Heart remodeling in case of isolated systolic arterial hypertension

Examination of 32 patients with isolated systolic arterial hypertension (office blood pressure 171.9 = -3.3/79.7 +/- 0.2 mm Hg) and 54 ones with systolic/diastolic hypertension) 179.8 +/- 3.9/114.8 +/- 1.9 mm Hg) showed that the former are characterized by isolated hypertrophy of interventricular septum, the latter by symmetric hypertrophy of the septum and free left ventricular wall. Septal hypertrophy affects the initial phase of diastolic filling of the left ventricle as appears from longer time of isovolume relaxation and low peak rate of early transmitral blood flow; it does not influence diastolic function of the right ventricle. Hypertrophy of the free left ventricular wall disturbs the final stage of early diastolic filling of both right and left ventricles manifest as increased duration of their slowed early filling.     

Functional status of the circulatory system in during dynamics of treating arterial hypertension in patients with vibration disease

AIM: To develop medicinal approaches to correction of hemodynamic disturbances in vibration disease (VD) associated with arterial hypertension. MATERIAL AND METHODS: The study compared hypotensive and hypodynamic efficiency of amlodipin, diltiazem, enalapril, perindopril and indapamide in 74 VD patients with arterial hypertension (SAP 140-179 mm Hg, DAP 90-109 mm Hg; mean age 54.8 years, mean exposure to vibration 26.8 years). Before and after the treatment course the patients were examined with ultrasound by the following parameters: left ventricular contractility, left and right ventricular diastolic function, left atrial function. RESULTS: Amlodipin reduced left ventricular volume both in systole and diastole as well as maximal intramyocardial tension without significant change in contractility, raised a contraction reserve of the left atrium, improved ventricular relaxation. Diltiazem potentiates contractility of the left ventricle and atrium without marked impact on relaxation and tension of the myocardium. Enalapril and perindopril cause positive hemodynamic shifts. Perindopril vs enalapril was more effective in easing intramyocardial systolic tension of the left ventricular wall and in improving the diastolic function. Indapamid vs calcium antagonists and ACE inhibitors had a weaker effect on arterial pressure, no significant effect on left ventricular contraction, peripheral hemodynamics. Left atrial function was hyperactive. This was observed also in response to the other drugs. CONCLUSION: Amlodipin produced in patients with VD and AH more positive hemodynamic effects, reduced isotonic hyperfunction of the left ventricle, improves diastolic function of the ventricles. Amlodipin and perindopril are more promising prognostically in relation to reduction of left ventricular myocardial mass.     

Incidence of arterial hypertension in relation to the blood sugar level in men and women aged 20 to 69 (a 1-factor epidemiological study)

Arterial blood pressure (BP) was measured in 1225 males and 1243 females aged 20 to 69 years, who were also screened for glycemia by means of the glucose tolerance test (GTT). According to WHO recommendations, arterial hypertension (AH) was defined as systolic BP elevated to or above 160 mm Hg or diastolic BP elevated to or above 95 mm Hg. The incidence of AH was shown to be significantly related to the degree of glycemia in both males and females, the relationship being much closer in the latter. The prevalence of systolic AH in the females showed highly significant correlation to glycemia at any point of the GTT, while that of diastolic AH was only correlated with basal and 1-hour glycemia. In the males, the prevalence of systolic AH was significantly related to basal and 1-hour glycemia, and that of diastolic AH was only related to the distribution of basal glycemia.     

持续不卧床腹膜透析患者中不同血压表型与左心室肥厚患病率之间的关系研究

目的探讨持续不卧床腹膜透析(continuous ambulatory peritoneal dialysis,CAPD)患者中不同的血压表型与左心室肥厚的患病率之间的关系及对左心室心肌重构的影响。方法选择127例CAPD患者,根据诊室测量的肱动脉血压将患者分为4组:正常血压组(46例):收缩压(SBP)140mmHg(1mm Hg=0.133kPa)且舒张压(DBP)90mm Hg;孤立收缩期高血压(isolated systolic hypertension,ISH)组(42例):SBP≥140mm Hg且DBP90mm Hg;双期高血压(systolic/diastolic hypertension,SDH)组(39例):SBP≥140mm Hg且DBP≥90mm Hg;孤立舒张期高血压(isolated diastolichypertension,IDH)组(0例):SBP140mm Hg且DBP≥90mm Hg。收集患者基本资料、血生化检查资料,并采用超声心动图检查评估3组患者的心脏形态功能及血流动力学指标,包括左心室质量(LVM)、左心室质量指数(LVMI,身高2.7标化的LVM)、左心室肥厚(LVH)患病率、左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)、左心室舒张期早晚期二尖瓣口血流频谱(E峰、A峰、E/A)、心输出量(CO)、心脏指数(CI)、心每搏输出量(SV)、心每搏指数(SI)、总外周阻力(TPR)和总外周血管阻力指数(TPRI)等,并将血压表型、体质量指数(BMI)、性别、透析龄、血肌酐(SCr)、TPRI等纳入左心室肥厚的可能危险因素进行多因素logistics回归分析。结果 3组间基本资料、血脂状态、贫血状况差异均无统计学意义(P0.05);SBP、DBP、平均动脉压(MAP)、脉压(PP),SDH组ISH组正常血压组(P0.01),LVM、LVMI在ISH组和SDH组均高于正常血压组(P0.05);LVH的患病率在ISH组为76.2%,在SDH组为71.8%,均高于正常血压组(50.0%,P0.05)。LVEF、LVFS,SDH组和ISH组均低于正常血压组(P0.01)。LVEDD和LVESD在SDH组和ISH组高于正常血压组(P0.01),E峰在3组间无差异,而A峰在SDH组低于ISH组(P0.01),E/A在SDH组高于ISH组及正常组(P0.01);TPR和TPRI在SDH组高于ISH组和正常血压组。多因素logistics回归分析显示,ISH组和SDH组患LVH的风险分别是正常血压组的2.01倍和1.74倍;女性患LVH的风险是男性的1.36倍;透析龄每增加一个月患LVH的风险增加0.03倍。结论 CAPD患者中,高血压表型是左心室肥厚的独立危险因素,SDH表型患者外周血管阻力较高,左心室舒张功能减低明显,而ISH表型患者LVH患病率和危险度较高,因此高血压不同表型对心血管损伤机制可能存在差异,其中ISH压型对心脏重构的影响较大,LVH患病危险度较高。     

