Effects of combination antihypertensive therapy on baroreflex sensitivity and heart rate variability in systemic hypertension

Earlier studies have shown that cardiovascular autonomic regulation is impaired in untreated or poorly controlled systemic hypertension. The purpose of this double-blind, randomized parallel trial was to evaluate whether improved blood pressure (BP) control can reverse this impairment. The study group consisted of 33 patients (age 45 to 63 years) with poor BP control who received randomized metoprolol or enalapril monotherapy. Baroreflex sensitivity (BRS) was assessed by phenylephrine test and time- and frequency-domain measurements of heart rate variability (HRV) were analyzed from 24-hour ambulatory electrocardiographic recordings during monotherapy and after 10 weeks of combination therapy with metoprolol + felodipine or enalaril + hydrochlorothiazide to lower casual BP to < 140/90 mm Hg. Intensified treatment decreased 24-hour systolic and diastolic BP from 139 +/- 12/86 +/- 8 mm Hg to 126 +/- 8/80 +/- 7 mm Hg (p <0.0001). BRS improved from 6.2 +/- 3.2 ms/mm Hg to 8.9 +/- 4.1 ms/mm Hg (p <0.0001) and measurements of HRV (e.g., SD of all RR intervals from 128 +/- 45 ms to 145 +/- 46 ms, p <0.001) improved significantly during the combination therapy. Changes in BRS and HRV were similar in magnitude in both treatment arms. Mean RR intervals were comparable before and after intensive antihypertensive therapy (850 +/- 124 ms vs 937 +/- 279 ms, p = NS). These data indicate that adequate BP control with modem antihypertensive combination therapy can improve cardiovascular autonomic function, which may partially explain the reduced cardiac mortality observed in patients with intensified antihypertensive therapy.     

Subnormal heart period variability in heart failure: effect of cardiac transplantation

Heart period variability and arterial baroreceptor-cardiac reflex function were studied in cardiac transplant patients to determine if correction of heart failure restores parasympathetic control mechanisms toward normal. Heart period variability (standard deviation [SD] of 120 consecutive RR or PP intervals) was measured at supine rest in 34 patients with congestive heart failure (23 patients receiving diuretics, digoxin or vasodilators and 11 patients weaned from all medications), 30 cardiac transplant patients (both innervated recipient and denervated donor atrial rates) and 16 age-matched healthy control subjects. Arterial baroreflex gain was evaluated with intravenous bolus injections of phenylephrine in 22 transplant patients. Mean heart period variability (+/- SEM) was significantly lower (p less than 0.05) in the heart failure groups (22 +/- 3 ms for medicated and 17 +/- 3 ms for nonmedicated) than in the transplant patients (41 +/- 5 ms) or control subjects (58 +/- 5 ms). Heart period variability of the transplant patients was less than that of the control patients (p less than 0.05). A stepwise regression model revealed that heart period variability was inversely related to systolic arterial pressure and directly related to time after transplantation (R2 = 0.39; p = 0.03) in the transplant patients. Baroreflex gain of normotensive transplant patients was normal (11.7 +/- 1.0 ms/mm Hg) and correlated directly with heart period variability (r = 0.62; p less than 0.001). These data suggest that subnormal levels of cardiac parasympathetic activity at rest associated with congestive heart failure can be restored progressively toward normal by correction of congestive heart failure after cardiac transplantation. Post-transplant hypertension opposes this correction of baseline parasympathetic activity.     

Baroreflex and blood pressure variations in borderline hypertension of the young adult

Blood pressure (BP) variability depends on external and internal factors. Among these, arterial baroreflex play an important role. The matter of this study is to assess the relationship between these two parameters in borderline hypertension (BL). Twenty six BL male hypertensive were recruited for the study, all gave informed consent. Age: 21 +/- 2 years, height: 177 +/- 8 cm, weight: 77 +/- 14 kg. An ambulatory BP monitoring was performed in each one using a Diasys (Novacor) recorder. Measurements were obtained each 15 minutes for 24 hours. Mean, standard deviation and variation coefficient (VC) of BP and heart rate (HR) were computed for 24 hours, daytime (9a.m.-7 p.m.), nighttime (11 p.m.-7 a.m.). Baroreflex sensitivity (BRS) was determined as the ratio of HR variation on systolic BP variation recorded with a Finapres device from the fourth phase of a Valsalva manoeuvre. Mean systolic and diastolic BP values for 24 hours, daytime and nighttime are: 129 +/- 11/73 +/- 13, 137 +/- 14/76 +/- 15, 114 +/- 11/69 +/- 12 mmHg. VC are: 12 +/- 3/15 +/- 3, 9 +/- 3/13 +/- 3, 10 +/- 3/13 +/- 4%. HR values are: 73 +/- 10, 84 +/- 14, 58 +/- 7 b/min, VC are: 24 +/- 5, 17 +/- 4, 17 +/- 7%. Index for BRS = 1.76 +/- 0.65%. There is no correlation between BRS and systolic BP or HR. BRS is correlated to the inverse of systolic daytime BP VC: r = -0.556, p = 0.003. There is no correlation with other parameters. This study provides evidence for a link between BRS and daytime BP variability in borderline hypertension.     

Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans.

Animal studies suggest that the 2 major omega3 fatty acids found in fish, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may have differential effects on blood pressure (BP) and heart rate (HR). The aim of this study was to determine whether there were significant differences in the effects of purified EPA or DHA on ambulatory BP and HR in humans. In a double-blind, placebo-controlled trial of parallel design, 59 overweight, mildly hyperlipidemic men were randomized to 4 g/d of purified EPA, DHA, or olive oil (placebo) capsules and continued their usual diets for 6 weeks. Fifty-six subjects completed the study. Only DHA reduced 24-hour and daytime (awake) ambulatory BP (P<0.05). Relative to the placebo group, 24-hour BP fell 5.8/3.3 (systolic/diastolic) mm Hg and daytime BP fell 3.5/2.0 mm Hg with DHA. DHA also significantly reduced 24-hour, daytime, and nighttime (asleep) ambulatory HRs (P=0. 001). Relative to the placebo group, DHA reduced 24-hour HR by 3. 5+/-0.8 bpm, daytime HR by 3.7+/-1.2 bpm, and nighttime HR by 2. 8+/-1.2. EPA had no significant effect on ambulatory BP or HR. Supplementation with EPA increased plasma phospholipid EPA from 1. 66+/-0.07% to 9.83+/-0.06% (P<0.0001) but did not change DHA levels. Purified DHA capsules increased plasma phospholipid DHA levels from 4.00+/-0.27% to 10.93+/-0.62% (P<0.0001) and led to a small, nonsignificant increase in EPA (1.52+/-0.12% to 2.26+/-0.16%). Purified DHA but not EPA reduced ambulatory BP and HR in mildly hyperlipidemic men. The results of this study suggest that DHA is the principal omega3 fatty acid in fish and fish oils that is responsible for their BP- and HR-lowering effects in humans. These results have important implications for human nutrition and the food industry.     

Inhibition of awake sympathetic nerve activity of heart failure patients with obstructive sleep apnea by nocturnal continuous positive airway pressure

OBJECTIVES: This study was designed to determine whether reductions in morning systolic blood pressure (BP) elicited by treatment of moderate to severe obstructive sleep apnea (OSA) in heart failure (HF) patients are associated with a reduction in sympathetic vasoconstrictor tone. BACKGROUND: Daytime muscle sympathetic nerve activity (MSNA) is elevated in HF patients with coexisting OSA. In our recent randomized trial in HF, abolition of OSA by continuous positive airway pressure (CPAP) increased left ventricular ejection fraction (LVEF) and lowered morning systolic BP. METHODS: Muscle sympathetic nerve activity, BP, and heart rate (HR) of medically treated HF patients (EF <45%) and OSA (apnea-hypopnea index > or =20/h of sleep) were recorded on the morning after overnight polysomnography, and again one month after patients were randomly allocated nocturnal CPAP treatment or no CPAP (control). RESULTS: In nine control patients, there were no significant changes in the severity of OSA, MSNA, systolic BP, or HR. In contrast, in the 8 CPAP-treated patients, OSA was attenuated, and there were significant reductions in daytime MSNA (from 58 +/- 4 bursts/min to 48 +/- 5 bursts/min; 84 +/- 4 bursts/100 heart beats to 72 +/- 5 bursts/100 heart beats; p < 0.001 and p = 0.003, respectively), systolic BP (from 135 +/- 5 mm Hg to 120 +/- 6 mm Hg, p = 0.03), and HR (from 69 +/- 2 min(-1) to 66 +/- 2 min(-1); p = 0.013). CONCLUSIONS: Treatment of coexisting OSA by CPAP in HF patients lowers daytime MSNA, systolic BP, and HR. Inhibition of increased central sympathetic vasoconstrictor outflow is one mechanism by which nocturnal CPAP reduces awake BP in HF patients with moderate to severe OSA.     

