Arterial hypertension – Clinical trials update 2021

AimThis review aims to summarize and discuss some of the most relevant clinical trials in epidemiology, diagnostics, and treatment of hypertension published in 2020 and 2021.Data synthesisThe trials included in this review are related to hypertension onset age and risk for future cardiovascular disease, reliability of different blood pressure monitoring methods, role of exercise-induced hypertension, treatment of hypertension in patients with SARS-CoV-2 infection, management of hypertension high-risk patient groups, e.g., in the elderly (≥80 years) and patients with atrial fibrillation, and the interplay between nutrition and hypertension, as well as recent insights into renal denervation for treatment of hypertension.ConclusionsHypertension onset age, nighttime blood pressure levels and a riser pattern are relevant for the prognosis of future cardiovascular diseases. The risk of coronary heart disease appears to increase linearly with increasing exercise systolic blood pressure. Renin-angiotensin system blockers are not associated with an increased risk for a severe course of COVID-19. In elderly patients, a risk-benefit assessment of intensified blood pressure control should be individually evaluated. A J-shaped association between cardiovascular disease and achieved blood pressure could also be demonstrated in patients with atrial fibrillation on anticoagulation. Salt restriction and lifestyle modification remain effective options in treating hypertensive patients at low cardiovascular risk. Sodium glucose co-transporter 2 inhibitors and Glucagon-like peptide-1 receptor agonists show BP-lowering effects. Renal denervation should be considered as an additional or alternative treatment option in selected patients with uncontrolled hypertension.     

Renal Denervation for Hypertension: A Systematic Review and Meta-Analysis of Randomized, Blinded,Placebo-Controlled Trials

ObjectivesThe authors performed an updated meta-analysis of randomized placebo-controlled trials of renal denervation and specifically compared the effect of renal denervation in patients taking medications and in those not taking medications.BackgroundRenal denervation has now undergone several blinded placebo-controlled trials, covering the spectrum from patients with drug-resistant hypertension to those not yet taking antihypertensive medications.MethodsAll blinded placebo-controlled randomized trials of catheter-based renal sympathetic denervation for hypertension were systematically identified, and a random-effects meta-analysis was performed. The primary efficacy outcome was the change in ambulatory systolic blood pressure beyond the effect of the placebo procedure. Analysis was stratified by whether there was background antihypertensive medication use.ResultsThere were 7 eligible trials, totaling 1,368 patients. Denervation significantly reduced ambulatory systolic (mean difference −3.61 mm Hg; 95% CI: −4.89 to –2.33 mm Hg; P < 0.0001), ambulatory diastolic (−1.85 mm Hg; 95% CI: −2.78 to −0.92 mm Hg; P < 0.0001), office systolic (−5.86 mm Hg; 95% CI: −7.77 to −3.94 mm Hg; P < 0.0001), and office diastolic (−3.63 mm Hg; 95% CI: −4.77 to −2.50; P < 0.0001) blood pressure. There was no evidence that the use of concomitant antihypertensive medication had a significant impact on the effect of denervation on any of these endpoints (P_interaction = NS for each comparison).ConclusionsThe randomized placebo-controlled trials show consistently that renal denervation provides significant reduction in ambulatory and office blood pressure. Although the magnitude of benefit, about 4/2 mm Hg, is modest, it is similar between patients on background antihypertensive medications and those who are not. Denervation could therefore be a useful strategy at various points for patients who are not willing to add antihypertensive agents. Whether the effect changes with time is currently unknown.     