The rhythms of arterial pressure and heart rate in individuals with arterial hypertension under the conditions of Far North

The circadian and ultradian rhythms of blood pressure (BP) and heart rate (HR) were studied by means of 24-hour BP monitoring in patients with arterial hypertension (AH) and practically healthy people working in Far North shifts. The subjects were 418 men. The main group consisted of 177 men aged 18 to 59 working in trans-polar shifts in Yamburg, Tyumen region, latitude 57 North. The comparison group included 158 residents of a moderate climatic zone (Tyumen, latitude 57 North). The control group consisted of 83 practically healthy men, of whom 43 worked in Far North shifts, and 40 were residents of Tyumen. The groups were comparable by age, AH duration, and office systolic and diastolic BP (SBP; DBP). The study demonstrates that even healthy people working in Far North shifts display high BP variability and the decrease of the stability and power of SBP, DBP and HR circadian rhythms due to the reduction of the amplitude, contribution of the rhythm to the total variability, and the increase of the amplitude of high-frequency harmonics of the spectrum (a manifestation of extracircadian dissemination), which may be a sign of accelerated ageing and biological age increase, and may facilitate AH development. Development of AH under the extreme conditions of Far North shifts, unlike the conditions of moderate climatic zones, is accompanied by progressive BH variability increase, the worsening of the chronological structure of SBP and DBP, the increase of extracircadian dissemination, which can be of both clinical and prognostic significance.     

24-Hour blood pressure profile in patients with mild and moderate arterial hypertension and sleep apnea/hypopnea

AIM: To evaluate 24-hour blood pressure (BP) profile in arterial hypertension (AH) patients (pts) with desaturation signs of sleep apnea/hypopnea syndrome (SAHS). MATERIAL AND METHODS: We investigated 61 pts (44 males and 17 females) aged between 23-70 (52 +/- 2) years with mild to moderate AH. BP monitoring was performed with multisensor system TM-2425 (A&D, Japan). We assessed the following parameters: mean 24-h, awake, sleep systolic (S), diastolic (D) and pulse (P) BPs, systolic and diastolic BP loads ("normalized area under the curve"--NAUC). A normal circadian rhythm of BP was defined when nocturnal fall of SBP was > 10% and < 20%. The morning rise of BP we assessed by speed of increase of mean BP from 4 a.m. to 12 a.m. The nocturnal monitoring of arterial oxygen saturation(SaO2) was performed with pulseoximeter "NONIN 8500M" (USA). The analysis of the results was performed with the original program ARM-SaO2". The presence of SAHS was confirmed when the number of 4% desaturations were greater than 15 per hour or in the presence of group episodes of 4% desaturation below 90%. In 19 pts we revealed desaturation signs of SAHS. The comparison group included pts without SAHS (n = 42). We compared the groups regarding 24-h BP profile parameters. RESULTS: SAHS group had the following parameters significantly higher: mean 24-h (151.7 +/- 4.5 vs 142.9 +/- 2.4 mm Hg, p < 0.07) and sleep SBPs (142.8 +/- 5.1 vs 132.7 +/- 2.6 mm Hg, p < 0.05); mean 24-h (65.2 +/- 2.6 vs 55.9 +/- 1.9 mm Hg, p < 0.008), daytime (65.6 +/- 2.7 vs 56.6 +/- 2.0 mm Hg, p < 0.01) and sleep PBPs (64.1 +/- 2.7 vs 53.1 +/- 1.9 mm Hg, p < 0.002); 24-h (20.1 +/- 3.8 vs 12.6 +/- 1.8 mm Hg, p < 0.05) and sleep NAUC of SBP (24.6 +/- 4.4 vs 15.3 +/- 2.2 mm Hg, p < 0.03). In the group with SAHS were significantly higher the frequency of abnormal circadian rhythm of SBP (84 vs 57%, p < 0.05) and the speed of morning rise of mean BP (23.3 +/- 5.9 vs 8.5 +/- 2.8 mm Hg/h, p < 0.01). CONCLUSION: Our results suggest that pts with desaturation signs of SAHS are characterized by unfavourable changes in 24-h BP profile parameters, first of all owning to sleep systolic and pulse blood pressures with alteration of circadian rhythm and high speed of morning rise of BP.     

