The impact of changing home blood pressure monitoring cutoff from 135/85 to 130/80 mmHg on hypertension phenotypes.

This study investigated the impact of changing abnormal home blood pressure monitoring (HBPM) cutoff from 135/85 to 130/80 mmHg on the prevalence of hypertension phenotypes, considering an abnormal office blood pressure cutoff of 140/90 mmHg. We evaluated 57 768 individuals (26 876 untreated and 30 892 treated with antihypertensive medications) from 719 Brazilian centers who performed HBPM. Changing the HBPM cutoff was associated with increases in masked (from 10% to 22%) and sustained (from 27% to 35%) hypertension, and decreases in white-coat hypertension (from 16% to 7%) and normotension (from 47% to 36%) among untreated participants, and increases in masked (from 11% to 22%) and sustained (from 29% to 36%) uncontrolled hypertension, and decreases in white-coat uncontrolled hypertension (from 15% to 8%) and controlled hypertension (from 45% to 34%) among treated participants. In conclusion, adoption of an abnormal HBPM cutoff of 130/80 mmHg markedly increased the prevalence of out-of-office hypertension and uncontrolled hypertension phenotypes.

Activation of Mechanoreflex, but not Central Command, Delays Heart Rate Recovery after Exercise in Healthy Men.

This study tested the hypotheses that activation of central command and muscle mechanoreflex during post-exercise recovery delays fast-phase heart rate recovery with little influence on the slow phase. Twenty-five healthy men underwent three submaximal cycling bouts, each followed by a different 5-min recovery protocol: active (cycling generated by the own subject), passive (cycling generated by external force) and inactive (no-cycling). Heart rate recovery was assessed by the heart rate decay from peak exercise to 30 s and 60 s of recovery (HRR30s, HRR60s fast phase) and from 60 s-to-300 s of recovery (HRR60-300s slow phase). The effect of central command was examined by comparing active and passive recoveries (with and without central command activation) and the effect of mechanoreflex was assessed by comparing passive and inactive recoveries (with and without mechanoreflex activation). Heart rate recovery was similar between active and passive recoveries, regardless of the phase. Heart rate recovery was slower in the passive than inactive recovery in the fast phase (HRR60s=20±8vs.27 ±10 bpm, p<0.01), but not in the slow phase (HRR60-300s=13±8vs.10±8 bpm, p=0.11). In conclusion, activation of mechanoreflex, but not central command, during recovery delays fast-phase heart rate recovery. These results elucidate important neural mechanisms behind heart rate recovery regulation.

Blood Pressure Increase in Hypertensive Individuals During Resistance Training Protocols With Equated Work to Rest Ratio.

Introduction: Despite growing evidence regarding the benefits of resistance training in hypertension, the large and abrupt rise of systolic blood pressure (SBP) observed during resistance exercise execution has resulted in concern about its safety. However, the manipulation of the resistance training protocol (RTP) organization, maintaining the work to rest ratio equated between protocols (W:R-equated), may reduce the SBP increase. Purpose: To compare cardiovascular responses during two W:R-equated RTPs (3 × 15:88 s vs. 9 × 5:22 s - sets × reps: rest between sets) performed in exercises for the lower and upper limbs. Methods: Twelve medicated hypertensives (48 ± 8 years) randomly performed two RTPs in the bilateral leg extension (BLE) and unilateral elbow flexion (UEF) exercises at 50% 1RM. Increases (Δ) of SBP, heart rate (HR) and rate pressure product (RPP) during the exercises were measured by photoplethysmography. Results: In both BLE and UEF exercises, Δ SBP was significantly greater during 3 × 15:88 s than 9 × 5:22 s (peak values: BLE = + 84 ± 39 vs. + 67 ± 20 mm Hg, and UEF = + 46 ± 25 vs. + 37 ± 18 mm Hg, respectively, both p < 0.05). ΔHR and ΔRPP were significantly higher in the 3 × 15:88 s than 9 × 5:22 s in BLE (peak values + 45 ± 17 vs. + 30 ± 8 bpm, and + 15,559 ± 5570 vs. + 10,483 ± 2614 mm Hg. bpm). Conclusion: In medicated hypertensives, a RTP combining more sets with less repetitions per set and shorter rest intervals between sets (i.e., 9 × 5:22 s) produced a smaller increase in cardiovascular load (ΔSBP, ΔHR and ΔRPP) during its execution than a protocol with fewer longer sets (i.e., 3 × 15:88 s).

