Elevated circulating platelet-derived extracellular vesicles (pEVs) have been associated with arterial hypertension. The role of hypertension-mediated organ damage (HMOD) to induce EV release is ...still unknown. We studied the micro- and macro-vascular changes (retinal vascular density and pulse wave velocity), endothelial function (flow-mediated vasodilation of brachial artery and finger plethysmography), and assessed the psychosocial status (anxiety and depression) in hypertensive patients to determine their relationship with EV release. Pulse wave velocity showed a significant positive correlation with pEVs (r = 0.33; p = 0.01). Systolic blood pressure (SBP) negatively correlated with retinal vascularity. The superficial retinal vascular plexus density in the whole image showed a significant negative correlation with 24 h SBP (r = −0.38, p < 0.01), day-SBP (r = −0.35, p = 0.01), and night-SBP (r = −0.27, p = 0.04). pEVs did not show significant associations with microvascular damage (retinal vascular density), endothelial function (flow-mediated vasodilation of brachial artery and finger plethysmography), or psychosocial status (anxiety and depression). Our results indicate that the pEV levels were associated with macrovascular damage measured by PWV, whereas no significant association between pEVs and microvascular damage, endothelial function, or emotional status could be detected. The potential utility of pEV in clinical practice in the context of HMOD may be limited to macrovascular changes.
Treatment inertia is a recognised barrier to blood pressure control, and simpler, more effective treatment strategies are needed. We hypothesised that a hypertension management strategy starting with ...a single pill containing ultra-low-dose quadruple combination therapy would be more effective than a strategy of starting with monotherapy.
QUARTET was a multicentre, double-blind, parallel-group, randomised, phase 3 trial among Australian adults (≥18 years) with hypertension, who were untreated or receiving monotherapy. Participants were randomly assigned to either treatment, that started with the quadpill (containing irbesartan at 37·5 mg, amlodipine at 1·25 mg, indapamide at 0·625 mg, and bisoprolol at 2·5 mg) or an indistinguishable monotherapy control (irbesartan 150 mg). If blood pressure was not at target, additional medications could be added in both groups, starting with amlodipine at 5 mg. Participants were randomly assigned using an online central randomisation service. There was a 1:1 allocation, stratified by site. Allocation was masked to all participants and study team members (including investigators and those assessing outcomes) except the manufacturer of the investigational product and one unmasked statistician. The primary outcome was difference in unattended office systolic blood pressure at 12 weeks. Secondary outcomes included blood pressure control (standard office blood pressure <140/90 mm Hg), safety, and tolerability. A subgroup continued randomly assigned allocation to 12 months to assess long-term effects. Analyses were per intention to treat. This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry, ACTRN12616001144404, and is now complete.
From June 8, 2017, to Aug 31, 2020, 591 participants were recruited, with 743 assessed for eligibility, 152 ineligible or declined, 300 participants randomly assigned to intervention of initial quadpill treatment, and 291 to control of initial standard dose monotherapy treatment. The mean age of the 591 participants was 59 years (SD 12); 356 (60%) were male and 235 (40%) were female; 483 (82%) were White, 70 (12%) were Asian, and 38 (6%) reported as other ethnicity; and baseline mean unattended office blood pressure was 141 mm Hg (SD 13)/85 mm Hg (SD 10). By 12 weeks, 44 (15%) of 300 participants had additional blood pressure medications in the intervention group compared with 115 (40%) of 291 participants in the control group. Systolic blood pressure was lower by 6·9 mm Hg (95% CI 4·9–8·9; p<0·0001) and blood pressure control rates were higher in the intervention group (76%) versus control group (58%; relative risk RR 1·30, 95% CI 1·15–1·47; p<0·0001). There was no difference in adverse event-related treatment withdrawals at 12 weeks (intervention 4·0% vs control 2·4%; p=0·27). Among the 417 patients who continued, uptitration occurred more frequently among control participants than intervention participants (p<0·0001). However, at 52 weeks mean unattended systolic blood pressure remained lower by 7·7 mm Hg (95% CI 5·2–10·3) and blood pressure control rates higher in the intervention group (81%) versus control group (62%; RR 1·32, 95% CI 1·16–1·50). In all randomly assigned participants up to 12 weeks, there were seven (3%) serious adverse events in the intervention group and three (1%) serious adverse events in the control group.
A strategy with early treatment of a fixed-dose quadruple quarter-dose combination achieved and maintained greater blood pressure lowering compared with the common strategy of starting monotherapy. This trial demonstrated the efficacy, tolerability, and simplicity of a quadpill-based strategy.