Disorders of 24-h rhythm of blood pressure in patients with chronic glomerulonephritis

AIM: To characterize 24-h profile of blood pressure (BP) and to clarify prognostic significance of 24-h BP variability in patients with chronic glomerulonephritis (CGN) with intact renal function and hypofunction of the kidneys. MATERIAL AND METHODS: A total of 38 hypertensive CGN patients (29 males and 9 females, mean age 37.9 +/- 12.4 years) entered the trial. All the patients had systolic BP (SBP) > 140 mm Hg and/or diastolic BP (DBP > 90 mm Hg. RESULTS: Twenty patients with renal hypofunction (creatinine > 1.4 mg/dl) had significantly higher (p < 0.05) SBP, day and 24-h SBP duration, high variability of day-time and 24-h SBP. Significantly higher mean day-time, night-time and 24-h SBP, SBP day-time and 24-h duration SBP duration, variability of SBP and DBP for a day and 24-h, respectively, were observed in 15 patients with left ventricular hypertrophy. Of prognostic significance in relation to renal survival estimated by Cox in 21 patients in multifactorial analysis were blood creatinine level, glomerular filtration rate, the patient's age, SBP duration for day, night and 24 hours. In multifactorial analysis, the final model included only age of the patient and blood creatinine. CONCLUSION: CGN patients with renal hypofunction had higher SBP and its variability associated with left ventricular variability.     

Digit preferences observed in the measurement of blood pressure: repercussions on the success criteria in current treatment of hypertension.

In a multicenter, open, noncomparative trial to assess the efficacy of an angiotensin-converting enzyme inhibitor, quinapril (Accupril; Parke-Davis), after 12 weeks of treatment in 667 adult patients 19-83 years of age with stage 1-3 hypertension, conducted by 85 physicians in primary health care, with systolic blood pressure (SBP) < 140 mm Hg and diastolic blood pressure (DBP) < 90 mm Hg as criteria for normalization, the efficacy of the drug was 75.1%. When an analysis was made of the frequency tables of BP recorded by the physicians in the case-report forms, a clear numerical preference was found in which the DBP was expressed in multiples of 5 in 81.3% of the cases and the SBP was expressed in multiples of 10 in 19% of the records, so that when a cutoff point <140/90 mm Hg is chosen in daily practice, 130/85 mm Hg is actually being selected. It suffices to change the criteria to accept as normal values less than or equal to instead of less than 140/90 mm Hg to increase the efficacy of the drug from 75.1% to 90.7% in our trial. Therefore, it is proposed to use multiples of 5 for DBP and multiples of 10 for SBP as cutoff points and the diffusion of clear recommendations on BP measurement.     

Association between human atrial natriuretic peptide Val7Met polymorphism and baseline blood pressure, plasma trough irbesartan concentrations, and the antihypertensive efficacy of irbesartan in rural Chinese patients with essential hypertension

BACKGROUND: Individual variations in the pharmacokinetics and pharmacodynamics of antihypertensive drugs are influenced by genetic and environmental factors. The ANP gene, which encodes the precursor of atrial natriuretic peptide (ANP), is among the candidate genes for genetic susceptibility to hypertension. OBJECTIVE: This study examined the relationship between ANP Val7Met polymorphism (Single Nucleotide Polymorphism database ID: rs5063) and baseline blood pressure (BP), plasma trough irbesartan concentrations, and the antihypertensive efficacy of irbesartan in rural Chinese patients with essential hypertension. METHODS: Patients with essential hypertension who had taken no antihypertensive medications within 4 weeks of study initiation received oral irbesartan 150 mg/d for 4 weeks. Genotyping was performed for all patients. BP was measured before dosing on the 1st and 28th days of treatment. Plasma irbesartan concentrations were measured using high-performance liquid chromatography with fluorescent detection. Antihypertensive efficacy was defined as attainment of a diastolic BP (DBP) <90 mm Hg (DBP analysis), a systolic BP (SBP) <140 mm Hg (SBP analysis), and a DBP <90 mm Hg and SBP <140 mm Hg (DBP and SBP analysis). RESULTS: The study included 756 patients, 621 with the Val/Val genotype and 135 with the Val/Met+Met/Met genotypes. There were no significant differences in age, body mass index, sex, education level, occupation, alcohol consumption, or smoking status between the 2 groups. Patients with the Val/Met+Met/Met genotypes had a significantly lower mean baseline DBP compared with those with the Val/Val genotype (adjusted regression coefficient [SE]: -2.5 [1.0] mm Hg; P = 0.012) and significantly lower mean steady-state plasma trough irbesartan concentrations (adjusted regression coefficient: -12.6 [4.1]; P = 0.002). No significant association was found between antihypertensive efficacy and Val7Met polymorphism in the overall population, but in an analysis by baseline DBP status, patients with the Val/Met+Met/Met genotype a baseline DBP > or =100 mm Hg had significantly smaller reductions in DBP (adjusted regression coefficient: -5.7 [1.4] mm Hg; P < 0.001) and SBP compared with those with the Val/Val genotype and a baseline DBP > or =100 mm Hg (adjusted regression coefficient: -9.8 [2.9] mm Hg; P < 0.001). CONCLUSION: The findings of this study suggest that in these rural Chinese patients with essential hypertension, ANP Val7Met polymorphism may be a genetic marker for baseline DBP, plasma irbesartan concentrations, and the antihypertensive efficacy of short-term irbesartan therapy.     

