The long-term effectiveness of the anti-obesity medication phentermine (LEAP) trial: Rationale, design, and baseline characteristics.

Change over time in the rates of adverse events in patients receiving systemic therapy for psoriasis: A cohort study

Rise in Blood Pressure Observed Among US Adults During the COVID-19 Pandemic

Objectives: To investigate whether arterial stiffening and baroreceptor dysfunction is associated with impaired blood pressure recovery after standing, which is considered to be a severe condition of orthostatic hypotension (OH). Methods: A total of 1056 patients with life-style related disease were included in the study. During the sit-to-stand test (consist of sitting position, 30 seconds [initial phase] and 90 seconds [late phase] after standing up), we measured blood pressure and heart rate variability (HRV) as an index of baroreceptor function (LF and HF: low and high frequency component). The patients were divided into 4 groups according to the response of orthostatic systolic blood pressure (SBP) change (Non-OH: SBP change > -20 both in the initial and the late phase, late-OH: SBP change ≤ -20 only in the late phase, initial-OH: SBP change ≤ -20 only in the initial phase, sustained-OH: SBP change ≤ -20 both in the initial and the late phase). We measured cardio-ankle vascular index (CAVI) as an index of arterial stiffness. Results: Mean age of the patients was 66.5 ± 11.9 years. Initial-OH and sustained-OH showed significant higher CAVI compared with non-OH (9.03 ± 1.25 versus 8.65 ± 1.48, p = 0.024; 9.35 ± 1.17 versus 8.65 ± 1.48, p = 0.010, respectively). Sustained-OH showed significant lower LF than non-OH both in the initial and the late phase (2.10 ± 0.50 versus 2.31 ± 0.44, p = 0.008; 1.67 ± 0.52 versus 1.95 ± 0.53, p = 0.005, respectively). Sustained-OH showed significant lower HF than non-OH in the late phase (1.39 ± 0.60 versus 1.68 ± 0.58, p = 0.005). Conclusion: Impaired SBP recovery after standing was associated with arterial stiffening and blunted autonomic nervous response. Patients with impaired SBP recovery after standing should be aware of severe arterial stiffening and baroreceptor dysfunction.

Background Exaggerated orthostatic changes in systolic blood pressure (SBP) were associated with adverse cardiovascular events. However, the predictive role of SBP hyperactivity to standing on incident atrial fibrillation (AF) is unclear. Purpose We aim to assess the association between orthostatic SBP changes and incident AF. Methods We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a randomized controlled trial comparing intensive (<120 mm Hg) and standard (<140 mm Hg) SBP interventions in participants with hypertension. Participants with standing SBP <110 mm Hg were not eligible for randomization according to the SPRINT protocol. Participants without AF who had seated and standing SBP measurements at baseline and available baseline or follow-up ECG were included in this analysis. Orthostatic SBP changes were defined as standing SBP minus seated SBP. Patients were grouped into tertiles of orthostatic SBP changes. AF was ascertained from the standard 12-lead ECG obtained at baseline, year 2, year 4, a close-out visit, and any visit when suspected of serious adverse events. We used Cox proportional regression models and restricted spline curves to assess the association of orthostatic SBP changes with incident AF. Results Among 8,455 participants included in this analysis, 327 incident AF cases occurred during follow-up. The restricted spline curve depicted a U-shaped relationship between orthostatic SBP changes and incident AF in the unadjusted model (P for nonlinearity = 0.012) (Figure 1). After adjusting for age, female, race, smoking, alcohol use, history of cardiovascular disease, history of chronic kidney disease, and body mass index, a SBP increase ≥ 6 mm Hg to standing was independently associated with a 43% higher risk of incident AF (HR: 1.43; 95% CI: 1.07-1.90; P = 0.014) compared to nonsignificant orthostatic SBP changes (>-4 mm Hg to <6 mm Hg). A SBP decrease ≥ 4 mm Hg to standing showed a nonsignificant higher risk of developing AF compared to SBP changes of >-4 mm Hg to <6 mm Hg (Figure 2). In subgroup analysis, the results presented a similar tendency to the main result. Sensitivity analyses also generated consistent results while additionally adjusting for seated and standing blood pressure or heart rate. Conclusion In this post hoc analysis of the SPRINT trial, exaggerated SBP increase to standing independently predicts incident AF.Figure 1Figure 2

