Arterial elasticity is associated with endothelial vasodilatory function and asymmetric dimethylarginine level in healthy subjects.

Arterial stiffening may be linked to the reduced bioactivity of nitric oxide (NO) and increased plasma concentrations of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA). The aim of this study was to investigate whether large (C1) and small artery (C2) elasticity is associated with endothelial function index (EFI) and plasma concentration of ADMA. We included 63 healthy subjects, aged 19 to 70 years, in the study. EFI, C1 and C2 were assessed by pulse wave analysis (PWA) and ADMA level was measured using an enzyme-linked immunoassay. Linear regression analysis revealed significant positive correlation between EFI and both C1 and C2 (R = 0.29, p = 0.02; R = 0.38, p = 0.002, respectively). A significant inverse association occurred between ADMA and C1 as well as C2 (R = -0.32, p = 0.03; R = -0.37, p = 0.009, respectively). In multiple regression analysis, C2 was determined by EFI, ADMA, age and BMI, and C1 was correlated with EFI, age and BMI. These findings suggest that endothelial vasodilatory dysfunction and accumulation of ADMA may be important mechanisms underlying reduced arterial elasticity in healthy subjects.

Hospital care of patients with ST-elevation myocardial infarction in four different European regions. Data from four regional myocardial infarction registries in Berlin, Dijon, Florence, and Tartu.

National surveys as well as European comparative studies suggest that differences in treatment of patients with ST-elevation myocardial infarction (STEMI) exist. The extent to which these variations influence the outcome of hospital care delivered to STE-MI patients in everyday routine is mostly unknown. In this study data representative of hospital care received by STEMI patients in four European regions (Berlin, Dijon, Florence and Tartu) were compared. The four registries are population based. The percentage of women and the mean age of the patients differed among the registries. Risk factors such as hypertension and hypercholesterolaemia also differed among the different regions, whereas a history of diabetes mellitus was similar among the registries. The percentage of patients receiving reperfusion therapy ranged from 47 to 81%. An appreciable difference also resulted after breaking down reperfusion therapy into thrombolysis and primary percutaneous coronary intervention (PCI). Hospital mortality as an outcome measure was very similar among the regions. After adjustment for age, the comparative magnitude of hospital mortality proportion was also very similar among three registries. Only the patients from Florence demonstrated a comparatively lower death rate, with a ratio of 0.81. In summary, there are important differences among baseline characteristics and hospital care of STE-Ml patients in the four study regions. Nevertheless, it was interesting to ascertain that the outcome measured in hospital mortality was very similar among the four registries compared.

The association between hyperglycaemia on admission and 180-day mortality in acute myocardial infarction patients with and without diabetes.

AIM: To evaluate the association between hyperglycaemia on admission, previously known diabetes and 180-day mortality in acute myocardial infarction (AMI) patients. METHODS: The study population consisted of 779 consecutive AMI patients from the Myocardial Infarction Registry in Estonia who had an admission venous plasma glucose level recorded and who were admitted to the Tartu University Clinics within a period of 2 years. Logistic regression analysis was used to estimate crude and adjusted odds ratios (OR) with 95% confidence interval (95% CI). RESULTS: In patients without a history of diabetes, glucose level was < or = 11.0 mmol/l in 556 patients (group 1) and > 11.0 mmol/l in 109 patients (group 2). Of those with diabetes, glucose level was < or = 11.0 mmol/l in 30 patients (group 3) and > 11.0 mmol/l in 84 patients (group 4). Non-diabetic hyperglycaemic patients underwent more resuscitations outside of hospital (group 2, 31.2% vs. group 1, 2.0% vs. group 3, 6.7% vs. group 4, 6.0%, P < 0.0001) and had a higher 180-day mortality compared with other groups (group 2, 47.7% vs. group 1, 14.1% vs. group 3, 26. 7% vs. group 4, 29.8%, P < 0.0001). After adjustment for potentially confounding factors, hyperglycaemic non-diabetic (OR 4.35, 95% CI 1.79-10.59), but not diabetic (OR 1.79, 95% CI 0.62-5.15) status, remained an independent predictor of 180-day mortality. CONCLUSIONS: AMI patients with hyperglycaemia on admission, independent of a history of diabetes, represent a high-risk population for 180-day mortality. The worst outcome occurs in non-diabetic hyperglycaemic patients. Further studies are warranted to clarify the questions of hyperglycaemia treatment in AMI patients.