National Health and Medical Research Council, Australia.
Recent sham-controlled randomized clinical trials have confirmed the safety and efficacy of catheter-based renal denervation (RDN). Long-term safety and efficacy data beyond 3 years are scarce. Here, ...we report on outcomes after RDN in a cohort of patients with resistant hypertension with an average of ≈9-year follow-up (FU).
We recruited patients with resistant hypertension who were previously enrolled in various RDN trials applying radiofrequency energy for blood pressure (BP) lowering. All participants had baseline assessments before RDN and repeat assessment at long-term FU including medical history, automated office and ambulatory BP measurement, and routine blood and urine tests. We analyzed changes between baseline and long-term FU.
A total of 66 participants (mean±SD, 70.0±10.3 years; 76.3% men) completed long-term FU investigations with a mean of 8.8±1.2 years post-procedure. Compared with baseline, ambulatory systolic BP was reduced by -12.1±21.6 (from 145.2 to 133.1) mm Hg (
<0.0001) and diastolic BP by -8.8±12.8 (from 81.2 to 72.7) mm Hg (
<0.0001). Mean heart rate remained unchanged. At long-term FU, participants were on one less antihypertensive medication compared with baseline (
=0.0052). Renal function assessed by estimated glomerular filtration rate fell within the expected age-associated rate of decline from 71.1 to 61.2 mL/min per 1.73 m
. Time above target was reduced significantly from 75.0±25.9% at baseline to 47.3±30.3% at long-term FU (
<0.0001).
RDN results in a significant and robust reduction in both office and ambulatory systolic and diastolic BP at ≈9-year FU after catheter-based RDN on less medication and without evidence of adverse consequences on renal function.
Blood pressure (BP) management is a vital aspect of stroke prevention and post-stroke care. Different surgical carotid endarterectomy (CEA) techniques may impact on BP control post-operatively. ...Specifically, the carotid sinus nerve, which innervates the carotid baroreceptors and carotid body, is commonly left intact during conventional CEA but is routinely transected as part of eversion CEA. The aim of this study was to assess long term BP control after eversion and conventional CEA.
Patients from the International Carotid Stenting Study (ICSS cohort) and a personal series of patients from the Stroke Clinical Trials Unit at University College London (UCL cohort) were separately analysed and divided into eversion and conventional CEA groups. Mixed effect linear models were fitted and adjusted for baseline demographic data and antihypertensive treatment to test for changes in BP from baseline over a three year follow up period after the respective procedures.
There were no differences in changes in baseline BP readings and follow up readings between eversion and conventional CEA in the ICSS or UCL cohorts. In the ICSS cohort a mild but significant systolic (–8.6 mmHg; 95% confidence interval CI –10.6 – –6.6) and diastolic (–4.9 mmHg; 95% CI –6.0 – –3.8) BP lowering effect was evident at discharge in the conventional group but not in the eversion CEA group. BP monitoring during follow up did not reveal any consistent BP changes with either conventional or eversion CEA vs. baseline levels.
Neither conventional nor eversion CEA seem to result in clinically significant long term BP changes. Potential concerns related to either short or long term alterations in BP levels with transection of the carotid sinus nerve during eversion CEA could not be substantiated.
Resistant hypertension is associated with an exceedingly high cardiovascular risk and there remains an unmet therapeutic need driven by pathophysiologic pathways unaddressed by guideline‐recommended ...therapy. While spironolactone is widely considered as the preferable fourth‐line drug, its broad application is limited by its side effect profile, especially off‐target steroid receptor‐mediated effects and hyperkalaemia in at‐risk subpopulations. Recent landmark trials have reported promising safety and efficacy results for a number of novel compounds targeting relevant pathophysiologic pathways that remain unopposed by contemporary drugs. These include the dual endothelin receptor antagonist, aprocitentan, the aldosterone synthase inhibitor, baxdrostat and the nonsteroidal mineralocorticoid receptor antagonist finerenone. Furthermore, the evidence base for consideration of catheter‐based renal denervation as a safe and effective adjunct therapeutic approach across the clinical spectrum of hypertension has been further substantiated. This review will summarise the recently published evidence on novel antihypertensive drugs and renal denervation in the context of resistant hypertension.
