Uncomplicated Primary Hypertension Research Articles

Urinary levels of cortisol but not catecholamines are associated with those of 8-hydroxy-2'-deoxyguanosine in uncomplicated primary hypertension.

The relationships between stress hormones and oxidative DNA damage have not yet been explored in human hypertension. We investigated the associations of urinary levels of cortisol or catecholamines with those of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative DNA damage in primary hypertension. Untreated 156 primary hypertensives without apparent cardiovascular diseases were entered into the study. Following blood sampling after an overnight fast, 24-h blood pressure monitoring and 24-h urinary sampling were performed simultaneously to determine 24-h averaged values for blood pressure and urinary levels of cortisol, catecholamines and 8-hydroxy-2'-deoxyguanosine. Urinary cortisol significantly correlated positively with urinary 8-hydroxy-2'-deoxyguanosine in all studied participants (r = 0.334, P < 0.001). Contrary, either urinary adrenaline or urinary noradrenaline did not significantly correlate with urinary 8-hydroxy-2'-deoxyguanosine (r = 0.050, P = 0.553 or r = 0.063, P = 0.435). Additionally, the positive association of urinary cortisol with urinary 8-hydroxy-2'-deoxyguanosine remained highly significant after the adjustments for multiple confounders of oxidative stress such as age, gender, body mass index, smoking status, 24-h blood pressure, C-reactive protein and estimated glomerular filtration rate (partial r = 0.323, P < 0.001), although only approximately 10% of the variance in urinary cortisol was attributable to differences in urinary 8-OHdG (partial r2 = 0.104). Thus, our data indicate that cortisol but not catecholamines could at least partially contribute to the occurrence of oxidative DNA damage in primary hypertensives. The present study suggested the possibility that the overactivation of hypothalamic-pituitary-adrenal axis rather than sympathoadrenal system could enhance oxidative stress and attendant DNA oxidation in uncomplicated primary hypertension.

Factors, associated with major adverse events in rural males with arterial hypertension at long-term follow-up

Background and Aims : To study the factors, associated with major adverse events (MAEs) in rural males with uncomplicated arterial hypertension (HTN) at long-term follow-up.Methods: The prospective study enrolled 160 rural males with uncomplicated primary HTN (mean age 50 ± 6 years). We analyzed clinical and instrumental data. High-to-very high SCORE cardiovascular risk was identified in 102 (63,7%) patients. Blood pressure visit-to-visit variability (VVV) was assessed by standard deviation and coefficient of variation (CV) (derived from the four consecutive visits). Left ventricular (LV) hypertrophy (by echo) was detected in 129 (80,6%) patients. The median of follow-up was 27 months (interquartile range 24-30 months). During the follow-up period, 14 (8,8%) patients presented with MAEs (totally, 17 events): acute cerebrovascular event (n=9); myocardial infarction (n=2); first-onset atrial fibrillation (AF) (n=2); AF transition in permanent pattern (n=2); and relative LV ejection fraction decline >10% (n=2).Results: At multivariable analysis, the factors, associated with MAEs at long-term follow-up, were as follows: SCORE cardiovascular risk (per 1 % increase: HR 1,09 (95% CI 1,01-1,17); р=0,034); mean arterial pressure (MAP) (per 1 mm Hg increase: HR 1,23 (95% CI 1,07-1,41); р=0,003); CV (MAP) (per 1% increase: HR 1,41 (95% CI 1,08-1,83); р=0,012); and LV myocardial mass, indexed by height2,7 (per 1 g/m2,7 increase: HR 1,07 (95% CI 1,03-1,11); р=0,001).Conclusions: Long-term MAEs in rural HTN males were associated with SCORE cardiovascular risk, MAP, MAP VVV (by CV) and LV myocardial mass index (by height2,7). These factors should be taken into account while MAEs risk stratification in rural males with uncomplicated HTN. Background and Aims : To study the factors, associated with major adverse events (MAEs) in rural males with uncomplicated arterial hypertension (HTN) at long-term follow-up. Methods: The prospective study enrolled 160 rural males with uncomplicated primary HTN (mean age 50 ± 6 years). We analyzed clinical and instrumental data. High-to-very high SCORE cardiovascular risk was identified in 102 (63,7%) patients. Blood pressure visit-to-visit variability (VVV) was assessed by standard deviation and coefficient of variation (CV) (derived from the four consecutive visits). Left ventricular (LV) hypertrophy (by echo) was detected in 129 (80,6%) patients. The median of follow-up was 27 months (interquartile range 24-30 months). During the follow-up period, 14 (8,8%) patients presented with MAEs (totally, 17 events): acute cerebrovascular event (n=9); myocardial infarction (n=2); first-onset atrial fibrillation (AF) (n=2); AF transition in permanent pattern (n=2); and relative LV ejection fraction decline >10% (n=2). Results: At multivariable analysis, the factors, associated with MAEs at long-term follow-up, were as follows: SCORE cardiovascular risk (per 1 % increase: HR 1,09 (95% CI 1,01-1,17); р=0,034); mean arterial pressure (MAP) (per 1 mm Hg increase: HR 1,23 (95% CI 1,07-1,41); р=0,003); CV (MAP) (per 1% increase: HR 1,41 (95% CI 1,08-1,83); р=0,012); and LV myocardial mass, indexed by height2,7 (per 1 g/m2,7 increase: HR 1,07 (95% CI 1,03-1,11); р=0,001). Conclusions: Long-term MAEs in rural HTN males were associated with SCORE cardiovascular risk, MAP, MAP VVV (by CV) and LV myocardial mass index (by height2,7). These factors should be taken into account while MAEs risk stratification in rural males with uncomplicated HTN.

