54.52 +/- 11.97 U/gHb, p < 0.01). CONCLUSION: Elevated Ox LDL, SOD and GSH-Px levels are associated with acute exercise in type 2 diabetic patients. We suggest that it could be a compensatory mechanism to preventing free radicals tissue damage. We hypothesize that a physical training program induces an enhance of muscular and liver antioxidant enzymes activity and reduces oxidative stress. Further studies are needed to explore the relationship between exercise and antioxidant system in diabetic patients with and without complications.

Effects of acute exercise on atherogenic lipids in untreated mild hypertensive patients.

BACKGROUND/AIM: Exercise can positively influence risk factors associated with cardiovascular disease. The mechanisms by which exercise reduces atherogenic risk remain unknown. The aim of the present study was to investigate the effect of acute exercise (cardiopulmonary exercise cycle ergometer test) on atherogenic lipids in untreated mild hypertensive patients with or without hypercholesterolemia. This testing allows determination of exercise capacity, peak heart rate, and ventilation per minute (VE), peak oxygen uptake (pVO2) and exercise time (ET). METHODS: The study group included 85 untreated mild hypertensive patients (according to VII Joint National Committee--JNC 7) divided into two subgroups: hypertensive hypercholesterolemic and hypertensive normocholesterolemic. The control grouip included 35 normotensive subjects divided into two subgroups: normotensive hypercholesterolemic and normotensive normocholesterolemic. Lipid profiles to determine were oxidized LDL (OxLDL)--a marker of oxidative stress, triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol, which were measured at rest and 30 minutes after the acute bout of cardiopulmonary exercise cycle ergometer test. Lipids profiles were measured by enzymatic methods. Oxidized LDL was determined by a commercially available sandwich ELISA (Mercodia AB, Uppsala, Sweden). C-reactive protein (CRP) was measured using chemiluminiscent methods (Immulite-DPC). RESULTS: In our study OxLDL was significantly higher in hypertensive patients with atherogenic lipid profiles in basal condition, compared to the hypertensive patients without atherogenic lipid profiles and controls. There was a significant difference in CRP (p < 0.001) between hypercholesterolemics (hypertensive and normotensive) and normocholesterolemics (hypertensive and normotensive). We found increased OxLDL after exercise in both groups (hypertensive patients and normotensive), but only in the hypertensive hypercholesterolemic patients the difference was statistically significant (90.47 +/- 15.31 vs. 105.94 +/- 14.17 IU/L, p < 0.001). Systolic and diastolic blood pressures were significantly higher during exercise only in the hypertensive patients. There were significantly lower values of pVO2 only in hypertensive hypercholesterolemic patients. There were no significant differences between hypertensive and normotensive ones for ET and VE. In hypertensive ones we found after exercise a negative correlation between pVO2 and OxLDL (r = -0.473; p < 0.05), and pVO2 and CRP (r = -0.478; p < 0.05). We also found in normotensive normocholesterolemic patients a positive correlation between VE and systolic blood pressure (r = 0.420; p < 0.05), a negative correlation between VE and OxLDL (r= -0.421; p < 0.05), and VE and CRP (r = -0.561; p < 0.05). CONCLUSION: This study showed that acute exercise induces and increases oxidative stress only in untreated mild hypertensive patients with atherogenic lipid profiles. These results imply the need to normalize atherogenic lipid profile in untreated patients with mild hypertension in order to prevent an increased lipid peroxidation under acute exercise.

[Diastolic dysfunction types in the prediction of viable myocardium functional recovery].