Elevated circulating platelet-derived extracellular vesicles (EVs) have been reported in conditions associated with thrombotic risk. The present study aimed to assess the relationship between ...circulating platelet-derived EV levels, cardiovascular risk stratification and vascular organ damage, as assessed by pulse wave velocity (PWV). A total of 92 patients were included in the present analysis. Platelet EV were evaluated by flow cytometry (CD41+/Annexin v+). The cardiovascular risk was determined using the 2021 ESC guideline stratification and SCORE2 and SCORE-OP. PWV was performed as a surrogate to assess macrovascular damage. Risk stratification revealed significant group differences in EV levels (ANOVA, p = 0.04). Post hoc analysis demonstrated significantly higher levels of EVs in the very high-risk group compared with the young participants (12.53 ± 8.69 vs. 7.51 ± 4.67 EV/µL, p = 0.03). Linear regression models showed SCORE2 and SCORE-OP (p = 0.04) was a predictor of EV levels. EVs showed a significant association with macrovascular organ damage measured by PWV (p = 0.01). PWV progressively increased with more severe cardiovascular risk (p < 0.001) and was also associated with SCORE2 and SCORE-OP (p < 0.001). Within the pooled group of subjects with low to moderate risk and young participants (<40 years), those with EV levels in the highest tertile had a trend towards higher nocturnal blood pressure levels, fasting glucose concentration, lipid levels, homocysteine and PWV. Levels of platelet-derived EVs were highest in those patients with very high CV risk. Within a pooled group of patients with low to moderate risk, an unfavourable cardiometabolic profile was present with higher EV levels.
Efforts to limit the impact of the coronavirus disease (COVID‐19) pandemic led to the implementation of public health measures and reallocation of health resources. To investigate trends in blood ...pressure (BP), hypertension and BMI in the Australian population during the COVID‐19 pandemic, data from publicly accessible health stations were analyzed.
Average BP and BMI measured by the SiSU Health Station network in Australia in over 1.6 million health screenings were compared between the years 2018 and 2021. Additionally, paired trajectories for BP and BMI development before and during the COVID‐19 pandemic were calculated.
Comparisons between pre‐COVID years and post‐COVID years of 2018 versus 2020, 2019 versus 2020, 2018 versus 2021, and 2019 versus 2021 showed increases in average adjusted systolic BP of 2.0, 1.7, 2.6, and 2.3 mmHg, respectively. Paired analysis of longitudinal data showed an overall increase in the trajectory of systolic BP of 3.2 mmHg between pre‐ and post‐COVID years. The prevalence of hypertension in users of the health stations increased by approximately 25% in the years 2020–2021. Similar trends were seen for BMI.
Data from public Australian health stations indicated a strong trend toward higher BP during the COVID‐19 pandemic. At the population level, BP increments have been shown to markedly increase cardiovascular disease risk. Anti‐pandemic measures need to be carefully evaluated in terms of secondary public health effects and health support systems extended to effectively target cardiovascular risk.
Effects of sympathetic modulation in metabolic disease Carnagarin, Revathy; Lambert, Gavin W.; Kiuchi, Marcio G. ...
Annals of the New York Academy of Sciences,
October 2019, 2019-10-00, 20191001, Letnik:
1454, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Sympathetic overdrive contributes to the derangement of glucose metabolism evident in clinical conditions, such as obesity, metabolic syndrome, type 2 diabetes, obstructive sleep apnea, and others. ...Targeting the sympathetic nervous system directly therefore appears as an attractive therapeutic approach to restore impaired glucose metabolism. Indeed, lifestyle interventions, including healthier diets and exercise, have been shown to exert their beneficial effects at least in part by reducing sympathetic nervous system activity. Pharmacologic inhibition of exaggerated central sympathetic outflow has also been demonstrated to beneficially impact on body weight and glucose and lipid metabolism. More recently, catheter‐based renal denervation, an intervention applied predominantly to lower elevated blood pressure in patients with resistant hypertension, revealed salutary effects on glucose metabolism. Here, we review the mechanisms that contribute to the beneficial effects of targeting the sympathetic nervous system directly and discuss how these approaches may best be embedded in routine clinical practice.
Sympathetic overdrive contributes to the derangement of glucose metabolism seen in obesity, metabolic syndrome, type 2 diabetes, obstructive sleep apnea, etc. Targeting the sympathetic nervous system directly is therefore an attractive therapeutic approach to restore impaired glucose metabolism. Our review discusses the mechanisms that contribute to the beneficial effects of this approach and how it may best be embedded in routine clinical practice.
PDF