Renal Denervation for Treating Hypertension: Current Scientific and Clinical Evidence

Initial studies of catheter-based renal denervation (RDN) for uncontrolled HTN using radiofrequency ablation in the main renal arteries showed that RDN was effective in lowering office blood pressure (BP). However, the first randomized sham-controlled trial, SYMPLICITY-HTN-3, did not show significantly lower office or 24-h ambulatory systolic BP compared with sham treatment. Subsequent studies in both animals and humans demonstrated the potential importance of more distal and branch renal artery radiofrequency ablation, and a second-generation multielectrode system became available. Two recent randomized sham-controlled trials in patients not taking antihypertensive drugs (SPYRAL HTN-OFF MED) or continuing to take drugs (SPYRAL HTN-ON MED) performed RDN with the second-generation radiofrequency ablation system using an ablation protocol that included treatment of the distal renal artery as well as the branch renal arteries. These studies showed that RDN significantly reduced office and 24-h ambulatory BP compared with sham treatment. Another recent randomized sham-controlled trial in patients not receiving medications showed that RDN with catheter-based ultrasound (RADIANCE-HTN SOLO) applied in just the main renal arteries significantly lowered daytime ambulatory and office BP compared with sham treatment. These trials have renewed clinical and scientific interest in defining the appropriate role of RDN in hypertension treatment. In addition, other important issues will need to be addressed in the future such as the development of tests to determine the extent of RDN at the time of the procedure and the potential of renal nerve fibers to regain their patency at some later stage following the ablation procedure.     

Alcohol-Mediated Renal Denervation Using the Peregrine System Infusion Catheter for Treatment of Hypertension

ObjectivesThe aim of this multicenter, open-label trial was to evaluate the safety and efficacy of alcohol-mediated renal denervation using a novel catheter system (the Peregrine System Infusion Catheter) for the infusion of dehydrated alcohol as a neurolytic agent into the renal periarterial space.BackgroundThe number of hypertensive patients with uncontrolled blood pressure (BP) remains unacceptably high. The renal sympathetic nervous system has been identified as an attractive therapeutic target.MethodsForty-five patients with uncontrolled hypertension on ≥3 antihypertensive medications underwent bilateral renal denervation using the Peregrine Catheter with 0.6 ml alcohol infused per renal artery.ResultsAll patients were treated as intended. Mean 24-h ambulatory BP reduction at 6 months versus baseline was −11 mm Hg (95% confidence interval [CI]: −15 to −7 mm Hg) for systolic BP and −7 mm Hg (95% CI: −9 to −4 mm Hg) for diastolic BP (p < 0.001 for both). Office systolic BP was reduced by −18/−10 mm Hg (95% CI: −25 to −12/−13 to −6 mm Hg) at 6 months. Antihypertensive medications were reduced in 23% and increased in 5% of patients at 6 months. Adherence to the antihypertensive regimen remained stable over time. The primary safety endpoint, defined as the absence of periprocedural major vascular complications, major bleeding, acute kidney injury, or death within 1 month, was met in 96% of patients (95% CI: 85% to 99%). Two patients had major adverse events of periprocedural access-site pseudoaneurysms, with major bleeding in one. There were no deaths or instances of myocardial infarction, stroke, transient ischemic attack, or renal artery stenosis. Transient microleaks were noted in 42% and 49% of the left and right main renal arteries, respectively. There were 2 cases of minor vessel dissection that resolved without treatment.ConclusionsPrimary results from this trial suggest that alcohol-mediated renal denervation using the Peregrine Catheter safely reduces blood pressure and as such may represent a novel approach for the treatment of hypertension.     

The REDUCE HTN: REINFORCE: Randomized,Sham-Controlled Trial of Bipolar Radiofrequency Renal Denervation for the Treatment of Hypertension

