[Is primary prevention of arterial hypertension with drugs possible? Results of the TROPHY Study].
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Biomedical subjects
Publications and source records attributed to Zh D Kobalava.
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AIM: To study effects of monotherapy with moxonidine and metformine on metabolic parameters in hypertensive patients with carbohydrate dysbolism (CD) regarding polymorphic markers of genes PPARalpha, PPARgamma and IRS type 1 and 2. MATERIAL AND METHODS: A total of 83 patients (31 male and 52 female patients aged 40-75 years) with untreated arterial hypertension stage I, obesity and CD (by glucose tolerance test) entered the trial. The patients were randomized into two groups. Patients of group I (n=42) received moxonidin in a dose 0.4 mg/day, of group 2 (n=41)--metformin in a dose 1000 mg/day. Measurement of arterial pressure, blood count and biochemistry, oral test for glucose tolerance with glucose and insulin measurement before meal and 1, 2 and 3 hours later was made initially and on the treatment week 16 Genotypes of polymorphic markers of genes PPARA, PPARG2, IRS1 and IRS2 were defined in all the patients. RESULTS: Changes in basic hemodynamic and metabolic indices in therapy with moxonidine depending on polymorphic markers of genes PPARA, PPARG2, IRS1 and IRS2 in patients with AH and CD showed that G allele PPARG2 is associated with greater weight loss, G allele PPARA--with weight loss, C allele PPARA--with maximal fall of diastolic blood pressure. CONCLUSION: Genetic factors participate in development of metabolic disturbances in hypertensive patients, obesity and CD and determine treatment efficacy in each individual patient.
AIM: To elucidate associations of polymorphic markers of PPAR, PPARG2, IRS1, IRS2 genes with disturbances of carbohydrate metabolism in patients with hypertension and excessive weight. MATERIAL: Patients (n=145, 53 men and 92 women, age 40-75 years) with untreated stage 1 hypertension (systolic BP 140-159 and diastolic BP <100 mm Hg) and excessive weight or obesity (body mass index >27 kg/m(2)) were divided into 2 groups: with (group 1, n=124) and without (group II, n=21) disturbances of carbohydrate metabolism. Group I comprised patients with insulin resistance, abnormal fasting blood glucose or glucose tolerance, type 2 diabetes. Results of oral glucose tolerance test were normal in 25 and abnormal in 99 of these patients. RESULTS: Carriers of Pro allele compared with carriers of Ala allele of PPARG2 gene had higher frequency of insulin resistance. No association was found between insulin resistance and alleles and genotypes of PPAR, IRS1, and IRS2 genes. There was an association between diastolic BP and polymorphic markers Pro12Ala of PPARG2 gene and C24313G of PPARA gene. Carriers of C allele of PPARA gene and Ala allele of PPARG2 gene had higher diastolic BP. No association was found between systolic BP and alleles and genotypes of polymorphic markers of PPARG2 and PPARA genes.
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AIM: To compare efficacy and tolerability of felodipine based antihypertensive therapy with those of standard hospital treatment of hypertension. MATERIAL: Inhospital patients were randomized 1:2 to standard antihypertensive therapy or to therapy which included felodipine (n=50 and 100, 36 and 35% men, mean age 66.0+/-8.4 and 64.3+/-8.1 years, initial blood pressure 162.4+/-9.3/99.3+/-6.4 and 163.2+/-10.3/98.2+/-6.5 mm Hg, respectively). Felodipine was used: (1) as first drug with subsequent addition of other drugs as required; (2) after cessation of previously ineffective therapy; (3) in cases of intolerance to previous therapy, (4) as supplementation to previously insufficiently effective therapy. Results. At discharge in felodipine group 6, 25, 29 and 40% of patients received mono- (felodipine 10 mg/day), 2, 3 and 4 component therapy, respectively. In standard treatment group all patients received combination therapy with 3 (48%) or 4 (52%) drugs. Felodipine group compared with group of standard therapy was characterized by less frequent correction of antihypertensive therapy (0.8+/-0.6 and 2.2+/-0.9, p<0.05), smaller number of drugs used (3.03+/-0.95 and 3.52+/-0.5, p<0.01), more frequently achievement of target blood pressure level (88 and 64%, p=0.0075), less pronounced difference between morning and evening self-measured blood pressure. CONCLUSION: The use of felodipine in hospitalized patients with hypertension allowed achieving target blood pressure with fewer drugs. Felodipine was safe and well tolerated.
