Publications by authors named "Markus P Schlaich"

228 Publications

Device Therapy of Hypertension.

Circ Res 2021 Apr 1;128(7):1080-1099. Epub 2021 Apr 1.

William Harvey Research Institute and Barts NIHR Cardiovascular Biomedical Research Centre, Queen Mary University of London, United Kingdom (M.D.L.).

In the past decade, efforts to improve blood pressure control have looked beyond conventional approaches of lifestyle modification and drug therapy to embrace interventional therapies. Based upon animal and human studies clearly demonstrating a key role for the sympathetic nervous system in the etiology of hypertension, the newer technologies that have emerged are predominantly aimed at neuromodulation of peripheral nervous system targets. These include renal denervation, baroreflex activation therapy, endovascular baroreflex amplification therapy, carotid body ablation, and pacemaker-mediated programmable hypertension control. Of these, renal denervation is the most mature, and with a recent series of proof-of-concept trials demonstrating the safety and efficacy of radiofrequency and more recently ultrasound-based renal denervation, this technology is poised to become available as a viable treatment option for hypertension in the foreseeable future. With regard to baroreflex activation therapy, endovascular baroreflex amplification, carotid body ablation, and programmable hypertension control, these are developing technologies for which more human data are required. Importantly, central nervous system control of the circulation remains a poorly understood yet vital component of the hypertension pathway and mandates further investigation. Technology to improve blood pressure control through deep brain stimulation of key cardiovascular control territories is, therefore, of interest. Furthermore, alternative nonsympathomodulatory intervention targeting the hemodynamics of the circulation may also be worth exploring for patients in whom sympathetic drive is less relevant to hypertension perpetuation. Herein, we review the aforementioned technologies with an emphasis on the preclinical data that underpin their rationale and the human evidence that supports their use.
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http://dx.doi.org/10.1161/CIRCRESAHA.121.318091DOI Listing
April 2021

Role of the sympathetic nervous system in cardiometabolic control: implications for targeted multiorgan neuromodulation approaches.

J Hypertens 2021 Mar 3. Epub 2021 Mar 3.

Dobney Hypertension Centre, School of Medicine - Royal Perth Hospital Unit, Faculty of Medicine, Dentistry & Health Sciences, The University of Western Australia, Perth, Western Australia Department of Radiology, Alfred Hospital Department of Surgery, Central Clinical School, Monash University, Melbourne, Victoria Medical School, The University of Western Australia, Perth, Western Australia Baker Heart and Diabetes Institute, Melbourne, Victoria Department of Endocrinology, Medical School, The University of Western Australia Department of Radiology, Royal Perth Hospital, Perth, Western Australia Human Neurotransmitter Lab Neurovascular Hypertension & Kidney Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria Departments of Cardiology and Nephrology, Royal Perth Hospital, Perth, Western Australia, Australia.

Sympathetic overdrive plays a key role in the perturbation of cardiometabolic homeostasis. Diet-induced and exercise-induced weight loss remains a key strategy to combat metabolic disorders, but is often difficult to achieve. Current pharmacological approaches result in variable responses in different patient cohorts and long-term efficacy may be limited by medication intolerance and nonadherence. A clinical need exists for complementary therapies to curb the burden of cardiometabolic diseases. One such approach may include interventional sympathetic neuromodulation of organs relevant to cardiometabolic control. The experience from catheter-based renal denervation studies clearly demonstrates the feasibility, safety and efficacy of such an approach. In analogy, denervation of the common hepatic artery is now feasible in humans and may prove to be similarly useful in modulating sympathetic overdrive directed towards the liver, pancreas and duodenum. Such a targeted multiorgan neuromodulation strategy may beneficially influence multiple aspects of the cardiometabolic disease continuum offering a holistic approach.
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http://dx.doi.org/10.1097/HJH.0000000000002839DOI Listing
March 2021

Increase in Bioavailability of Nitric Oxide After Renal Denervation Improves Kidney Function in Sheep With Hypertensive Kidney Disease.

Hypertension 2021 Apr 1;77(4):1299-1310. Epub 2021 Mar 1.

From the Cardiovascular Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Australia (R.R.S., Z.M.M., K.M.D.).