LOW DOSE-EPLERENONE TREATMENT DECREASES AORTIC STIFFNESS IN PATIENTS WITH METABOLIC SYNDROME

Objective: Metabolic syndorme is a well-established cardiovascular risk factor with increasing prevalence and incidence globally. Our aim in this study was to analyse the effect of a low dose steroidal mineralocorticoid receptor antagonist on metabolic parameters, aortic stiffness parameters and endothelial function (as assessed by measuring baseline nitric oxide activity) of the macrovasculature in patients with metabolic syndrome. Design and method: Patients with mild uncomplicated primary arterial hypertension and at least 2 of the following traits of the metabolic syndrome (Adult Treatment Panel III criteria: abdominal obesity (abdominal girth &gt; 102 cm in males), triglyceride level &gt; 150 mg/dL or treatment for elevated triglycerides, HDL &lt; 40 mg/dL or treatment for low HDL, fasting blood glucose &gt; 100 mg/dL and &lt; 126 mg/dl) were included in the study. After the wash-out of antihypertensive medication (if applicable), patients were treated with eplerenone (EPL) 25 mg for the next 10 weeks. Pulse wave analysis was performed before and after infusion of L-NMMA (=nitric oxide-synthase inhibitor) at baseline and after treatment with EPL. Results: In patients with metabolic syndrome (n = 23), HbA1c (5.8 ± 0.3 vs. 6.0 ± 0.3 %; p = 0.012) and HDL (41.5 ± 8.1 vs. 44.1 ± 10 mg/dl; p = 0.046) increased significantly with EPL treatment. Central systolic pressure (132 ± 11.6 vs. 124.8 ± 12.9 mmHg; p = 0.015), augmentation pressure (15.2 ± 26.9 vs. 11.9 ± 23.1 mmHg; p = 0.011), augmentation index (22.5 ± 7.8 vs. 18 ± 11.1 %; p = 0.028, independent of systolic office blood pressure (BP) reduction), and augmentation index normalized to heart rate of 75/min (18.6 ± 7.8 vs. 14.5 ± 8.8 %; p = 0.006, independent of systolic office BP reduction) reduced significantly with EPL treatment. Augmentation index normalized to heart rate of 75/min increased significantly with infusion of L-NMMA after treatment with EPL (14.7 ± 8.8 vs. 17.6 ± 8.3 %; p = 0.004), whereas no such difference could be noticed at baseline (p = 0.230) thereby indicating an increased nitric oxide availability. Conclusions: Our data show that EPL beneficially affects markers of arterial stiffness in patients with metabolic syndrome, independent of systolic office BP reduction. Whether the observed benefits could be noticed with nonsteroidal mineralocorticoid receptor antagonists without change in metabolic parameters warrants further investigation.

VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY IN RURAL MALES WITH ARTERIAL HYPERTENSION: THE POSSIBILITIES OF MODIFYING IN REAL CLINICAL SETTINGS

Purpose: to establish the possibilities of modifying blood pressure visit-to-visit variability (VVV) in rural males with arterial hypertension (HTN) by the use of antihypertensive therapy (AHT), considering also the correction of dyslipidemia and certain lifestyle aspects, as well as the changes in compliance with pharmacotherapy (CP).&#x0D; Material and methods. The prospective study enrolled 160 rural males with uncomplicated primary HTN (mean age 50 ± 6 years). Seventy three (45,6 %) patients were overweight; 85 (53,1 %) patients were active smokers. An alcohol consumption ≥1 time per week was pointed out by 77 (48,1 %) males. VVV (of systolic (SBP) and diastolic blood pressure (DBP)) was assessed by means of standard deviation (SD) and coefficient of variation (CV). We prescribed a fixed perindopril/amlodipine (P/A) combination, with indapamide (IND) addition as required. With the aim dyslipidemia correction, we prescribed atorvastatin (daily doses 10-40 mg). Optimal CP was pointed out by 37 (23,1 %) patients.&#x0D; Results. At 1yFU, all enrolled patients achieved SBP/DBP targets (&lt;140/90 mm Hg), and strict SBP/DBP targets (&lt;130/80 мм Hg) were achieved in 159 (99,4 %) cases. More than 90 % of patients achieved the following prespecified «target» BP VVV levels: SD (SBP) &lt;4,8 mm Hg; CV (SBP) &lt;3,9 %; SD (DBP) &lt;3,7 mm Hg; CV (DBP) &lt;5,1 %. Aimed to predict SD (SBP) reduce &gt;9,7 mm Hg probability at 1yFU, we built the 6-factors logistic regression model: 1) improvement and maintenance of optimal CP (by MGLS) (β = 1,27; р&lt;0,001); 2) body mass index reduce &gt;1,3 kg/m2 (β = 0,57; p=0,035); 3) alcohol consumption modifying (0,72; p=0,007); 4) optimal compliance with atorvastatin daily doses 30-40 mg (1,25; p&lt;0,001); 5) smoking status modifying (0,43; р=0,097); 6) SBP reduce &gt;46,7 mm Hg (0,47; р=0,098). The probability of status «reduction of SD (SBP) &gt;9,7 mm Hg at 1yFU» increase was associated with the higher sum of predictors` β-coefficients.&#x0D; Conclusions. In rural HTN males, at 1yFU, the AHT (based on P/A, with IND addition as required) favored the significant blood pressure VVV reduction in the vast majority of cases. The SBP VVV reduction was determined to be additively affected by the modifying of certain factors, as well as by achievement and maintenance of maximum CP.

VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY AND TARGET ORGAN DAMAGE IN RURAL DWELLERS WITH UNCOMPLICATED ARTERIAL HYPERTENSION

The aim: To examine the association of hypertensive mediated target organ damage with blood pressure visit-to-visit variability in Ukrainian rural dwellers with uncomplicated hypertension. Material and methods: The cross-sectional study enrolled 160 adult males with uncomplicated primary hypertension (mean age 50±6 yo). We analyzed office systolic and diastolic blood pressure levels, obtained at four consecutive visits. We used standard deviation (SD) value to assess blood pressure visit-to-visit variability. The patients were referred to the group with high (n=82; 51.3%) vs low (n=78; 48.7%) blood pressure variability (HBPV, LBPV). Results: HBPV patients were characterized by higher left ventricular myocardial mass indexed to height 2.7: median, interquartile range: 70.9 (61.3-78.2) vs 50.9 (44.9-54.4) g/m2.7, respectively p<0.001. The cases of severe left ventricular hypertrophy prevailed in HBPV group (vs LBPV): 68% vs 5%, respectively, p<0.001. HBPV group was characterized by larger common carotid artery intima-media complex thickness, advanced hypertensive retinopathy, higher urine albumin/creatinine ratio value and worse kidneys' glomerular filtration rate. The obtained results might be helpful in the context of global monitoring of vulnerable high risk population of hypertensive rural males. Conclusions: The HBPV in rural hypertensive males was associated with more pronounced target organ damage. Further regional research on the various clinical aspects of hypertension, including blood pressure variability, might be useful in extending the existed evidence on prevention of hypertension-related complications.

Effect of nurse-led home-based biofeedback intervention on the blood pressure levels among patients with hypertension: Pretest-posttest study.

