Influence of Blood Pressure Reduction on Pulse Wave Velocity in Primary Hypertension: A Meta-Analysis and Comparison With an Acute Modulation of Transmural Pressure.

BACKGROUND: Increased arterial stiffness and pulse wave velocity (PWV) of the aorta and large arteries impose adverse hemodynamic effects on the heart and other organs. Antihypertensive treatment reduces PWV, but it is unknown whether this results from an unloading of stiffer elements in the arterial wall or is due to an alternate functional or structural change that might differ according to class of antihypertensive drug. METHODS: We performed a systematic review and meta-analysis of the effects of different antihypertensive drug classes and duration of treatment on PWV with and without adjustment for change in mean arterial blood pressure (BP; study 1) and compared this to the change in PWV after an acute change in transmural pressure, simulating an acute change in BP (study 2). RESULTS: A total of 83 studies involving 6200 subjects were identified. For all drug classes combined, the reduction of PWV was 0.65 (95% CI, 0.46-0.83) m/s per 10 mm Hg reduction in mean arterial BP, a change similar to that induced by an acute change in transmural pressure in a group of hypertensive subjects. When adjusted for change in mean arterial BP, the reduction in PWV after treatment with beta-blockers or diuretics was less than that after treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists or calcium channel antagonists. CONCLUSIONS: Reduction in PWV after antihypertensive treatment is largely explained by the reduction in BP, but there are some BP-independent effects. These might increase over time and contribute to better outcomes over the long term, but this remains to be demonstrated in long-term clinical trials.

Ethnicity Differences in Geometric Remodeling and Myocardial Composition in Hypertension unveiled by Cardiovascular Magnetic Resonance.

AIMS: Hypertensive patients of African-ancestry (Afr-a) have higher incidences of heart failure and worse clinical outcomes than hypertensive patients of European-ancestry (Eu-a), yet the underlying mechanisms remain misunderstood. This study investigated right (RV) and left (LV) ventricular remodeling alongside myocardial tissue derangements between Afr-a and Eu-a hypertensives. METHODS AND RESULTS: Sixty-three Afr-a and forty-seven Eu-a hypertensives underwent multi-parametric cardiovascular-magnetic-resonance. Biventricular volumes, mass, function, mass/end-diastolic volume (M/V) ratios, T2- and pre/post-contrast T1-relaxation-times, synthetic-extracellular-volume (s-ECV) and myocardial fibrosis (MF) were measured. Three-dimensional shape modeling was implemented to delineate ventricular geometry.LV and RV-mass (indexed to body-surface-area) and M/V ratios were significantly greater in Afr-a than Eu-a hypertensives (67.1±21.7 vs. 58.3±16.7g/m2, 12.6±3.48 vs. 10.7±2.71g/m2, 0.79±0.21 vs. 0.70±0.14g/ml, 0.16±0.04 vs. 0.13±0.03g/ml, respectively; P<0.03) mirroring LV remodeling. Afr-a patients showed greater basal-interventricular-septum thickness than Eu-a patients, which may influence LV hypertrophy and RV cavity changes. This biventricular remodeling was associated with prolonged T2-relaxation-time (47.0±2.2 vs. 45.7±2.2ms, P=0.005) and higher prevalence (23% vs. 4%, P=0.001) and extent of MF (2.3[0.6-14.3] vs. 1.6[0.9-2.5] % of LV-mass, P=0.008) in Afr-a patients. Multivariable linear regression showed modifiable cardiovascular risk-factors and greater end-diastolic volume were independently associated with greater LV or RV-mass. Furthermore, ethnicity was independently associated with greater RV-mass, supporting our hypothesis of ethnic-specific hypertensive remodeling. CONCLUSIONS: Afr-a hypertensives had distinctive biventricular remodeling, including increased RV-mass and septal thickening, and subtle myocardial tissue abnormalities compared to Eu-a hypertensives. From this study, modifiable cardiovascular risk-factors, and ventricular geometry, but not ethnicity, were independently associated with higher LV mass.

'Legacy publication of a 2009 validation of the Riester Big Ben Square Desk aneroid device for blood pressure measurement according to the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults (2002)'.