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16718DOI Listing
April 2021

Combined renal and common hepatic artery denervation as a novel approach to reduce cardiometabolic risk: technical approach, feasibility and safety in a pre-clinical model.

Clin Res Cardiol 2021 Feb 26. Epub 2021 Feb 26.

Dobney Hypertension Centre, Faculty of Medicine, School of Medicine-Royal Perth Hospital Unit, Dentistry and Health Sciences, The University of Western Australia, Level 3, MRF Building, Rear 50 Murray St, Perth, WA, 6000, Australia.

Background: Cardiovascular and metabolic regulation is governed by neurohumoral signalling in relevant organs such as kidney, liver, pancreas, duodenum, adipose tissue, and skeletal muscle. Combined targeting of relevant neural outflows may provide a unique therapeutic opportunity for cardiometabolic disease.

Objectives: We aimed to investigate the feasibility, safety, and performance of a novel device-based approach for multi-organ denervation in a swine model over 30 and 90 days of follow-up.

Methods: Five Yorkshire cross pigs underwent combined percutaneous denervation in the renal arteries and the common hepatic artery (CHA) with the iRF Denervation System. Control animals (n = 3) were also studied. Specific energy doses were administered in the renal arteries and CHA. Blood was collected at 30 and 90 days. All animals had a pre-terminal procedure angiography. Tissue samples were collected for norepinephrine (NEPI) bioanalysis. Histopathological evaluation of collateral structures and tissues near the treatment sites was performed to assess treatment safety.

Results: All animals entered and exited the study in good health. No stenosis or vessel abnormalities were present. No significant changes in serum chemistry occurred. NEPI concentrations were significantly reduced in the liver (- 88%, p = 0.005), kidneys (- 78%, p < 0.001), pancreas (- 78%, p = 0.018) and duodenum (- 95%, p = 0.028) following multi-organ denervation treatment compared to control animals. Histologic findings were consistent with favourable tissue responses at 90 days follow-up.

Conclusions: Significant and sustained denervation of the treated organs was achieved at 90 days without major safety events. Our findings demonstrate the feasibility of multi-organ denervation using a novel iRF Denervation System in a single procedure.
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http://dx.doi.org/10.1007/s00392-021-01814-1DOI Listing
February 2021

Plasma lipocalin-2/NGAL is stable over 12 weeks and is not modulated by exercise or dieting.

Sci Rep 2021 Feb 18;11(1):4056. Epub 2021 Feb 18.

Hypertension Research Laboratory, School of Biological Sciences, Faculty of Science, Monash University, 25 Rainforest Walk, Melbourne, Clayton, VIC, 3800, Australia.

Amongst other immune cells, neutrophils play a key role in systemic inflammation leading to cardiovascular disease and can release inflammatory factors, including lipocalin-2 (LCN2). LCN2 drives cardiac hypertrophy and plays a role in maladaptive remodelling of the heart and has been associated with renal injury. While lifestyle factors such as diet and exercise are known to attenuate low-grade inflammation, their ability to modulate plasma LCN2 levels is unknown. Forty-eight endurance athletes and 52 controls (18-55 years) underwent measurement for various cardiovascular health indicators, along with plasma LCN2 concentration. No significant difference in LCN2 concentration was seen between the two groups. LCN2 was a very weak predictor or absent from models describing blood pressures or predicting athlete status. In another cohort, 57 non-diabetic overweight or obese men and post-menopausal women who fulfilled Adult Treatment Panel III metabolic syndrome criteria were randomly allocated into either a control, modified Dietary Approaches to Stop Hypertension (DASH) diet, or DASH and exercise group. Pre- and post-intervention demographic, cardiovascular health indicators, and plasma LCN2 expression were measured in each individual. While BMI fell in intervention groups, LCN2 levels remained unchanged within and between all groups, as illustrated by strong correlations between LCN2 concentrations pre- and 12 weeks post-intervention (r = 0.743, P < 0.0001). This suggests that circulating LCN2 expression are stable over a period of at least 12 weeks and is not modifiable by diet and exercise.
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http://dx.doi.org/10.1038/s41598-021-83472-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893047PMC
February 2021

Prospective meta-analysis protocol on randomised trials of renin-angiotensin system inhibitors in patients with COVID-19: an initiative of the International Society of Hypertension.

BMJ Open 2021 02 16;11(2):e043625. Epub 2021 Feb 16.