BACKGROUND/AIM: It is well known that patients with coronary artery disease and viable tissue as a guarantee of contractile recovery (CR), despite of decreasing ejection fraction (EF) and systolic dysfunction, could have benefit from surgical revascularization. Therefore, relationship between diastolic filling type and early postoperative recovery and complications need to be established. The aim of this study was to investigate the relation between different left ventricular (LV) diastolic filling types and CR in patients after surgical revascularization with differently preserved systolic function. METHODS: We investigated 60 patients. All of them had CR estimated by stress echocardiography regardless the extent of recovery of the heart systolic function. Echocardiographic evidence of diastolic dysfunction was estimated by Doppler examination of transmitral diastolic flow. According to the derived different diastolic filling types the patients were divided into three groups: I--patients with disorder of LV relaxation, II--with pseudovascularisation, and III--with restrictive filling type, and according to the value of systolic function into two subgroups: (1) relatively recovered systolic function--EF > 40% and (2) pronounced LV dysfunction--EF < 40%. Echocardiographic evaluation was performed before and two week after surgical revascularization. In the preoperative period the medication therapy was optimized. We estimated CR by echocardiografic pare meters but also by detection of cardiovascular events. RESULTS: After CABG the mean value of WMISI LV tended to decrease in any groups: in the group I (n = 12) from 1.64 +/- 0.22 to 1.34 +/- 0.22; in the group II (n = 22) from 1.85 +/- 0.16 to 1.53 +/- 0.42, and in the group III (n=26) from 1.92 +/- 0.29 to 1.81 +/- 0.52. The lowest improvement of systolic function according to EF value expressed by the number of patients was found in the group of patients with restrictive LV filling type (12; 53.8%) as contrasting to the group with pseudonormalisation (15; 78.9%). In the group of patients with restrictive diastolic filling type also was recorded the highest number of lethal outcomes (6; 23.1%), as well as cardiovascular complications (10; 38.5%). CONCLUSIONS: Restrictive LV diastolic filling type was the marker of poor prognosis in the patients with clinical heart failure undergoing surgical revascularization. The patients with heart failure and preserved systolic function were associated with similar prognosis.

The cardioprotective role of preinfarction angina as shown in outcomes of patients after first myocardial infarction.

This prospective study evaluated the relationship between preinfarction angina (2 months before a 1st acute myocardial infarction) and the extent of postinfarction myocardial injury, myocardial perfusion, contractile function, and late recovery of global left ventricular contractile function. We enrolled 46 patients who had been admitted for a 1st, single-vessel-disease, acute myocardial infarction. Low-dose dobutamine echocardiography and technetium-99m-tetrofosmin scintigraphy were performed on all patients 7 to 10 days after acute myocardial infarction; and resting echocardiography was performed 7 to 12 months later. Twenty-seven of 46 (58.7%) patients had experienced angina before acute myocardial infarction, and 19 of 46 (41.3%) had not. There was no difference between the 2 groups in acute basal left ventricular ejection fraction (P=0.17) or in basal wall motion score index (P=0.521). The maximal creatine kinase-MB level was lower in the preinfarction-angina group (P=0.039). Patients with preinfarction angina had significantly more myocardial segments with preserved regional contractile function (P <0.0001) and significantly fewer segments with less than 50% perfusion (P=0.008). Stepwise regression analysis identified preinfarction angina (r2=0.317, P=0.032) as a significant predictor of the percentage of left ventricular ejection fraction recovery after the follow-up period. In our study, preinfarction angina was associated with decreased infarct size and with better protection of global and regional left ventricular contractility and improved preservation of the microvasculature. A history of preinfarction angina should be of value in predicting the late clinical outcomes of patients after a 1st acute myocardial infarction.

[Effects of reperfusion on late potentials of the QRS complex in acute myocardial infarction].

INTRODUCTION: Cardiac rhythm disorders are common in patients after myocardial infarction. They play an important role in the course and in prognosis of this illness. Signal-averaged electrocardiogram (SAECG) is a non-invasive diagnostic method for the induction of sustained monomorphic ventricular tachycardia. Early opening of the infarct-related artery decreases occurrence of ventricular disorders in these patients. The aim of this study was to establish the connection between the late potentials of the QRS complex (SAECG) and unsuccessful reperfusion in patients with acute myocardial infarction (AMI). MATERIAL AND METHODS: After myocardial infarction, presence of SAECG was examined in patients receiving reperfusion therapy in order to establish the treatment outcome. Late potentials in SAECG were determined by computer measurements in regard to criteria for its positivity. RESULTS: The study group consisted of 33 patients. Out of 23 patients with successful reperfusion, only 6 (26.1%) had late potentials, in contrast to the group without reperfusion, 8 (80%) out of 10 patients had late potentials. CONCLUSION: Based on our results, we can conclude that there is a significant association between the presence of late ORS-complex potentials (SAECG) and unsuccessful reperfusion. Also, we can conclude that presence of late potentials is an independent predictor of infarct-related artery patency in patients with AMI treated with thrombolytic therapy.

[Natriuretic peptides and multimarker approach to risk stratification of patients with acute coronary syndromes].