Rates of Adverse Events per Patient-Year in a Randomized, Phase 3 Study of CPX-351 Versus 7+3 in Older Adults with Newly Diagnosed, Treatment-Related Acute Myeloid Leukemia (AML) or AML with Myelodysplasia-Related Changes

Diabetes affects around 20 million persons in the United States and is the fifth leading cause of death worldwide, consumes a large percentage of our health care resources, and remains a leading cause of cardiovascular (CV) and kidney disease. With the increasing rates of obesity in the United States, there are 41 million people with prediabetes, 50% of whom will develop frank type 2 diabetes mellitus over the next several years. Several clinical trials of subjects with hypertension or underlying CV disease have suggested that agents that block the renin-angiotensin system (RAS) prevent the development of new-onset diabetes (NOD). Pooled analyses of these trials have found, on average, a 25% reduction in NOD with angiotensin-converting enzyme (ACE) inhibitor–or angiotensin II receptor blocker (ARB)–based treatment regimens (usually with a diuretic). It remains unclear, however, whether this finding is attributable to the specific use of these agents or to the effects of the comparator agents studied, usually a β-blocker or thiazide-type diuretic. In addition, the progression to diabetes in these trials has always been a secondary outcome, which is, by definition, only hypothesis-generating. NOD has never been studied as a primary outcome. The Diabetes Reduction Assessment With Ramipril and Rosiglitazone Medication (DREAM) trial was conducted by the Canadian Institutes of Health Research, with additional financial support from industry. Subjects from 21 countries in 191 centers were enrolled to evaluate whether the ACE inhibitor, ramipril, reduces the risk of NOD in persons at high risk for its development. They had to be at least 30 years of age and have impaired fasting glucose (IFG) (fasting plasma glucose levels at least 110 mg/dL but <126 mg/dL) or impaired glucose tolerance (IGT) (fasting plasma glucose levels of at least 140 mg/dL but <200 mg/dL 2 hours after an oral glucose load) but no history of diabetes, CV disease, or intolerance to an ACE inhibitor. This double-blind placebo-controlled trial was performed using a 2 × 2 factorial design whereby both the ACE inhibitor ramipril and the thiazolidinedione rosiglitazone were compared with placebo. The 2 pharmacologic agents were reported separately; this review will deal only with the ACE inhibitor ramipril compared with placebo. Between July 2001 and August 2003, 24,592 participants were screened and 5808 entered a 17-day run-in period. The most common reasons for exclusion were ineligibility (94%) and refusal to participate (3%). After the run-in period, 2623 participants were randomly assigned to receive ramipril and 2646 participants received placebo. Ramipril was given as 5 mg daily for the first 2 months and then increased to 10 mg at the 2-month visit and to 15 mg after 1 year. Visits were scheduled at 2 months and 6 months after randomization and then at regular 6-month intervals until the final visit between February and April 2006. At each visit, adherence to study drug was assessed and reinforced, as was a healthy diet and lifestyle. Electrocardiography was performed at baseline, at 2 years, and at the end of the study. At the 2-year and final visits, a glucose tolerance test was performed if the fasting plasma glucose was 126 mg/dL or higher, if the fasting plasma glucose level exceeded 95 mg/dL and the glycosylated hemoglobin level exceeded 93% of the upper limit of normal, and to confirm or eliminate the diagnosis of diabetes in people in whom diabetes had not developed. Diabetes was diagnosed if 2 consecutive plasma glucose levels performed on separate days exceeded the diagnostic thresholds within a 3-month period (ie, a fasting plasma glucose of ≥126 mg/dL or a 2-hour plasma glucose ≥200 mg/dL) or if the outside physician following the patient prescribed an antidiabetic agent after a single abnormal glucose value. Glucose levels were available for 92.6% of individuals who had not reached a primary outcome by the end of the study. Participants were followed for a median of 3.0 years. The mean systolic BP at baseline was 136.1 mm Hg in the ramipril group and 136.0 mm Hg in the placebo group. At 2 months, mean systolic BP decreased by 8.2 mm Hg among those receiving ramipril and 3.9 mm Hg among those receiving placebo, a difference of 4.3 mm Hg, which persisted throughout the trial. Changes in diastolic BP were 4.3 mm Hg in the ramipril group and 1.6 mm Hg in the placebo group at 2 months (difference of 2.7 mm Hg) and also remained significant throughout the trial. Mean serum creatinine level did not change significantly in either group throughout the trial. The prespecified primary outcome was the development of NOD or death. Key secondary outcomes were fasting glucose levels, regression to normal glucose levels (fasting glucose level <110 mg/dL or 2-hour post-load glucose level <140 mg/dL) and a composite of cardiorenal events, defined as either CV events (clinical or silent myocardial infarction, stroke, death from CV events, revascularization procedures, heart failure, newly diagnosed angina with objective evidence of ischemia, or a ventricular arrhythmia requiring resuscitation) or renal events (on the basis of measurements in urine or blood at a central laboratory). Renal event data will be published at a future date. During the study, there was no difference in the occurrence of NOD or death (the primary end point) between individuals who received ramipril or placebo (18.1% of ramipril-treated patients compared with 19.5% of those who received placebo). There was also no difference in the development of NOD alone, which developed in 17.1% of the ramipril group and 18.5% of the placebo group. The rates of the primary outcomes were similar even after controlling for the use of other types of antihypertensive therapy, including thiazide-type diuretic (10% of participants), non-thiazide diuretic (6%), β-blocker (17%), calcium channel blocker (13%), or ARB (6%) therapy. The groups also did not differ in the incidence of CV events or hospitalization; however, significantly more ramipril than placebo recipients noted regression to normal glucose levels (43% vs 38%). There was no significant interaction with rosiglitazone; the hazard ratios for the primary outcome among those receiving ramipril were similar regardless of whether they received rosiglitazone. The authors conclude that the use of 15 mg of ramipril daily for 3 years in people with IFG or IGT and no evidence of established CV disease does not significantly prevent NOD or death.