ObjectivesThe aim of this study was to investigate bipolar radiofrequency renal denervation in patients with hypertension not receiving medications at baseline.BackgroundA blood pressure–reducing effect of renal denervation has been difficult to isolate in clinical investigations.MethodsREDUCE HTN: REINFORCE (Renal Denervation Using the Vessix Renal Denervation System for the Treatment of Hypertension) was a randomized, sham-controlled multicenter trial. Patients with office systolic blood pressure (SBP) of 150 to 180 mm Hg and average 24-h ambulatory SBP of 135 to 170 mm Hg after medication washout underwent bipolar radiofrequency renal denervation or a sham procedure. The planned outcome was 8-week change in 24-h ambulatory SBP. Enrollment was terminated for apparent futility before a sufficient sample for powered efficacy comparisons was enrolled. Safety assessments included all-cause death, renal failure, severe hypotension or syncope, hypertensive crisis, and renal artery stenosis.ResultsBaseline 24-h blood pressure was 148.3 ± 10.9/85.7 ± 9.1 mm Hg for the denervation group (n = 34, mean age 58.5 ± 10.1 years, 47% women) and 149.1 ± 7.2/86.4 ± 9.8 mm Hg for the control group (n = 17, mean age 58.2 ± 9.8 years, 24% women). At 8 weeks, mean 24-h SBP reductions for the renal denervation and control groups were −5.3 mm Hg (95% confidence interval [CI]: −8.8 to −1.8 mm Hg) and −8.5 mm Hg (95% CI: −13.3 to −3.8 mm Hg), respectively (difference 3.3 mm Hg; 95% CI: −2.8 to 9.3 mm Hg; p = 0.30). Antihypertensive medications could then be added. By 6 months, decreases in SBP were greater for the denervation group, yielding between-group differences of −7.2 mm Hg (95% CI: −15.2 to 0.8 mm Hg; p = 0.08), −9.7 mm Hg (95% CI: −17.7 to −1.7 mm Hg; p = 0.02), and −11.4 mm Hg (95% CI: −19.2 to −3.7 mm Hg; p < 0.01) for 24-h, daytime ambulatory, and office measurements, respectively. Through 12 months, 1 patient (renal denervation group) had a hypertensive urgency requiring immediate management, and 1 experienced progression of renal artery stenosis.ConclusionsFuture studies of radiofrequency renal denervation must anticipate delayed treatment effects. (Renal Denervation Using the Vessix Renal Denervation System for the Treatment of Hypertension [REDUCE HTN: REINFORCE]; NCT02392351)     

Comprehensive Assessment of Human Accessory Renal Artery Periarterial Renal Sympathetic Nerve Distribution

ObjectivesThe aim of this study was to understand the anatomy of periarterial nerve distribution in human accessory renal arteries (ARAs).BackgroundRenal denervation is a promising technique for blood pressure control. Despite the high prevalence of ARAs, the anatomic distribution of periarterial nerves around ARAs remains unknown.MethodsKidneys with surrounding tissues were collected from human autopsy subjects, and histological evaluation was performed using morphometric software. An ARA was defined as an artery arising from the aorta above or below the dominant renal artery (DRA) or an artery that bifurcated within 20 mm of the takeoff of the DRA from the aorta. The DRA was defined as an artery that perfused >50% of the kidney.ResultsA total of 7,287 nerves from 14 ARAs and 9 DRAs were evaluated. The number of nerves was smaller in the ARA than DRA (median: 30 [interquartile range: 17.5 to 48.5] vs. 49 [interquartile range: 36 to 76]; p < 0.0001). In both ARAs and DRAs, the distance from the arterial lumen to nerve was shortest in the distal, followed by the middle and proximal segments. On the basis of the post-mortem angiography, ARAs were divided into large (≥3 mm diameter) and small (<3 mm) groups. The number of nerves was greatest in the DRA, followed by the large and small ARA groups (53 [41 to 97], 38 [25 to 53], and 24.5 [10.5 to 36.3], respectively; p = 0.001).ConclusionsARAs showed a smaller number of nerves than DRAs, but these results were dependent on the size of the ARA. Ablation, especially in large ARAs, may allow more complete denervation with the potential to further reduce blood pressure.     

