The role of hypersympathycotony in development of arterial hypertension in patients with metabolic syndrome: potential of pathogenetically sound therapy

AIM: To assess hypotensive efficacy and metabolic neutrality of moxonidine (physiotenz)--a selective agonist of imidasoline receptors--in patients with mild and moderate arterial hypertension (AH) associated with diabetes mellitus (DM) type 2. MATERIAL AND METHODS: Follow-up and treatment were conducted in 30 hypertensive diabetics (mean age 52.43 +/- 4.65 years). Mean duration of DM and AH was 4.77 +/- 2.69 and 6.93 +/- 2.98 years, respectively. The study was made of lipid exchange, glycemia, levels of glycosylated hemoglobin (GH), fasting and postprandial immunoreactive insulin. Hypotensive efficacy was examined by 24-h monitoring of arterial pressure after 16 weeks of therapy. RESULTS: Mean 24-h systolic arterial pressure fell by 8.02%, diastolic arterial pressure--by 6.47%. The drug had a good effect on a 24-h profile of arterial pressure: a significant decrease of day and night pressure load index, lowering of initially high 24-h variability of systolic and diastolic arterial pressure, normalization of two-phase profile of arterial pressure. Carbohydrate metabolism improved also: GH, glycemia, immunoreactive insulin decreased. There was a significant trend to a change in qualitative composition of blood lipid--a decrease in lipoproteins atherogenic fractions and a rise in HDLP. CONCLUSION: Physiotens is a highly effective hypotensive drug for use in mild and moderate AH in DM of type 2.     

老年男性高血压患者降压治疗后血压变异性与心室重构的相关性研究

目的探讨老年男性高血压患者降压治疗后动态血压变异性与心室重构的关系。方法入选老年男性原发性高血压患者212例(高血压组),均单用长效钙通道阻滞剂降压治疗超过1年,行动态血压监测(ABPM),根据24h收缩压平均实际变异性(24 hSBP AVR)的第50百分位数(P50)将高血压组分为两组:高AVR组(AVR≥10.17 mmHg)和低AVR组(AVR<10.17 mmHg),各106例。另入选48例同期年龄相匹配的非高血压老年男性患者为对照组。测定入选患者所有血压水平、24 hSBP AVR等血压变异性指标及舒张期室间隔厚度(IVST)、舒张期左心室后壁厚度(LVPWT)、左心室舒张末内径(LVEDd),计算左心室质量指数(LVMI),比较各组差异。结果与对照组比较,高血压组24 h、日间及夜间平均收缩压,24 hSBP AVR值均高于对照组(P<0.05),高AVR组IVST及IVEDd高于低AVR组(P<0.05)。相关分析显示,LVMI与24 hSBP(r=0.361,P<0.05)及24 hSBP AVR(r=0.210,P<0.05)呈正相关。结论老年男性原发性高血压患者降压治疗后收缩压水平及收缩压变异性与左心室重构有关。     

Meditation reduces sympathetic activation and improves the quality of life in elderly patients with optimally treated heart failure: a prospective randomized study

OBJECTIVE: We tested whether meditation can reduce sympathetic activation, evaluated by norepinephrine blood levels (NE), and improve quality of life in elderly persons with congestive heart failure (CHF). DESIGN AND SETTING: This was a prospective, randomized study conducted from April 2000 to October 2001 in an ambulatory care teaching hospital in S?o Paulo, Brazil. SUBJECTS: We studied 19 patients with CHF, 74.8 +/- 6.7 years old, receiving diuretics, optimal doses of an angiotensin-converting enzyme inhibitor or angiotensin II inhibitor, maximum tolerated carvedilol dose (23.1 +/- 13.6 mg) and spironolactone 25 mg (10 patients). INTERVENTIONS: After 2 months of optimal treatment with carvedilol, patients were randomized into two groups. The meditation group (M) was provided an audiotape, 30 minutes long, to listen to at home, twice a day, for 12 weeks, plus a weekly meeting. The control group (C) just had weekly meetings. MAIN OUTCOME MEASURES: We determined before and after 14 +/- k1 weeks, NE (in pg/mL); quality of life with the Minnesota Living with Heart Failure Questionnaire (MLWHFQ); VO2 and VE/VCO2 slope by cardiopulmonary exercise testing; left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume index (LVDDi) measured by echocardiography. RESULTS: Meditation reduced NE (mean +/- SEM) from 677.7 +/- 96.6 to 387.1 +/- 39.1 pg/mL (p = 0.008) in M versus 491.4 +/- 35.9 to 470.6 +/- 31.2 (p = 0.34) in C; improved MLWHFQ total score (mean +/- SEM) from 33.2 +/- 6.6 to 21.6 +/- 6.8 points (p = 0.02) in M versus 18.4 +/- 8.0 to 25.1 +/- 8.9 (p = 0.41) in C; and reduced the VE/VCO2 slope (mean +/- SEM) from 31.2 +/- 3.0 to 28.2 +/- 2.6 (p = 0.04) in M versus 28.4 +/- 2.7 to 28.8 +/- 2.6 (p = 0.24) in C. No changes occurred in LVEF, LVDDi, and VO(2). CONCLUSIONS: In elderly patients with optimally treated CHF, meditation reduced NE, improved quality of life, and reduced the VE/VCO(2) slope. Our results support the possible role of meditation as a new hope in the treatment of CHF.     