Aim:To investigate the effect of nurse-led home-based biofeedback intervention on the blood pressure levels among patients with hypertension.Background:Nurse-led interventions are emerging as cost-effective as well as clinically proven in chronic illness management. Hypertension, a leading long-term cardiovascular condition, has autonomic dysregulation and increased sympathetic tone as its pathophysiological background. Complementary interventions evidenced to interplay hypertension pathophysiology.Design:A pretest–posttest design.Materials and Methods:Uncomplicated primary hypertension outpatients were randomly assigned as study group (n = 173) and control group (n = 173) at a tertiary care hospital. Sociodemographic, clinical, and outcome variables [the baseline blood pressure and galvanic skin response (GSR)] were collected. Study group patients were given four teaching sessions of abdominal breathing-assisted relaxation facilitated by GSR biofeedback. Daily home practice was encouraged and monitored to measure the effects on blood pressure and GSR at the end of the 1st, 2nd, and 3rd month of intervention.Results:The study group participants showed significant decrease in mean (SD) systolic [140.77 (8.31) to 136.93 (7.96), F = 469.08] and diastolic blood pressure [88.24 (5.42) to 85.77 (4.66), F = 208.21]. In contrast, control group participants had a mild increase in the mean systolic (F = 6.02) and diastolic blood pressure (F = 4.70) values from pretest to posttests. GSR showed a significant increase from 559.63 (226.33) to 615.03 (232.24), (F = 80.21) from pretest to posttest III.Conclusions:Use of home-based biofeedback-centered behavioral interventions enabled BP reduction among hypertensive patients. Further studies should use biochemical markers of sympathetic nervous system activity to endorse this home-based chronic illness intervention.

Microalbuminuria and plasma aldosterone levels in nondiabetic treatment-naïve patients with hypertension.

Identification of factors that contribute to urinary albumin losses in hypertensive nephropathy is crucial for prevention of renal deterioration. The aim of this study was to investigate the relationship of low-grade albuminuria with plasma aldosterone levels in treatment-naïve hypertensive patients free of additional comorbidities that might affect renal function. In 242 newly diagnosed patients with uncomplicated primary hypertension, we obtained duplicate 24-h urine collections for measurement of urinary albumin/creatinine ratio (UACR) and measured plasma aldosterone levels. Patients with diabetes, overt proteinuria (>300 mg/day), glomerular filtration rate less than 30 ml/min per 1.73 m, and previous renal diseases were excluded. Increasing UACR was associated with significantly and progressively higher blood pressure (BP), HDL-cholesterol, and plasma aldosterone levels, and with lower glomerular filtration. Microalbuminuria (30-300 mg/day) was detected in 41 (17%) of 242 hypertensive patients, and these patients had significantly higher BP and plasma aldosterone levels (178 ± 113 vs. 128 ± 84 pg/ml; P = 0.001), and lower glomerular filtration than patients without microalbuminuria. UACR was directly and independently correlated with BP and plasma aldosterone levels. In a logistic regression model, presence of microalbuminuria was associated with plasma aldosterone levels independently of glomerular filtration and demographic, anthropometric, and metabolic variables. In nondiabetic, treatment-naïve patients with hypertension, low-grade albuminuria is independently associated with elevated plasma aldosterone. These findings suggest a contribution of aldosterone to the early glomerular changes occurring in hypertensive nephropathy.

Incidence of Captopril–Induced Cough in Newly Diagnosed Hypertensive Patients: Incidence in an Outpatient Medical Clinic Population in Iran in 2011-2012

Introduction: In patients with uncomplicated primary hypertension (HTN), angiotensin converting enzyme inhibitors (ACEIs) are considered as monotherapy. In some studies, cough was not related to age, sex, underlying disease, or drug dosage. However, in previous studies, the incidence of cough was greater in females than males. The aim of this study is to determine the incidence of captopril-induced cough in patients with HTN and to evaluate some associated parameters such as sex and age. Materials and Methods: In this cross-sectional epidemiologic study, 877 patients with new onset HTN, referring to our outpatient clinic, were assessed and underwent treatment by captopril as first-line medical treatment. All patients were enrolled in four different age groups ( 55 years old) and comparison was made between the groups. Results: The overall incidence of captopril-induced cough was 15.5%, with a significant difference between females and males and obviously a higher rate in females (P=0.017). In addition, cough was significantly more common in females than males in 36- to 45-year-old group (46.42% vs. 24.71%). The incidence of cough after treatment with captopril decreased by increasing age of patients and this reduction in both male and female patients was statistically significant (P<0.001). Conclusion: A persistent, dry cough in a hypertensive patient, treated by captopril, should be considered as an adverse effect of ACE inhibitor therapy. Our study demonstrated the higher incidence of cough in female patients, receiving captopril. Thus, identification of this adverse effect may prevent unnecessary treatment of patients using captopril.