Sodium-glucose co-transporter-2 inhibitors: peculiar “hybrid” diuretics that protect from target organ damage and cardiovascular events

AimsSodium-glucose co-transporter-2 inhibitors (SGLT2i) have been proven to lead to relevant cardiovascular benefits, regardless of glycemic control function. SGLT2i have on the one hand led to reduction in cardiovascular events such as heart failure and on the other hand to renal protection. Blood pressure reduction and kidney function play a central role in these outcomes. This focused review describes the main mechanisms and clinical aspects of SGLT2i.Data synthesisThese drugs act on the proximal renal tubule and behave as diuretics with a “hybrid” mechanism, as they can favour both natriuresis and enhanced diuresis due to an osmotic effect dependent on glycosuria, resulting in blood pressure decrease. The exclusive peculiarity of these “diuretics”, which distinguishes them from loop and thiazide diuretics, lies also in the activation of the tubule-glomerular feedback.ConclusionsThis mechanism, resulting in modulation of arterioles’ tone and renin secretion, contributes to the favorable outcomes, suggesting a wider use of SGLT2i in internal medicine, nephrology and cardiology.     

Advanced Therapies for Ventricular Arrhythmias in Patients With Chagasic Cardiomyopathy: JACC State-of-the-Art Review

Chagas disease is caused by infection from the protozoan parasite Trypanosoma cruzi. Although it is endemic to Latin America, global migration has led to an increased incidence of Chagas in Europe, Asia, Australia, and North America. Following acute infection, up to 30% of patients will develop chronic Chagas disease, with most patients developing Chagasic cardiomyopathy. Chronic Chagas cardiomyopathy is highly arrhythmogenic, with estimated annual rates of appropriate implantable cardioverter-defibrillator therapies and electrical storm of 25% and 9.1%, respectively. Managing arrhythmias in patients with Chagasic cardiomyopathy is a major challenge for the clinical electrophysiologist, requiring intimate knowledge of cardiac anatomy, advanced training, and expertise. Endocardial-epicardial mapping and ablation strategy is needed to treat arrhythmias in this patient population, owing to the suboptimal long-term success rate of endocardial mapping and ablation alone. We also describe innovative approaches to improve acute and long-term clinical outcomes in patients with refractory ventricular arrhythmias following catheter ablation, such as bilateral cervicothoracic sympathectomy and bilateral renal denervation, among others.     

Denervación renal para el tratamiento de la hipertensión arterial resistente en España. Registro Flex-Spyral

Introduction and objectivesRenal denervation is a percutaneous intervention for the treatment of resistant hypertension. Randomized studies have shown contradictory results on its efficacy. We present the results of a renal denervation registry for the treatment of resistant hypertension in real-life patients in Spain.MethodsMulticenter registry of consecutive patients with resistant hypertension treated with renal denervation in Spain between 2009 and 2018.ResultsWe included 125 patients (mean age, 56 years; 41% female; mean onset of hypertension 14 ± 9 years previously). Office systolic and diastolic blood pressure and ambulatory blood pressure monitoring decreased 6 months after the intervention (166 ± 20/95 ± 16 to 149 ± 22/87 ± 16 mmHg and 151 ± 14/89 ± 12 to 143 ± 15/84 ± 11, both P < .0001). At 12 months, the blood pressure reduction was maintained and the number of antihypertensive drugs decreased from 4.9 ± 1.2 to 4.4 ± 1.5 (P = .0001). There were no significant procedure-related complications. The response rate to denervation at 1 year was 80%, but there were wide differences between centers.ConclusionsIn patients with resistant hypertension, treatment with renal denervation was related to a decrease in office blood pressure and, more importantly, in ambulatory blood pressure monitoring, with a significant reduction in pharmacological treatment.     

Diuretic Therapy for Patients With Heart Failure: JACC State-of-the-Art Review

Expansion of extracellular fluid volume is central to the pathophysiology of heart failure. Increased extracellular fluid leads to elevated intracardiac filling pressures, resulting in a constellation of signs and symptoms of heart failure referred to as congestion. Loop diuretics are one of the cornerstones of treatments for heart failure, but in contrast to other therapies, robust clinical trial evidence to guide the use of diuretics is sparse. A nuanced understanding of renal physiology and diuretic pharmacokinetics is essential for skillful use of diuretics in the management of heart failure in both the inpatient and outpatient settings. Diuretic resistance, defined as an inadequate quantity of natriuresis despite an adequate diuretic regimen, is a major clinical challenge that generally portends a poor prognosis. In this review, the authors discuss the fundamental mechanisms and physiological principles that underlie the use of diuretic therapy and the available data on the optimal use of diuretics.     