老年单纯收缩期高血压患者血压变异性与左心室肥厚的关系

目的：研究老年单纯收缩期高血压患者血压变异性与左心室肥厚（LVHC）的关系,。方法：对31例老年收缩期高血压患者和24例老年正常血压组,分别进行动态血压测定,计算出平均血压、24小时、白天、夜间收缩压和舒张压变异性,超声心动图测量左室内径、室间厚度、左室后壁厚度、计算出左室重量指数（LVMI）。结果：老年收缩期高血压组血压变异性,LVM和LVMI大于老年正常血压组,结论血压变异性和平均血压水平与左室肥厚有关。     

I/D-polymorphism of ACE gene, morphofunctional heart condition and blood pressure 24-h profile in young men with arterial hypertension

AIM: To study the effects of ACE gene polymorphism on morphofunctional condition of the heart and 24-h blood pressure profile (BPP) in young men with hypertension. MATERIAL AND METHODS: A total of 174 young and middle-aged hypertensive men (mean age 32 +/- 4.6 years and 48 +/- 3.1 years, respectively) were examined (echocardiography, 24-h BP monitoring, tests for I/D-polymorphism of ACE gene). RESULTS: Genotype ID appeared most prevalent both in the young and middle-aged examinees (56 and 49%, respectively). Interventricular septal thickness and left ventricular myocardial mass were the largest in young hypertensive patients carrying genotype DD. Mean 24-h and nocturnal diastolic BP was significantly higher in young hypertensive patients with genotype II vs middle-aged patients with the same genotype. Carriers of genotype II had maximal variability of systolic and pulse blood pressure. CONCLUSION: Genotype DD appeared most unfavourable in relation to left ventricular myocardial hypertrophy. Its carriers had the thickest right ventricular myocardium, the largest mass of the left ventricle. Homozygotes by allele-I had most pronounced changes in a 24-h BP profile.     

Nocturnal hypoxic episodes and structural changes in left ventricular myocardium in patients with mild-to-moderate arterial hypertension

AIM: To study correlations between structural changes of the left ventricle (LV) in patients with mild and moderate arterial hypertension (AH) and severity of hypoxic night episodes. MATERIAL AND METHODS: The examination of 50 patients (mean age 52 +/- 1 year) with mild and moderate hypertension included echocardiographic measurement of LV myocardial mass, calculation of LV myocardial mass index. LV hypertrophy was stated in the index 125 g/m2 for men and 110 g/m2 for women. 24-h monitoring of arterial pressure (TM-2425) and night monitoring of hemoglobin saturation of arterial blood with oxygen (SaO2) using pulsoxymeter NONIN 8500M were made. The data processing was performed with the use of original program ARM-SaO2. Dissaturation was stated if SaO2 fell by 4% and more compared to the previous stable level at initial SaO2 level above 90%. The patients were divided into two groups according to the number of dissaturation episodes: group 1 (more than 20 dissaturation episodes) and group 2 (less than 20 episodes). RESULTS: The groups were comparable by gender, duration of hypertension, body mass index, systolic and diastolic arterial pressure, heart rate. In group I, pulse arterial pressure, systolic arterial pressure load for 14 hours, day and night were significantly higher. Patients with dissaturation had a significantly higher LV myocardial mass and more frequent LV hypertrophy (128 +/- 6 and 106 +/- 5 g/m2 and 56 and 20%, respectively). The correlation and multifactor regression analysis showed a predictive value not only of the pressor parameters but also of indices of night hypoxia in relation to structural changes of LV myocardium. CONCLUSION: The presence of significant hypoxic episodes in sleep in AH patients indicates risk to develop structural changes of LV myocardium.     