Changes in home versus clinic blood pressure with antihypertensive treatments: a meta-analysis

Home blood pressure (HBP) monitoring is recommended for assessing the effects of antihypertensive treatment, but it is not clear how the treatment-induced changes in HBP compare with the changes in clinic blood pressure (CBP). We searched PubMed using the terms "home or self-measured blood pressure," and selected articles in which the changes in CBP and HBP (using the upper arm oscillometric method) induced by antihypertensive drugs were presented. We performed a systematic review of 30 articles published before March 2008 that included a total of 6794 subjects. As there was significant heterogeneity in most of the outcomes, a random effects model was used for the meta-analyses. The mean changes (+/-SE) in CBP and HBP (systolic/diastolic) were -15.2+/-0.03/-10.3+/-0.03 mm Hg and -12.2+/-0.04/-8.0+/-0.04 mm Hg respectively, although there were wide varieties of differences in the reduction between HBP and CBP. The reductions in CBP were correlated with those of HBP (systolic BP; r=0.66, B=0.48, diastolic BP; r=0.71, B=0.52, P<0.001). In 7 studies that also included 24-hour BP monitoring, the reduction of HBP was greater than that of 24-hour BP in systolic (HBP; -12.6+/-0.06 mm Hg, 24-hour BP; -11.9+/-0.04 mm Hg, P<0.001). In 5 studies that included daytime and nighttime systolic BP separately, HBP decreased 15% more than daytime ambulatory BP and 30% more than nighttime ambulatory BP. In conclusion, HBP falls approximately 20% less than CBP with antihypertensive treatments. Daytime systolic BP falls 15% less and nighttime systolic BP falls 30% less than home systolic BP.     

Lacidipine and blood pressure variability in diabetic hypertensive patients

The aim of our study was to assess the effects of lacidipine, a long-acting calcium antagonist, on 24-hour average blood pressure, blood pressure variability, and baroreflex sensitivity. In 10 mildly to moderately hypertensive patients with type II diabetes mellitus (aged 18 to 65 years), 24-hour ambulatory blood pressure was continuously monitored noninvasively (Portapres device) after a 3-week pretreatment with placebo and a subsequent 4-week once daily lacidipine (4 mg) or placebo treatment (double-blind crossover design). Systolic blood pressure, diastolic blood pressure, and heart rate means were computed each hour for 24 hours (day and night) at the end of each treatment period. Similar assessments were also made for blood pressure and heart rate variability (standard deviation and variation coefficient) and for 24-hour baroreflex sensitivity, which was quantified (1) in the time domain by the slope of the spontaneous sequences characterized by progressive increases or reductions of systolic blood pressure and RR interval and (2) in the frequency domain by the squared ratio of RR interval and systolic blood pressure spectral power approximately 0.1 and 0.3 Hz over the 24 hours. Compared with placebo, lacidipine reduced the 24-hour, daytime, and nighttime systolic and diastolic blood pressure (P<0.05) with no significant change in heart rate. It also reduced 24-hour, daytime, and nighttime standard deviation (-19.6%, -14.4%, and -24.0%, respectively; P<0.05) and their variation coefficient. The 24-hour average slope of all sequences (7.7+/-1.7 ms/mm Hg) seen during placebo was significantly increased by lacidipine (8.7+/-1.8 ms/mm Hg, P<0.01), with a significant increase being obtained also for the 24-hour average alpha coefficient at 0.1 Hz (from 5.7+/-1.5 to 6.4+/-1.3 ms/mm Hg, P<0.01). Thus, in diabetic hypertensive patients, lacidipine reduced not only 24-hour blood pressure means but also blood pressure variability. This reduction was accompanied by an improvement of baroreflex sensitivity. Computer analysis of beat-to-beat 24-hour noninvasive blood pressure monitoring may offer valuable information about the effects of antihypertensive drugs on hemodynamic and autonomic parameters in daily life.     

