Twenty-Four-Hour Urine α1 -Microglobulin as a Marker of Hypertension-Induced Renal Impairment and Its Response on Different Blood Pressure-Lowering Drugs.

The purpose of this study was to assess the role of urine α1 -microglobulin as a marker of hypertension-induced renal damage compared with estimated glomerular filtration rate, (eGFR), urine albumin, and urine albumin-to-creatinine ratio (ACR). Its response on different blood pressure (BP)-lowering drugs was also studied. Sixty never-treated hypertensive patients (65.0% men, 46.9 years, BP 141.4/94.0 mm Hg) were randomized to an irbesartan (an angiotensin receptor blocker [ARB]) or a diltiazem (a nondihydropyridine calcium channel blocker [CCB])-based regimen. Patients with diabetes or established cardiovascular, renal, or liver disease were excluded. Blood samples and 24-hour urine were analyzed at baseline and 6 months after pharmaceutical BP normalization. Serum creatinine was measured and eGFR was calculated. Urine albumin, creatinine, and α1 -microglobulin were measured and ACR was calculated. Minor changes (P=not significant [NS]) in eGFR were noted during follow-up in both groups (from 111.0 mL/min/1.73 m2 to 108.4 mL/min/1.73 m2 in the ARB group and from 111.3 mL/min/1.73 m2 to 114.0 mL/min/1.73 m2 in the CCB group). Twenty-four-hour urine indices were all significantly improved (P<.01) in the ARB group (albumin from 19.4 mg/L to 8.2 mg/L, ACR from 21.5 mg/g to 10.0 mg/g, α1 -microglobulin from 5.06 mg/L to 3.64 mg/L) but not (P=NS) in the CCB group (albumin from 15.6 mg/L to 13.9 mg/L, ACR from 17.6 mg/g to 17.1 mg/g, α1 -microglobulin from 4.94 mg/L to 4.79 mg/L). These differences between groups remained significant (P<.05) after adjusting for office heart rate and BP. α1 -Microglobulin was significantly correlated (P<.05) with albumin and ACR both at baseline (r=0.283 and 0.299, respectively) and at the end of follow-up (r=0.432 and 0.465, respectively) but not (P=NS) with eGFR. It was also significantly related (P<.05) to cardiovascular risk scores (Framingham and HeartScore) both at baseline (r=0.264 and 0.436, respectively) and at the end of follow-up (r=0.308 and 0.472, respectively). Urine α1 -microglobulin emerges as a potentially usable marker of hypertension-induced renal impairment. Its excretion rate and its response to treatment appears similar to that of albumin. Irbesartan but not diltiazem seems to be associated with reduced excretion of α1 -microglobulin in urine.

Correlation of 24-Hour Blood Pressure and Heart Rate Variability to Renal Function Parameters in Hypertensive Patients. The Effect of Smoking.

Intrarenal hemodynamics depend on blood pressure (BP), heart rate (HR), and smoking. Although BP levels have been associated with kidney function, the effect of HR levels, BP, and HR variability on renal function are less well clarified. This cross-sectional study sought to determine the association of 24-hour BP and HR variability with kidney function in hypertensive patients, stratified by smoking. The study comprised 9600 nondiabetic, never-treated hypertensive individuals without evident renal impairment examined from 1985 to 2014 (aged 53.3±13.4 years, 55.3% males). The 24-hour systolic BP (SBP) and HR variability were estimated via their coefficient of variation (CV =standard deviation×100/mean value) derived from ambulatory recording. The CV SBP-to-CV HR ratio (CV R) was used as a marker of the interplay between 24-hour SBP and HR variability. Renal function was estimated via 24-hour urine creatinine clearance (CrCl), estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), and 24-hour urine α1 -microglobulin. After adjustment for age, sex, and smoking, CV SBP was found to be weakly correlated to eGFR (r=-0.017, P=.1) and somewhat more strongly to CrCl, ACR, and α1 -microglobulin (r=-0.032, 0.072, and 0.065; P=.002, <.001 and <.001, respectively). CV HR was much better related to renal function, with stronger adjusted correlations to CrCl, eGFR, ACR, and α1 -microglobulin (r=0.185, 0.134, -0.306, -0.247; all P<.001, respectively). CV R also showed equally good adjusted correlations (r=-0.175, -0.125, 0.336, 0.262; all P<.001, respectively). Most adjusted correlations for CV HR and CV R were even better in smokers (r=0.213, 0.158, -0.332, -0.272 and -0.183, -0.118, 0.351, 0.275, respectively; all P<.001). CV HR and CV R emerge as better related to kidney function than CV SBP, especially in smokers. The correlation of CV HR and CV SBP to renal function is inverse to each other. ACR and α1 -microglobulin are better related to variability indices than CrCl and eGFR. However, causal relations cannot be proved.