Antihypertensive efficacy and tolerability of two fixed-dose combinations of valsartan and hydrochlorothiazide compared with valsartan monotherapy in patients with stage 2 or 3 systolic hypertension: an 8-week, randomized, double-blind, parallel-group trial

BACKGROUND: Combination therapy with at least 2 antihypertensive agents is usually needed to achieve appropriate blood pressure (BP) control in patients with isolated or predominant systolic hypertension. A currently recommended combination is a diuretic added to an angiotensin-receptor blocker. OBJECTIVE: This was a study of the effects on sitting systolic BP (SBP)of 2 combinations of valsartan and hydrochlorothiazide (HCTZ) compared with valsartan monotherapy in patients with stage 2 or 3 systolic hypertension (SBP > or =160 mm Hg and < or =200 mm Hg) with or without other cardiovascular risk factors. METHODS: After a placebo run-in period, patients were randomized to receive double-blind treatment with either valsartan 80 mg OD(monotherapy group) or valsartan 160 mg OD (combination-therapy groups) for 4 weeks, followed by forced titration to valsartan 160 mg OD (V160), valsartan 160 mg plus HCTZ 12.5 mg OD (V160 +HCTZ12.5), or valsartan 160 mg plus HCTZ 25 mg OD (V160 +HCTZ25) for an additional 4 weeks. End points were the change in SBP between the groups receiving combination therapy and the monotherapy group, between-group changes in diastolic BP (DBP), responder rates (SBP <140 mm Hg or a reduction in SBP of > or =20 mm Hg), and tolerability. RESULTS: A total of 774 patients were randomized to treatment: 261 to V160, 258 to V160+HCTZ12.5, and 255 to V160 +HCTZ25. The intent-to-treat population consisted of 767 patients (411 men, 356 women; mean age, 60 years; mean weight, 84 kg; clinic mean [SD] baseline BP, 167.5 [8.1]/93.4 [9.1] mm Hg). All treatments produced significant reductions in SBP from baseline (mean [SD] reduction, 20.7 [15.7] mm Hg with V160, 27.9 [13.8] mm Hg with V160 +HCTZ12.5, and 28.3 [13.1] mm Hg with V160+HCTZ25; all, P < 0.05). DBP was reduced by 6.6 (8.9) mm Hg in the V160 group and by 10.2 (7.7) and 10.1 (7.8) mm Hg in the V160+HCTZ12.5 and V160 +HCTZ25 groups, respectively (all, P < 0.05). The additional reductions in BP with V160+HCTZ25 did not reach statistical significance compared with V160+HCTZ12.5. Responder rates were 56.9% in the V160 group, 74.4% in the V160+HCTZ12.5 group, and 75.0% in the V160 +HCTZ25 group P < 0.05, combination therapy vs monotherapy). Adverse events were reported by 27.5% of patients in the monotherapy group, compared with 28.6% and 34.0% in the groups that received V160+HCTZ12.5 and V160+HCTZ25, respectively; the differences were not significant between treatment groups. CONCLUSIONS: Monotherapy with V160 was effective in these patients with stage 2 or 3 systolic hypertension. Significant additional reductions in SBP and DBP and an increase in responder rates were achieved with the addition to V160 of HCTZ12.5 and HCTZ25, with no significant effect on tolerability.     

A systematic review and meta-analysis of the efficacy and safety of a fixed, low-dose perindopril-indapamide combination as first-line treatment of hypertension

BACKGROUND: A low-dose combination of perindopril and indapamide may effectively reduce blood pressure (BP) in hypertensive patients, but some factors related to study design might have contributed to the between-group differences in the rate of reduction of BP observed in some trials. OBJECTIVE: The aim of this study was to systematically assess the efficacy and safety profiles (through review of randomized, controlled trials) of the fixed, low-dose combination perindopril 2 mg and indapamide 0.625 mg given as 1 tablet daily as first-line antihypertensive therapy in patients with mild to moderate hypertension. METHODS: We searched MEDLINE (1966-April 2003), EMBASE (1980-March 2003), BIOSIS (1999-December 2002), and the Cochrane Library, using the medical subject headings with the search terms perindopril, indapamide, hypertension, randomized controlled trials, randomly, random, randomization, perindopril-indapamide, essential hypertension, and primary hypertension. Additional articles were obtained from the reference lists of relevant reviews and papers. RESULTS: We reviewed 11 trials (5936 individuals). In 5 studies of perindopril-indapamide versus placebo, the between-group weighted mean differences (WMDs) for both systolic and diastolic BP (SBP and DBP, respectively) favored perindopril-indapamide (SBP, -9.03 mm Hg [95% CI, -9.54 to -8.52]; DBP, -5.09 mm Hg [95% Cl, -5.42 to -4.77]; both P < 0.01 for z score for overall effect). In 6 studies of perindopril-indapamide versus routine antihypertensives, the between-group WMDs for SBP and DBP favored perindopril-indapamide (SBP, -3.72 mm Hg [95% CI, -7.11 to 0.33], P = 0.03 for z score for overall effect; DBP, -1.71 mm Hg [95% CI, -2.27 to -1.16], P < 0.01 for z score for overall effect). Five studies compared perindopril-indapamide and placebo; in the remaining 3 studies, which assessed perindopril-indapamide versus routine antihypertensives, the between-group WMDs for SBP and DBP favored perindopril-indapamide (SBP, -4.00 mm Hg [95% CI, -6.54 to -1.47], P < 0.01; DBP, -1.02 mm Hg [95% CI, -1.73 to -0.31], P < 0.01). Adverse events and withdrawals were not significantly different between perindopril-indapamide, placebo, or routine antihypertensive drugs. CONCLUSION: The studies in our analysis consistently demonstrated that a fixed, low-dose perindopril-indapamide combination has a favorable safety profile and may be efficacious as first-line treatment for patients with mild to moderate essential hypertension.     