Analysis of factors that affect short-term blood pressure variability in patients with chronic renal failure

Recent reports suggest the relationship of short-term blood pressure (BP) variability to cardiovascular target organ damage. In this study, short-term BP variability was assessed as the standard deviation of daytime and nighttime BP in 36 hospitalized patients with chronic renal failure (CRF) who underwent ambulatory BP monitoring. Positive correlations were observed between body mass index (BMI) and daytime systolic and diastolic BP variability, BMI and nighttime diastolic BP variability, cholesterol and daytime systolic BP variability, cholesterol and nighttime systolic and diastolic BP variability, nocturnal decline in BP and nighttime diastolic BP variability, and plasma concentration of norepinephrine (p-NE) and nighttime systolic BP variability. In multivariate linear regression analyses, BMI showed the strongest association with daytime and nighttime diastolic BP variability (p < .005 and p < .05). On the other hand, cholesterol and p-NE were the primary determinants of daytime and nighttime systolic BP variability, respectively (p < .01 and p < .0005). Interestingly, CRF patients with ischemic heart disease (IHD) had significantly increased daytime systolic and diastolic BP variability and nighttime systolic BP variability (p < .05 or less). Furthermore, logistic regression analysis demonstrated that nighttime systolic BP variability was an independent risk factor of IHD in patients with CRF (odds ratio 1.50 [95% confidence interval 1.01 to 2.25]; p < .05). Taken together, short-term BP variability is suggested to be affected by BMI, cholesterol, and p-NE in CRF patients. Furthermore, sympathetic nerve overactivity may be involved in cardiovascular complications in CRF patients through the increase in nighttime systolic BP variability.     

Decreased spontaneous heart rate variability in congestive heart failure

Heart rate (HR) variability is a noninvasive index of the neural activity of the heart. Although also dependent on the sympathetic activity of the heart, HR variability is mainly determined by the vagal outflow of the heart. Several HR abnormalities have been described in patients with congestive heart failure (CHF); however, there are no data on HR variability in CHF patients. In the present study HR variability was assessed in 20 CHF patients and 20 control subjects from 24-hour Holter tapes. HR variability was evaluated by calculating the mean hourly HR standard deviation and by analyzing the 24-hour RR histogram. Mean hourly HR standard deviation was markedly and significantly reduced in CHF patients both over the 24-hour period (97.5 +/- 41 vs 233.2 +/- 26 ms, p less than 0.001) as well as during most of the individual hours examined. The 24-hour RR histogram of CHF patients had a different shape and had a decreased variation compared to control subjects (total variability 356 +/- 102 vs 757 +/- 156 ms, p less than 0.001). Thus, CHF patients with depressed ejection fraction (less than 30%) have a low HR variability compared to normal individuals. This result can be interpreted as adjunctive evidence for decreased parasympathetic activity to the heart during CHF.     

Left ventricular function in patients with obstructive sleep apnoea syndrome before and after treatment with nasal continuous positive airway pressure

BACKGROUND: Previous studies have yielded disparate results regarding the effect of obstructive sleep apnoea (OSA) syndrome on left ventricular (LV) function. OBJECTIVES: In order to clarify this, we performed a prospective study investigating OSA patients with no history of systemic hypertension, coronary artery disease, myocardial, pericardial or valvular problems, asthma or chronic obstructive pulmonary disease before and after treatment with nasal continuous positive airway pressure (nCPAP). METHODS: Fifteen patients (3 women, 12 men) with an apnoea/hypopnoea index >15 (mean +/- SD = 52 +/- 21) were studied with complete polysomnography, ambulatory blood pressure monitoring, M-mode two-dimensional echocardiography and pulsed Doppler echocardiography in two phases, i.e. before and after 12-14 weeks of nCPAP therapy. We measured systolic and diastolic blood pressure (BP) separately in the daytime and night-time, isovolumic relaxation time (IVRT), the ratio of peak early filling velocity (E) to peak late velocity (A) diastolic transmitral flow (E/A), posterior wall thickness (PWT) and septal thickness (IVST). The shortening fraction (SF) was also calculated. Eleven overweight non-apnoeic normal subjects matched for age were used as the control group. RESULTS: Our results showed that the patient group exhibited, before treatment, LV diastolic, but not systolic, dysfunction compared with the normal group (IVRT = 94.3 +/- 11.6 ms, p < 0.05; E/A = 0.94 +/- 0.26, p < 0.02; SF = 39.9 +/- 4.1%, not significant (NS); IVST = 9.9 +/- 1.2 mm, NS; PWT = 8.3 +/- 1.2 mm, NS). Moreover, the patient group developed diastolic hypertension both in the daytime and night-time (BP/diastolic/daytime = 93.3 +/- 9.2 mm Hg, BP/diastolic/night-time = 90.3 +/- 10.7 mm Hg). After 12-14 weeks of nCPAP treatment (no change in body mass index), significant improvement in LV diastolic function and a drop in blood pressure were noticed (IVRT = 85.6 +/- 8.8 ms, p < 0.05; E/A = 1.07 +/- 0.3, p < 0.05; BP/diastolic/daytime = 86.3 +/- 5.5 mm Hg, p < 0.02; BP/diastolic/night-time = 83.9 +/- 8. 6 mm Hg, p < 0.05) in our patient group. CONCLUSIONS: We conclude that repetitive apnoeas/hypopnoeas are very important factors in the development of both LV diastolic dysfunction and diastolic systemic hypertension in patients with OSA syndrome. Treatment with nCPAP leads to significant improvement in both ventricular function and systemic hypertension.     