Impaired glucose homeostasis in non-diabetic Greek hypertensives with diabetes family history. Effect of the obesity status.

Arterial hypertension (AH) and diabetes mellitus (DM) are established cardiovascular risk factors. Impaired glucose homeostasis (IGH; impaired fasting glucose or/and impaired glucose tolerance) or pre-diabetes, obesity, and DM family history identify individuals at risk for type 2 DM in whom preventive interventions are necessary. The aim of this study was to determine the glycemic profile in non-diabetic Greek adult hypertensive men and women according to DM family history and the obesity status. Diabetes family history, obesity markers (waist-to-hip ratio, WHR; body mass index, BMI), glycemic parameters (fasting and 2-hour post-load plasma glucose, if necessary; glycated hemoglobin, HbA1c; fasting insulin), insulin resistance indices (homeostasis model assessment, HOMA; quantitative insulin sensitivity check index, QUICKI; Bennett; McAuley), and IGH prevalence were determined in a large cohort of 11,540 Greek hypertensives referred to our institutions. Positive DM family history was associated with elevated fasting glucose (98.6 ± 13.1 vs 96.5 ± 12.3 mg/dL), HbA1c (5.58% ± 0.49% vs 5.50% ± 0.46%), fasting insulin (9.74 ± 4.20 vs 9.21 ± 3.63 µU/mL) and HOMA (2.43 ± 1.19 vs 2.24 ± 1.01) values, lower QUICKI (0.342 ± 0.025 vs 0.345 ± 0.023), Bennett (0.285 ± 0.081 vs 0.292 ± 0.078) and McAuley (6.73 ± 3.43 vs 6.95 ± 3.44) values, and higher IGH prevalence (45.3% vs 38.7%); P < .01 for all comparisons. The difference in the prevalence of IGH according to DM family history was significant (P < .01) in both genders and every WHR and BMI subgroup (except for women with BMI <20 kg/m(2)). Non-diabetic hypertensives with positive DM family history present with higher IGH prevalence and worse glycemic indices levels compared with those with negative family history, especially in the higher WHR/BMI subgroups.

The interplay of exercise heart rate and blood pressure as a predictor of coronary artery disease and arterial hypertension.

Delayed blood pressure (BP) and heart rate (HR) decline at recovery post-exercise are independent predictors of incident coronary artery disease (CAD). Delayed BP recovery and exaggerated BP response to exercise are independent predictors of future arterial hypertension (AH). This study sought to examine whether the combination of two exercise parameters provides additional prognostic value than each variable alone. A total of 830 non-CAD patients (374 normotensive) were followed for new-onset CAD and/or AH for 5 years after diagnostic exercise testing (ET). At the end of follow-up, patients without overt CAD underwent a second ET. Stress imaging modalities and coronary angiography, where appropriate, ruled out CAD. New-onset CAD was detected in 110 participants (13.3%) whereas AH was detected in 41 former normotensives (11.0%). The adjusted (for confounders) relative risk (RR) of CAD in abnormal BP and HR recovery patients was 1.95 (95% confidence interval [CI], 1.28-2.98; P=.011) compared with delayed BP and normal HR recovery patients and 1.71 (95% CI, 1.08-2.75; P=.014) compared with normal BP and delayed HR recovery patients. The adjusted RR of AH in normotensives with abnormal BP recovery and response was 2.18 (95% CI, 1.03-4.72; P=.047) compared with delayed BP recovery and normal BP response patients and 2.48 (95% CI, 1.14-4.97; P=.038) compared with normal BP recovery and exaggerated BP response individuals. In conclusion, the combination of two independent exercise predictors is an even stronger CAD/AH predictor than its components.

The effects of angiotensin receptor blockers vs. calcium channel blockers on the acute exercise-induced inflammatory and thrombotic response.