Blood Pressure and Metabolic Effect of a Combination of Lercanidipine with Different Antihypertensive Drugs in Clinical Practice

The aim of this study is to assess the blood pressure (BP) and metabolic effects of lercanidipine when combined with other classes of first-line antihypertensive drugs in day-to-day clinical practice. For this study, we consecutively enrolled 162 patients with uncomplicated primary hypertension, who are partial responders to the treatment with lercanidipine over a period of 24 months. Patients were then allocated to the combination of lercanidipine (10–20 mg/day) with β-blockers, diuretics, angiotensin-converting enzyme inhibitors, and angiotensin-II receptor blockers according to compelling indications (if any) and/or suggestions of European Society of Hypertension–European Society of Cardiology (ESH–ESC) guidelines. All the enrolled patients completed the study and no adverse drug reaction was registered during the research period. The association of a second drug with lercanidipine determined an additional BP decrease of either systolic BP or diastolic BP independently from the type of drug added (P always &lt;0.05). The additional effect of lercanidipine appears widely distributed with no significant differences in the size of BP decrease. From the metabolic point of view, the addition of a second drug did not determine a significant variation in the serum levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (P always &gt;0.05). Conversely, a significant decrease in fasting plasma glucose and serum levels of triglycerides has been observed in patients where lercanidipine has been combined with an angiotensin-converting enzyme inhibitor or an angiotensin-II receptor blocker. In conclusion, in our study we observed that lercanidipine-based protocols are well tolerated and efficacious in reducing BP. Moreover, the association of lercanidipine with renin–angiotensin system blockers is also associated with significant improvements in triglycerides and fasting plasma glucose.

Blood Pressure and Metabolic Effect of a Combination of Lercanidipine with Different Antihypertensive Drugs in Clinical Practice

The aim of this study is to assess the blood pressure (BP) and metabolic effects of lercanidipine when combined with other classes of first-line antihypertensive drugs in day-to-day clinical practice. For this study, we consecutively enrolled 162 patients with uncomplicated primary hypertension, who are partial responders to the treatment with lercanidipine over a period of 24 months. Patients were then allocated to the combination of lercanidipine (10–20 mg/day) with β-blockers, diuretics, angiotensin-converting enzyme inhibitors, and angiotensin-II receptor blockers according to compelling indications (if any) and/or suggestions of European Society of Hypertension–European Society of Cardiology (ESH–ESC) guidelines. All the enrolled patients completed the study and no adverse drug reaction was registered during the research period. The association of a second drug with lercanidipine determined an additional BP decrease of either systolic BP or diastolic BP independently from the type of drug added (P always <.05). The additional effect of lercanidipine appears widely distributed with no significant differences in the size of BP decrease. From the metabolic point of view, the addition of a second drug did not determine a significant variation in the serum levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (P always >.05). Conversely, a significant decrease in fasting plasma glucose and serum levels of triglycerides has been observed in patients where lercanidipine has been combined with an angiotensin-converting enzyme inhibitor or an angiotensin-II receptor blocker. In conclusion, in our study we observed that lercanidipine-based protocols are well tolerated and efficacious in reducing BP. Moreover, the association of lercanidipine with renin–angiotensin system blockers is also associated with significant improvements in triglycerides and fasting plasma glucose.

Efficacy and Safety of a New Long-acting Drug Combination, Trandolapril/Verapamil as Compared to Monotherapy in Primary Hypertension