OBJECTIVE: To report a validation of the Riester Big Ben Square Desk Aneroid Sphygmomanometer according to the international protocol developed by the Working Group on Blood Pressure Monitoring of the European Society of Hypertension 2002 (ESH-IP 2002) in the interest of transparency. This legacy publication is intended to assure users that the device satisfied the requirements in place at that time. METHODS: Performance of the device was assessed by participants' age, sex, arm circumference and entry SBP/DBP. Validation was performed in 33 participants. The sphygmomanometer was assessed according to the ESH-IP, which defines zones of accuracy compared to the mercury standard as ≤5, ≤10, ≤15 mmHg or more. RESULTS: The mean (± SD) age was 50.5 ±â€…13.0 years, range 29-71 years, entry SBP 142.6 ±â€…23.7 mmHg, entry DBP 89.0 ±â€…17.8 mmHg. The device passed all the requirements listed and the validation protocol. The Riester Big Ben Square Desk aneroid sphygmomanometer slightly underestimated the observer-measured SBP, yet slightly overestimated DBP. The observer-device disagreement was -0.8 ±â€…6.4 mmHg SBP and +0.6 ±â€…4.0 mmHg DBP. CONCLUSION: These data show that the Riester Big Ben Square Desk aneroid sphygmomanometer fulfilled the ESH-IP 2002 requirements for the validation of BP monitors. It was on this basis that the British and Irish Hypertension Society recommended it for clinical use in the adult population.

Impaired ß 2 -adrenergic endothelium-dependent vasodilation in patients previously hospitalized with coronavirus disease 2019.

AIM: The pulse wave response to salbutamol (PWRS) - change in augmentation index (AIx) - provides a means to assess endothelial vasodilator function in vivo . Endothelial dysfunction plays a relevant role in the pathogenesis of hypertension and cardiovascular disease and appears to underlie many of the complications of coronavirus disease 2019 (COVID-19). However, to what degree this persists after recovery is unknown. METHODS: Individuals previously hospitalized with COVID-19, those recovered from mild symptoms and seronegative controls with well known risk factors for endothelial dysfunction were studied. To assess the involvement of nitric oxide-cyclic guanosine monophosphate pathway (NO-cGMP) on PWRS, sildenafil was also administrated in a subsample. RESULTS: One hundred and one participants (60 men) aged 47.8 ±â€Š14.1 (mean ±â€ŠSD) years of whom 33 were previously hospitalized with COVID-19 were recruited. Salbutamol had minimal effect on haemodynamics including blood pressure and heart rate. It reduced AIx in controls ( n  = 34) and those recovered from mild symptoms of COVID-19 ( n  = 34) but produced an increase in AIx in those previously hospitalized: mean change [95% confidence interval] -2.85 [-5.52, -0.188] %, -2.32 [-5.17,0.54] %, and 3.03 [0.06, 6.00] % for controls, those recovered from mild symptoms and those previously hospitalized, respectively ( P  = 0.001). In a sub-sample ( n  = 22), sildenafil enhanced PWRS (change in AIx 0.05 [-2.15,2.24] vs. -3.96 [-7.01. -2.18], P  = 0.006) with no significant difference between hospitalized ( n  = 12) and nonhospitalized participants ( n  = 10). CONCLUSIONS: In patients previously hospitalized with COVID-19, there is long-lasting impairment of endothelial function as measured by the salbutamol-induced stimulation of the NO-cGMP pathway that may contribute to cardiovascular complications.

A meta-analysis of the haemodynamics of primary hypertension in children and adults.

We performed a systematic review and meta-analysis to determine the relative contributions of elevated cardiac output and systemic vascular resistance to hypertension in children and adults. This included 27 studies on 11 765 hypertensive and normotensive children and adults in whom cardiac output was measured. Cardiac output but not systemic vascular resistance was elevated in hypertensive compared to normotensive children and young adults (difference in means 1.15 [0.78-1.52] l/min, P < 0.001). In older hypertensive adults, both were elevated compared to normotensive individuals (0.40 [0.26-0.55] l/min, P < 0.001 and 3.21 [1.91-4.51] mmHg min/l, P < 0.001 for cardiac output and systemic vascular resistance, respectively). The main haemodynamic alteration in primary hypertension (including obesity-hypertension) in both children and young to middle-aged adults is an elevation of cardiac output. With longer duration and greater severity of hypertension there may be progression from a 'cardiac' to a 'vascular' phenotype with increased systemic vascular resistance.

A pilot study to evaluate the erythrocyte glycocalyx sensitivity to sodium as a marker for cellular salt sensitivity in hypertension.