Arterial hypertension is an established risk factor for acute coronary syndromes, and physical exertion may trigger the onset of such an event. The mechanisms involved include the rupture of a small, inflamed, coronary plaque and the activation of thrombogenic factors. Blood pressure (BP)-lowering treatment has been associated with beneficial effects on subclinical inflammation and thrombosis at rest and during exercise. This prospective study sought to compare the effect of different antihypertensive drugs on the inflammatory and thrombotic response during exercise. A total of 60 never-treated hypertensive patients were randomized to an angiotensin receptor blocker (ARB)- or non-dihydropyridine calcium channel blocker (CCB)-based regimen. Patients with inflammatory or coronary artery disease were excluded. Six months after pharmaceutical BP normalization, the patients underwent a maximal treadmill exercise testing. High-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), white blood cells (WBC), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), total fibrinogen (TF) and von Willebrand factor (vWF) levels, as well as plasminogen activator inhibitor-1 (PAI-1) activity were measured in blood samples taken while the patients were at rest and during peak exercise. All of these biomarkers increased with exercise, except PAI-1, which decreased (P<0.05 for the difference between resting and peak exercise for all biomarkers). The ARB group had less marked (P<0.05) exercise-induced changes than the CCB group in hsCRP (5.8% vs. 7.7%), SAA (4.2% vs. 7.2%), WBC (46.8% vs. 52.6%), TNF-α (16.3% vs. 24.3%), TF (9.5% vs. 16.9%) and PAI-1 (-9.5% vs. -12.3%) but a similar (P=NS) change in IL-6 (39.4% vs. 38.6%) and vWF (29.2% vs. 28.6%). In conclusion, ARBs are most likely more effective than CCBs at suppressing the exercise-induced acute phase response. Potential protection against exercise-related coronary events remains to be elucidated.

The antihypertensive treatment effect on left ventricular diastolic function is reflected in exercise electrocardiogram.

BACKGROUND/PURPOSE: Exercise electrocardiographic hump sign is associated with uncontrolled arterial hypertension (AH), left ventricular (LV) diastolic dysfunction, and false-positive exercise testing (ET). The aim of this prospective study was to evaluate the antihypertensive treatment effect on hump and on pseudoischemic ST-segment depression and potential correlations to LV diastolic function and mass changes. METHODS: The study comprised 59 non-coronary artery disease patients (45.9 years; 67.8% men) with never-treated arterial hypertension (143.2/95.1 mm Hg). Treadmill ET and echocardiography were performed at baseline and 6 months after pharmaceutical blood pressure normalization. Prevalence of hump and ST depression, transmitral (E/A) and tissue Doppler imaging (E'/A') early/late velocities ratios, E/E' ratio, and LV mass index (LVMI) were all defined. RESULTS: Prevalence of hump was reduced from 69.5% to 23.7% and false-positive ETs from 35.6% to 18.6% (P < .05). Significant improvement (P < .05) was found in E'/A' ratio (0.68 vs 0.84), E/E' ratio (9.3 vs 7.9), and LVMI (109.2 vs 99.8 g/m(2)). Changes in hump were related to ST-depression changes (r = 0.632, P < .001) and to LV diastolic indices changes; patients with hump only at first ET (54.2%) improved E/A and E'/A' ratios, whereas patients with hump only at second ET (8.5%) worsened diastolic indices with similar changes in blood pressure and LVMI. CONCLUSIONS: Antihypertensive treatment reduces the prevalence of hump and exercise ischemic-appearing ST depression probably through LV diastolic function improvement.

Differential impact of metabolic syndrome on arterial stiffness and wave reflections: focus on distinct definitions.

BACKGROUND: Arterial stiffness and wave reflections are independent predictors of cardiovascular disease. Metabolic syndrome (MS) is related to increased aortic stiffness in several populations. However, it is unclear whether the association of MS with aortic stiffness differs according to the considered definition. Moreover, data regarding the association of wave reflections with MS are limited. For this purpose, we examined the relationship of arterial stiffness and wave reflections with MS by using four current definitions and a score. METHODS: We studied 732 never treated, non-diabetic hypertensive patients. Metabolic syndrome was defined by Adult Treatment Panel III, American Heart Association, World Health Organization (WHO), International Diabetes Federation criteria and MS (GISSI) score. Arterial stiffness was assessed by measuring carotid-femoral pulse wave velocity (PWVc-f). Heart rate-corrected augmentation index (AIx(75)) was estimated as a measure of wave reflections. RESULTS: By all definitions, hypertensive patients with MS had higher PWVc-f compared to hypertensives without MS. On the contrary, no significant difference was observed in AIx(75) between patients with and those without MS except when MS was defined by WHO criteria. An independent association emerged between PWVc-f and GISSI score and MS components (p=0.038 and 0.033 respectively) in patients with MS, after adjustment for age, gender, LDL cholesterol and smoking. Nevertheless, after further adjustment for systolic blood pressure or body mass index, the strength of this association was reduced to a non-significant level. CONCLUSION: Arterial stiffness is increased in patients with metabolic syndrome irrespective of the definition criteria. On the contrary, metabolic syndrome has no effect on wave reflections, except when this is defined by WHO criteria. Regarding the high prognostic significance of both arterial stiffness and wave reflections, these findings might have important clinical implications.