Salt Reduction to Prevent Hypertension and Cardiovascular Disease: JACC State-of-the-Art Review

There is strong evidence for a causal relationship between salt intake and blood pressure. Randomized trials demonstrate that salt reduction lowers blood pressure in both individuals who are hypertensive and those who are normotensive, additively to antihypertensive treatments. Methodologically robust studies with accurate salt intake assessment have shown that a lower salt intake is associated with a reduced risk of cardiovascular disease, all-cause mortality, and other conditions, such as kidney disease, stomach cancer, and osteoporosis. Multiple complex and interconnected physiological mechanisms are implicated, including fluid homeostasis, hormonal and inflammatory mechanisms, as well as more novel pathways such as the immune response and the gut microbiome. High salt intake is a top dietary risk factor. Salt reduction programs are cost-effective and should be implemented or accelerated in all countries. This review provides an update on the evidence relating salt to health, with a particular focus on blood pressure and cardiovascular disease, as well as the potential mechanisms.     

Dietary acid load and risk of hypertension: A systematic review and dose-response meta-analysis of observational studies

Background and aimPrevious studies have assessed diet-induced mild metabolic acidosis in relation to blood pressure, however, data are conflicting. Current systematic review and dose-response meta-analysis aimed to summarize earlier findings from observational studies on the association between dietary acid load and hypertension.Methods and resultsWe searched the online databases for relevant publications up to Feb 2019, using relevant keywords. Overall, 14 studies (3 prospective and 11 cross-sectional studies) that included 306,183 individuals and 62,264 cases of hypertension were included in the current meta-analysis. Combining effect sizes from both prospective and cross-sectional studies revealed no significant non-linear association between dietary acid load (based on net endogenous acid production (NEAP) method) and hypertension. However, stratified analysis based on study design showed a significant non-linear association between dietary acid load and hypertension in prospective studies (P = 0.006), but not cross-sectional ones. According to linear dose-response analysis, no significant association was found between dietary acid load (based on NEAP) and hypertension (combined effect size: 1.01, 95% CI: 0.97–1.06, P = 0.51). In terms of dietary acid load based on potential renal acid load (PRAL) method, no significant non-linear association was seen with hypertension (P = 0.52). However, in linear dose-response analysis, a-20 unit increase in PRAL values was associated with 3% increased risk of hypertension (combined effect size: 1.03, 95% CI: 1.00–1.06, P = 0.03).ConclusionWe found a significant positive association between dietary acid load and hypertension. Further studies, particularly those with prospective nature, are needed to confirm our findings.     

Prediabetes and incident heart failure in hypertensive patients: Results from the Swedish Primary Care Cardiovascular Database