Beneficial Effect of a Long-Term Antihypertensive Therapy on Blood Pressure Response to Isometric Handgrip Exercise in Patients with Essential Hypertension

To elucidate the effect of a long-term antihypertensive therapy on blood pressure (BP) response to isometric handgrip exercise (IHG) in patients with essential hypertension (EHT, n = 16), IHG was carried out at 30% maximal voluntary contraction of right hand for 3 min before therapy and after a long-term antihypertensive therapy. BP responsiveness to IHG was estimated by the difference between values obtained at rest and at 3 min during IHG (change of systolic BP = DeltaSBP, change of diastolic BP = DeltaDBP. Both DeltaSBP and DeltaDBP before therapy were markedly greater in EHT (DeltaSBP = 64 plus minus 18 mm Hg, DeltaDBP = 33 plus minus 9 mm Hg) than in age-mathced normotensive controls (NT, n = 8, 29 plus minus 4 mm Hg, 18 plus minus 4 mm Hg). By antihypertensive therapy, SBP and DBP in EHT were decreased from 152 plus minus 22 mm Hg to 136 plus minus 14 mm Hg and from 90 plus minus 18 mm Hg to 83 plus minus 10 mm Hg, respectively, but both SBP and DBP in EHT after antihypertensive therapy were still greater than those in NT. Both DeltaSBP and DeltaDBP in EHT after a long-term antihypertensive therapy were significantly smaller than those in EHT before therapy but were still significantly larger than those in NT. These results demonstrate that a long-term antihypertensive therapy reduces the exaggerated BP response to IHG in EHT.     

A multicenter, randomized, double-blind comparison of the efficacy and safety of irbesartan and enalapril in adults with mild to moderate essential hypertension, as assessed by ambulatory blood pressure monitoring: the MAPAVEL Study (Monitorización Ambulatoria Presión Arterial APROVEL)

BACKGROUND: When blood pressure (BP)-lowering efficacy is assessed by measurements taken in a clinic setting, angiotensin II-receptor antagonists show similar efficacy to angiotensin-converting enzyme inhibitors and better tolerability. A search of MEDLINE to date, however, reveals no randomized, double-blind studies using ambulatory BP monitoring (ABPM) to compare the BP-lowering efficacy of irbesartan and enalapril in a large number of patients ( > 200) with essential hypertension. OBJECTIVE: This study compared 24-hour BP reduction and BP control, as assessed by ABPM, in patients with mild to moderate essential hypertension treated with irbesartan or enalapril. The relative tolerability of the 2 treatments was also evaluated. METHODS: This was a multicenter, randomized, double-blind study in patients with mild to moderate essential hypertension (office diastolic BP [DBP] 90-109 mm Hg or systolic BP [SBP] 140-179 mm Hg). After a 3-week, single-blind placebo washout phase, patients with a mean daytime DBP > or = 85 mm Hg, as measured by ABPM between 10 AM and 8 PM, were randomized to 12 weeks of active treatment with irbesartan or enalapril. Starting doses were 150 and 10 mg/d, respectively, with titration to 300 or 20 mg/d if clinic DBP was > or = 90 mm Hg at week 4 or 8. Based on clinic measurements, BP control was defined as a BP reading < 140/90 mm Hg after 12 weeks of treatment; patients achieving a reduction in DBP of > or = 10 mm Hg at 12 weeks were considered responders. The ABPM criterion for BP control, independent of clinic values, was achievement of a daytime BP < 130/85 mm Hg after 12 weeks of treatment; patients achieving a reduction in 24-hour DBP > or = 5 mm Hg at 12 weeks were considered responders, in dependent of clinic values. RESULTS: A total of 238 patients were randomized to treatment, 115 to irbesartan and 123 to enalapril. The study population was approximately 52.0% female and 48.0% male, with a mean ( +/- SD) age of 52.7 +/- 10.6 years. The study was completed by 111 patients in the irbesartan group (dose titrated to 300 mg/d in 72.0% of patients) and 115 patients in the enalapril group (dose titrated to 20 mg/d in 76.5% of patients). BP reductions were similar in the 2 groups, both as measured in the clinic (DBP, 12.7 +/- 8.8 mm Hg irbesartan vs 12.4 +/- 7.4 mm Hg enalapril; SBP, 19.0 +/- 14.1 mm Hg vs 17.5 +/- 14.0 mm Hg) and by 24-hour ABPM (DBP, 9.4 +/- 8.5 mm Hg vs 8.8 +/- 8.5 mm Hg: SBP, 14.7 +/- 14.7 mm Hg vs 12.6 +/- 13.1 mm Hg). As assessed by ABPM, rates of BP control were 40.5% (45/111) for irbesartan and 33.9% (39/115) for enalapril, and the response rates were a respective 71.2% (79/111) and 71.3% (82/115). The overall incidence of adverse events (40.0% irbesartan, 51.2% enalapril) was not statistically different between groups, although the incidence of adverse events considered probably related to antihypertensive treatment was significantly higher with enalapril than with irbesartan (24.6% vs 9.2%, respectively; P = 0.026), essentially because of the higher incidence of cough (8.1% vs 0.9%). CONCLUSIONS: As assessed by ABPM, irbesartan 150 to 300 mg/d was as effective in lowering BP and achieving BP control as enalapril 10 to 20 mg/d. Based on the number of treatment-related adverse events, irbesartan was better tolerated than enalapril.     