Baroreflex sensitivity changes with calcium antagonist therapy in elderly subjects with isolated systolic hypertension

In order to study the effects of calcium-blocking therapy on cardiovascular homeostasis in elderly subjects with isolated systolic hypertension, we performed a randomised double-blind placebo-controlled crossover study of 6 weeks therapy with modified-release nifedipine or placebo. Changes with calcium-blocker treatment in clinic and 24-h blood pressure (BP), heart rate, BP variability, baroreflex sensitivity (BRS) by three methods (Valsalva manoeuvre, phenylephrine and sodium nitroprusside injection), and in baroreflex- and non-baroreflex-mediated reflexes (tilt and cold face stimulus) were studied in 14 elderly subjects (mean age [+/- SEM] 70 +/- 1 years) with sustained isolated systolic hypertension (clinic BP 179 +/- 3/85 +/- 1 mm Hg). Clinic systolic BP, but not diastolic BP, was reduced with treatment (by 14 +/- 6 mm Hg, P = 0.03, diastolic BP 4 +/- 3 mm Hg, P = 0.16). Twenty-four hour BP was also reduced by nifedipine treatment (by 18 +/- 3/9 +/- 2 mm Hg, both P < 0.001). Clinic and 24-h heart rate, and daytime BP variability, were unchanged with treatment. BRS was significantly increased during nifedipine therapy by all three measurement methods (all P < 0.05). With 60 degrees tilt during active treatment, subjects exhibited a greater heart rate increase (P < 0.01), and a reduced fall in systolic (P < 0.05) and diastolic BP (P < 0.05). Thus despite the arteriosclerosis and reductions in large artery compliance described in elderly patients with isolated systolic hypertension, clinically important improvements in clinic and ambulatory BP and some aspects of cardiovascular homeostasis can be achieved with calcium-channel blocking therapy.     

Abnormal baroreflex control of heart rate in decompensated congestive heart failure and reversal after compensation

Congestive heart failure (CHF) causes impairment of baroreflex control of heart rate (HR). To determine if this derangement is reversible, the cardiac chronotropic control was assessed in 10 patients with class IV chronic CHF of various etiologies before and after compensation achieved by bed rest, salt restriction, diuretics and vasodilators. Mean time between the 2 studies was 15 +/- 3 days. The management was modified 3 days before the second autonomic evaluation, so as to reestablish the same diet and pharmacologic conditions of the previous study. Compensation led to significant reduction in symptom-based class, body weight, and pulmonary and systemic congestion. Mean +/- standard error of the mean HR responses (beats/min) before and after compensation were, respectively: (1) to atropine (0.04 mg/kg): 10 +/- 2 and 27 +/- 2 (p less than 0.01); (2) to handgrip (30% maximum capacity, 1 minute): 9 +/- 2 and 19 +/- 3 (p less than 0.005); (3) to headup tilt (5 minutes): 4 +/- 3 and 20 +/- 4 (p less than 0.005). Mean +/- standard error of the mean baroreflex sensitivity (ms/mm Hg) of RR responses to phenylephrine and amyl nitrate-induced changes in systolic pressure was, respectively, in each condition: phenylephrine, 0.9 +/- 0.2 and 8 +/- 2.3 (p less than 0.05); amyl nitrate, 0.3 +/- 0.2 and 4.1 +/- 1.1 (p less than 0.05). A significant correlation between improvement in HR responses to atropine and tilt and changes in body weight was obtained. These findings show a reversible component of impaired baroreflex control of HR in severe CHF, possibly due to its congestive effects.     