Objective: To evaluate the clinical efficacy and safety of a new antihypertensive drug combination of trandolapril/verapamil compared to monotherapy with verapamil or trandolapril, in patients with mild to moderate primary hypertension. Design: A multicentre, prospective, randomized, double-blind, controlled cross-over study with specific statistical considerations. Settings: Eighteen primary health care centres and out-patient hospital clinics in Sweden. Patients: Two hundred and twenty-six outpatients with uncomplicated primary hypertension with a baseline sitting diastolic blood pressure (BP) between 95 and 115 mmHg. Interventions: After a 4-week placebo period, patients were randomized to treatment for 8 weeks with trandolapril/verapamil (2 mg/180 mg) or each drug alone (verapamil 240 mg, trandolapril 2 mg) for 8 weeks. Main outcome measures: Treatment responses (blood pressure (BP) fall and rate pressure product) to the three regimens with statistical comparison and also in relation to plasma concentrations of active renin (AR). Adverse events and safety were also evaluated. Results: The mean BP fall was significantly greater with the combination (20/15 mmHg), p < 0.00054, as compared to both trandolapril (14/11 mmHg) or verapamil (13/11) mmHg. The difference between verapamil and trandolapril was not significant. Rate pressure product decreased significantly more on the combination, p < 0.001, than on trandolapril or verapamil alone. Treatment response to trandolapril was positively correlated to initial AR (r = 0.30-0.43). All treatments were well tolerated and safe. Conclusions: The new fixed drug combination trandolapril/verapamil was superior to monotherapy with either of these drugs alone regarding reduction of both BP and rate pressure product. This combination can be safely and effectively used for the treatment of mild to moderate primary hypertension.

Effects of modulators of the renin???angiotensin???aldosterone system on cough

To compare the incidence of cough in patients with a history of angiotensin converting enzyme (ACE) inhibitor-related cough who received losartan [a type 1 angiotensin II (Ang II) receptor antagonist], lisinopril (an ACE inhibitor) or hydrochlorothiazide (a diuretic). An international, multicentre, randomized double-blind, parallel-group controlled trial. Outpatient clinics at 20 tertiary care medical centres in 11 countries. One hundred and thirty-five patients with uncomplicated primary hypertension with a history of ACE inhibitor-related cough were randomly assigned to the double-blind treatment phase and completed the study. After confirming that the cough was ACE inhibitor-related by a single-blind rechallenge, followed by a placebo washout period, patients were randomly assigned to receive 50mg losartan, 20mg lisinopril or 25mg hydrochlorothiazide once a day for 8 weeks. Cough incidence, severity and frequency were assessed by a self-administered questionnaire and a visual analogue scale. The percentage of patients who complained of cough was significantly higher with lisinopril than with losartan or hydrochlorothiazide. The mean visual analogue scale scores for patients treated with lisinopril demonstrated that these patients coughed more frequently than those who received losartan or hydrochlorothiazide. The incidence of cough related to the type 1 Ang II receptor antagonist losartan is significantly lower than that observed with lisinopril, and similar to that observed with hydrochlorothiazide in patients with a rechallenged ACE inhibitor cough. Type 1 Ang II receptor antagonists represent a potential new treatment for hypertensive patients in whom ACE inhibitors are indicated, but who develop a cough with these agents.

Serotonin-induced platelet aggregation predicts the antihypertensive response to serotonin receptor antagonists.

The 5-HT2-receptor antagonist ketanserin (20-40 mg b.i.d.) was administered to 62 patients of both sexes with uncomplicated primary hypertension. After 4 weeks of treatment about 50% of the patients had reached the target diastolic blood pressure of 90 mm Hg or below. Interindividual variability was large. In a retrospective analysis the variability could not be explained by sex or the dose of ketanserin. There was a weak association between age and systolic blood pressure response (r = 0.24; P = 0.06), which could be entirely accounted for by the higher base line blood pressure in the elderly patients. In one group of patients (n = 12), the ex vivo aggregation to serotonin (10(-6) M) was studied during treatment with placebo and ketanserin. Ketanserin completely inhibited 5-HT-induced aggregation in all patients. There was a close correlation between the area under the 5-HT-induced platelet aggregation curve during placebo and the subsequent reduction in diastolic blood pressure after 4 weeks of treatment with ketanserin. The present data suggest that the blood pressure response to ketanserin can be predicted from the ex vivo sensitivity of platelets to serotonin. By implication, they also support a role for serotonergic mechanisms in hypertension.

Supernormal contractility in primary hypertension without left ventricular hypertrophy.