降压治疗对老老年高血压患者靶器官损害的影响

目的观察研究降压治疗对老老年高血压患者靶器官损害的影响。 方法将167例老老年高血压患者随机分为降压治疗组和安慰剂对照组，对比治疗1年。对两组病例分别在治疗开始及治疗1年结束时各进行一次24h动态血压监测、超声心动图检查和尿微量白蛋白、尿肌酐监测，歼使用SPSS10．0软什包对所测的数据进行分析． 结果治疗组治疗后动态血压指标中除日间舒张压、心率（24h、日间和夜间）外，其他指标改善均优于对照组（P〈0．05）；左心室各参数与肾功能指标的改善也优于对照组（P〈0．05）。 结论老老年高血压患者降压治疗后，左心室肥厚和肾功能损害明显改善。     

Effects of delapril in combination with indapamide on blood pressure and left ventricular mass in elderly hypertensive patients

We present a single-blinded, placebo-controlled trial of the effects on blood pressure and left ventricular mass and of the safety of a combined antihypertensive treatment with delapril, a new nonsulfhydryl angiotensin-converting enzyme inhibitor, and indapamide, a sulfonamide diuretic. We studied 28 elderly patients aged 65-85 years (mean age, 69 +/- 1) with sitting systolic/diastolic blood pressure of 160-200/95-115 mm Hg (at the end of the placebo period). After a 2-week placebo run-in, patients took 30 mg delapril in combination with 1.25 mg indapamide once daily for 24 weeks. Twenty-four-hour ambulatory blood pressure was monitored and M- and B-mode echocardiography were performed before and after 24 weeks of treatment. Blood pressure decreased from 156 +/- 1.5/101 +/- 1 mm Hg before treatment to 133 +/- 1/73 +/- 1 mm Hg after treatment. The total blood pressure burden also decreased; the percentage of measurements with a systolic blood pressure > or = 140 mm Hg and a diastolic blood pressure > or = 90 mm Hg decreased from 48.7% +/- 5%/31.5% +/- 4.3% to 23.5% +/- 4%/20.5% +/- 2.9% (p < 0.0005 and p < 0.05). The area under the curve of the 24-hour blood pressure decreased from 250 +/- 41/103 +/- 21 mm Hg to 97 +/- 21/37 +/- 8.5 mm Hg (p < 0.001 and p < 0.005). The left ventricular mass index (LVMI) in the 15 patients with pretreatment left ventricular hypertrophy was reduced after therapy from 167.5 +/- 8.5 g/m 2 to 152.2 +/- 7.6 g/m 2 (p < 0.05). A positive correlation was observed between percent changes of the area under the curve of the 24-hour diastolic blood pressure and percent changes of LVMI (r = 0.6; p < 0. 05) in the 15 patients with left ventricular hypertrophy. Only 2 patients reported side effects: 1 developed skin rash and 1 developed headache. The safety of the treatment was confirmed by laboratory tests. In elderly hypertensive patients, the combination of delapril and indapamide at low doses reduced blood pressure and had favorable effects on LVMI with few side effects.     

The effects of delapril in combination with indapamide on glomerular filtration rate in elderly hypertensive patients.

We performed a placebo-controlled trial on the effects of a combined antihypertensive treatment with delapril, a new nonsulfhydryl angiotensin-converting enzyme inhibitor, and indapamide, a sulfonamide diuretic. We studied 28 elderly patients aged 65-85 years (mean age, 69 +/- 1 years) who took 30 mg delapril in combination with 1.25 mg indapamide once daily for 24 weeks. In the present study (performed simultaneously with our trial on the effects of delapril/indapamide on left ventricular mass in elderly patients with hypertension and on the same patients), we report the effects of this drug combination on glomerular filtration rate. Sitting arterial pressure (mean +/- SE) decreased from 156 +/- 1. 5/101 +/- 1 mm Hg at baseline to 133 +/- 1/73 +/- 1 mm Hg at the end of the 24-week treatment period (p < 0.0001). No significant changes in heart rate or episodes of orthostatic hypotension were observed. Glomerular filtration rate increased from 91.8 +/- 4.42 mL/min at baseline to 106.3 +/- 4.5 mL/min (p < 0.001) at the end of treatment. Our results show that the combination of delapril and indapamide is effective in the elderly hypertensive patient, with a favorable effect on the prevention of deterioration of kidney function.     