Morning blood pressure peak,QT intervals,and sympathetic activity in hypertensive patients

We investigated the relation between morning blood pressure (BP) variations, sympathetic activity, and QT intervals in 156 never-treated subjects with essential hypertension and different patterns of morning BP increase. The morning BP peak (MP) was defined as a rise in systolic BP >or=50 mm Hg and/or diastolic BP >or=22 mm Hg during early morning (6:00 to 10:00 AM) compared with mean BP during the night. Clinical characteristics of patients with morning BP peak (MP+, n= 69, morning systolic BP=+54+/-4, diastolic BP=+32+/-5 mm Hg) did not differ from patients without BP peak (MP-, n= 87, morning systolic BP=+24+/-5, diastolic BP=+19+/-3 mm Hg). The daytime (10:00 AM to 10:00 PM) and the nighttime (10:00 PM to 6:00 AM) BP profile did not differ between the two groups. During daytime and nighttime ECG monitoring, the corrected QT (QTc) interval, and QTc dispersion did not differ significantly between the two groups, whereas during the morning period the QT values were significantly broader in the MP+ group compared with the MP- group (P相似文献   

Nycthemeral blood pressure monitoring in the diagnosis of borderline arterial hypertension in young adults

PURPOSE: Evaluating Blood Pressure Monitoring contribution at rest to the diagnosis and pathophysiology of borderline (BL) hypertension in the twenties. METHOD: a nycthemeral blood pressure recording each 15 minute has been performed during the 48 first hours of hospitalisation on two groups of white twenties males with a Dinamap: 143 Controls. Mean age: 21.1 +/- 2 yrs, mean height: 177 +/- 7 cm, mean weight: 71 +/- 11 kg; 104 BL hypertensive patients. Mean age: 21 +/- 2 yrs, mean height: 178 +/- 7 cm, mean weight: 78 +/- 12 kg. Mean BP recording levels are smaller than casual measurements in two groups: Controls (Casual BP: 125/71, BP recording on 24 hours: 117/60, day time: 121/63, nighttime: 110/54 mmHg). BL hypertensives (Casual BP: 144/83, BP recording on 24 h: 132/69, daytime: 137/73, nighttime: 121/60 mmHg). Nycthemeral BP variability measured by the standard deviation of mean pressure is not different in two groups for systolic variability, it significantly differs for diastolic variability (BL: 7.6/Controls: 5.5, p less than 0.01). Correlations between casual BP and diurnal records are stronger in controls than in BL patients showing a lower predictive value of clinical assessment in BL patients. Though the same heart rate at sleep, BP is significantly higher in BL than in controls. It probably means that factors different from sympathetic activity are involved in pathophysiology of borderline hypertension. The whole measurement study on 24 hours of two groups show an important overlap (the 65th percentile in BL systolic BP correspond with the 95th of controls, the 74th percentile in BL diastolic BP correspond with the 95th in controls). That make difficult the recording evaluation for a given patient.     

Ambulatory 24-hour blood pressure monitoring in patients with resistant hypertension

The aim of the study was to assess the usefulness of 24-hour blood pressure (BP) and heart rate (HR) monitoring in patients with "resistant" hypertension. 30 patients (44.1 +/- 9.9 years) with diastolic BP 100 mm Hg or more in spite of treatment with three or more antihypertensive drugs were studied. Ambulatory recording of BP and HR was performed by means of Del Mar Avionics monitoring system 9000. Mean recording time was 21.5 hours and mean number of measurements during one recording--56.7. Mean ambulatory systolic and diastolic BP values were significantly lower than mean value of three casual measurements (146.0 +/- 24.6 vs 171.5 +/- 21.2 mm Hg for systolic and 97.2 +/- 11.3 vs 110.4 +/- 7.5 mm Hg for diastolic BP p less than 0.01) In 14 (46.6%) systolic BP and in 10 patients (33.3%) diastolic BP were normal. The patients with normal and abnormal ambulatory BP recordings did not differ in regard to age and mean clinic BP levels. However, patients with abnormal ambulatory BP recordings were more often overweight and showed a greater frequency of left ventricular hypertrophy and family history of hypertension and its complications. The results of the study show that ambulatory BP monitoring may be of value in assessing the response to antihypertensive treatment in patients with so called resistant hypertension as judged on the basis of clinic pressure.     