Backgrounds and aimsThe cardiovascular risk conferred by concomitant prediabetes in hypertension is unclear. We aimed to examine the impact of prediabetes on incident heart failure (HF) and all-cause mortality, and to describe time in therapeutic blood pressure range (TTR) in a hypertensive real-world primary care population.Methods and resultsIn this retrospective cohort study, 9628 hypertensive individuals with a fasting plasma glucose (FPG) in 2006–2010 but no diabetes, cardiovascular or renal disease were followed to 2016; median follow-up was 9 years. Prediabetes was defined as FPG 5.6–6.9 mmol/L, and in a secondary analysis as 6.1–6.9 mmol/L. Study outcomes were HF and all-cause mortality. Hazard ratios (HR) were compared for prediabetes with normoglycemia using Cox regression. All blood pressure values from 2001 to the index date (first FPG in 2006–2010) were used to calculate TTR. At baseline, 51.4% had prediabetes. The multivariable-adjusted HR (95% confidence intervals) was 0.86 (0.67–1.09) for HF and 1.06 (0.90–1.26) for all-cause mortality. For FPG defined as 6.1–6.9 mmol/L, the multivariable-adjusted HR were 1.05 (0.80–1.39) and 1.42 (1.19–1.70), respectively. The prediabetic group had a lower TTR (p < 0.05).ConclusionsPrediabetes was not independently associated with incident HF in hypertensive patients without diabetes, cardiovascular or renal disease. However, prediabetes was associated with all-cause mortality when defined as FPG 6.1–6.9 mmol/L (but not as 5.6–6.9 mmol/L). TTR was lower in the prediabetic group, suggesting room for improved blood pressure to reduce incident heart failure in prediabetes.     

ACC/AHA Versus ESC/ESH on Hypertension Guidelines: JACC Guideline Comparison

This study compares the recommendations of the most recent American College of Cardiology (ACC)/American Heart Association (AHA) and European Society of Cardiology (ESC)/European Society of Hypertension (ESH) blood pressure guidelines. Both guidelines represent updates of previous guidelines and reinforce previous concepts of prevention regarding elevated blood pressure. Specifically, a low-sodium diet, exercise, body weight reduction, low to moderate alcohol intake, and adequate potassium intake are emphasized. Overall, both guidelines agree on the proper method of blood pressure measurement, the use of home blood pressure and ambulatory monitoring, and restricted use of beta-blockers as first-line therapy. The major disagreements are with the level of blood pressure defining hypertension, flexibility in identifying blood pressure targets for treatment, and the use of initial combination therapy. Although initial single-pill combination therapy is strongly recommended in both guidelines, the ESC/ESH guideline recommends it as initial therapy in patients at ≥140/90 mm Hg. The ACC/AHA guideline recommends its use in patients >20/10 mm Hg above blood pressure goal. Thus, the only real disagreement is that the ACC/AHA guidelines maintain that all people with blood pressure >130/80 mm Hg have hypertension, and blood pressure should be lowered to <130/80 mm Hg in all. In contrast, the ESC/ESH guidelines state that hypertension is defined as >140/90 mm Hg, with the goal being a level <140/90 mm Hg for all targeting to <130/80 mm Hg only in those at high cardiovascular risk, but always considering individual tolerability of the proposed goal.     

Assessment of Vascular Dysfunction in Patients Without Obstructive Coronary Artery Disease: Why,How, and When

Ischemic heart disease secondary to coronary vascular dysfunction causes angina and impairs quality of life and prognosis. About one-half of patients with symptoms and signs of ischemia turn out not to have obstructive coronary artery disease, and coronary vascular dysfunction may be relevant. Adjunctive tests of coronary vasomotion include guidewire-based techniques with adenosine and reactivity testing, typically by intracoronary infusion of acetylcholine. The CorMicA (Coronary Microvascular Angina) trial provided evidence that routine management guided by an interventional diagnostic procedure and stratified therapy improves angina and quality of life in patients with angina but no obstructive coronary artery disease. In this paper, the COVADIS study group provide a comprehensive review of why, how, and when coronary vascular dysfunction should be assessed invasively. They discuss the rationale through a shared understanding of vascular pathophysiology and clinical evidence. They propose a consensus approach to how an interventional diagnostic procedure is performed with focus on practical aspects. Finally, the authors discuss the clinical scenarios in patients with stable and acute coronary syndromes in which measurement of coronary vascular function may be helpful for patient care.     