Effects of ACEi and ARB on post-exercise hypotension induced by exercises conducted at different times of day in hypertensive men.

BACKGROUND: Post-exercise hypotension (PEH) is greater after evening than morning exercise, but antihypertensive drugs may affect the evening potentiation of PEH. Objective: To compare morning and evening PEH in hypertensives receiving angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB). METHODS: Hypertensive men receiving ACEi (n = 14) or ARB (n = 15) underwent, in a random order, two maximal exercise tests (cycle ergometer, 15 watts/min until exhaustion) with one conducted in the morning (7 and 9 a.m.) and the other in the evening (8 and 10 p.m.). Auscultatory blood pressure (BP) was assessed in triplicate before and 30 min after the exercises. Changes in BP (post-exercise - pre-exercise) were compared between the groups and the sessions using a two-way mixed ANOVA and considering P < .05 as significant. RESULTS: In the ARB group, systolic BP decrease was greater after the evening than the morning exercise, while in the ACEi group, it was not different after the exercises conducted at the different times of the day. Additionally, after the evening exercise, systolic BP decrease was lower in the ACEi than the ARB group (ARB = -11 ± 8 vs -6 ± 6 and ACEi = -6 ± 7 vs. -8 ± 5 mmHg, evening vs. morning, respectively, P for interaction = 0.014). CONCLUSIONS: ACEi, but not ARB use, blunts the greater PEH that occurs after exercise conducted in the evening than in the morning.

Oral Fludrocortisone Test for Salt-Sensitive Screening in Hypertensive Patients: A Randomized Crossover Trial.

BACKGROUND: Salt sensitivity is associated with an increased cardiovascular risk, but the gold standard method (diet cycles) requires 24-h urine samples and has poor patient compliance. OBJECTIVES: Test the hypothesis that oral fludrocortisone (0.4 mg per day for 7 days) is a good alternative in identifying salt-sensitive patients. METHODOLOGY: We conducted a randomized crossover study with 30 hypertensive individuals comprising the following steps: (1) washout; (2) phase A (low- and high-sodium diet cycles); (3) washout 2; (4) phase B (fludrocortisone test). Phase A and B steps were performed in a random way. Consistent with the literature, we found that 53.3% were salt-sensitive according to the reference test. Using the ROC curve, the fludrocortisone test defined salt sensitivity by a median blood pressure increase of ≥3 mmHg. A good accuracy of fludrocortisone in detecting salt sensitivity was observed (AUC: 0.732±0.065; p<0.001), with 80% sensitivity and 53% specificity. CONCLUSION: The fludrocortisone test is a good option for screening salt sensitivity in hypertensive patients. However, the low specificity prevents this test from being an ideal substitute to the labor-intensive diet cycles exam in the definition of salt sensitivity. This clinical trial is registered with NCT01453959.

Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension: The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment).

The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P=1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01643434.

Effects of long term device-guided slow breathing on sympathetic nervous activity in hypertensive patients: a randomized open-label clinical trial.

PURPOSE: Device-guided slow breathing (DGB) is indicated as nonpharmacological treatment for hypertension. The sympathetic nerve activity (SNA) reduction may be one of the mechanisms involved in blood pressure (BP) decrease. The aim of this study is to evaluate the long-term use of DGB in BP and SNA. SUBJECTS AND METHODS: Hypertensive patients were randomized to listen music (Control Group-CG) or DGB (aim to reduce respiratory rate to less than 10 breaths/minute during 15 minutes/day for 8 weeks). Before and after intervention ambulatory blood pressure monitoring (ABPM), catecholamines and muscle sympathetic nerve activity (MSNA) by microneurography were performed. RESULTS: 17 volunteers in the DGB and 15 in the CG completed the study. There was no change in office BP before and after intervention in both groups. There was a reduction in systolic and diastolic BP in the awake period by ABPM only in the CG (131 ± 10/92 ± 9 vs 128 ± 10/88 ± 8mmHg, p < 0.05). In relation to SNA, no difference in catecholamines was observed. In the volunteers who had a microneurography record, there was no change the MSNA (bursts/minute): DGB (17(15-28) vs 19(13-22), p = 0.08) and CG (22(17-23) vs 22(18-24), p = 0.52). CONCLUSION: Long-term DGB did not reduce BP, catecholamines levels or MSNA in hypertensive patients. ClinicalTrials.gov identifier: NCT01390727.