Safety profile and hemodynamic responses to beta-adrenergic stimulation by dobutamine in heart transplant patients

STUDY OBJECTIVE: Dobutamine stress echocardiography (DSE) has been used as a screening tool for coronary artery disease after heart transplantation and in the identification of patients at risk for development of cardiac events. However, the safety profile of high-dose dobutamine in heart transplant patients has not been systematically examined. Accordingly, we studied the safety profile and hemodynamic responses to escalating doses of dobutamine to determine the influence of denervation. DESIGN: We assessed the hemodynamic responses, heart rate (HR), and arterial BP indexes (mean arterial pressure, systolic BP [SBP], diastolic BP [DBP], and pulse pressure) to dobutamine in 87 heart transplant patients ([mean +/- SD] age, 51 +/- 1 years) and compared the results with 97 nontransplant patients (age, 63.0 +/- 1 years) who served as innervated control subjects. MEASUREMENTS AND RESULTS: The baseline HR (84 +/- 2 vs 69 +/- 1 beats/minute, respectively; p < 0.001) and peak HR response (144 +/- 2 vs 117 +/- 2 beats/minute, respectively; p < 0.001) were significantly higher in heart transplant patients than in the nontransplant patients. SBP was lower in heart transplant patients than in nontransplant patients at baseline (131 +/- 2 vs 138 +/- 2 mm Hg, respectively; p < 0.02) and at peak (150 +/- 3 vs 158 +/- 3 mm Hg, respectively; p < 0.03). However, baseline DBP was higher in transplant patients than in nontransplant patients (86 +/- 1 vs 77 +/- 1 mm Hg, respectively; p < 0.001). The decrease in DBP was similar in both groups (15 mm Hg). The dose-response curve for HR was shifted leftward in heart transplant patients. Heart transplant patients attained a higher absolute HR at each infusion stage and higher rates of increase, but the decrease in DBP was not significantly different in the two groups. CONCLUSIONS: These results show that there is augmented chronotropic response and expected decline in DBP in response to dobutamine infusion in heart transplant patients. This increase in myocardial oxygen demand and a decrease in coronary perfusion pressure may be important mechanisms in the development of ischemic abnormalities that are detectable as regional dysynergy on echocardiography.     

Furosemide withdrawal improves postprandial hypotension in elderly patients with heart failure and preserved left ventricular systolic function.

OBJECTIVE: To assess the effects of furosemide withdrawal on postprandial blood pressure (BP) in elderly patients with heart failure and preserved left ventricular systolic function. METHODS: Noninvasive measurement of blood pressure (BP) and heart rate, computation of stroke volume and cardiac output (after a 1247-kJ (297-kcal) meal, and Doppler echocardiography before and 3 months after placebo-controlled withdrawal of furosemide therapy. RESULTS: Of 20 patients with heart failure (mean+/-SEM age, 75+/-1 years; left ventricular ejection fraction, 61%+/-3%), 13 were successfully able to discontinue furosemide therapy. At baseline, 11 (55%) of the 20 patients (had maximum postprandial systolic BP declines of 20 mm Hg or more. In the withdrawal group, the maximum systolic BP decline lessened from -25+/-4 to -11+/-2 mm Hg (P<.001) and the maximum diastolic BP from -18+/-3 to -9+/-1 mm Hg (P= .01), compared with no changes in the continuation group. In the withdrawal group, maximum postprandial declines in stroke volume and cardiac output decreased from -9+/-1 to -4+/-2 mL (P =.01) and from -0.6+/-0.2 to -0.2+/-0.1 L/min) (P = .04), respectively. The baseline maximum postprandial systolic BP decrease was correlated with the ratio of early to late flow (n = 20; Spearman rank correlation coefficient, 0.58; P = .007). For patients in the withdrawal group, the changes in postprandial systolic BP response were independently related to changes in peak velocity of early flow (n = 13; r2= 0.61; P = .003). CONCLUSIONS: Postprandial hypotension is common in elderly patients with heart failure and preserved left ventricular systolic function. The withdrawal of furosemide therapy ameliorates postprandial BP homeostasis in these patients, possibly by improving left ventricular diastolic filling.     

Multiple clinic and home blood pressure measurements versus ambulatory blood pressure monitoring.