The George Institute for Global Health; University of New South Wales, Sydney, New South Wales, Australia

Introduction: Whether ACE inhibitors (ACEi) or angiotensin II receptor blocker (ARB) therapy should be continued, initiated or ceased in patients with COVID-19 is uncertain. Given the widespread use of ACEi/ARBs worldwide, guidance on the use of these drugs is urgently needed. This prospective meta-analysis aims to pool data from randomised controlled trials (RCTs) to assess the safety and efficacy of ACEi/ARB therapy in adults infected with SARS-CoV-2.

Methods And Analysis: RCTs will be eligible if they compare patients with COVID-19 randomised to ACEi/ARB continuation or commencement versuss no ACEi/ARB therapy; study duration ≥14 days; recruitment completed between March 2020 and May 2021. The primary outcome will be all-cause mortality at ≤30 days. Secondary outcomes will include mechanical ventilation, admission to intensive care or cardiovascular events at short-term follow-up (≤30 days) and all-cause mortality at longer-term follow-up (>1 month). Prespecified subgroup analyses will assess the effect of sex; age; comorbidities; smoking status; ethnicity; country of origin on all-cause mortality. A search of ClinicalTrials.gov has been performed, which will be followed by a formal search of trial registers, preprint servers, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials to identify RCTs that meet inclusion criteria. To date, a search of ClinicalTrials.gov identified 21 potentially eligible trials for this meta-analysis. We will request trial investigators/sponsors to contribute standardised grouped tabular outcome data.

Ethics And Dissemination: Ethics approval and informed consent will be the responsibility of the individual RCTs. Dissemination of results will occur by peer-reviewed publication. The results of our analysis can inform public health policy and clinical decision making regarding ACEi/ARB use in patients with COVID-19 on a global scale.
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http://dx.doi.org/10.1136/bmjopen-2020-043625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887864PMC
February 2021

Effects of testosterone treatment, with and without exercise training, on ambulatory blood pressure in middle-aged and older men.

Clin Endocrinol (Oxf) 2021 Feb 12. Epub 2021 Feb 12.

Medical School, University of Western Australia, Perth, WA, Australia.

Context: With age, testosterone (T) and physical activity levels often decline in parallel. The effect of combining T treatment and exercise training on ambulatory blood pressure (ABP) is unclear.

Objective: To assess T and exercise effects, alone and in combination, on ABP in men aged 50-70 years, waist circumference ≥ 95 cm and low-normal serum T (6-14 nmol/L), without organic hypogonadism.

Design: A 2 × 2 factorial randomised, placebo-controlled study.

Intervention: Randomization to daily transdermal AndroForte5 (Testosterone 5.0%w/v, 100 mg in 2 ml) cream (T), or matching placebo (P) (double-blind), and to supervised exercise (Ex) or no additional exercise (NEx), for 12 weeks.

Results: Average 24-h systolic blood pressure (SBP) increased with T treatment (testosterone*time, p = .035). Average 24-h SBP increased in T+Ex (T+Ex:+3.0 vs. P+NEx: -3.0 mmHg, p = .026) driven by day-time changes (T+Ex:+3.5 vs. P+NEx: -3.0 mmHg, p = .026). There was an effect of T for 24-h average diastolic blood pressure (DBP, testosterone*time, p = .044) driven by the decrease in P+Ex (P+Ex: -3.9 vs. T+NEx: -0.5 mmHg, p = .015). Night-time DBP was lower with exercise (P+Ex: -4.0 vs. P+NEx: +0.7 mmHg, p = .032). The effect of exercise to lower night-time DBP was not apparent in the presence of T (T+Ex: -0.4 vs. P+NEx: +0.7 mmHg, p > .05). Ex increased average 24-h pulse pressure (PP, exercise*time, p = .022), largely during daytime hours (exercise*time, p = .013).

Conclusions: There was a main effect of T to increase 24-h SBP, primarily seen when T was combined with Ex. Exercise alone decreased 24-h and night-time DBP; an effect attenuated by T. BP should be carefully assessed and monitored, when prescribing T treatment to middle-aged and older men, especially when combined with exercise training.
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http://dx.doi.org/10.1111/cen.14442DOI Listing
February 2021

Increased pulse wave velocity in patients with an orthostatic blood pressure rise independent of other cardiovascular risk factors.