Metoprolol is a selective beta(1)-adrenergic antagonist extensively used in major fields of cardiology since 1975. Metoprolol has proven its efficacy in reducing cardiovascular events and mortality in patients with hypertension and coronary heart disease in large clinical trials. Recently developed controlled release/extended release (CR/XL) formulation of metoprolol succinate was designed to provide relatively constant metoprolol plasma concentrations and beta(1)-blockade while retaining the convenience of once daily administration. The avoidance of high peak plasma concentrations with metoprolol succinate is associated with lesser degree of adverse effects and may improve patients compliance. This formulation of metoprolol has demonstrated efficacy in reducing cardiovascular events and mortality in patients with heart failure. More recently evidence for antiatherogenic activity of metoprolol succinate has been also obtained.
AIM: To evaluate relationships between structural-functional state of the left ventricle (LV) and genotype of angiotensin converting enzyme (ACE) gene in patients with postinfarction chronic cardiac failure (CCF) and effects of ACE inhibitor perindopril on hemodynamics depending on ACE gene polymorphism. MATERIAL AND METHODS: In 52 patients with CCF (functional class III-IV by NYHA criteria) who had survived macrofocal myocardial infarction we studied ACE gene using thermostable DNA-polymerase Taq. Isolation of genome DNA from human venous blood was made by phenolchloroform extraction with the use of chelate polymer Chelex-100. Polymerase chain reaction was conducted on amplificator PHC-2 or PolyChain II. LV contractile function was studied on echocardiograph "Toshiba SSH-160A (Japan). Echocardiography was performed before intake of perindopril, in the end of titration phase, on therapy month 6 and 12. RESULTS: Genotype II of ACE gene was detected in 11(21.1%) patients, ID genotype--in 20(38.5%), DD genotype--in 21(40.4%). Patients with ACE gene genotype II and ID have no differences by parameters of central hemodynamics. They were divided into two groups: group 1--patients with genotypes II and ID of ACE gene, group 2--patients with genotype DD. End diastolic volume (EDV), end systolic volume (ESV), index of LV myocardial mass were significantly less in group 1 than in group 2 (by 45.7, 81.6 and 31.2%, respectively). In group 1 ejection fraction (EF) and %delta S were higher by 35.3 and 35.7%, respectively. The hemodynamic effect of perindopril was higher in group 2. A month therapy resulted in a 8.7 and 14.8% reduction in group 2 EDV and ESV, respectively (p < 0.05). This entailed an increase in EF and %delta S by 18.3% (p < 0.05) and 19.8% (p < 0.05). Later, perindopril retained influence on central hemodynamics. Diastolic function to the end of therapy in both groups differed insignificantly. CONCLUSION: In CCF patients functional class III-IV with the history of myocardial infarction, structural-functional LV parameters depend on genotype of ACE gene. Perindopril is most effective in DD-genotype of ACE gene.