Captopril does not Potentiate Post-Exercise Hypotension: A Randomized Crossover Study.

To evaluate whether captopril (3×50 mg/day) potentiates post-resistance exercise hypotension (PREH) in hypertensives (HT), 12 HT men received captopril and placebo for 4 weeks each in a double-blinded, randomized-crossover design. On each therapy, subjects underwent 2 sessions: Control (C - rest) and Resistance Exercise (RE - 7 exercises, 3 sets to moderate fatigue, 50% of 1 RM -repetition maximum). Measurements were taken before and after 30-60 min (Post1) and 7 h (Post2), and ambulatory blood pressure (BP) was monitored for 24 h. There were no differences in PREH characteristics and mechanisms between the placebo and captopril periods. At Post1, systolic/diastolic BP decreased significantly and similarly after RE with both therapies (Placebo=-13±2/-9±1 mmHg vs. Captopril=-12±2/-10±1 mmHg, P<0.05). RE reduced cardiac output in some subjects and systemic vascular resistance in others. Heart rate and cardiac sympathetic modulation increased, while stroke volume and baroreflex sensitivity decreased after RE (Placebo: +13±2 bpm, +21±5 nu, -11±5 ml, -4±2 ms/mmHg; Captopril: +13±2 bpm, +35±4 nu, 17±5 ml, -3±1 ms/mmHg, P<0.05). At Post2, all variables returned to pre-intervention values. Ambulatory BP was similar between the sessions. Thus, captopril did not potentiate the magnitude and duration of PREH in HT men, and it did not influence PREH mechanisms.

Chronic kidney disease and risk factors responsible for sudden cardiac death: a whiff of hope?

Several studies have shown a strong independent association between chronic kidney disease (CKD) and cardiovascular events, including death, heart failure, and myocardial infarction. Recent clinical trials extend this range of adverse cardiovascular events, also including ventricular arrhythmias and sudden cardiac death. Furthermore, other studies suggest structural remodeling of the heart and electrophysiological alterations in this population. These processes may explain the increased risk of arrhythmia in kidney disease and help to identify patients who are at increased risk of sudden cardiac death. Sympathetic hyperactivity is well known to increase cardiovascular risk in CKD patients and is a hallmark of essential hypertensive state that occurs early in the clinical course of the disease. In CKD, the sympathetic hyperactivity seems to be expressed at the earliest clinical stage of the disease, showing a direct relationship with the severity of the condition of renal failure, being more pronounced in the terminal stage of CKD. The sympathetic efferent and afferent neural activity in kidney failure is a key mediator for the maintenance and progression of the disease. The aim of this review was to show that the feedback loop of this cycle, due to adrenergic hyperactivity, also aggravates many of the risk factors responsible for causing sudden cardiac death and may be a potential target modifiable by percutaneous renal sympathetic denervation. If it is feasible and effective in end-stage renal disease, little is known.

Post-Exercise Hypotension Is Mediated by a Decrease in Sympathetic Nerve Activity in Stages 2-3 CKD.