Forty-three subjects with uncomplicated primary hypertension and without echocardiographic left ventricular hypertrophy and 54 normotensive volunteers were studied by two-dimensional targeted M-mode echocardiography to evaluate systolic function and contractility before the development of compensatory hypertrophy. The ratio of peak systolic pressure to end-systolic dimension was used to assess left ventricular performance and was divided for either posterior wall thickness or cross-sectional area to generate hypertrophy-independent indices of inotropic state. Fractional shortening was normal in the hypertensive group, despite the increase in end-systolic stress. Systolic pressure/dimension ratio was higher in hypertensive subjects (p less than 0.001), as were hypertrophy-independent indices of inotropic state (p less than 0.005), which were inversely correlated to left ventricular mass (p less than 0.001). Values in 11 hypertensive subjects were above the upper confidence limit of the normal shortening/stress relation, which provides a load-independent measure of inotropic state. They showed high hypertrophy-independent indices of inotropic state (p less than 0.01), while the other hypertensive subjects did not. High fractional shortening, wall stress, and systolic pressure (p less than 0.01) were found in the subgroup with supernormal performance, while left ventricular mass was not different from that of other subgroups, depicting inadequate left ventricular hypertrophy. The duration of hypertension was the same in the subgroups. Supernormal inotropic state could be considered one form of primary adaptation to high wall stress that serves to maintain systolic ventricular performance.

The Inconsistent Effects of Calcium Supplements upon Blood Pressure in Primary Hypertension

The effects of 800 mg of elemental calcium per day (calcium carbonate or calcium citrate) on blood pressure were compared with a placebo in a controlled randomized, crossover, double-blinded trial involving 26 patients with uncomplicated primary hypertension. Each patient took two of the three forms of therapy orally for 8-week intervals with a 2-week washout period in between. Standing mean blood pressure rose an average of 5.7 mm Hg on placebo, rose an average of 0.5 mm Hg on calcium carbonate, and fell an average of 2.2 mm Hg on calcium citrate. Changes in sitting mean pressures averaged +1.9 mm Hg on placebo, -0.4 mm Hg on calcium carbonate, and -0.4 mm Hg on calcium citrate. Some patients had a fall, others had a rise in blood pressure on each form of calcium. Similarly, inconsistent responses were noted among the nine patients who took both forms of calcium. Neither initial nor post-treatment biochemical measures nor patient characteristics were predictive of the blood pressure response. Combinations of various measures and characteristics analyzed by the multiple regression technique explained only 30% of the overall variability in blood pressure. Therefore, until ways can be found to predict the response, calcium supplements should not be routinely prescribed for the treatment of hypertension and, if given for any indication, blood pressure should be monitored.

Left ventricular mass and blood pressure during ergometric exercise in primary hypertension.

The pathophysiology of left ventricular hypertrophy (LVH) in hypertensive patients is still an intriguing point. The lack of a close relationship between LVH and systolic or diastolic blood pressure at rest, previously observed by other investigators, was confirmed in our group of 45 patients with uncomplicated primary hypertension. The strength of correlation between echocardiographic left ventricular mass (LVMe) and blood pressure, expressed as incremental area (IA = total area under the curve--basal area), however, increased during bicycle exercise testing (r = 0.33, p less than 0.05 for diastolic blood pressure; r = 0.39, p less than 0.01 for systolic blood pressure; r = 0.41, p less than 0.01 for mean arterial pressure). Other echocardiographic parameters of myocardial mass such as LVM index (LVMI) and septal thickness (ST) were also significantly correlated with blood pressure during exercise. These results suggest either that blood pressure during exercise is a better index of the cardiac workload than resting blood pressure or that the pathogenesis of cardiac hypertrophy involves an enhanced reactivity to adrenergic drive, particularly stimulated during ergometric exercise. Increased blood pressure alone, however, only partly accounts (about 20%) for the increase in myocardial mass in hypertensive patients; other factors, therefore, need to be further investigated for a better understanding of the pathophysiology of left ventricular hypertrophy.

Pulmonary vascular supersensitivity to catecholamines in systemic high blood pressure

Pulmonary pressure and arteriolar resistance are elevated in uncomplicated primary systemic hypertension. This study was carried out in 16 men with this form of hypertension and in 9 healthy men to compare 1) their pulmonary vascular reactivity to endogenous catecholamines released during mental arithmetic and cold pressor tests, and 2) the dose-response relation to exogenous epinephrine and norepinephrine. Arithmetic and cold pressor tests were associated, respectively, with a predominant increase in plasma epinephrine and norepinephrine concentration; changes were significantly greater in hypertensive men. During the two tests, pulmonary arteriolar resistance in the normotensive group was reduced by 13% and augmented by 7% of baseline, respectively, whereas it was raised by 31 and 70%, respectively, in the hypertensive group. In normal subjects, the dose (microgram)-response (delta dynes) relation to epinephrine was 1 = -4, 2 = -9, 3 = -9 and 4 = -10; to norepinephrine it was 2 = +3, 4 = +6, 6 = +7 and 8 = +7. In hypertensive patients, the respective relations were 1 = +18, 2 = +44, 3 = +59 and 4 = +77; and 2 = +39, 4 = +54, 6 = +76 and 8 = +98. Group differences were highly significant. In each of these circumstances, the driving pressure across the lungs was significantly augmented in the hypertensive but not the normotensive group. Both epinephrine and norepinephrine have a vasoconstrictor influence on the lesser circulation as a consequence of vascular overreactivity. The opposite changes in resistance between normotensive and hypertensive subjects produced by epinephrine suggest that a constrictor vascular supersensitivity becomes active in the pulmonary circuit with the development of systemic high blood pressure.