A comparison of the efficacy and safety of irbesartan/hydrochlorothiazide combination therapy with irbesartan monotherapy in the treatment of moderate or severe hypertension in diabetic and obese hypertensive patients: a post-hoc analysis review

Hypertension is difficult to treat in patients with type 2 diabetes mellitus (T2DM) or obesity. Combination therapies are often required to effectively lower blood pressure (BP) and attain BP goals. In this post-hoc analysis of 2 prospective, randomized, controlled studies in patients with uncontrolled or untreated moderate or severe hypertension, the efficacy and safety of treatment with irbesartan/hydrochlorothiazide (HCTZ) and irbesartan was assessed in 2 separate analyses: patients with diabetes (n=143) and by obesity status (n=1125). Patients received irbesartan/HCTZ (150 mg/12.5 mg titrated to 300 mg/25 mg) or irbesartan (150 mg titrated to 300 mg) for 7 (severe hypertension study) or 12 (moderate hypertension study) weeks. Efficacy comparisons between treatment groups were performed using Fisher's exact tests. After 7 to 8 weeks of treatment, systolic BP (SBP)/diastolic BP (DBP) decreased in patients with diabetes by 26.9/17.8 mm Hg and 21.8/15.8 mm Hg after irbesartan/HCTZ and irbesartan treatment, respectively (P [SBP]=0.09, P [DBP]=0.27). In obese patients (n=544), SBP/DBP decreased by 29.4/20.2 mm Hg and 20.1/15.9 mm Hg after irbesartan/HCTZ and irbesartan treatment, respectively (P<0.0001). More patients with T2DM reached the BP goal of <130/80 mm Hg at week 7 to 8 in the irbesartan/HCTZ group than in the irbesartan group (12% vs 5%), although not statistically significant (P=0.22). Significantly more obese patients reached their respective BP goals in the irbesartan/HCTZ group than in the irbesartan group (48% vs 23%; P<0.0001). Treatment-emergent adverse event rates were similar between treatment groups regardless of the presence of diabetes or body mass index (BMI) status. In patients with moderate or severe hypertension and with a BMI ≥ 30 kg/m(2), initial treatment with irbesartan/HCTZ combination therapy was more effective than irbesartan monotherapy.     

Relationship of variability of blood pressure, cardiac sinus rhythm, and structural and functional characteristics of the left ventricular myocardium in elderly and senile patients with arterial hypertension

The variability of blood pressure (BP), autonomic cardiac sinus rhythm regulation, and myocardial structural and functional characteristics of the left ventricle (LV) was comparatively analyzed in 201 patients aged 65-88 years who had uncomplicated systolic and diastolic and isolated systolic arterial hypertension (SDAH and ISAH, respectively). There was a greater variability of systolic and diastolic BP no matter what the type of arterial hypertension (AH) was. It was ascertained that ISAH was characterized by absolute parasympaticotonia and SDAH was marked by relative sympaticotonia with the involvement of central ergotropic and humoral-and-metabolic mechanisms. In elderly and senile patients, uncomplicated AH was accompanied in 86.6% of cases by LV remodeling, mainly as its concentric hypertrophy (52.7%), characterizing primarily by non-restrictive diastolic dysfunction. There were no significant differences in the types of LV remodeling and diastolic dysfunction in patients with combined AH and ISAH. Moreover, the development of LV remodeling and associated diastolic dysfunction in SDAH was followed by a decrease in the overall variability of cardiac sinus rhythm with a smaller contribution of a segmental link of the parasympathetic portion of the autonomic nervous system and by the development of relative sympaticotonia due to suprasegmental and humoral-and-metabolic influences.     

An 18-week, prospective, randomized, double-blind, multicenter study of amlodipine/ramipril combination versus amlodipine monotherapy in the treatment of hypertension: the assessment of combination therapy of amlodipine/ramipril (ATAR) study