BACKGROUND: This study aimed at evaluating the after effects of a single bout of aerobic exercise on muscle sympathetic nerve activity (MSNA), peripheral vascular resistance and blood pressure (BP) in stages 2-3 chronic kidney disease (CKD) patients. We hypothesized that CKD patients present a greater decline in these variables after the exercise than healthy individuals. METHODS: Nine patients with stages 2-3 CKD (50 ± 8 years) and 12 healthy volunteers (50 ± 5 years) underwent 2 sessions, conducted in a random order: exercise (45 min, cycle ergometer, 50% of peak oxygen uptake) and rest (seated, 45 min). Sixty minutes after either intervention, MSNA (by microneurography), BP (by oscillometry), and forearm vascular resistance (FVR) were measured. A 2-way analysis of variance with group (between) and session (within) as main factors was employed, accepting p < 0.05 as significant. RESULTS: Diastolic BP and MSNA were higher in the CKD than the control group in both sessions. Responses after exercise were similar in both groups. Systolic BP, diastolic BP, MSNA and FVR were significantly lower after the exercise than after the rest session in both the CKD and the control groups (162 ± 15 vs. 152 ± 23 and 155 ± 11 vs. 145 ± 16 mm Hg, 91 ± 11 vs. 85 ± 14 and 77 ± 5 vs. 71 ± 10 mm Hg, 38 ± 4 vs. 31 ± 4 and 34 ± 2 vs. 27 ± 4 burst/min, 59 ± 29 vs. 41 ± 29 and 45 ± 20 vs. 31 ± 8 U, respectively, all p < 0.05). CONCLUSION: These results showed that aerobic exercise may produce hemodynamic and neural responses that can be beneficial to these patients in spite of CKD.

Proof of concept study: Improvement of echocardiographic parameters after renal sympathetic denervation in CKD refractory hypertensive patients.

AIM: Evaluation of the effectiveness of the renal sympathetic denervation (RSD) in reducing lesions of target organs such as the heart and kidneys, in resistant hypertensive CKD patients. METHODS AND RESULTS: Forty-five patients were included and treated with an ablation catheter with open irrigated tip. RSD was performed by a single operator following the standard technique. Patients included with CKD were on stages 2 (n=22), 3 (n=16), and 4 (n=7). Data were obtained at baseline and monthly until the 6th month of follow-up. Twenty-six out of the 45 patients had LVH and nineteen did not present LVH. The LV mass index decreased from 123.70±38.44g/m(2) at baseline to 106.50±31.88g/m(2) at the 6th month after RSD, P<0.0001. The end-diastolic left ventricular internal dimension (LVIDd) reduced from 53.02±6.59mm at baseline to 51.11±5.85mm 6months post procedure, P<0.0001. The left ventricular end-diastolic posterior wall thickness (PWTd) showed a reduction from 10.58±1.39mm at baseline to 9.82±1.15mm at the 6th month of follow-up, P<0.0001. The end-diastolic interventricular septum thickness (IVSTd) also decreased from 10.58±1.39mm at baseline to 9.82±1.15mm 6months post procedure, P<0.0001. The left ventricular ejection fraction (LVEF) improved from 58.90±10.48% at baseline to 62.24±10.50% at the 6th month of follow-up, P<0.0001. When the ∆ between baseline and the 6th month post RSD in LVH patients and non LVH patients were compared to the same parameters no significant difference was found. CONCLUSIONS: The RSD seemed to be feasible, effective, and safe resulting in an improvement of echocardiographic parameters in LVH and non LVH CKD refractory hypertensive patients.

Oral estrogen therapy may mitigate the effects of aerobic training on cardiorespiratory fitness in postmenopausal women: a double-blind, randomized clinical pilot study.

OBJECTIVE: The aim of this study was to evaluate the isolated and associated effects of oral estrogen therapy and aerobic training on cardiorespiratory fitness in postmenopausal women. METHODS: Forty-two hysterectomized healthy postmenopausal women were randomly divided (in a double-blind manner) into four groups: placebo-control (n = 9), estrogen therapy-control (n = 12), placebo-aerobic training (PLA-AT; n = 11), and estrogen therapy-aerobic training (ET-AT; n = 10). The estrogen therapy groups received estradiol valerate (1 mg/day) and the aerobic training groups trained on a cycle ergometer three times per week at moderate intensity. Before and 6 months after the interventions, all women underwent a maximal cardiopulmonary exercise test on a cycle ergometer. RESULTS: Regardless of hormone therapy, aerobic training increased oxygen uptake at anaerobic threshold (P = 0.001), oxygen uptake at respiratory compensation point (P = 0.043), and oxygen uptake at peak exercise (P = 0.020). The increases at respiratory compensation point and peak exercise were significantly greater in the groups receiving placebo than in the groups receiving estrogen (oxygen uptake at respiratory compensation point: PLA-AT +5.3 [2.8] vs ET-AT +3.0 [2.5] mL kg(-1) min(-1), P = 0.04; oxygen uptake at peak exercise: PLA-AT +5.8 [3.4] vs ET-AT +2.8 [1.4] mL kg(-1) min(-1), P = 0.02). CONCLUSIONS: Oral estrogen therapy may mitigate the cardiorespiratory fitness increase induced by aerobic training in hysterectomized healthy postmenopausal women.