—Bosch J, Yusuf S, Gerstein HC, et al, for the DREAM Trial Investigators. Effect of ramipril on the incidence of diabetes. N Engl J Med. 2006;355:1551–1562. ACE inhibitors are among the most widely prescribed antihypertensive agents in the United States. They are currently recommended for the 6 compelling indications noted in the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). In addition to the benefits seen in patients with established CV disease, a number of widely publicized clinical trials have reported that the use of ACE inhibitors or ARBs decrease the incidence of NOD. These include the Heart Outcomes Prevention Evaluation (HOPE), where the use of the ACE inhibitor ramipril, given 10 mg daily (in addition to multiple other drugs), reduced the risk of NOD by 34% when compared with a group of patients on medications other than ramipril. This, however, was not a prespecified outcome, and the development of diabetes was ascertained only by self-report. By contrast, the use of ramipril was not associated with a reduction in NOD in the DREAM study. What explains the different results found in this recent trial? Unlike previous studies that evaluated the effect of antihypertensive drug therapy on the development of NOD, the DREAM investigation was specifically designed to evaluate the association of pharmacologic treatment and NOD as the primary end point. Previous studies, including HOPE, evaluated the development of diabetes either as a secondary outcome or in a post hoc analysis and, in many cases, the diagnosis of NOD was made primarily by self-report. Second, in contrast to other studies, patients in the DREAM study were only included in the trial if they had IFG or IGT and did not have established type 2 diabetes. Patients were screened at baseline with fasting glucose and an oral glucose tolerance test, and those who had overt diabetes or normal glucose levels were excluded. In previous studies, patients with undiagnosed diabetes may have been included, since baseline fasting plasma glucose and glucose tolerance were not routinely assessed. Finally, patients enrolled in the DREAM trial were younger (mean age, 55 years, compared with 65 years in other studies) and did not have evidence of CV disease on entry into the study. In previous studies, like HOPE, patients most often had known CV disease on entry. It is possible that ACE inhibitor therapy has a greater effect in individuals with established CV disease who may have increased activation of the renin-angiotensin-aldosterone system. It is also possible that the DREAM trial was too short in duration to detect a difference in incidence of NOD. In DREAM, the median follow-up was approximately 3 years compared with previous studies with ACE inhibitor and ARB therapy, which had a median follow-up of about 4.5 years. The Kaplan-Meier curves in DREAM suggest a trend toward benefit of ramipril in the prevention of NOD beginning at 3.5 years. Whether this is real or a chance phenomenon remains unclear, as does its clinical significance. Clinical trial evidence up to 6 years in duration continues to affirm the benefits and safety of thiazide-type diuretics despite their adverse effects on plasma glucose. For example, while there was a 3% increased risk of NOD noted with initial thiazide-type diuretic therapy compared with ACE inhibitor therapy in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), CV outcomes with initial thiazide-type diuretics were unsurpassed. This result and other data led to the recommendation in JNC 7 that thiazide-type diuretics should be used as initial antihypertensive therapy for most patients with hypertension. Whether possible metabolic effects moderate the clinical benefits of thiazide-type diuretics over a longer follow-up period continues to be debated. The most recent estimates predict that the prevalence of type 2 diabetes mellitus will more than double, from 5.6% in 2005 to 12.0% in 2050, and that 48.3 million people will have a diagnoses of diabetes in the United States by 2050. In addition, the tremendous increase in the rates of obesity and insulin resistance has led to an epidemic of individuals with IFG and/or IGT who are at high risk for progressing to type 2 diabetes. Whether small incremental changes in glucose over many years associated with some antihypertensive drug therapy carries the same risk as obesity-associated diabetes mellitus continues to be debated. For now, reduction of BP seems to be the most important target for improving clinical outcome in people both with and at risk for developing diabetes mellitus. Since most individuals require multiple antihypertensive agents to control their BP, combination regimens that target complementary pathophysiologic BP-lowering mechanisms are a rational approach to achieve BP control. While it is possible that a longer (ie, >3 years) and larger study would have shown a reduction in the development of NOD, the present 3-year trial with the use of the ACE inhibitor ramipril did not indicate that NOD was prevented among persons with IFG or IGT. The hypertension community awaits the outcomes of the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) study, evaluating initial fixed-dose combination therapy with an ACE/calcium channel blocker (benazepril/amlodipine) compared with an ACE/thiazide-type diuretic (benazepril/HCTZ) in individuals with and without diabetes. At present, continued use of thiazide-type diuretics with ACE inhibitors or ARBs as combination antihypertensive therapy is often required to control BP in most individuals with hypertension. With the publication of the DREAM results, enthusiasm for including RAS antagonists to decrease the risk of NOD has lessened. Traditional Chinese acupuncture (TCA) is advocated by some as an effective and well-tolerated treatment for essential hypertension. While a few case reports and several small clinical trials have suggested a benefit from acupuncture in patients with hypertension, the methodologic limitations of these trials have made it impossible to draw any definitive conclusions about the efficacy of TCA in lowering blood pressure (BP). The Stop Hypertension With Acupuncture Research Program (SHARP) pilot trial was designed to overcome the methodologic limitations of previous studies and evaluate the BP-lowering benefits of acupuncture. The SHARP trial was a prospective, double-blind, randomized, sham-controlled, parallel-group clinical pilot trial that was designed to test the safety and efficacy of 6 weeks of TCA in patients with moderate essential hypertension who were not receiving any antihypertensive medication. To be eligible, subjects had to be at least 18 years of age and have a systolic BP of 140–179 mm Hg or a diastolic BP of 90–109 mm Hg for 3 qualifying visits after cessation of all previous antihypertensive medications. In addition, they could not have had any TCA in the previous 6 months or have a medical contraindication to either TCA or the suspension of antihypertensive medications. Participants were randomly allocated into 1 of 3 treatment groups: (1) individualized TCA (IND); (2) standardized TCA (STD); or (3) sham acupuncture (CNTL). IND consisted of corporal acupuncture at 10–12 points selected and stimulated as prescribed for each individual by an experienced acupuncturist trained originally in China, plus auricular acupuncture at the 2 most active sites as identified by a point detector at the start