BACKGROUND: A combination of antihypertensive agents of different drug classes in a fixed-dose combination (FDC) may offer advantages in terms of efficacy, tolerability, and treatment compliance. Combination of a calcium channel blocker with an angiotensin-converting enzyme inhibitor may act synergistically to reduce blood pressure (BP). OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of an amlodipine/ramipril FDC with those of amlodipine monotherapy. METHODS: This 18-week, prospective, randomized, double-blind study was conducted at 8 centers across Brazil. Patients with stage 1 or 2 essential hypertension were enrolled. After a 2-week placebo run-in phase, patients received amlodipine/ramipril 2.5/2.5 mg or amlodipine 2.5 mg, after which the doses were titrated, based on BP, to 5/5 then 10/10 mg (amlodipine/ramipril) and 5 then 10 mg (amlodipine). The primary end point was BP measured in the intent-to-treat (ITT) population. Hematology and serum biochemistry were assessed at baseline and study end. Tolerability was assessed using patient interview, laboratory analysis, and physical examination, including measurement of ankle circumference to assess peripheral edema. RESULTS: A total of 222 patients completed the study (age range, 40-79 years; FDC group, 117 patients [mean dose, 7.60/7.60 mg]; monotherapy, 105 patients [mean dose, 7.97 mg]). The mean (SD) changes in systolic BP (SBP) and diastolic BP (DBP), as measured using 24-hour ambulatory blood pressure monitoring (ABPM) and in the physician's office, were significantly greater with combination therapy than monotherapy, with the exception of office DBP (ABPM, -20.76 [1.25] vs -15.80 [1.18] mm Hg and -11.71 [0.78] vs -8.61 [0.74] mm Hg, respectively [both, P = 0.004]; office, -27.51 [1.40] vs -22.84 [1.33] mm Hg [P = 0.012] and -16.41 [0.79] vs -14.64 [0.75] mm Hg [P = NS], respectively). In the ITT analysis, the mean changes in ambulatory, but not office-based, BP were statistically significant (ABPM: SBP, -20.21 [1.14] vs -15.31 [1.12] mm Hg and DBP, -11.61 [0.72] vs -8.42 [0.70] mm Hg, respectively [both, P = 0.002]; office: SBP, -26.60 [1.34] vs -22.97 [1.30] mm Hg and DBP, -16.48 [0.78] vs -14.48 [0.75] mm Hg [both, P = NS]). Twenty-nine patients (22.1%) treated with combination therapy and 41 patients (30.6%) treated with monotherapy experienced > or =1 adverse event considered possibly related to study drug. The combination-therapy group had lower prevalence of edema (7.6% vs 18.7%; P = 0.011) and a similar prevalence of dry cough (3.8% vs 0.8%; P = NS). No clinically significant changes in laboratory values were found in either group. CONCLUSIONS: In this population of patients with essential hypertension, the amlodipine/ramipril FDC was associated with significantly reduced ambulatory and office-measured BP compared with amlodipine monotherapy, with the exception of office DBP. Both treatments were well tolerated.     

老年男性颈动脉斑块形成与血压关系的研究

目的探讨老年男性颈动脉斑块的形成与血压水平高低、脉压差大小、平均血压值之间的关系。方法以1461例因动脉硬化所致慢性疾病住院的老年男性患者为研究对象,将入选对象通过血管超声检查,根据有无颈动脉斑块分为两组（颈动脉斑块组1012例和无颈动脉斑块组449例）,通过24h动态血压监测（ABPM）记录的收缩压（SBP）、舒张压（DBP）的变化,分别计算每个患者的脉压差（PP）、平均动脉压（MBP）,并分析这些数据与颈动脉斑块形成的关系。结果颈动脉斑块组患者的年龄明显高于非颈动脉斑块组[（80．5±5．4）岁与（77．3±5．9）岁,t=-4．233,P〈0．01];颈动脉斑块组和无颈动脉斑块组比较,24h的SBP[（132．2±17．0）mmHg与（127．5±16．0）mmHg,t=-4．893,P〈0．001]、PP[（60．8±13．4）mmHg与（55．9±12．5）mmHg,t=-5．021,P〈0．001]、MBP[（92．6±10．3）mmHg与（91．0±9．9）mmHg,t=-3．987,P〈0．01]明显高于无颈动脉斑块组。颈动脉斑块组的发病率与年龄（OR=1．061,P=0．0001）、心肌梗死（OR=1．896,P=0．0135）、高血压分级（OR=1．177,P=0．0019）、高血脂（OR=1．353,P=0．0335）、心脏收缩功能降低（OR=2．466,P=0．0001）、下肢动脉斑块（OR=5．453,P=0．0001）密切相关。结论在老年男性人群中,颈动脉斑块的形成与SBP升高、PP增大、MBP的升高密切相关,而与舒张压的水平关系不甚明显。     

不同类型的降压药物对高血压患者脉搏波速度的影响

目的探讨不同类型的降压药物对高血压患者臂一踝脉搏波速度（brachio—anklepulsewavevelocity,baPWV）的影响。方法健康体检首次确诊的高血压患者120例随机分为四组,每组30例,A组（苯磺酸左旋氨氯地平组）、B组（培多普利组）、C组（琥珀酸美托洛尔缓释片组）、D组（缬沙坦组）,与正常对照组对比分析血压、血糖、血脂和baPWV的变化。分别给予苯磺酸左旋氨氯地平、培多普利、琥珀酸美托洛尔缓释片、缬沙坦治疗12周后重复测量上述指标,前后对比分析血压和baPWV的变化。结果高血压患者与同期健康体检者对比,收缩压（SBP）、舒张压（DBP）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL—C）和baPWV显著高于正常对照组（P〈0．05）。前述药物治疗12周后,患者SBP、DBP和baPWV显著下降（P〈0．05）,苯磺酸左旋氨氯地平收缩压下降幅度（△SBP）（30．6±6．7）mmHgvs（20．7±5．3）mmHg、（19．6±6．1）mmHg、（21.5±4．3nllnHg）和舒张压下降幅度（ADBP）（20．8±7．1）mmHgvs（13．97±7．6）mmHg、（14．1±6．8）mmHg、（14．9±4．2）mmHg明显高于其他三种药物（P〈0．05）。结论常用降压药物可以降低高血压患者的脉搏波速度,改善动脉顺应性。     

Spirapril - a new long-acting ACE inhibitor: efficacy and safety in patients with arterial hypertension in combination with diabetes mellitus and impaired kidney function