Supressed plasma renin in patients with primary hypertension is thought to be an indirect marker of sodium-induced volume expansion which is associated with more severe hypertension and hypertension-mediated organ damage. A novel test for erythrocyte glycocalyx sensitivity to sodium (eGCSS) has been proposed as a direct measure of sodium-induced damage on erythrocyte surfaces and a marker of sensitivity of the endothelium to salt in humans. Here we explore if eGCSS relates to plasma renin and other clinical and biochemical characteristics in a cohort of patients with primary hypertension. Hypertensive subjects (n = 85, 54% male) were characterised by blood biochemistry (including plasma renin/aldosterone), urine analysis for albumin-creatinine ratio (ACR), 24-h urine sodium/potassium excretion. eGCSS was measured using a commercially available kit. Correlations between eGCSS and clinical and biochemical characteristics were explored using Spearman's correlation coefficient and characteristics compared across tertiles of eGCSS. eGCSS was inversely correlated with renin (p < 0.05), with renin 17.72 ± 18 µU/l in the highest tertile of eGCSS compared to 84.27 ± 146.5 µU/l in the lowest (p = 0.012). eGCSS was positively correlated with ACR (p < 0.01), with ACR 7.37 ± 15.29 vs. 1.25 ± 1.52 g/mol for the highest vs. lowest tertiles of eGCSS (p < 0.05). eGCSS was not correlated with other clinical characteristics or biochemical measures. These results suggests that sodium retention in hypertension characterised by a low-renin state is associated with cell membrane damage reflected by eGCSS. This may contribute to the hypertension-mediated organ damage and the excess mortality associated with sodium overload and "salt sensitivity".

Sensitivity and Reproducibility of Inferior Vena Cava Diameter and Superior Vena Cava Flow Velocity Measurements to Changes in Cardiac Preload in Subjects with Hypertension.

Objectives: We investigated the sensitivity and reproducibility of inferior vena cava (IVC) diameters and superior vena cava (SVC) flow velocities in detecting changes in cardiac preload in clinically euvolemic subjects with hypertension. Methods: Measurements were obtained during passive leg raising (PLR) and lower limb venous occlusion (LVO), interventions which respectively transiently increase and decrease cardiac preload. Measurements were made in 36 subjects and repeated on two separate occasions to examine reproducibility. Results: During PLR, there was no significant change in IVC diameters, but peak flow velocity of the SVC S wave increased by 6.5 (95% confidence interval 1.6-11.3) cm/s (P = 0.01). During LVO, IVC diameter in expiration decreased by 3.2 (1.7-4.7) mm and the SVC S wave decreased by 9.7 (4.4-14.7) cm/s (P < 0.001). Venae cavae-derived indices can be used to assess changes in preload within the physiological range in euvolemia. Conclusions: Despite suboptimal reproducibility of baseline measurements, high agreeability between the changes in IVC diameter and SVC flow after LVO suggests that these indices can be used to monitor changes in cardiac preload.

Effect of diuretics on plasma aldosterone and potassium in primary hypertension: A systematic review and meta-analysis.

AIM: By contrast with drugs inhibiting the renin-angiotensin-aldosterone system (RAAS), diuretics stimulate renin release by the kidneys. Although plasma aldosterone (PA) is thought to be mainly regulated by RAAS activity, serum potassium has been shown to be an important factor in animal models and humans. Here we perform a systematic review and meta-analysis of randomised controlled trials (RCT) in hypertension investigating the effects of diuretic therapy on PA and the correlation of change in PA with that of potassium and blood pressure (BP). METHODS: Three databases were searched: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). Titles were first screened by title and abstract for relevance before full-text articles were assessed for eligibility according to a predefined inclusion/exclusion criteria. RESULTS: A total of 1139 articles were retrieved, of which 42 met the prespecified inclusion/exclusion criteria. The average standardised difference in mean PA was similar for all classes of diuretic: thiazide/thiazide-like 0.299 (95% confidence interval [CI] 0.150, 0.447), loop 0.927 (0.37, 1.49), MRA/potassium-sparing 0.265 (0.173, 0.357) and combination 0.466 (0.137, 0.796), Q = 6.33, P = .097. In subjects untreated with another antihypertensive, there was a significant relationship between change in PA and change in systolic BP but no relationship with the change in potassium. CONCLUSION: In RCTs of diuretic therapy in hypertension, there is an increase in PA with all classes of diuretic and no significant between-class heterogeneity. Change in PA is not related with potassium but correlates with the change in BP in subjects untreated with another antihypertensive medication.

Species of Dickeya and Pectobacterium Isolated during an Outbreak of Blackleg and Soft Rot of Potato in Northeastern and North Central United States.