Effect of low-dose aspirin on the markers of oxidative stress.

UNLABELLED: The present study estimates effects of low-dose enteric coated aspirin (ECA) on oxidative stress (OS) markers in a group of middle-aged men (mean age 51.2 +/- 6.9 years) free of pre-existing ischemic heart disease. METHODS: Serum products of lipid peroxidation, and measures of antioxidative status were detected in 25 healthy men in baseline and after two-week treatment period. RESULTS: In respect to serum products of lipid peroxidation and markers of antioxidant status, no statistically significant differences between the pre- and after-treatment data were observed for any measures, with the exception of values of serum antioxidative capacity (39.0 +/- 2.5 and 42 +/- 4.6, respectively). CONCLUSIONS: Administration of ECA does not initiate the OS in blood and improves the general antioxidative potency of blood. This may imply towards certain antiatherogenic influence of low-dose ECA, exhibited even with a short-term treatment period. Regarding OS markers, a variety of individual responses observed in the selected subgroups should be investigated and possibly taken into account while treatment with ECA is initiated for primary prevention of cerebrovascular events.

Heart rate variability in patients with the first and recurrent myocardial infarction.

Impairment of heart rate variability (HRV) has been reported in patients after myocardial infarction (MI). However, it is currently unknown whether the similar alterations of autonomic profile that accompany the first MI will evolve after a recurrent MI. Forty male outpatients with a previous first MI (group I) and 20 age-matched male patients with a recurrent MI (group II) were studied and measures of HRV were estimated from 24-hour electrocardiograms. In comparison with group I, group II had significantly higher values of ratio of low- to high-frequency power (6.9 +/- 5.7 vs 3.7 +/- 1.8, respectively, p < 0.05), and a tendency to lower values of all other measures of HRV. We conclude our study indicates that in comparison to group I, group II demonstrated augmented sympathetic drive as assessed by the indices of HRV. The shift toward adrenergic predominance detected after recurrent MI may result from altered afferent feedback from abnormally contracting left ventricular segments to the autonomic modulation of sinus node, or accompany subclinical state of heart failure not readily accessible with hemodynamic measurements.

Antihypertensive and renal effects of isradipine in essential hypertension: focus on renin system activity.

Calcium antagonists are known to exert various effects on the kidney that might modulate their antihypertensive potential. This study evaluated the renal effects, along with the efficacy, of isradipine in two subgroups of patients with mild to moderate essential hypertension (EH), defined according to plasma renin activity (PRA). Twenty-six patients were randomly assigned to receive 12-week treatment with slow-release isradipine (2.5-5 mg) or placebo. Assessment of PRA related to concurrent 24-hour sodium excretion was used to define patients with high/medium (n=16) and low renin profile (n=10). Urinary albumin excretion (UAE), serum creatinine and glomerular filtration rate (GFR, as endogenous creatinine clearance) were measured. Blood pressure (BP) decrease with isradipine was greater in the low PRA group as compared with the high/medium PRA group (P<0.05), and normalization of BP was achieved in all low-renin patients compared with 57% in the high/medium PRA group. BP reduction in the placebo group was statistically not significant. Isradipine, but not placebo, induced significant reduction in UAE (P<0.05); the decrease was similar in both PRA groups. Treatment did not cause any significant changes in GFR, PRA, urinary sodium or creatinine excretion, or serum aldosterone or creatinine concentrations. The decrease of BP in the whole isradipine-treated group was inversely correlated with pretreatment serum creatinine as well as with basal urinary creatinine excretion. In conclusion, the antihypertensive effect of isradipine was more pronounced in low-renin EH patients, despite similar effects on renal function and UAE in both PRA groups.