NATRIURETIC PEPTIDES IN ACUTE CORONARY SYNDROMES: Brain natriuretic peptides (BNP) and N-terminal prohormone brain natriuretic peptides (N-proBNP) have been shown to provide important prognostic information in patients with acute coronary syndrome (ACS). Ischemia may be an important stimulus for BNP release. This does not imply, however, that BNP is useful for diagnosing ischemia, and BNP is unlikely to prove sensitive or specific enough for this purpose. SIGNIFICANCE OF NATRIURETIC PEPTIDES IN ASSESSING PROGNOSIS IN PATIENTS WITH ACUTE CORONARY SYNDROMES: In patients with ST-elevation and non-ST-elevation myocardial infarction, higher BNP and N-proBNP levels have been shown to predict a greater likelihood of death or heart failure, independent of other prognostic factors. THERAPEUTIC IMPLICATIONS OF BNP ELEVATION IN ACUTE CORONARY SYNDROMES: Patients with BNP or NT-proBNP elevation following ACS are clearly at high risk for death and for developement of heart failure, but specific therapeutic implications of BNP elevation have not been defined. In particular, it is not known how patients with BNP elevation should be treated considering the fact that they have normal troponin levels and no clinical evidence of heart failure. MULTIMARKER STRATEGIES FOR RISK STRATIFICATION IN ACUTE CORONARY SYNDROMES: It has been shown recently that in patients with acute coronary syndromes the risk increased sequentially among those with one, two or three elevated biomarkers. THERAPEUTIC APPLICATIONS OF CARDIAC BIOMARKERS IN ACUTE CORONARY SYNDROMES: Multimarker strategies, that incorporate panels of cardiac biomarkers, are likely to be used in the future for risk stratification and for pathophysiologically-guided treatment of patients with ACS.

Late ventricular potentials in risk assessment of the occurrence of complex ventricular arrhythmia in patients with myocardial infarction and heart failure.

AIM: To determine the prognostic significance of late ventricular potentials on signal-averaged electrocardiogram and left ventricular ejection fraction for the occurrence of complex ventricular arrhythmia in patients treated with accelerated tissue-type plasminogen activator, using the rapid protocol, within six months of acute myocardial infarction. METHODS: In this analytic observational prospective study patients were divided into four groups: patients with left ventricular ejection fraction bellow 40% and late ventricular potentials, patients with left ventricular ejection fraction bellow 40% and without late ventricular potentials, patients with left ventricular ejection fraction over 40% and late ventricular potentials, and patients with left ventricular ejection fraction over 40% and without late ventricular potentials. Complex ventricular arrhythmias (Lown grade IVa, IVb, and V) were recorded using standard electrocardiography and 24-hour Holter monitoring 21, 60, and 90 days after acute myocardial infarction, respectively. Serial recordings of signal-averaged electrocardiogram were obtained 30, 90, and 180 days after acute myocardial infarction. Left ventricular ejection fraction was determined by echocardiography between 15 and 21 days after acute myocardial infarction. Multivariant logistic regression analysis was used to evaluate the relation between late ventricular potentials and left ventricular ejection fraction with the occurrence of complex ventricular arrhythmias. Sensitivity, specificity, positive and negative predictive values of late ventricular potentials and left ventricular ejection fraction for the occurrence of complex ventricular arrhythmias were determined. RESULTS: The prospective study included 80 patients (73% men), mean age 64 +/- 3.5 years. Complex ventricular arrhythmias were recorded in 34 (42.5%) of patients, all 17 (50%) of which were from the first group (p < 0.01). Complex ventricular arrhythmias were recorded in 25 (73.5%) patients with late ventricular potentials, and in 23 (67.6%) patients with left ventricular ejection fraction bellow 40%. Left ventricular ejection fraction bellow 40% and late ventricular potentials represented independent predictors for the occurrence of complex ventricular arrhythmias (RR = 14.33, p < 0.01). When combined with left ventricular ejection fraction bellow 40%, late ventricular potentials had sensitivity (0.50), specificity (0.93), and positive predictive accuracy (0.85) higher than late ventricular potentials alone (0.44, 0.67, and 0.37, respectively) for the occurrence of complex ventricular arrhythmias following acute myocardial infarction. CONCLUSION: In this study, late ventricular potentials in patients with left ventricular ejection fraction bellow 40% represented the independent predictor for the occurrence of complex ventricular arrhythmias in the first six months after the first myocardial infarction treated with accelerated tissue-type plasminogen activator, using the rapid protocol.