J Hypertens 2021 Jan 19. Epub 2021 Jan 19.

Dobney Hypertension Centre, School of Medicine - Royal Perth Hospital Unit, Faculty of Medicine, Dentistry & Health Sciences, The University of Western Australia, Perth, Western Australia, Australia Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany Departments of Cardiology and Nephrology, Royal Perth Hospital, Perth, Western Australia Neurovascular Hypertension & Kidney Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.

Background: Positional changes in blood pressure (BP) have been shown to have effects on long-term outcomes. Although a BP drop with upright posture is frequently observed, an orthostatic rise in BP can also occur. Here, we aimed to investigate whether the phenotype of orthostatic hypertension is associated with more pronounced vascular hypertension-mediated organ damage (HMOD) and whether this is associated with other cardiovascular risk factors.

Methods: In a cohort of 200 patients referred to our tertiary hypertension clinic, we prospectively assessed unattended seated automated office BP and the response to 1 min of upright posture. The difference in BP after standing up was calculated and pulse wave velocity (PWV) was assessed as a marker of vascular HMOD. Routine clinical cardiovascular risk markers were also assessed. Regression models were used to assess the association between orthostatic BP changes and pulse wave velocity.

Results: Baseline characteristics and clinic cardiovascular risk factors were similar between orthostatic BP response groups. A U-shaped association was evident between PWV and orthostatic BP changes with elevated PWV in patients with either a fall or a rise in BP in response to upright posture. The regression models remained significant after adjusting for other cardiovascular risk factors, including 24 h ambulatory BP.

Conclusion: Both an orthostatic BP drop and rise were associated with elevated PWV. Although standing BP is commonly measured in elderly hypertensive patients to exclude significant orthostatic hypotension, this simple measurement may provide an additional independent risk factor for vascular HMOD at any age.
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http://dx.doi.org/10.1097/HJH.0000000000002787DOI Listing
January 2021

Retinal capillary rarefaction is associated with arterial and kidney damage in hypertension.

Sci Rep 2021 Jan 13;11(1):1001. Epub 2021 Jan 13.

Dobney Hypertension Centre, School of Medicine - Royal Perth Hospital Unit/Medical Research Foundation, University of Western Australia, Perth, Australia.

Microvascular disease and rarefaction are key pathological hallmarks of hypertension. The retina uniquely allows direct, non-invasive investigation of the microvasculature. Recently developed optical coherence tomography angiography now allows investigation of the fine retinal capillaries, which may provide a superior marker of overall vascular damage. This was a prospective cross-sectional study to collect retinal capillary density data on 300 normal eyes from 150 hypertensive adults, and to investigate possible associations with other organ damage markers. The average age of participants was 54 years and there was a greater proportion of males (85; 57%) than females. Multivariate, confounder adjusted linear regression showed that retinal capillary rarefaction in the parafovea was associated with increased pulse wave velocity (β = - 0.4, P = 0.04), log-albumin/creatinine ratio (β = - 0.71, P = 0.003), and with reduced estimated glomerular filtration rate (β = 0.04, P = 0.02). Comparable significant associations were also found for whole-image vascular-density, for foveal vascular-density significant associations were found with pulse wave velocity and estimated glomerular filtration rate only. Our results indicate that retinal capillary rarefaction is associated with arterial stiffness and impaired kidney function. Retinal capillary rarefaction may represent a useful and simple test to assess the integrated burden of hypertension on the microvasculature irrespective of current blood pressure levels.
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http://dx.doi.org/10.1038/s41598-020-79594-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806760PMC
January 2021

Microvascular changes at different stages of chronic kidney disease.

J Clin Hypertens (Greenwich) 2021 Feb 19;23(2):309-316. Epub 2020 Dec 19.

Dobney Hypertension Centre, School of Medicine - Royal Perth Hospital Unit / Medical Research Foundation, University of Western Australia, Perth, WA, Australia.