AIM: To study clinicogenetic determinants of left ventricular hypertrophy (LVH) regress in 52-week antihypertensive therapy to achieve the target arterial pressure (AP) < 140/90 mm Hg. MATERIAL AND METHODS: I/D-polymorphism of angiotensin converting enzyme gene, T174M-polymorphism of angiotensinogen gene, A1166C-polymorphism of angiotensin II ATI-receptor gene (ATII), 4a/b-polymorphism of endothelial NO-synthetase gene (eNOS) were determined in 64 patients (24 males, 40 females, mean age 54 +/- 1.1 years) with arterial hypertension (AH) and LVH. Echocardiography, laboratory tests, clinical measurements of blood pressure (BP) and 24-h AP monitoring were made after 4 weeks of placebo and 52 weeks of treatment. RESULTS: Baseline values of LV myocardium mass index (LVMMI) correlated significantly with mean 24 hour and night systolic arterial pressure; 24-h, day and night pulse pressure (PP). In patients with regress of LVH the degree of LVMMI reduction significantly correlated with lowering of day and night PP, baseline level of neutrophils, uric acid and creatinine 52 weeks after treatment. Groups made by polymorphism, did not significantly differ by initial LVMMI, frequency of achievement of target AP. In patients with genotypes ID/II and aa, the level of achieved diastolic arterial pressure was significantly lower than in other groups. Resistant LVH was seen in 42.2% patients. Frequency of AP normalization was higher in the group of patients with LVH regress (48.6% vs 25.9%; p < 0.05). Resistant LVH occurred more frequently in patients with genotype DD (64.0 vs 28.2% in patients with II/ID, p < 0.05) and in patients with genotype 4ab (62.9 vs 30.4% in patients with genotype aa and 21.4%--with genotype bb; p < 0.05 in both cases). In patients with resistant LVH frequency of DD genotype increased (59.3 vs 24.3% in patients with regress of LVH; p < 0.01), genotype AA (74.5 vs 48.6%; p < 0.01) and genotype ab (63.0 vs 27.0%, p < 0.01). CONCLUSION: Regress of LVH in AH patients depends on dynamics and complex interactions of some hemodynamic, laboratory and genetic parameters.
Evaluation of nocturnal blood pressure (BP) fall is important for prognosis and selection of antihypertensive therapy. We assessed stability of BP diurnal rhythm in 56 hospitalized hypertensive patients by means of 48-hour ambulatory BP monitoring. According to the degree of congruence of BP fall during two nights of monitoring the following groups of patients were distinguished: with similar diurnal BP rhythm in both nights (72% of all patients, including 42% with sufficient and 30% with insufficient nocturnal BP decline), with different diurnal BP rhythms - with sufficient fall of BP in one night and insufficient in another (28% of all patients). BP variability in all patients did not change and could be considered very stable. Thus when insufficient nocturnal BP fall is detected its stability should be confirmed by repeat BP monitoring.
Open noncomparative multicenter study of tolerability and efficacy of a retard form of indapamide (1.5 mg o.d. for 3 months) in patients older then 55 years was conducted in 14 centers in Russia. Numbers of patients included into was analysis of safety and tolerability were 1277 and 1121, respectively. After 3 months systolic, diastolic and pulse blood pressure (BP) decreased by 20.2, 13.2, 27.5% (supine) and by 19.4, 11.8, 26.9% (standing), respectively. There were no significant changes of heart rate. Effect of treatment was considered positive in 92.4% of patients. Normalization of blood pressure occurred in 51.8% of patients (in 46.2% and 53.4% among men and women, respectively, p=0.0252; in 55.7% and 48% among patients aged <65 and >65 years, respectively). In patients with type II diabetes rates of positive effect and achievement of target BP <130/85 mm Hg were 60.8% and 31.4%, respectively. Hypokaliemia (3.0-3.5 mmol/l) was registered in 43 patients (3.4%), age of 27 of these patients was 65 years. There were no pronounced changes of blood serum levels of creatinine, glucose and uric acid. Significant lowering of atherogeneity cholesterol index occurred in the whole group while both this index and total cholesterol significantly decreased in patients with baseline hypercholesterolemia. Thus in patients older that 55 years monotherapy with retard form of indapamide was demonstrated to be safe and effective antihypertensive intervention.
AIM: To study renal functional changes in patients with essential hypertension (EH) and normal blood creatinine levels during antihypertensive therapy with currently available drugs to achieve blood pressure lower than 140/90 mm Hg. MATERIALS AND METHODS: Renal functional changes were studied in 114 patients with EH and normal blood creatinine levels during antihypertensive therapy aimed at achieving blood pressure lower than 140/90 mm Hg. Glomerular filtration rate (GFR) was calculated by the Cockcroft-Gault formula and blood creatinine levels were measured before and 6, 12, 24, 52 weeks of treatment. RESULTS: Renal dysfunction was detected in 43.9% of the patients as GFR < 80 ml/min in 35.1% and hyperfiltration (GFR > 140 ml/min) in 8.8%. The patients with baseline decreased GFR were older, had a longer history of EH, and lower body-mass index than those with hyperfiltration (p < 0.05). There was a considerable renal functional improvement in patients with baseline decreased GFR and achieved BP < 140/90 mm Hg. Target BP could be achieved only in 20% of the patients with hyperfiltration. Antihypertensive therapy caused reduced hyperfiltration in these patients. In patients aged over 60 years who had a baseline GFR < 80 ml/min, achievement of target BP also promoted renal functional improvement. CONCLUSION: Most patients with EH and normal blood creatinine levels have renal dysfunction. Normalization of BP substantially improves renal functional parameters irrespective of age.