of each session. STD consisted of corporal acupuncture with neutral stimulation at 5 bilateral points (10 total) plus auricular acupuncture at heart and jiang ya gou points as determined a priori by an expert panel convened for the purposes of this study. All diagnoses and treatment for IND and STD followed TCA principles previously established in the literature. CNTL consisted of sham acupuncture with no stimulation at 5 bilateral points (10 total) that do not correspond to any traditional Chinese meridians plus auricular acupuncture in Darwin's tubercle and the posterior ear lobe—all points considered inactive according to the tenets of TCA. Treatment consisted of no more than 12 twice-weekly 30-minute acupuncture sessions over 6 weeks. All participants received TCA from a team of licensed acupuncturists in a clinic established at the Massachusetts General Hospital. Treatment allocation was stratified by presence or absence of previous use of antihypertensive medications in the 6 months before study entry. All antihypertensive medications were tapered off according to a predetermined schedule before study initiation. After randomization, BP was measured at scheduled visits every 14 days until week 10 and subsequently at 4, 6, 9, and 12 months using a standardized technique by trained staff blinded to treatment allocation. In addition, blood chemistries, lipid profiles, complete blood cell counts, urinalysis, electrocardiography, and adverse events were analyzed at 10 weeks, 6 months, and 12 months. Quality-of-life data were obtained through use of the Medical Outcomes Study-Short Form self-administered questionnaires at baseline, 10 weeks, and 12 months. The predetermined primary end point was change in systolic BP from baseline to week 10, and the primary comparison was change in systolic BP for active (IND+STD) vs sham (CNTL) TCA. Between March 2001 and July 2002, 424 individuals underwent initial screening, of whom 192 met eligibility criteria and were randomized. Four subjects were lost to follow-up and 188 participants were available for the final evaluation. Patient characteristics in the 3 treatment groups were similar, with an average age of 55 years, 55% male, and an average baseline BP 149/93 mm Hg. Nearly all subjects (96%) received 12 treatments during an average of 42 days Mean systolic BP declined in all 3 groups between baseline and week 10 (the primary end point), with no statistically significant difference between those allocated to active (IND+STD, −3.56±1.92 mm Hg) compared with sham (CNTL, −3.84±1.93 mm Hg) acupuncture (P=.90). There was also no significant difference in diastolic BP decline between active (IND+STD) and sham (CNTL) acupuncture. In addition, there was no difference in systolic or diastolic BP between the 2 active treatment arms, IND and STD. When followed for 6 or 12 months, no significant treatment effect was noted on systolic or diastolic BP. Categorization of participants by age, race, sex, baseline BP, history of antihypertensive use, obesity, or primary TCA, diagnosis did not identify any subgroup that benefited from active TCA. Although BP increased modestly between measurements taken before and after an acupuncture session, no difference was seen between treatment groups. Ten-week change in physiologic and quality-of-life parameters did not differ between groups, except for fasting glucose, which was slightly lower in the CNTL group. Among the 141 participants who completed a masking assessment evaluation at 4 months, there was a nonsignificant trend toward subjects being able to determine their treatment assignment, but the number who guessed correctly was similar in all 3 groups (about 67%). Three study-related adverse events occurred—2 STD subjects experienced a hypertensive emergency and 1 CNTL subject experienced an episode of heart failure. In this well-designed prospective randomized clinical trial using an appropriate control group, 6 weeks of biweekly TCA has no demonstrable benefit on reducing BP in individuals with stage 1 hypertension who were not receiving antihypertensive drug therapy.—Macklin EA, Wayne PM, Kalish LA, et al. Stop Hypertension with the Acupuncture Research Program (SHARP): results of a randomized, controlled clinical trial. Hypertension. 2006;48:838–845. Previous evidence, mostly anecdotal observation, has suggested that TCA may have a role in the treatment of hypertension. The SHARP investigators appropriately considered these findings hypothesis-generating, leading them to design and execute a well-conceived prospective randomized clinical trial to test the hypothesis. Perhaps the most important design characteristics of this clinical trial were the use of appropriate blinding of acupuncturists and subjects, an appropriate control group (sham acupuncture in CNTL), and the use of 2 different previously validated types of TCA treatments (IND and STD). The study also benefited from careful measurement of an appropriate clinical outcome, the 10-week change in systolic BP. Like all randomized clinical trials, however, SHARP does have some shortcomings that may cause some to question the validity of the findings. As the investigators point out, the relatively wide confidence intervals in this small pilot study do not exclude the possibility of a small, but perhaps clinically significant, benefit (likely <4 mm Hg). The exclusion of subjects concomitantly treated with antihypertensive drug therapy does not rule out a possible beneficial effect when TCA is used in combination with BP-lowering medication, and the relatively short treatment period may not have allowed the full effects of TCA to be realized. Therefore, the results of this well-designed clinical trial make it unlikely that TCA provides substantial clinical benefit in patients with hypertension. Some of the perceived benefits of TCA, as pointed out by the SHARP investigators, may be the result of being treated by a clinician who “creates an expectation of medical improvement.” Practitioners of alternative medicine, including TCA, create confidence in the safety and efficacy of the treatments they offer, even though, in most cases and as in this study, they have not been shown to have a measurable clinical benefit. In contrast, much of the dialogue surrounding the use of drug therapy for the treatment of hypertension, both in the practitioner's office and in the media, focuses on the potential adverse effects associated with these agents. While it is important that clinicians not underestimate the potential tolerability issues of antihypertensive drug medications, it is also important to balance these issues with a clear explanation of the important clinical benefits and our confidence in these interventions. This should improve outcome and patient acceptance and adherence. As patients in the United States continue to use alternative medicines to treat hypertension, it is imperative that future clinical trials be designed and funded to determine the potential value of these treatments for improving the control of BP and other outcomes in hypertension.