An outbreak of bacterial soft rot and blackleg of potato has occurred since 2014 with the epicenter being in the northeastern region of the United States. Multiple species of Pectobacterium and Dickeya are causal agents, resulting in losses to commercial and seed potato production over the past decade in the Northeastern and North Central United States. To clarify the pathogen present at the outset of the epidemic in 2015 and 2016, a phylogenetic study was made of 121 pectolytic soft rot bacteria isolated from symptomatic potato; also included were 27 type strains of Dickeya and Pectobacterium species, and 47 historic reference strains. Phylogenetic trees constructed based on multilocus sequence alignments of concatenated dnaJ, dnaX and gyrB fragments revealed the epidemic isolates to cluster with type strains of D. chrysanthemi, D. dianthicola, D. dadantii, P. atrosepticum, P. brasiliense, P. carotovorum, P. parmentieri, P. polaris, P. punjabense, and P. versatile. Genetic diversity within D. dianthicola strains was low, with one sequence type (ST1) identified in 17 of 19 strains. Pectobacterium parmentieri was more diverse, with ten sequence types detected among 37 of the 2015-2016 strains. This study can aid in monitoring future shifts in potato soft rot pathogens within the U.S. and inform strategies for disease management.

Effect of diuretics on plasma renin activity in primary hypertension: A systematic review and meta-analysis.

AIMS: Plasma renin activity (PRA) is regarded as a marker of sodium and fluid homeostasis in patients with primary hypertension. Whether effects of diuretics on PRA differ according to class of diuretic, whether diuretics lead to a sustained increase in PRA, and whether changes in PRA relate to those in blood pressure (BP) is unknown. We performed a systematic review and meta-analysis of trials investigating the antihypertensive effects of diuretic therapy in which PRA and/or other biomarkers of fluid homeostasis were measured before and after treatment. METHODS: Three databases were searched: MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials. Titles were firstly screened by title and abstract for relevancy before full-text articles were assessed for eligibility according to a predefined inclusion/exclusion criteria. RESULTS: A total of 1684 articles were retrieved of which 61 met the prespecified inclusion/exclusion criteria. PRA was measured in 30/61 studies. Diuretics led to a sustained increase in PRA which was similar for different classes of diuretic (standardised mean difference [95% confidence interval] 0.481 [0.362, 0.601], 0.729 [0.181, 1.28], 0.541 [0.253, 0.830] and 0.548 [0.159, 0.937] for thiazide, loop, mineralocorticoid receptor antagonists/potassium-sparing and combination diuretics respectively, Q = 0.897, P = .826), and did not relate to the average decrease in blood pressure. CONCLUSION: In antihypertensive drug trials, diuretics lead to a sustained increase in average PRA, which is similar across different classes of diuretic and unrelated to the average reduction in blood pressure.

Post-exertional increase in first-phase ejection fraction in recreational marathon runners.

OBJECTIVES: Running a marathon has been equivocally associated with acute changes in cardiac performance. First-phase ejection fraction is a novel integrated echocardiographic measure of left ventricular contractility and systo-diastolic coupling which has never been studied in the context of physical activity. The aim of this study was to assess first-phase ejection fraction following recreational marathon running along with standard echocardiographic indices of systolic and diastolic function.Design and participants: Runners (n = 25, 17 males), age (mean ± standard deviation) 39 ± 9 years, were assessed before and immediately after a marathon race which was completed in 4 h, 10 min ± 47 min. MAIN OUTCOME MEASURES: Central hemodynamics were estimated with applanation tonometry; cardiac performance was assessed using standard M-mode two-dimensional Doppler, tissue-doppler imaging and speckle-tracking echocardiography. First-phase ejection fraction was calculated as the percentage change in left ventricular volume from end-diastole to the time of peak aortic blood flow. RESULTS: Conventional indices of systolic function and cardiac performance were similar pre- and post-race while aortic systolic blood pressure decreased by 9 ± 8 mmHg (P < 0.001) and first-phase ejection fraction increased by approximately 48% from 16.3 ± 3.9% to 22.9 ± 2.5% (P < 0.001). The ratio of left ventricular transmitral Doppler early velocity (E) to tissue-doppler imaging early annular velocity (e') increased from 5.1 ± 1.8 to 6.2 ± 1.3 (P < 0.01). CONCLUSION: In recreational marathon runners, there is a marked increase in first-phase ejection fraction after the race despite no other significant change in cardiac performance or conventional measure of systolic function. More detailed physiological studies are required to elucidate the mechanism of this increase.

Differences in hypertension phenotypes between Africans and Europeans: role of environment.