Patients with progressing chronic kidney disease (CKD) are more likely to experience cardio- and cerebrovascular events than progressing to end-stage renal disease. The authors explored whether retinal microvascular calibers differed with the degree of renal impairment and between the standard and extended optic disk and may serve as a simple additional tool for risk stratification in this highly vulnerable patient cohort. The authors analyzed central retinal arteriolar and venular equivalent calibers (CRAE, CRVE) at different retinal zones (zone B&C) using digital retinal imaging in hypertensive patients with stage 2 (n = 66) or stage 3 CKD (n = 30). Results were adjusted for age, sex, HbA1c, and 24-hour diastolic blood pressure. Mean eGFR was 77.7 ± 8.9 and 48.8 ± 7.9 ml/min/1.73 m for stage 2 and 3 CKD, respectively. CRAE and CRVE in zones B and C were significantly lower in patients with stage 3 CKD compared to patients with stage 2 CKD (CRAE-B:141.1 ± 21.4 vs. 130.5 ± 18.9 µm, p = .030; CRAE-C:137.4 ± 19.4 vs 129.2 ± 18.2 µm, p = .049; CRVE-B:220.8 ± 33.0 vs. 206.0 ± 28.4 µm, p = .004; and CRVE-C:215.9 ± 33.0 vs. 201.2 ± 25.1µm, p = .003). In patients with stage 2 CKD, CRAE-B was higher than CRAE-C (141.1 ± 21.4 vs. 137.4 ± 19.4µm, p < .001). In contrast, such a difference was not found in patients with stage 3 CKD. CRAE of both retinal zones correlated with eGFR for the entire cohort. In patients with stage 3 CKD, retinal narrowing is more pronounced compared to patients with stage 2 CKD. Whether the novel observation of difference in arteriolar caliber between zones B and C in stage 2 CKD could serve as an early marker of CKD progression warrants further investigation.
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http://dx.doi.org/10.1111/jch.14138DOI Listing
February 2021

Supine blood pressure-A clinically relevant determinant of vascular target organ damage in hypertensive patients.

J Clin Hypertens (Greenwich) 2021 Jan 3;23(1):44-52. Epub 2020 Dec 3.

Dobney Hypertension Centre, School of Medicine - Royal Perth Hospital Unit, Faculty of Medicine, Dentistry & Health Sciences, The University of Western Australia, Perth, WA, Australia.

Night-time blood pressure (BP) is an important predictor of cardiovascular outcomes. Its assessment, however, remains challenging due to limited accessibility to ambulatory BP devices in many settings, costs, and other factors. We hypothesized that BP measured in a supine position during daytime may perform similarly to night-time BP when modeling their association with vascular hypertension-mediated organ damage (HMOD). Data from 165 hypertensive patients were used who as part of their routine clinic workup had a series of standardized BP measurements including seated attended office, seated and supine unattended office, and ambulatory BP monitoring. HMOD was determined by assessment of kidney function and pulse wave velocity. Correlation analysis was carried out, and univariate and multivariate models were fitted to assess the extent of shared variance between the BP modalities and their individual and shared contribution to HMOD variables. Of all standard non-24-hour systolic BP assessments, supine systolic BP shared the highest degree of variance with systolic night-time BP. In univariate analysis, both systolic supine and night-time BP were strong determinants of HMOD variables. In multivariate models, supine BP outperformed night-time BP as the most significant determinant of HMOD. These findings indicate that supine BP may not only be a clinically useful surrogate for night-time BP when ambulatory BP monitoring is not available, but also highlights the possibility that unattended supine BP may be more closely related to HMOD than other BP measurement modalities, a proposition that requires further investigations in prospective studies.
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http://dx.doi.org/10.1111/jch.14114DOI Listing
January 2021

SGLT2 Inhibitor-Induced Sympathoexcitation in White Adipose Tissue: A Novel Mechanism for Beiging.

Biomedicines 2020 Nov 18;8(11). Epub 2020 Nov 18.

Dobney Hypertension Centre, School of Biomedical Science-Royal Perth Hospital Unit, University of Western Australia, Crawley, WA 6009, Australia.