AIM: To examine effectiveness and safety of quadropril. MATERIAL AND METHODS: Changes in blood pressure (BP), heart rate (HR), levels of glucose, potassium and creatinine, creatinine clearance were studied in 120 patients (48 males and 72 females, mean age 60.6 +/- 0.7 years) with mild to moderate arterial hypertension (AH) with average duration 13.8 +/- 0.7 years. The patients were divided into 3 groups: with AH (n = 40), AH + noninsulindependent diabetes mellitus (DM) (n = 43), AH and nephropathy (n = 37). 8-week treatment was performed with a standard dose of 6 mg/day (1 tablet of quadropril). Control examinations were made 2, 4 and 8 weeks after the treatment. RESULTS: After 8 weeks of treatment a decrease in systolic blood pressure in AH group was 24.0 +/- 3.0 mm Hg and in diastolic blood pressure 16.3 +/- 1.3 mm Hg (P < 0.001). In the group with DM this decrease was 22.4 +/- 2.8 mm Hg and 15.7 +/- 1.4 mm Hg (p < 0.001), respectively. In the group with nephropathy this decrease was 26.4 +/- 2.4 and 16.5 +/- 1.3 mm Hg (p < 0.001), respectively. Heart rate changed significantly only in diabetics: from 75.1 +/- 1.7 to 72.9 +/- 1.3 beats/min. Biochemical parameters in the hypertensive and diabetic patients did not change significantly. In the nephropathy group there was a significant decrease in creatinine and increase in creatinine clearance. Their level of glucose and potassium changed insignificantly. CONCLUSION: The treatment with quadropril results in a significant decrease in blood pressure, does not influence parameters of carbohydrate metabolism, improves nitrogen eliminating function of the kidneys.     

A twelve-week, multicenter, randomized, double-blind, parallel-group, noninferiority trial of the antihypertensive efficacy and tolerability of imidapril and candesartan in adult patients with mild to moderate essential hypertension: the Iberian Multicenter Imidapril Study on Hypertension (IMISH)

OBJECTIVE: The aim of this study was to evaluate the annhypertensive efficacy and tolerability of the angiotensin-converting enzyme inhibitor imidapril and the angiotensin II type 1 receptor antagonist candesartan in mild to moderate essential hypertension. METHODS: The trial was conducted at 8 centers across Portugal and Spain (the Iberian Multicenter Imidapril Study on Hypertension [IMISH] Study Group). Patients aged between 30 and 70 years with essential hypertension were eligible. Following a 2- to 4-week, single-blind, placebo run-in period, patients were randomly assigned to receive imidapril at doses of up to 20 mg/d, or candesartan at doses up to 16 mg/d, once daily in a double-blind, parallel-group design with a 12-week active-treatment period. To achieve the target systolic/diastolic blood pressure (SBP/DBP) of <140/<90 mm Hg, imidapril was titrated from 5 to 20 mg/d and candesartan was titrated from 4 to 16 mg/d. The main end point was the change from baseline in sitting blood pressure (BP) at trough. Secondary end points were response rate, evaluation of SBP and DBP throughout the study, and change of SBP and DBP in subgroup of patients with moderate hypertension, as well as incidence and severity of adverse events related to treatment reported throughout the study. RESULTS: The intent-to-treat analysis consisted of 122 patients (imidapril group, 60 patients; 32 men, 28 women; mean [SD] age, 54.7 [9.2] years; white race, 59 [99.2%], Hispanic race, 1 [0.8%]; mean [SD] weight, 80.1 [12.8] kg; candesartan group, 62 patients; 36 men, 26 women; mean [SD] age, 53.9 [9.9] years; white race, 62 [100%]; mean [SD] weight, 77.6 [14.1] kg). In the imidapril group, the mean (SD) SBP and DBP were, respectively, 155.7 (10.2) and 96.7 (4.7) mm Hg at baseline and 139.4 (11.9) and 86.9 (7.6) mm Hg at the end of the 12-week treatment period (visit 5); SBP had decreased significantly from baseline, by 10.5% (mean [SD] Delta, -16.3 [12.3] mm Hg [95% CI, -19.5 to -13.1; P < 0.001]) and DBP had decreased significantly, by 10.1% (mean [SD] A, -9.8 [7.8] mm Hg [95% CI, -11.8 to -7.8; P < 0.001]). In the candesartan group, the mean (SD) SBP and DBP values were, respectively, 158.4 [11.2] and 98.3 [4.1] mm Hg at baseline and 139.8 [12.5] and 87.6 7.5] mm Hg at 12 weeks, corresponding to decreases of 11.7% in SBP (mean [SD] A, -18.6 [12.8] mm Hg [95% CI, -21.9 to -15.4; P < 0.001]) and 10.9% in DBP (mean [SD] A, -10.7 [7.3] mm Hg [95% CI, -12.5 to -8.8; P < 0.001]). Response rates were 78.3% (47/60) with imidapril and 69.4% (43/62) with candesartan, and BP normalization (<140/<90 mm Hg) was achieved in 55.0% (33/60) of patients with imidapril and 45.2% (28/62) of patients with candesartan. The incidences of adverse events were similar between groups. Most (73.9%) adverse events were mild in intensity. A serious adverse event (severe anxiety) was reported in the candesartan group and led to study discontinuation. No cases of dry cough or hypotension were reported. CONCLUSIONS: The results of this study suggest that imidapril once daily at doses up to 20 mg and candesartan once daily at doses up to 16 mg were effective in this population of mildly to moderately hypertensive patients. Both treatments were well tolerated.