Navigating the “Optimal Implantation Depth” With a Self-Expandable TAVR Device in Daily Clinical Practice

ObjectivesThis study sought to predict whether different methods of calculating the implantation depth (ID) influence clinical and hemodynamic outcome reporting in patients undergoing transcatheter aortic valve replacement (TAVR) with a self-expandable device.BackgroundDifferent approaches exist to calculate the ID, which may influence uniform and reliable reporting because the updated Valve Academic Research Consortium (VARC-2) criteria do not provide specific instructions.MethodsThe clinical and hemodynamic outcomes of 258 patients undergoing TAVR with a third-generation self-expandable device were analyzed with regard to the method used to assess the ID as follows: arithmetic mean, the arithmetic mean of the measured distances from the noncoronary cusp and the left coronary cusp to the distal prosthesis end; noncoronary cusp distance, the distance from the noncoronary cusp to the distal prosthesis end; and deepest edge, the deepest edge of the distal prosthesis end.ResultsRegardless of the measurement method, the optimal ID (OID) was reached in <30% (arithmetic mean, 25.4%; noncoronary cusp distance, 28.4%; deepest edge, 20.5%; p = 0.008). The deepest edge method is the most stringent to differentiate the relevant outcome parameters, such as the need for permanent pacemaker implantation (OID 3.7% vs. no OID 14.6%; p = 0.033). The hemodynamic outcome (i.e., mean pressure gradient reduction after TAVR: OID 7.4 ± 3.4 mm Hg vs. no OID 8.3 ± 4.0 mm Hg; p = 0.093) was not affected.ConclusionsThe OID was reached in <30% of TAVR procedures. The various methods applied for ID calculation significantly influence the outcome reporting and do not allow a uniform perception of the ID. (Multi Modal Cardiac Imaging Prior Transcatheter Aortic Valve Implantation; NCT01805739)     

Effect of High Dietary Sodium Intake in Patients With Postural Tachycardia Syndrome

BackgroundHigh sodium intake is recommended for the treatment of postural tachycardia syndrome (POTS) to counteract the hypovolemia and elevated plasma norepinephrine that contribute to excessive orthostatic tachycardia, but evidence of its efficacy is not available.ObjectivesThis study tested whether a high sodium (HS) diet reduces orthostatic tachycardia (Δ heart rate) and upright heart rate compared with a low sodium (LS) diet in POTS patients, and secondarily its effect on plasma volume (PV) and plasma norepinephrine.MethodsA total of 14 POTS patients and 13 healthy control subjects (HC), age 23 to 49 years, were enrolled in a crossover study with 6 days of LS (10 mEq sodium/day) or HS (300 mEq sodium/day) diet. Supine and standing heart rate, blood pressure, serum aldosterone, plasma renin activity, blood volume, and plasma norepinephrine and epinephrine were measured.ResultsIn POTS, the HS diet reduced upright heart rate and Δ heart rate compared with the LS diet. Total blood volume and PV increased, and standing norepinephrine decreased with the HS compared with the LS diet. However, upright heart rate, Δ heart rate, and upright norepinephrine remained higher in POTS than in HC on the HS diet (median 117 beats/min [interquartile range: 98 to 121 beats/min], 46 beats/min [interquartile range: 32 to 55 beats/min], and 753 pg/ml [interquartile range: 498 to 919 pg/ml] in POTS vs. 85 beats/min [interquartile range: 77 to 95 beats/min], 19 beats/min [interquartile range: 11 to 32 beats/min], and 387 pg/ml [interquartile range: 312 to 433 pg/ml] in HC, respectively), despite no difference in the measured PV.ConclusionsIn POTS patients, high dietary sodium intake compared with low dietary sodium intake increases plasma volume, lowers standing plasma norepinephrine, and decreases Δ heart rate. (Dietary Salt in Postural Tachycardia Syndrome; NCT01547117)     