Whether hyperuricemia is a true risk factor for elevated blood pressure (BP) is controversial, and the sex-specific effects of serum uric acid (SUA) on BP during a follow-up period remain unclear. We investigated whether the association of SUA level with systolic or diastolic BP during a 10-year period differs by sex in a Japanese general population of individuals who received annual health examinations (n = 28,990). After exclusion of subjects who had no BP or SUA data at baseline, a total of 22,994 subjects (male/female: 14,603/8391, age: 47 ± 11 years) were recruited. After adjustment for age; body mass index; BP; SUA level; use of drugs for hyperuricemia and hypertension; diagnosis of diabetes mellitus, dyslipidemia, and chronic kidney disease; family history of hypertension; habits of current smoking and alcohol consumption at baseline; the duration of the observation period; and the interaction between each covariate and the duration of the observation period indicated a significant association of SUA level with change in systolic or diastolic BP over time. There was a significant interaction between sex and SUA level for the change in systolic BP (P = 0.003) but not the change in diastolic BP (P = 0.081). The SUA level at baseline (per 1 mg/dL) was significantly associated with a change in systolic BP over time in females (estimate: 0.073 mmHg/year, P = 0.003) but not in males (estimate: 0.020 mmHg/year, P = 0.160). In conclusion, a high SUA level at baseline is significantly associated with an increase in systolic BP over time in female individuals but not in male individuals.