Beneficial effect of angiotensin II type 1 receptor blocker antihypertensive treatment on arterial stiffness: the role of smoking.

The purpose of the present study was to assess angiotensin receptor blocker (ARB) treatment on arterial stiffness in select hypertensive patients and define possible differences between smokers and nonsmokers. The authors evaluated 81 consecutive, nondiabetic patients (mean age, 52 years; 47 men) with uncomplicated essential hypertension with high plasma renin activity who were administered monotherapy with irbesartan, an ARB, at maximal dose. Patients were divided into smokers (n=24) and nonsmokers (n=57). Carotid-radial pulse wave velocity (PWVc-r), carotid-femoral pulse wave velocity (PWVc-f), and augmentation index (AIx) were measured before and 6 months after ARB antihypertensive treatment. All mean values of elastic effect indices were decreased after irbesartan monotherapy (AIx, from 26.3%to 21.2% [P<.01;] PWVc-f, from 7.7 m/s to 7.3 m/s [P<.05], and PWVc-r, from 8.9 m/s to 8.3 m/s [P<.001]). When comparing smokers vs nonsmokers, no difference was noted in AIx and PWVc-f change (P=not significant), while PWVc-r change was greater in smokers compared with nonsmokers (P<.05). Chronic ARB treatment may favorably affect arterial stiffness and wave reflections in hypertensive chronic smokers with elevated plasma renin levels.

Nocturnal blood pressure fall and metabolic syndrome score in hypertensive patients.

BACKGROUND: Data relating dipping status to metabolic syndrome (MS) scores are not available. The purpose of this study is to investigate any possible association of different dipping patterns to MS scores in untreated patients with essential hypertension. METHODS: The study included 6256 consecutive, treatment-naive patients with essential hypertension who attended our outpatient clinics. All underwent repeated office blood pressure measurements, 24-h ambulatory blood pressure monitoring, and full clinical and laboratory evaluation. The diagnosis of MS was made according to the Adult Treatment Panel III criteria and patients were classified into five groups: group I (hypertension), group II (hypertension+any one component), group III (hypertension+any two components), group IV (hypertension+any three components), and group V (all five components). Dipping pattern was defined as 'dippers' with nocturnal systolic blood pressure (NSBP) falling >or=10 but <20%, 'nondippers' with NSBP falling >or=0% but <10%, 'extreme dippers' with NSBP falling >or=20%, and 'reverse dippers' with NSBP increasing. RESULTS: Hypertensive patients with MS (n=2573) had higher clinical and ambulatory blood pressure values (P<0.001), whereas the dominant dipping pattern in the non-MS group was nondippers (47.6%), and in the MS group, extreme dippers (37.8%). Furthermore, a considerable decrease in the prevalence of dippers was noticed with the increasing number of MS components (21.1 vs. 19.2 vs. 14.5 vs. 8.4 vs. 7.2%, P<0.001). In contrast, a significant rise in the prevalence of reverse dippers was observed with the increasing number of MS components (7.4 vs. 10.1 vs. 14.9 vs. 20.4 vs. 31.2%, P<0.001). CONCLUSIONS: It seems that hypertensive patients have an increased prevalence of abnormal dipping patterns as the number of MS components rises.

Alpha-1 microglobulin as a new inflammatory marker in newly diagnosed hypertensive patients.