Oxidative stress and hyperinsulinaemia in essential hypertension: different facets of increased risk.

OBJECTIVE: To evaluate oxidative stress markers in normo- and hyperinsulinaemic essential hypertension patients, and to relate these parameters to plasma glucose and insulin levels. METHODS: Diene conjugates, thiobarbituric acid reactive substances, iron-stimulated thiobarbituric acid reactive substances and anti-oxidative capacity of serum were detected in 32 untreated essential hypertension patients with normal glucose tolerance, divided into hyperinsulinaemic (n = 12, fasting plasma insulin level > 13.5 mU/l, means 2 SD of controls) and normo-insulinaemic (n = 20) subgroups, compared with 26 age- and body mass index-matched controls. Plasma glucose and insulin levels were measured during an oral glucose tolerance test. RESULTS: Levels of lipid peroxidation products (diene conjugates, thiobarbituric acid reactive substances and iron-stimulated thiobarbituric acid reactive substances) were elevated and serum anti-oxidative capacity decreased both in hyper- and in normo-insulinaemic patients compared with those in controls, with no significant differences between the hypertensive subgroups. No independent correlations were detected between oxidative stress markers and fasting or stimulated plasma insulin and glucose levels. The essential hypertension patients were characterized by a lower fasting glucose: insulin ratio and enhanced plasma insulin response to oral glucose test compared with controls. CONCLUSIONS: The results suggest that oxidative stress occurs, in addition to disturbances in glucose metabolism, in essential hypertension patients, thus potentially exposing them to increased risk of developing complications. Factors other than plasma insulin level are likely to contribute to oxidative stress in hypertensive patients with normal glucose tolerance.

Evidence for oxidative stress in essential hypertension: perspective for antioxidant therapy.

BACKGROUND: Despite therapy, arterial hypertension continues to be a risk factor of coronary artery disease (CAD). The role of oxidative stress, an important source of vascular injury, in the genesis of this increased risk also needs to be defined, because several antihypertensive drugs have demonstrated antioxidant effects. This study tested the existence of oxidative stress in young (< 40 years) untreated patients with uncomplicated essential hypertension (EH). METHODS: Lipid peroxidation (LP) products (diene conjugates, basal and Fe-stimulated levels of thiobarbituric acid reactive substances) were detected spectrophotometrically in serum together with markers of antioxidant status (serum antioxidative capacity (AOC), red blood cell (RBC) glutathione) in 32 patients with mild-to-moderate EH and in 26 matched normotensive controls. RESULTS: All LP products were elevated (P < 0.01), while serum AOC was decreased (P < 0.001) and RBC glutathione increased (P < 0.05) in EH patients compared with controls. The presence of hypercholesterolaemia was not found to influence the differences in the measured parameters between hypertensive patients and controls significantly. CONCLUSIONS: The results indicate that oxidative stress occurs in young patients with uncomplicated EH. Therefore antihypertensive treatment; especially in patients whose vascular disease is still reversible, should provide antioxidant protection.

Fibrinogen and the albumin-globulin ratio in essential hypertension: relations to plasma renin system activity.