Effectiveness of an mHealth intervention to improve the cardiometabolic profile of people with prehypertension in low-resource urban settings in Latin America: a randomised controlled trial

Objective: Deprescribing of antihypertensive medications is recommended in some elderly patients with polypharmacy and multi-morbidity. However, the evidence base for this strategy is limited. We aimed to establish whether antihypertensive medication reduction is possible without significant hazard or changes in systolic blood pressure (SBP) control at 12-week follow-up. Design and method: This study used a randomised, controlled, open label, non-inferiority trial design. Participants aged at least 80 years with SBP &lt; 150 mmHg and receiving 2 or more antihypertensive medications, whose GP considered appropriate for medication reduction were recruited from 69 general practices across England. Those enrolled were randomised (1:1 ratio) to antihypertensive medication reduction (intervention) or usual care (control). The primary outcome was difference (&lt;10%) in proportion of participants with clinically acceptable SBP (&lt;150 mmHg) at 12-week follow-up. Secondary outcomes included difference in SBP and adverse events. Trial registration EudraCT (2016-004236-38), ISRCTN (97503221). Results: Of 569 participants who were randomised, 35 (6%) were lost to follow-up. Overall, 229 (86.4%) patients in the intervention group and 236 (87.7%) patients in the control group had clinically acceptable systolic blood pressure at follow-up (Adjusted RR 0.98, 95% CI 0.92 to 1.04). Since the lower 95% confidence interval was greater than 0.9, medication reduction was assumed to be non-inferior to usual care. Medication reduction was sustained in 187 (66.3%) participants in the intervention group who were taking 0.63 (95% CI 0.56 to 0.71) fewer antihypertensive medications than the control group at 12 weeks. Systolic blood pressure corrected for baseline was 3.5 mmHg higher (95% CI 1.1 to 5.9 mmHg) in the intervention group. Adverse events were higher in the intervention group but there was no significant difference in rates of serious adverse events. Conclusions: Antihypertensive medication reduction can be achieved in two thirds of older multi-morbid patients with systolic blood pressure remaining within clinically acceptable limits. However, potential benefits must be balanced against the possible harms from increased systolic blood pressure (and therefore cardiovascular risk) plus increased adverse events (although most were apparently unrelated).