Effects of estrogen therapy and aerobic training on sympathetic activity and hemodynamics in healthy postmenopausal women: a double-blind randomized trial.

OBJECTIVE: The aim of this study was to evaluate the isolated and associated effects of aerobic training and estrogen therapy on sympathetic nerve activity and hemodynamics in healthy postmenopausal women. METHODS: Forty-five postmenopausal women (mean [SD] age, 51 [3] y) were randomly divided into four groups: sedentary-placebo (SED-PLA; n = 11), sedentary-estrogen therapy (SED-ET; n = 14), aerobic training-placebo (AT-PLA; n = 12), and aerobic training-estrogen therapy (AT-ET; n = 8). The ET groups received oral estradiol valerate (1 mg/d), whereas the PLA groups received placebo. The AT groups performed aerobic exercise three times a week on a cycle ergometer for 50 minutes, whereas the SED groups remained sedentary. All participants were evaluated before and after 6 months. Muscle sympathetic nerve activity (MSNA; microneurography), forearm blood flow (plethysmography), blood pressure (oscillometry), and heart rate (HR) were measured at rest for 10 minutes. Data were analyzed by three-way analysis of variance. RESULTS: Estrogen administration itself did not change any of the studied parameters. AT improved forearm blood flow (AT-PLA, 2.02 [0.85] vs 2.92 [1.65] mL min(-1) 100 mL(-1), P = 0.03; AT-ET, 1.68 [1.11] vs 2.27 [0.76] mL min(-1) 100 mL(-1), P = 0.03), reduced MSNA in the AT-PLA group (39 [6] vs 34 [5] bursts/min(-1), P = 0.01), and decreased HR in the AT-ET group (65 [8] vs 62 [7] beats/min, P = 0.01). CONCLUSIONS: AT reduces sympathetic nerve activity and improves muscle blood flow in healthy hysterectomized postmenopausal women. Moreover, AT decreases HR when combined with ET. However, ET abolishes the reducing effect of AT on MSNA.

Felypressin increases blood pressure during dental procedures in hypertensive patients.

BACKGROUND: Felypressin has been added to local anesthetic to increase the length of the anesthetic effect and reduce toxicity during dental procedures. However, the effect on blood pressure remains uncertain, and this may be highly relevant in the dental treatment of hypertensive patients. OBJECTIVE: To investigate the effect of felypressin on blood pressure in hypertensive patients with controlled BP. METHODS: 71 subjects with these characteristics and in need of periodontal treatment were studied. After 10 minutes of rest, local anesthesia (prilocaine) was infiltrated with and without addition of felypressin. Then, a deep subgingival scaling was performed. Blood pressure was measured by an automated oscillometric device (DIXTAL DX2010). Ten minutes after the administration of the anesthetic, peak anesthetic action was recorded. The State-Trait Anxiety Inventory (STAI) was used to assess the patients' trait anxiety. RESULTS: Systolic blood pressure increased after anesthesia, regardless of association with felypressin, throughout the dental procedure (p<0.05) and this response can be explained, at least in part, by the trait anxiety levels of the subjects. However, a further increase in diastolic blood pressure was observed when prilocaine was associated with felypressin (p<0.05), but this response did not change with trait anxiety levels. CONCLUSION: Felypressin increased the diastolic blood pressure of hypertensive patients with controlled blood pressure. Patients with high trait anxiety presented increases in systolic blood pressure upon some procedures, suggesting that an increase in blood pressure might also be related to fear or anxiety.