The present study was designed to evaluate the blood albumin-globulin ratio and fibrinogen levels in untreated patients with essential hypertension according to their renin profile, and to investigate the relationship between these hemorheologic variables and metabolic cardiovascular risk factors. Patients with uncomplicated essential hypertension (n = 36, DBP = 95-115 mm Hg) were studied. Normotensive, age and sex matched volunteers (n = 19) served as controls. Assessment of plasma renin activity (PRA) related to concurrent 24 h sodium excretion was used to define patients with high (n = 12), medium (n = 16) and low renin profile (n = 8). Plasma fibrinogen levels and the albumin-globulin ratio (A-G ratio) were determined. The A-G ratio was significantly lower (P < 0.05) in the high PRA group compared to the low renin group or the controls. The A-G ratio was significantly negatively related to PRA (r = -0.348; P = 0.043) and serum C-peptide (r = -0.395; P = 0.017). Fibrinogen levels were lower (P < 0.05) in the controls when compared to high and medium PRA group. Fibrinogen was associated with total cholesterol (r = 0.479; P = 0.037), HDL cholesterol (r = -0.467; P = 0.028), plasma triglycerides (r = 0.414; P = 0.012) and fasting plasma glucose level (r = 0.358; P = 0.032). In conclusion, essential hypertensive patients with high PRA display more pronounced alterations in blood proteins, particularly in the decrease of the A-G ratio than patients with low PRA. This may be one additional factor accounting for the higher incidence of cardiovascular disease previously reported in high PRA group.

Association between plasma renin activity and metabolic cardiovascular risk factors in essential hypertension.

OBJECTIVES: To study the relationships between plasma renin activity and metabolic cardiovascular risk factors in patients with essential hypertension. SUBJECTS AND DESIGN: Patients with uncomplicated essential hypertension (n = 36) with a diastolic blood pressure of 95-115 mmHg were studied. Assessment of plasma renin activity (PRA) related to urinary sodium excretion was used to define subgroups with high (n = 12), medium (n = 16) and low renin profiles (n = 8). MAIN OUTCOME MEASURES: Fasting plasma lipid levels were determined. Glucose, insulin and C-peptide responses to standard oral glucose tolerance test (OGTT) were measured. RESULTS: Patients with high PRA had higher levels of plasma cholesterol (6.13 +/- 0.81 versus 4.67 +/- 0.7 mmol L-1, P < 0.05) and triglycerides (2.14 +/- 0.18 versus 0.98 +/- 0.13 mmol L-1, P < 0.05), than the low PRA group. HDL-cholesterol levels were lower in the high renin group than in the low renin group (1.05 +/- 0.04 versus 1.26 +/- 0.09 mmol L-1, P < 0.05). Insulin and C-peptide sums were higher in high PRA group (33.8 +/- 1.2 versus 25.1 +/- 0.9 and 2.6 +/- 0.3 versus 1.9 +/- 0.4 ng L-1, P < 0.05), than in the low PRA group. CONCLUSIONS: Essential hypertensive patients with a high renin profile display more pronounced dyslipidaemia and higher levels of plasma insulin than patients with a low renin profile. This may be one explanation for higher incidence of cardiovascular disease previously reported in high PRA group.

Platelet Aggregation, Thromboxane A(2), Prostacyclin Generation and Platelet Sensitivity to Prostacyclin during the First Month after Myocardial Infarction.

This study was designed to investigate platelet aggregation, plasma thromboxane A, and prostacyclin concentration and platelet sensitivity to prostacyclin simultaneously during the first month after myocardial infarction (MI). Spontaneous platelet aggregation and aggregation responses to ADP and adrenaline were low on the day of admission, increased rapidly by the 7th day post-MI, remained elevated during the second week post-MI and reached the level of chronic coronary artery disease patients but not healthy persons at the end of the fourth week of illness. An increase in plasma thromboxane B, the spontaneous and stable breakdown product of thromboxane A, level and enhanced prostacyclin production, with a maximum on the third post-MI day, were observed. We also demonstrated a significant platelet resistance to prostacyclin in MI patients. Thrombocyte sensitivity to prostacyclin normalized by the end of the fourth post-MI week. These results indicate the need for therapy with platelet inhibitors in patients with MI.

Antiaggregative therapy with acetylsalicylic acid and diclofenac in patients with acute myocardial infarction.