Evaluation of myocardial perfusion in patients with hypertrophic cardiomyopathy in comparison with clinical and echocardiographic data

AIM: To study peculiarities of myocardial perfusion in patients with hypertrophic cardiomyopathy (HCMP) in correlation with clinical and echocardiographic data. MATERIAL AND METHODS: 62 patients with HCMP (23 females and 39 males, mean age 44.4 +/- 11.2 years, the disease duration 13.0 +/- 10.4 years) have undergone ECG, 24-h ECG monitoring, echocardiography, perfusion scintigraphy of the myocardium with 99m-TcMIBI at rest and in combination with bicycle ergometry. The patients were divided into two groups: 35 patients of group 1 had moderate left ventricular hypertrophy (the septal thickness in diastole under 20 mm; 27 patients of group 2 had severe hypertrophy (the thickness was over 20 mm). RESULTS: Dyspnea and syncopal states occurred more frequently in patients from group 2. They also had a higher functional class of heart failure (2.0 +/- 0.8 and 1.2 +/- 0.7 for group 1 and 2, respectively, p < 0.05). Cardiac performance was significantly higher in patients of group 1. The size of the left atrium, left ventricular myocardium mass, the septal thickness and thickness of posterior wall of the left ventricle, gradient of pressure in the outflow tract of the left ventricle proved higher in patients of group 2. Deep stable defects of myocardial perfusion were detected in 5 (15%) patients of group 1 and 10 (37%) patients of group 2. Transient defects of myocardial perfusion were found in 9 (26%) patients of group 1 and 12 (44%) patients of group 2. The index of myocardial ischemia in group 1 patients was significantly lower than in patients of group 2 (3.5 +/- 2.2 and 8.3 +/- 2.5, respectively, p < 0.05). CONCLUSION: Patients with severe hypertrophy of the left ventricle had severe clinical picture, low exercise tolerance, marked hemodynamic changes, more frequent defects of left ventricular perfusion defects compared to patients with moderate hypertrophy of the left ventricular myocardium.     

Effects of arterial compliance on geometry of the left ventricle in patients with pre-dialysis chronic renal failure]

AIM: To examine relationships between left ventricular geometry and general arterial compliance (GAC) in patients with predialysis chronic renal failure (CRF). 102 patients with predialysis CRF unrelated to diabetes mellitus (males 46, females 56, mean age 49.1 +/- 18.3 years). CRF was caused by chronic glomerulonephritis and essential hypertension (77.4%). 92 (90.2%) patients were hypertensive. Serum creatinin was 432.1 +/- 165.3 mcmol/l. GAC was defined as stroke volume/pulse arterial pressure. Echocardiography determined the index of the left ventricular myocardial mass (ILVMM), relative thickness of the left ventricular wall (RTW). Left ventricular hypertrophy (LVH) was diagnosed in 86 (84.3%) patients. In 64 patients it was concentric and in 22 patients--excentric). Multivariance regression analysis showed that systolic arterial pressure and anemia have a direct independent effect on ILVMM (p = 0.004). Independent inverse relationship was between GAC and RTW. Patients with concentric LVH had GAC lower than those with excentric LVH (p = 0.003). Reduction of GAC is an independent factor influencing the development of concentric LVH in patients with predialysis CRF.     

Comparative effects of amlodipine (stamlo) and enalapril (enam) on arterial pressure, painless myocardial ischemia and diastolic function of left ventricle in patients with arterial hypertension

43 patients with mild and moderate arterial hypertension received monotherapy with either stamlo (Dr. Reddy's laboratories, India) in a daily dose 9.5 +/- 0.5 mg (n = 33), or enam (n = 26) in a daily dose 28 +/- 1.5 mg, or stamlo treatment was followed in 10 days by enam (n = 16). Before and after the treatment 24-h monitoring was made of arterial pressure, left ventricular diastolic function and silent myocardial ischemia. Adequate lowering of arterial pressure was observed in 90 and 77% of patients after stamlo and enam treatment, respectively. Stamlo showed more potent antiischemic action and had a positive effect on left ventricular filling.     