BACKGROUND: The alpha-1 microglobulin (A1M) is considered to be a marker of renal insufficiency, suggesting disturbed tubular function. In the present study we examined the ability of urinary A1M excretion to reflect the overall inflammatory status in patients with newly diagnosed essential hypertension and normal renal function. METHODS: The study population consisted of 1445 nondiabetic patients with newly diagnosed arterial hypertension and no evidence of renal insufficiency. Serum levels of C-reactive protein (CRP), serum amyloid alpha (SAA), and plasma fibrinogen, as well as urinary A1M excretion, were estimated. Multivariate analysis was performed to evaluate the associations between hypertension; A1M urinary excretion; and circulating levels of CRP, SAA, and fibrinogen. RESULTS: Patients with systolic hypertension had higher CRP, SAA, fibrinogen, and A1M compared with patients with isolated diastolic hypertension (P < .0001 for all). In multivariate analysis, systolic (but not diastolic) blood pressure (BP) was independently associated with A1M, CRP, and SAA (P < .0001 for all), whereas urinary A1M was also independently correlated with inflammatory markers such as CRP (P = .0001) and SAA (P = .0001). CONCLUSIONS: Urinary A1M is independently associated with circulating acute phase proteins in patients with newly diagnosed hypertension, whereas it is closely associated with systolic but not diastolic BP. Our findings suggest that urinary alpha-1 microglobulin may reflect the overall inflammatory status in patients with newly diagnosed essential hypertension, beyond its value as a marker of renal function.

Left ventricular (LV) geometry and dipping state are determinants of LV mass reduction with angiotensin-converting enzyme inhibitor antihypertensive treatment.

OBJECTIVES: Left ventricular hypertrophy is a major risk predictor in hypertensive patients and its regression is beneficial in terms of prognosis. The aim of this observational, open-labeled study was to investigate the effect of left ventricular geometry and dipping pattern on left ventricular mass reduction after chronic treatment with angiotensin-converting enzyme inhibitors, in a large population of hypertensive patients. METHODS: We evaluated untreated patients with mild to moderate essential hypertension, before and 6 months after treatment with angiotensin-converting enzyme inhibitor monotherapy or angiotensin-converting enzyme inhibitor-low-dose thiazide combination. Left ventricular mass index, relative wall thickness and geometry pattern were derived from echocardiography. Dipping state was determined with 24-h ambulatory blood pressure monitoring at enrollment. RESULTS: Overall, left ventricular mass index decrease in the 1400 patients (mean age 52.5 years) who completed the study was 12.9% of baseline value (P<0.00001). After adjusting for pretreatment value, left ventricular mass index reduction was similar with all angiotensin-converting enzyme inhibitors used [P= NS (not significant)], but it was higher in nondippers than dippers (14.1 vs. 12.3%, P<0.0001) and in patients with than without baseline left ventricular hypertrophy (14.6 vs. 11.3%, P<0.0001). We observed a stepwise augmentation of left ventricular mass index decrease with worsening left ventricular geometry (P<0.001). In multivariable analysis, impaired left ventricular geometry and blunted nocturnal blood pressure fall before treatment were independent predictors of a high left ventricular mass index reduction after treatment, independent of blood pressure fall, pretreatment left ventricular mass index, and other potential confounders. CONCLUSION: In essential hypertension, left ventricular geometry and dipping state are independent determinants of left ventricular mass reduction with angiotensin-converting enzyme inhibitor treatment. All angiotensin-converting enzyme inhibitors are efficient in decreasing left ventricular mass.

Beneficial effects of angiotensin II type 1 receptor blocker antihypertensive treatment on inflammation indices: the effect of smoking.

The effect of long-term angiotensin II type 1 receptor blocker (ARB) therapy on inflammation indices has not been fully investigated in a hypertensive population. The authors evaluated 323 consecutive nondiabetic patients (mean age, 57 years; 176 men; 92 smokers) with high renin activity and uncomplicated essential hypertension whose blood pressure levels normalized (from 163.9/100.7 mm Hg to 131.6/82.8 mm Hg) after 4 weeks of ARB or ARB/diuretic treatment. All patients underwent full laboratory evaluation (routine examination of blood and urine, liver, kidney, thyroid function, and lipid and glucose profiles), including measurement of high-sensitivity C-reactive protein and serum amyloid A levels, at drug-free baseline, which was repeated after 6 months of ARB or ARB/diuretic treatment. A significant (P<.001) overall decrease was noted in both high-sensitivity C-reactive protein (-0.41+/-1.56 mg/dL) and serum amyloid A (-0.62+/-2.03 mg/dL), but a smaller decrease in high-sensitivity C-reactive protein and serum amyloid A change was seen in the smoker subgroup compared with nonsmokers (P<.05), indicating that the ARB or ARB/diuretic anti-inflammatory effect may be adversely affected by smoking status.