A total of 109 male patients with acute transmural myocardial infarction (MI) were studied. 26 patients received a dose of acetylsalicylic acid (aspirin, ASA) 500 mg/d and 29 patients of 50 mg/d. 27 patients were given diclofenac (25 mg/d). 27 patients received no antiplatelet therapy. We observed thrombocyte hyperaggregation on the 1st MI day, a rapid increase in platelet activity by the 7th day and a considerable decrease in platelet aggregation during the 3rd and 4th weeks of illness in the group without antiaggregative treatment. The present study clearly demonstrated high antiaggregatory efficacy of ASA in dose of 50 mg/d which was significantly higher than that in daily dose of 500 mg ASA. Low-dose aspirin had fewer side-effects than aspirin 500 mg/d. However, although daily dose of 50 mg aspirin significantly inhibited platelet hyperaggregation on 7th day of MI, the hyperactivity of thrombocytes was not abolished. Diclofenac 25 mg daily had only a moderate antiaggregative efficacy in acute MI patients.

The influence of prostacyclin on hemodynamic and coronary blood flow in dogs.

Continuous intravenous infusion of prostacyclin (PGI2) was carried out for 30 to 120 min at the rates 25, 50, 75, 100 ng/kg/min in 149 experiments in 30 anesthetized dogs. PGI2 caused significant dose-dependent rise in heart rate, cardiac output, stroke volume and mean coronary artery blood flow. At the same time arterial blood pressures, total peripheral resistance and coronary vascular resistance decreased significantly while pulmonary artery pressures, central venous pressure, mean femoral artery blood flow and pressure rise velocity in left ventricle remained practically unaltered. Stady state of hemodynamic parameters was reached in 10 to 12 min. after the beginning of infusion. After discontinuation of infusion of PGI2 the values of recorded hemodynamic parameters returned to pre-infusion level in 10 to 15 min. Hemodynamic changes were well reproducible during repetitive infusions of PGI2 The purpose of this study was to determine the effects of PGI2 on various hemodynamic parameters.

[Assessment of the hemodynamic state of ischemic heart disease patients following aortocoronary shunting in relation to indices during surgery]. / Otsenka sostoianiia gemodinamiki u bol'nykh ishemicheskoi bolezn'iu serdtsa posle aortokoronarnogo shuntirovaniia v zavisimosti ot pokazatelei vo vremia operatsii.

Ninety-one coronary patients, aged 30 to 66 years, were investigated following aortocoronary shunting (ACS). The operations made use of assisted circulation (AC) and cold pharmacologic cardioplegia (CP). Three different cardioplegic solutions were used to achieve heart arrest and myocardial protection. Postoperative hemodynamic status was influenced by the duration of AC and CP as well as the composition of the cardioplegic solutions used, the number of shunts applied and the quality of revascularization. Temporary depression of the heart's pump function (within 1-2 months after ACS) was more pronounced in cases of: 1) longer time under AC and CP; 2) the use of a cardioplegic solution with a relatively low potassium content; 3) multiple shunts, and 4) partial revascularization.

[Dynamics of the insulin, somatotropic hormone, glucose and free fatty acid content in the blood during a direct myocardial revascularization operation under neuroleptanalgesia]. / Dinamika soderzhaniia insulina, somatotropnogo gormona, gliukozy i svobodnykh zhirnykh kislot v krovi pri operatsii priamoi revaskuliarizatsii miokarda v usloviiakh neiroleptanal'gezii.

The dynamics of the content of insulin, somatotropic hormone, glucose and the free fatty acids were studied in 32 male patients with ischaemic heart disease subjected to direct revascularization on the myocardium under neuroleptanalgesia and artificial circulation with moderate hypothermia and haemodilution. It is established that during operations on the coronaries under these conditions insulin secretion is not depressed, despite stable increase of the somatotropic hormone in the blood. High concentrations of glucose and insulin in the blood prevent the rise of the free fatty acids.