OBJECTIVES: Hypertension phenotypes differ between Africans and Europeans, with a greater prevalence of low renin salt-sensitive hypertension and greater predisposition to adverse cardiac remodelling in Africans. To elucidate the roles of inheritance and environment in determining hypertension phenotypes in sub-Saharan Africans and white-Europeans, we compared phenotypes in white individuals in the UK (n = 132) and in African individuals in the UK (n = 158) and Nigeria (n = 179). METHODS: Biochemistry, blood pressure, left ventricular structure (echocardiography) and 24-h urinary collections of sodium and potassium were measured. RESULTS: Twenty-four-hour urinary sodium/potassium ratio was lower in individuals living in Europe (both African and white: 2.32 ±â€Š0.15 and 2.28 ±â€Š0.17) than in individuals in Nigeria (4.09 ±â€Š0.26, both P < 0.001) reflecting proportionately higher potassium intake in Europeans (African or white) than African residents. Plasma renin was lower in Africans irrespective of residency than white Europeans, but aldosterone was higher in Africans in Europe than those in Africa (466.15 ±â€Š32.95 vs. 258.60 ±â€Š17.42 pmol/l, P < 0.001). Left ventricular mass index adjusted for blood pressure and other confounders was greatest in Africans in Europe (103.27 ±â€Š2.32 g/m) compared with those in Africa (89.28 ±â€Š1.98 g/m) or white Europeans (86.77 ±â€Š2.63 g/m, both P < 0.001). CONCLUSION: Despite a similar low renin state in African origin individuals living in Europe and Africa, a higher aldosterone level, possibly related to higher potassium intake or other environmental factors, may contribute to greater cardiac remodelling in Africans in Europe.

A review of the prescribing trend of thiazide-type and thiazide-like diuretics in hypertension: A UK perspective.

Thiazide diuretics have been the cornerstone of hypertension treatment for >5 decades. Most recent European and American guidelines recommend both thiazide-type and thiazide-like diuretics as first-line drugs for all patients with hypertension. In contrast, diuretics are not regarded as first-line treatment in the UK and in patients who are to be initiated on a diuretic treatment, thiazide-like molecules, such as chlortalidone and indapamide are the preferred option. This review examines the prescribing trend of the 4 most commonly prescribed thiazide diuretics for the treatment of hypertension in the UK. Prescription cost analysis data were obtained for both 2010 and 2016/2017 for each region of the UK to analyse the impact of the 2011 National Institute for Health and Care Excellence hypertension guidelines on the trend in thiazide diuretic prescribing. Overall, the prescriptions of thiazide diuretics declined over the years. Bendroflumethiazide is the most commonly prescribed diuretic in the UK and despite some geographical differences, thiazide-type diuretics are more widely used than thiazide-like. The use of indapamide increased significantly between 2010 and 2016/2017 while chlortalidone was rarely employed. Of the many factors affecting trends in prescriptions, clinical inertia, treatment adherence, availability of the products and the lack of fixed dose combinations may play a role.

Arterial Stiffness Can Be Modulated by Pressure-Independent Mechanisms in Hypertension.

Background Effects of short-term interventions on large-artery stiffness assessed by pulse wave velocity (PWV) have mainly been explained by concomitant changes in blood pressure (BP). However, lower body negative pressure, which increases sympathetic activity and has other hemodynamic effects, has a specific effect on PWV in healthy volunteers. Methods and Results We examined effects of lower-limb venous occlusion (LVO), a similar intervention to lower-body negative pressure that reduces BP but increases sympathetic activity and device-guided breathing (DGB), which reduces both BP and sympathetic activity, on PWV in patients with essential hypertension (n=70 after LVO, n=45 after DGB and LVO in random order). The short-acting calcium channel antagonist nifedipine was used as a control for changes in BP. LVO produced a small but significant reduction in mean arterial pressure of 1.8 (95% CI 0.3-3.4) mm Hg. Despite this, aortic and carotid-femoral PWV increased during LVO by 0.8 (0.2-1.4) m/s and 0.7 (0.3-1.05) m/s, respectively. DGB reduced PWV by 1.2 (0.9-1.4) m/s, to a greater extent than did nifedipine 10 mg (reduction of 0.7 [0.1-1.3] m/s, P<0.05 compared with reduction during DGB). This occurred despite a greater decrease in BP with nifedipine compared with DGB. Conclusions Arterial stiffness can be modulated independently of BP over the short term. The mechanism could involve alterations in sympathetic activity or other as yet uncharacterized effects of LVO and DGB.