Hypertensive patients with false-positive thallium-201 scintigraphic results in the infero-posterior wall are in high risk for coronary artery disease development.

BACKGROUND: It has been previously postulated that Thallium-201 (Tl201) scintigraphy is characterized by relatively low specificity in hypertensive patients. This study was undertaken to assess any possible influence of false-positive scintigraphic results on the prognosis of hypertensive patients. METHODS: The study group comprised 179 consecutive hypertensive patients (128 men and 51 women), aged 50+/-7 years, who underwent exercise Tl(201) scintigraphy and coronary angiography (patients with normal scintigraphic results underwent coronary angiography due to persistent angina-like symptoms). All patients with normal coronary arteries underwent a second Tl201 scintigraphy within 36+/-6 months. Patients with reversible ischemia in the second scintigraphy underwent also a second coronary angiography. RESULTS: Coronary artery disease (CAD) was detected in 78 (44%) patients, while the rest 101 (56%) patients had normal coronary arteries. Abnormal scintigraphic results were revealed in 66 (85%) patients with CAD and in 38 (38%) patients without CAD. Twenty-two (58%) of the 38 hypertensive patients with false-positive scintigraphic results presented reversible ischemia of the infero-posterior wall of the left ventricle. Coronary artery disease was detected in 7 (32%) of these patients during the follow-up period. CONCLUSIONS: Hypertensive patients with normal coronary arteries and false-positive scintigraphic results usually present with reversible ischemia of the infero-posterior wall of the left ventricle. This group of patients seems to be at increased risk of developing CAD in a long-term follow-up period.

Effects of antihypertensive treatment with angiotensin II receptor blockers on lipid profile: an open multi-drug comparison trial.

INTRODUCTION: Dyslipidaemia is associated with high risk for cardiovascular disease and lipid management is arguably necessary, especially in hypertensive subjects. There is an implication that angiotensin receptor blockers (ARB) are characterised by a beneficial effect on lipid profile in addition to their blood pressure lowering properties. This study was conducted to evaluate blood pressure control and the plasma lipid profile in hypertensive patients after six months' treatment with ARB. METHODS: We studied 2438 consecutive, untreated patients with uncomplicated essential hypertension (mean blood pressure [BP] 167/100 mmHg). All patients underwent full lab and echo examination at drug-free baseline, which was repeated after at least 6 months of ARB monotherapy. RESULTS: Overall, ARB treatment reduced BP levels significantly (p<0.0001). Evaluating lipid profile changes, a significant (p<0.0001) reduction was noted in total cholesterol (TC: from 220 +/- 39 to 216 +/- 36 mg/dL), low density lipoprotein cholesterol (LDL: from 146 +/- 35 to 141 +/- 33 mg/dL), ratio of TC to high density lipoprotein cholesterol (HDL) (from 4.80 +/- 1.35 to 4.64 +/- 1.25), apolipoprotein (Apo) B (from 129 +/- 32 to 124 +/- 28 mg/dL), and triglyceride levels (from 130 +/- 63 to 128 +/- 61 mg/dL, p=0.015), while ApoA1 and lipoprotein(a) levels were not significantly affected (149 +/- 23 vs. 149 +/- 22 and 24.9 +/- 26.3 vs. 24.7 +/- 26.4 mg/ dL, respectively, p=NS). Additionally, HDL levels increased from 48.2 +/- 12.2 to 48.8 +/- 11.9 mg/ dL, p<0.0001. According to the individual agent used, a different effect on lipid indices was observed. CONCLUSIONS: ARB antihypertensive therapy may have a uniquely beneficial metabolic effect in addition to blood pressure lowering.

Assessment of arterial ventricular coupling changes in patients under therapy with various antihypertensive agents by a non-invasive echocardiographic method.