Effect of nebivolol on QT dispersion in hypertensive patients with left ventricular hypertrophy.

Hypertensive patients with left ventricular hypertrophy (LVH) have increased QT dispersion, which is considered an early indicator of end-organ damage and a non-invasive marker of risk for clinically important ventricular arrhythmias and cardiac mortality. The purpose of this study was to examine the effect of nebivolol antihypertensive therapy on QT dispersion in hypertensive subjects. Twenty-five subjects (15 men and 10 women, mean age 53.6 +/- 4.5 years) with essential arterial hypertension and mild-to-moderate LVH (blood pressure: 147.2 +/- 6.2/90.6 +/- 3.8 mmHg; left ventricular mass indexed: 149.1 +/- 10.7 g/m(2)) were compared with 25 age-matched healthy control subjects. All the participants underwent a complete clinical examination, including electrocardiogram for QT interval measurements. The QT dispersion was defined as the difference between the longest and the shortest QT interval occurring in the 12-lead electrocardiogram. The QT dispersion was corrected (QTc) with Bazett's formula. Hypertensive subjects were treated with 5 mg daily of nebivolol. The ECG and echocardiogram were repeated after four weeks of treatment. At baseline, hypertensive patients showed QT dispersion (56.9 +/- 6.4 vs. 31.7 +/- 8.4 ms, P < 0.001) and QTc dispersion (58.3 +/- 6.2 vs. 33.2 +/- 7.8 ms, P < 0.001) significantly higher than control subjects. Four-week nebivolol treatment reduced blood pressure from 147.2 +/- 6.2/90.6 +/- 3.6 mmHg to 136.3 +/- 3.1/83.3 +/- 2.5 mmHg (P < 0.0001), and resting heart rate from 75.3 +/- 4.7 to 64.2 +/- 3.0 bpm (P < 0.001), without significant change in left ventricular mass (LVMi: 149.1 +/- 10.7 vs. 151.4 +/- 9.8 g/m(2), ns). Nebivolol-based treatment improved QT dispersion (56.9 +/- 6.4 vs. 40.5 +/- 5.8 ms, P < 0.001) and QTc dispersion (58.3 +/- 6.2 vs. 42.2 +/- 5.6 ms, P < 0.001), which remained higher than in control subjects (P < 0.001 in both cases). The reduction of QT dispersion did not correlate with arterial BP reduction. In conclusion, nebivolol reduced increased QT dispersion in hypertensive subjects after four weeks. This effect, occurred without any change in LVM, did not seem to be related to the blood pressure lowering and could contribute to reduce arrhythmias as well as sudden cardiac death in at-risk hypertensive patients.     

Labile hypertension in elderly: clinical features, autonomic regulation of circulation, approaches to treatment

Blood pressure in some elderly hypertensive patients is characterized by marked lability. This affects quality of life and may deteriorate prognosis. Conventional anti-hypertensive medication does not lead to stabilization of blood pressure. We call this form of hypertension "labile hypertension of the elderly" (LHE). The aim of the study was investigation of autonomic regulation of blood pressure and of clonazepam effectiveness in patients with LHE. Fifty-six patients with LHE (mean age 67.0 +/- 6.3 years) entered the study (87.5% women). Control group consisted of 38 patients with stable hypertension and 27 normotensives matched by sex and age. The patients and the controls underwent clinical and psychological examinations, regular measurement of blood pressure during one month before and after the treatment, cardiovascular tests and spectral analysis of the heart rate variability. It was found that LHE patients have higher level of anxiety and depression, low standard deviation of RR interval, low normalized LF and HF components and increased normalized VLF component. The cardiovascular tests showed signs of diminished parasympathetic regulation. Clonazepam treatment in a dose 1-2 mg/day brought about a significant stabilization of blood pressure in 82.0% of patients with LHE. Thus, LHE is an original form of hypertension in patients over 60 years old characterized by frequent, short-term, small symptomatic, spontaneous fluctuations of blood pressure with development of both hypertensive and hypotensive reactions. Pathogenesis of LHE is linked with disorders of heart rate autonomic regulation, marked anxiety and depression. Clonazepam stabilizes blood pressure in most LHE cases.     

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.     