The aim of this study was to compare the effect of two different high-intensity resistance exercise (RE) set configurations on the following: systolic blood pressure (SBP), rate pressure product (RPP), heart rate (HR) variability (HRV), and HR complexity (HRC). Ten well-trained males performed three parallel squat sets until failure (traditional training; TT) with the four repetitions maximum load (4RM), and a rest of 3min between sets. Thereafter, participants performed a cluster training session (CT) of equated load but with resting time distributed between each repetition. Dependent variables were recorded before, during, and after RE. Mean SBP (25·7 versus 10·9% percentage increase; P=0·016) and RPP (112·5 versus 69·9%; P=0·01) were significantly higher in TT. The decrease in HRV after exercise and the drop of HRC during exercise were similar in CT and TT. Change of standard deviation of normal RR intervals after TT correlated with change in SBP (r=0·803; P=0·009) while the change of Sample Entropy during exercise correlated with the increment of RPP during CT (ρ=-0·667; P=0·05). This study suggests that set configuration influences acute cardiovascular responses during RE. When intensity, volume and work-to-rest ratio are equated, CT is less demanding in terms of SBP and RPP. A greater hemodynamic response during exercise would be associated with a faster parasympathetic recovery.

Prevention of cardiovascular events in end-stage renal disease: Results of a randomized trial of fosinopril and implications for future studies

<i>Hypertension</i> Editors’ Picks

Although international recommendations corroborate the antihypertensive effects of regular endurance training (ET), interindividual responses are widely heterogeneous, differing between responders (RE) and non-responders (NR). Previous studies have shown the decrease in the activity of the autonomic nervous system (ANS) is involved in the ET-induced reduction of blood pressure (BP). However, it is not yet known whether this mechanism is related to the variability of BP response. PURPOSE: Associate baseline ANS variables with interindividual BP responses in hypertensive women undergoing ET. METHODS: Forty-four women performed 12 weeks of ET on cycle ergometer (50 min.day-1, 3 days.week-1 at 60-70% heart rate reserve). Pre and post ET 20 min beat-to-beat BP waveforms were recorded by finger photoplethysmography and ANS was assessed by heart rate (HR) variability (HRV) recorded from HR monitor and analyzed in the time and frequency domain. Participants were identified as RE by a magnitude of reduction in systolic BP (SBP) greater than the typical error (TE) of measurement (1xTE=7.4 mmHg) and participants with changes less or increase greater than 1xTE as NR. Associations between baseline HRV variables and changes (Δ) in BP after ET were analyzed using Pearson’s correlation coefficient and multiple linear regression. Student's t-test to comparisons RE vs. NR. Receiver operator characteristic (ROC) curve to identify predictors cut-off values for RE and NR discrimination. RESULTS: Ten individuals were considered RE (Δ=-15.6±7.6 mmHg) and 34 NR (Δ=4.3±7.9 mmHg). SBP changes were correlated with: SDNN (r=0.395; p=0.008), RMSSD (r=0.384; p=0.010), LF (r=0.318; p=0.036) and HF (r=0.348; p=0.02). SDNN was able to predict 15.6% of variance in SBP changes (β=0.39, p=0.008). Compared to RE, NR demonstrated greater SDNN (29.6±21.4 vs. 16.1±4.9, p=0.09), RMSSD (32.7±27.3 vs. 17.4±8.6, p=0.013) and LF (591±1380 vs. 110±71, p=0.001) and HF (668±1340 vs. 154±164, p=0.012). For SDNN, a cut-off value of 18.7 discriminated RE and NR with good accuracy (AUC=0.81, sensitivity=80%, specificity=76%, p=0.03). CONCLUSION: Baseline cardiac autonomic function can predict interindividual SBP responses to ET. Predictors cut-off values could be used to determine whether patients with hypertension are likely to benefit from ET.

Evaluating a web-based self-management program for employees with hypertension and prehypertension: A randomized clinical trial

Blood Pressure, Heart Rate Variability, and Renal Function in Nonsmoker and Smoker Hypertensive Patients.