To compare multiple clinic and home blood pressure (BP) measurements and ambulatory BP monitoring in the clinical evaluation of hypertension, we studied 239 middle-aged pharmacologically untreated hypertensive men and women who were referred to the study from the primary healthcare provider. Ambulatory BP monitoring was successfully completed for 233 patients. Clinic BP was measured by a trained nurse with a mercury sphygmomanometer and averaged over 4 duplicate measures. Self-recorded home BP was measured with a semiautomatic oscillometric device twice every morning and twice every evening on 7 consecutive days. Ambulatory BP was recorded with an auscultatory device. Two-dimensionally controlled M-mode echocardiography was successfully performed on 232 patients. Twenty-four-hour urinary albumin was determined by nephelometry. Clinic BP was 144.5+/-12.6/94.5+/-7.4 mm Hg, home BP (the mean of 14 self-recorded measures) was 138.9+/-13.1/92.9+/-8.6 mm Hg, home morning BP (the mean of the first 4 duplicate morning measures) was 137.1+/-13.7/92.4+/-9.2 mm Hg, daytime ambulatory BP was 148.3+/-13. 9/91.9+/-7.8 mm Hg, nighttime ambulatory BP was 125.5+/-16.4/75. 6+/-8.9 mm Hg, and 24-hour ambulatory BP was 141.7+/-14.0/87.2+/-7.6 mm Hg. Pearson correlation coefficients of clinic, home, home morning, and daytime ambulatory BPs to albuminuria and to the characteristics of the left ventricle were nearly equal. In multivariate regression analyses, 36% (P<0.0001) of the cross-sectional variation in left ventricular mass index was attributed to gender and home morning systolic BP in models that originally included age, gender, and clinic, self-measured home morning, and ambulatory daytime, nighttime, and 24-hour systolic and diastolic BPs. We concluded that carefully controlled nonphysician-measured clinic and self-measured home BPs, when averaged over 4 duplicate measurements, are as reliable as ambulatory BP monitoring in the clinical evaluation of untreated hypertension.     

Ambulatory blood pressure and heart rate in hypertensives with renal failure: comparison between diabetic nephropathy and non-diabetic glomerulopathy

The purpose of this study was to examine a possible difference in the 24-h blood pressure (BP) profile between hypertensives with diabetic nephropathy (DN) and those with non-diabetic glomerulopathy (non-DN). We measured 24-h ambulatory BP in 34 type 2 DN and 34 non-DN patients who were hospitalized for the educational program in our hospital. There were no significant differences in 24-h and daytime systolic BP between DN (143 vs. 136 mmHg, NS for 24-h systolic BP) and non-DN (143 vs. 138 mmHg, NS for daytime systolic BP). Although both groups disclosed blunted nocturnal decrease in BP and were classified as "non-dipper" type, DN patients had a significantly higher nighttime systolic BP than patients with non-DN (142 vs. 132 mmHg, p = 0.0217). BP and heart rate (HR) variabilities were also estimated, and patients with DN showed a reduced nighttime HR variability than those with non-DN (4.8 vs. 6.6 beats/min, p = 0.0115). DN patients had an increase in urinary protein excretion (3.0 vs. 1.4 g/day, p = 0.0095) and a decrease in serum albumin concentration (3.1 vs. 3.7 mg/dl, p < 0.0001). Furthermore, urinary protein excretion was significantly correlated with nighttime systolic BP (r = 0.480, p = 0.0031) but not with nighttime HR variability. Taken together, these results demonstrate that the circadian rhythms of BP and HR are affected by underlying diseases and suggest that an elevated nighttime BP level may contribute to the enhanced urinary protein excretion in hypertensives with DN.     

Amlodipine added to quinapril vs quinapril alone for the treatment of hypertension in diabetes: the Amlodipine in Diabetes (ANDI) trial

This randomized, comparative, parallel-group trial investigated strategies of blood pressure (BP)-lowering in patients with diabetes and hypertension. Patients not reaching goal BP (<130/80 mm Hg) after 4-week open-label treatment with quinapril 20 mg/d (n=374) received 40 mg/d quinapril (n=167) or 20 mg/d quinapril plus amlodipine besylate (5 mg/d; n=162) for 6 weeks. Patients receiving combination therapy vs monotherapy had significantly greater reductions in mean +/- SE sitting systolic BP (9.9+/-1.0 mm Hg vs 4.3+/-1.1 mm Hg; P<.001) and diastolic BP (6.5+/-0.6 mm Hg vs 2.7+/-0.6 mm Hg; P<.001). No significant differences between groups were observed in percentage of patients achieving goal BP (10.1% with combination therapy vs 8.2% with monotherapy). A clinically neutral effect was observed on high-sensitivity C-reactive protein in both groups. Treatments were well tolerated; fewer than 3% of patients in any group discontinued due to treatment-emergent or treatment-related adverse events. In diabetic hypertensive patients, 20 mg/d quinapril plus 5 mg/d amlodipine besylate was a more effective BP-lowering strategy than monotherapy with 40 mg/d quinapril.