Complex assessment of efficacy and tolerance of metoprolol CR/ZOK in treating hypertension

AIM: To study efficacy and tolerance of betaloc ZOK (Astra-Zeneca, UK) in patients with stage I-II (WHO classification) essential hypertension. MATERIAL AND METHODS: 27 patients were enrolled in the study (13 men and 14 women, mean age 40.6 +/- 1.57 years). Complete physical examination, ambulatory blood pressure monitoring, assessment of central hemodynamics, microcirculation were made before the treatment and on the treatment week 8. RESULTS: Monotherapy with betalok ZOK (50-100 mg/day) resulted in a significant lowering of mean daily, day and night systolic and diastolic arterial pressure. Variability index was reduced, circadian rhythm of blood pressure did not change. 28% had to take diuretics (arifon or hypotiazide). CONCLUSION: Betaloc ZOK (50-100 mg) is highly effective in patients with mild to moderate essential hypertension.     

The effects of left ventricular hypertrophy on the respiratory changes in transmitral Doppler flow patterns of hypertension patients

BACKGROUND: Left ventricular early diastolic fillings can be reduced by inspiration. However, the effects of left ventricular hypertrophy on such changes have not been studied before. This study was undertaken to investigate whether respiratory changes in transmitral Doppler flow were affected by left ventricular hypertrophy in hypertension patients. METHODS: Eighty-three patients (mean age 46 +/- 8 years, 49 males) with untreated essential hypertension were included in this study. Transmitral Doppler flow velocity was measured both at end-expiration and end-inspiration. Left ventricular mass was measured by M-mode echocardiography. We divided patients into two groups based on the presence of left ventricular hypertrophy or not. RESULTS: Twenty-one patients were diagnosed to have left ventricular hypertrophy. In patients without left ventricular hypertrophy, the peak early filling velocity decreased significantly (from 74 +/- 15 to 71 +/- 18 cm s(-1), P = 0.003), the peak atrial velocity increased significantly (from 65 +/- 17 to 74 +/- 15 cm s(-1), P < 0.001) and the early filling to atrial velocity ratio decreased significantly (from 1.2 +/- 0.3 to 1.1 +/- 0.3, P < 0.001) from end-expiration to end-inspiration. In patients with left ventricular hypertrophy, the parameters of transmitral Doppler flow pattern did not change during respiration. CONCLUSION: Respiratory changes in the transmitral Doppler flow velocity are blunted by left ventricular hypertrophy in hypertension patients. This phenomenon is probably contributed by the increased left ventricular wall stiffness in the left ventricular hypertrophy.     

Beta2-adrenergic receptor polymorphisms and treatment-induced regression of left ventricular hypertrophy in hypertension

OBJECTIVES: Although blood pressure is considered the major determinant of left ventricular hypertrophy in hypertension, genetic variability is increasingly being considered among the factors influencing this complication. beta(2)-Adrenergic receptors (beta(2)ARs) are up-regulated in hypertension and largely polymorphic within the human population. Recently, we have shown that the Glu27 beta(2)AR variant is strongly associated with cardiac hypertrophy in hypertension. The objective of this study is to verify whether this polymorphism also affects hypertrophy regression in response to antihypertensive therapy. METHODS: In a prospective follow-up study we screened 970 hypertensive patients of Caucasian descent for the Gly16Arg, Gln27Glu, and Thr164Ile beta(2)AR polymorphisms and left ventricular echocardiographic hypertrophy and assigned selected patients to enalapril or atenolol to assess left ventricular hypertrophy regression after 2-year follow-up. Results were stratified according to treatment and the Glu27Gln polymorphism of the beta(2)AR. In cells with stable overexpression of the Glu27 or Gln27 variant of beta(2)AR, we also explored the implications of this polymorphism on hypertrophy-related intracellular signal transduction. RESULTS: Among hypertensive patients, the Gly16 allele was found in 63% of patients and the Glu27 allele was found in 40.6%. Both polymorphisms were in linkage disequilibrium, as expected. Four hundred forty-one hypertrophic hypertensive patients completed the 2-year follow-up. At baseline, patients carrying at least 1 allele of the Glu27 variant presented with a larger cardiac size despite similar blood pressure levels (142.9 +/- 22.5 g/m(2) in Glu27 carriers versus 138.2 +/- 18.4 g/m(2) in Gln27 carriers, P < .02). Blood pressure normalization was achieved by both drugs. At follow-up, compared with the Gln27 patients, the Glu27 patients showed a larger reduction in hypertrophy when treated with enalapril (percent change in left ventricular mass, -6.3% +/- 7.7% in Glu27 carriers versus -2.18% +/- 7.9% in Gln27 carriers; P < .05) but not with atenolol therapy (-2.8% +/- 8.9% in Glu27 carriers versus -2.4% +/- 8.8% in Gln27 carriers, P = not significant). In in vitro studies the activation of p38 and extracellular signal-regulated kinase (ERK-) 1/2 (data not shown) and the activity of the atrial natriuretic factor (ANF) promoter after isoproterenol (INN, isoprenaline) stimulation were larger in Glu27 beta(2)AR overexpressing cells than in Gln27 beta(2)AR overexpressing cells (fold difference compared with unstimulated cells, 9.7 +/- 2.9 for Glu27 beta(2)AR versus 4.2 +/- 0.3 for Gln27 beta(2)AR; P < .05). CONCLUSIONS: The Glu27 variant of beta(2)AR enhances hypertension-induced left ventricular hypertrophy. In these patients angiotensin-converting enzyme inhibitors are more efficient than beta-blockers in reducing cardiac size.     