Allelic and genotypic distributions of the polymorphic markers C1167T and Pro197Leu of the genes of catalase (CAT) and glutathione peroxidase (GPX1), respectively, were studied in patients with non-insulin-dependent diabetes mellitus (NIDDM) and hypertension without complications (the control group, n = 52) and with complications: myocardial infarction (MI, n = 53) or stroke (n = 50). No significant differences were found between complicated and uncomplicated patients with respect to the allelic or phenotypic distribution. Thus, there were no association between these polymorphic regions and either MI or stroke in hypertensive NIDDM patients.
AIM: To study the hypotensive effect of the first dose in administration of perindopril and enalapril in patients with chronic cardiac failure (CCF). MATERIAL AND METHODS: The trial enrolled 213 patients with CCF of functional class II-III (mean age 57 +/- 1.4 years, 155 males and 58 females). The patients were randomized into 2 groups. Group 1 received perindopril in a dose 2 mg, group 2 received enalapril. Arterial pressure was measured for 10 hours with a 30-min interval, in the last 3 hours--once an hour. First dose hypotension was stated if systolic pressure was < 90 mmHg, diastolic under 60 mmHg, mean pressure < 75 mmHg after the first intake of the drug. RESULTS: Significant differences in the baseline pressure between the groups were absent. None of the patients demanded therapy of arterial hypotension. Side effects of hypotension were absent. In group 1 systolic pressure fell under 90 mmHg in 8(7.7%) patients, in group 2--in 24(22.0%) patients (p = 0.004), diastolic pressure fell under 60 mmHg in 47(45.2%) and 60(55.1%) patients, respectively (p = 0.151). Mean arterial pressure was < 75 mmHg in 42(40.4%) and 62(56.9%) patients, respectively, (p = 0.016). Multivariate correlation analysis has revealed a direct correlation between the first dose hypotension and age (r = 0.159, p < 0.01) and age > 70 years (r = 0.258, p < 0.01), acute myocardial infarction (r = 0.244, p < 0.01) and inverse correlation with the initial arterial pressure (r = -0.208, p < 0.01).
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AIM: To analyse epidemiologically chronic heart failure (CHF) according to 1996 records for patients admitted to therapeutic and cardiological departments of Moscow city hospital N 64. MATERIALS AND METHODS: An individual sheet has been developed for computer. The statistical processing has been conducted according to Access 97 program. It has covered 4019 case histories for 1996. 1232 patients were hospitalized for chronic cardiac failure this making 30.6% of all the hospitalizations. RESULTS: CHF was encounted in 60.9% of females and 39.1% of males. It was due to: ischemic heart disease (63.7%, with myocardial infarction in 73%), hypertension (17.5%), valvular disease (13.7%), dilated cardiomyopathy (3.7%), myocarditides and perocarditis (1.4%). Age groups 30-39 years, 40-49, 50-59, 60-69, 70-79, 80-89, 90-99 consisted of 0.6, 4, 11, 35.2, 31.4, 16.9, 0.6% of patients respectively. Females prevailed in the oldest age groups. The time from CHF diagnosis was 2, 3, 4, 5, 6, 7, 8, 9 and > 10 years in 26, 10.9, 4, 5.7, 0.9, 1.4, 1.7, 0.6 and 4% of patients, respectively. 72.9% of patients were admitted to hospital once a year. 19.7%, 5.2%, 0.9%, 0.6%, 0.9% of patients were hospitalized 2, 3, 4, 5 and more than 6 times, respectively. CHF was responsible for 50(27.8%) lethal outcomes of 180. Lethality resulted from cardiovascular insufficiency (50%), thromboembolism (30%), pneumonia (10%). CONCLUSION: CHF is a frequent cause of hospitalizations. Development of CHF, lethality, age groups distribution are closely associated with the patients' gender.
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