BACKGROUND: The integration between arterial and ventricular function has been studied by mostly invasive techniques. We considered assessing the influence of various antihypertensive medications on arterial-ventricular coupling (AVC) with the use of a non-invasive echocardiographic method. METHODS: A total of 9037 patients, who had been under treatment for essential arterial hypertension were studied echocardiographically at baseline prior to therapy and after 6 months of antihypertensive monotherapy (diuretics, beta-blockers without intrinsic sympathomimetic activity (ISA), beta-blockers with ISA, a-blockers, angiotensin converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (AIIRA), non-dihydropyridine calcium antagonists, and dihydropyridine calcium antagonists). The AVC was calculated by echocardiographic measurements based on the equation: AVC=ESV/SV (ESV, end systolic volume; SV, stroke volume). RESULTS: ACEI, AIIRA, and dihydropyridine calcium antagonists decreased (P<0.0001 for all) while diuretics, alpha-blockers, both beta-blocker groups, and non-dihydropyridines increased significantly the AVC values compared to baseline measurements (P<0.0001 for all, except P=0.02 for alpha-blockers). Changes in AVC were the most highly correlated with changes in EF (r=-0.979, P<0.0001). CONCLUSION: Various antihypertensive drugs have a differential effect on AVC with ACEI, AIIRA, and dihydropyridine calcium antagonists having the most favorable effect on this index. AVC provides a meaningful index of cardiovascular performance in hypertension and offers the possibility of wide employment and serial follow-up in large numbers of patients because of its completely non-invasive nature.

The impact of third-generation beta-blocker antihypertensive treatment on endothelial function and the prothrombotic state: effects of smoking.

BACKGROUND: The significance of beta-blockers in the treatment of cardiovascular diseases is well established. The effect of vasodilating beta-blockers on endothelial function and prothrombotic state has not been investigated. METHODS: The study comprised 550 consecutive patients with uncomplicated essential hypertension. They were treated with celiprolol, carvedilol or nebivolol monotherapy (171, 179, and 200 patients, respectively), achieving comparable blood pressure reduction. Plasma levels of fibrinogen and homocystine and serum levels of plasminogen activator inhibitor-1 (PAI-1) were obtained before and 6 months after initiation of treatment. RESULTS: The three drugs differentiated in regard to homocystine (P <.00001) and fibrinogen level changes (P =.00003), but not (P = NS) in PAI-1 change. In smokers, differentiation was found in all three parameters (P =.0002, P =.001, and P =.006 for fibrinogen, PAI-1, and homocystine, respectively), but in nonsmokers differentiation was found only in homocystine change (P =.00003). In smokers, fibrinogen, PAI-1, and homocystine were reduced more (P =.002, P =.0009, and P <.0001, respectively) than in nonsmokers in the whole study cohort. The effect of nebivolol was more prominent in smokers than nonsmokers in reducing all three parameters (P =.0001,.003, and.003, respectively), whereas in celiprolol and carvedilol-treated groups, differentiation between smokers and nonsmokers was significant (P =.00003 and.01, respectively) only in homocystine level change. CONCLUSIONS: In hypertensive smokers, nebivolol resulted in a significant decrease of plasma PAI-1, fibrinogen and homocystine. Celiprolol also significantly affected these parameters but to a lesser degree, whereas carvedilol had no significant favorable action. In nonsmokers, homocystine was reduced significantly by nebivolol. We conclude that smoking status should be a determinant of antihypertensive treatment choice.

Impact of abnormal nocturnal blood pressure fall on vascular function.

BACKGROUND: It is well known that nondipping pattern of arterial hypertension has a harmful effect on target organs such as the brain, heart, and kidneys. However, it remains uncertain whether abnormal dipping patterns of nocturnal blood pressure (BP), such as extreme and reverse dipping, influence vascular function. METHODS: This study comprised consecutive 2800 individuals (1554 men and 1246 women). All were nondiabetic and had uncomplicated, untreated essential sustained hypertension based on office measurements. After a 2-week wash-out period, 24-h ambulatory BP recordings were obtained and patients were classified by their nocturnal systolic BP fall (132 extreme dippers with >20% nocturnal systolic BP fall; 1235 dippers with >10% but <20% fall; 1146 nondippers with >0% but <10% fall; and 287 reverse dippers with <0% fall). Microalbumin, ACR (albumin/creatinine ratio), and microglobulin values were measured in all groups. RESULTS: Extreme dippers did not differ from dippers with regard to microalbumin, microglobulin excretion, or ACR. On the contrary, reverse dippers had significantly (P <.0001) higher values, compared with nondippers, for microalbumin (49.5 v 37.2 mg/dL), microglobulin (10.33 v 8.71 mg/dL), ACR (104.9 v 65.2), and percentages of abnormal values for these parameters. CONCLUSIONS: Microalbuminuria, an index of vascular function, differentiates reverse dippers from nondippers, but not extreme dippers from dippers among hypertensive patients.