The impaired flow reserve capacity of penetrating intramyocardial coronary arteries in apical hypertrophic cardiomyopathy.

BACKGROUND: Coronary flow reserve (CFR) capacity of penetrating intramyocardial coronary artery (PICA) in apical hypertrophic (AH) cardiomyopathy has not been studied yet. METHODS: We studied 65 patients with normal coronary angiogram results (mean age 56 +/- 10 years; 33 men, 32 women). Of these, 30 were normotensive without any left ventricular hypertrophy (control group), 24 had hypertension (HTN) without any left ventricular hypertrophy (HTN group), and 11 had AH cardiomyopathy (AH group). PICA-CFR and PICA-width ratio were calculated after the intravenous infusion of adenosine (140 microg/kg/min) just beneath the apical impulse window at a depth of 3 to 5 cm by using high-frequency transthoracic Doppler echocardiography. RESULTS: PICA-CFR was successfully measured in 59 (90.8%) of 65 patients. PICA-CFR was 1.65 +/- 0.49 in AH group, 2.50 +/- 0.77 in HTN group, and 2.42 +/- 0.73 in control group ( P < .005 vs HTN and control). PICA-width ratio was 1.45 +/- 0.42 in AH group, 2.14 +/- 0.72 in HTN group, and 1.81 +/- 0.55 in control group ( P = .025 vs HTN and control). PICA-CFR was closely related to width-ratio of PICA ( r = 0.448, P = .002). Conclusion PICA in AH has higher resting diastolic velocity, wider diameter, and impaired CFR compared with nonhypertrophied myocardium.     

Cerebral oxygenation responses to standing in elderly patients with predominantly diastolic dysfunction

Patients with left ventricular dysfunction may have different orthostatic responses of blood pressure (BP) and cerebral oxygenation than healthy elderly subjects. We investigated orthostatic changes in systemic haemodynamic variables and cerebral oxygenation in 21 elderly patients with heart failure New York Heart Association class I-III in stable condition (age 70-83 years) after withdrawal of furosemide and captopril for 2 weeks, and in 18 healthy elderly subjects (age 70-84 years). Frontal cortical concentration changes of oxyhaemoglobin ([O2Hb]) and deoxyhaemoglobin ([HHb]) were continuously measured by near-infrared spectrophotometry and BP changes by Finapres before and during 10 min of standing. Upon standing [O2Hb] reflecting blood flow, changed by -1.2 +/- 0.9 micromol L-1 (mean +/- SEM) in the patients, whereas it decreased by -4.5 +/- 0.6 micromol L-1 (P<0.01) in the healthy subjects after standing (P<0.05 between groups). [HHb] reflecting the sum of cerebral blood flow, arterial oxygen saturation and cerebral oxygen uptake, increased by 1.5 +/- 0.5 micromol L-1 (P<0.05) and 1.7 +/- 0.6 micromol L-1 (P<0.05), respectively. Compared with healthy elderly subjects, elderly patients with left ventricular dysfunction showed smaller orthostatic [O2Hb] decreases (P<0.01), in relation to higher orthostatic BP rises (P<0.05). These findings indicate that BP changes and an altered cardiovascular balance may influence orthostatic cortical haemodynamic responses in elderly subjects.