Acute effect of labetalol on blood pressure in relation to the sympathetic nervous system and plasma renin activity.

A single oral dose of 300 mg labetalol was given to 10 subjects with uncomplicated primary hypertension; its effects on blood pressure, heart rate (HR), plasma renin activity (PRA), and plasma concentration of catecholamines and of their major metabolites, octopamine ( OTP ), and dopamine-beta hydroxylase (DbH) were investigated. Although HR did not change after dosing, both systolic and diastolic blood pressure decreased in 2 hr and remained below control up to 12 hr. There was symptomatic orthostatic hypotension in two subjects in the first 2 hr after dosing. PRA decreased in the first 2 hr and followed a gradual rise that became significant at 24 hr. Although DbH did not change, plasma concentrations of norepinephrine (NE) and its major metabolites and of OTP increased between 2 and 4 hr after dosing and remained elevated up to 12 hr. There was no correlation between change in blood pressure and control levels or changes of PRA or NE concentrations.

Cardiac performance in hypertension re-evaluated through a combined haemodynamic ultrasonic method.

From echocardiographic measurements, 39 patients with established, uncomplicated primary hypertension (diastolic pressure > 100 mmHg) were classified as follows: normal-sized heart (group 1, 10 cases); concentric left ventricular hypertrophy (group 2, 18 cases); left ventricular hypertrophy and cavity enlargement (group 3, 11 cases). Eighteen age-matched healthy subjects were investigated as a control group. Systolic and diastolic arterial pressure increased progressively from group 1 to 2 to 3. Left ventricular function, assessed from the relation between diastolic diameter and stroke index, was maintained in group 1, increased in group 2 (in spite of the greater pressure load), and reduced in group 3, in comparison with controls. Similarly, the mean velocity of circumferential fibre shortening (VCF) was normal in group 1, significantly increased in group 2, and reduced in group 3. It was impossible to discern whether the different behaviour of VCF in group 2 and in group 3 reflected opposite changes in ventricular contractility, or in wall stress during ejection, or in both. At variance with previous conclusions (which were based on utilisation of electrocardiographic and chest x-ray criteria to define hypertrophy) it is suggested that left ventricular concentric hypertrophy in man consequent to sustained hypertension is associated with an improved function. Whether this feature depends upon an augmented contractility or a ventricular unloading effect related to hypertrophy remains uncertain.

Hypertension and propranolol therapy: Effect on blood pressure, plasma catecholamines and platelet aggregation

The effects of propranolol on blood pressure, plasma catecholamine concentration and platelet aggregation were examined in 16 patients with uncomplicated primary hypertension. The patients were studied at rest, during isometric handgrip stress and 48 hours after sudden discontinuation of propranolol therapy. Plasma catecholamine concentration and platelet aggregation studies were also carried out in 11 age-matched normotensive and healthy subjects at rest. Plasma catecholamine concentration and platelet aggregation were greater in the hypertensive than in the normotensive subjects, but the difference reached statistical significance for aggregation only. Exercise significantly increased catecholamines and platelet aggregability. The administration of propranolol (240 mg/day) produced a significant decrease in systolic and diastolic blood pressure and in aggregation (the percent of light transmission at 1 μM adenosine diphosphate, at rest) and a significant increase in catecholamine concentration. However, propranolol did not prevent the changes in all these variables with exercise. The abrupt discontinuation of propranolol was not associated with any subjective or objective untoward cardiovascular effect or abnormal changes in plasma catecholamines. However, in some patients the platelet aggregation studies demonstrated a hyperaggregable state, which may be due to a state of supersensitivity of platelets to circulating catecholamines.