Changes in Plasma Renin Activity After Renal Artery Sympathetic Denervation

BackgroundThe renin-angiotensin-aldosterone system plays a key role in blood pressure (BP) regulation and is the target of several antihypertensive medications. Renal denervation (RDN) is thought to interrupt the sympathetic-mediated neurohormonal pathway as part of its mechanism of action to reduce BP.ObjectivesThe purpose of this study was to evaluate plasma renin activity (PRA) and aldosterone before and after RDN and to assess whether these baseline neuroendocrine markers predict response to RDN.MethodsAnalyses were conducted in patients with confirmed absence of antihypertensive medication. Aldosterone and PRA levels were compared at baseline and 3 months post-procedure for RDN and sham control groups. Patients in the SPYRAL HTN-OFF MED Pivotal trial were separated into 2 groups, those with baseline PRA ≥0.65 ng/ml/h (n = 110) versus <0.65 ng/ml/h (n = 116). Follow-up treatment differences between RDN and sham control groups were adjusted for baseline values using multivariable linear regression models.ResultsBaseline PRA was similar between RDN and control groups (1.0 ± 1.1 ng/ml/h vs. 1.1 ± 1.1 ng/ml/h; p = 0.37). Change in PRA at 3 months from baseline was significantly greater for RDN compared with control subjects (?0.2 ± 1.0 ng/ml/h; p = 0.019 vs. 0.1 ± 0.9 ng/ml/h; p = 0.14), p = 0.001 for RDN versus control subjects, and similar differences were seen for aldosterone: RDN compared with control subjects (?1.2 ± 6.4 ng/dl; p = 0.04 vs. 0.4 ± 5.4 ng/dl; p = 0.40), p = 0.011. Treatment differences at 3 months in 24-h and office systolic blood pressure (SBP) for RDN versus control patients were significantly greater for patients with baseline PRA ≥0.65 ng/ml/h versus <0.65 ng/ml/h, despite similar baseline BP. Differences in office SBP changes according to baseline PRA were also observed earlier at 2 weeks post-RDN.ConclusionsPlasma renin activity and aldosterone levels for RDN patients were significantly reduced at 3 months when compared with baseline as well as when compared with sham control. Higher baseline PRA levels were associated with a significantly greater reduction in office and 24-h SBP. (SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study; NCT02439749)     

Impact of Pre-Procedural Blood Pressure on Long-Term Outcomes Following Percutaneous Coronary Intervention

BackgroundHigh systolic blood pressure (SBP) increases cardiac afterload, whereas low diastolic blood pressure (DBP) may lead to impaired coronary perfusion. Thus, wide pulse pressure (high systolic, low diastolic [HSLD]) may contribute to myocardial ischemia and also be a predictor of adverse cardiovascular events.ObjectivesThe purpose of this study was to determine the relationship between pre-procedural blood pressure and long-term outcome following percutaneous coronary intervention (PCI).MethodsThe study included 10,876 consecutive patients between August 2009 and December 2016 from the Melbourne Interventional Group registry undergoing PCI with pre-procedural blood pressure recorded. Patients with ST-segment elevation myocardial infarction, cardiogenic shock, and out-of-hospital cardiac arrest were excluded. Patients were divided into 4 groups according to SBP (high ≥120 mm Hg, low <120 mm Hg) and DBP (high >70 mm Hg, low ≤70 mm Hg).ResultsMean pulse pressure was 60 ± 21 mm Hg. Patients with HSLD were older and more frequently women, with higher rates of hypercholesterolemia, renal impairment, diabetes, and multivessel and left main disease (all p ≤ 0.0001). There was no difference in 30-day major adverse cardiac events, but at 12 months the HSLD group had a greater incidence of myocardial infarction (p = 0.018) and stroke (p = 0.013). Long-term mortality was highest for HSLD (7.9%) and lowest for low systolic, high diastolic (narrow pulse pressure) at 2.1% (p = 0.0002). Cox regression analysis demonstrated significantly lower long-term mortality in the low systolic, high diastolic cohort (hazard ratio: 0.50; 99% confidence interval: 0.25 to 0.98; p = 0.04).ConclusionsPulse pressure at the time of index PCI is associated with long-term outcomes following PCI. A wide pulse pressure may serve as a surrogate marker for risk following PCI and represents a potential target for future therapies.