Recent preclinical data show that sodium glucose cotransporter 2 (SGLT2) inhibitors are able to reduce weight gain and induce beiging in white adipose tissue (WAT). We have previously shown that in neurogenic hypertensive Schlager (BPH/2J) mice, treatment with the SGLT2 inhibitor, Dapagliflozin, reduced blood pressure and prevented weight gain. Here we show that chemical sympathetic denervation achieved by systemic administration of 6-hydroxy-dopamine (6-OHDA) reduces body weight and the heightened sympathetic nervous system (SNS) innervation in WAT. Furthermore, we demonstrate that 2 weeks of Dapagliflozin treatment increases SNS innervation in WAT of hypertensive mice. This increase is accompanied by a non-significant elevation in mRNA levels of the and genes, which are markers of beiging. No significant difference in the mRNA levels of the inflammatory mediators and were detected in WAT of Dapagliflozin treated mice. These findings suggest that SGLT-2 inhibitor-associated prevention of weight gain may be mediated, at least in part, by inducing the beiging of WAT.
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http://dx.doi.org/10.3390/biomedicines8110514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698773PMC
November 2020

Implementation, mechanisms of impact and key contextual factors involved in outcomes of the Modification of Diet, Exercise and Lifestyle (MODEL) randomised controlled trial in Australian adults: protocol for a mixed-method process evaluation.

BMJ Open 2020 11 11;10(11):e036395. Epub 2020 Nov 11.

School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.

Introduction: The Modification of Diet, Exercise and Lifestyle (MODEL) study aims to examine the impact of providing visualisation and pictorial representation of advanced structural vascular disease (abdominal aortic calcification), on 'healthful' improvements to diet and lifestyle. This paper reports the protocol for the process evaluation for the MODEL study.

Methods And Analysis: The overall aim of the process evaluation is to understand the processes that took place during participation in the MODEL study trial and which elements were effective or ineffective for influencing 'healthful' behavioural change, and possible ways of improvement to inform wider implementation strategies. A mixed-method approach will be employed with the use of structured questionnaires and semistructured in-depth interviews. All 200 participants enrolled in the trial will undertake the quantitative component of the study and maximum variation sampling will be used to select a subsample for the qualitative component. The sample size for the qualitative component will be determined based on analytical saturation. Interviews will be digitally recorded and transcribed verbatim. Qualitative data will be analysed thematically and reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines.

Ethics And Dissemination: The MODEL study process evaluation has received approval from Edith Cowan University Human Research Ethics Committee (Project Number: 20513 HODGSON). Written informed consent will be obtained from all participants before they are included in the study. The study results will be shared with the individuals and institutions associated with this study as well as academic audiences through peer-reviewed publication and probable presentation at conferences.

Trial Registration Number: ACTRN12618001087246.
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http://dx.doi.org/10.1136/bmjopen-2019-036395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661373PMC
November 2020

Modification of diet, exercise and lifestyle (MODEL) study: a randomised controlled trial protocol.

BMJ Open 2020 11 11;10(11):e036366. Epub 2020 Nov 11.

School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.

Introduction: Most cardiovascular disease (CVD)-related events could be prevented or substantially delayed with improved diet and lifestyle. Providing information on structural vascular disease may improve CVD risk factor management, but its impact on lifestyle change remains unclear. This study aims to determine whether providing visualisation and pictorial representation of structural vascular disease (abdominal aortic calcification (AAC)) can result in healthful diet and lifestyle change.

Methods And Analysis: This study, including men and women aged 60-80 years, is a 12-week, two-arm, multisite randomised controlled trial. At baseline, all participants will have AAC assessed from a lateral spine image captured using a bone densitometer. Participants will then be randomised to receive their AAC results at baseline (intervention group) or a usual care control group that will receive their results at 12 weeks. All participants will receive information about routinely assessed CVD risk factors and standardised (video) diet and lifestyle advice with three simple goals: (1) increase fruit and vegetable (FV) intake by at least one serve per day, (2) improve other aspects of the diet and (3) reduce sitting time and increase physical activity. Clinical assessments will be performed at baseline and 12 weeks.

Outcomes: The primary outcome is a change in serum carotenoid concentrations as an objective measure of FV intake. The study design, procedures and treatment of data will adhere to Standard Protocol Items for Randomized Trials guidelines.

Ethics And Dissemination: Ethics approval for this study has been granted by the Edith Cowan University and the Deakin University Human Research Ethics Committees (Project Numbers: 20513 HODGSON and 2019-220, respectively). Results of this study will be published in peer-reviewed academic journals and presented in scientific meetings and conferences. Information regarding consent, confidentiality, access to data, ancillary and post-trial care and dissemination policy has been disclosed in the participant information form.

Trial Registration Number: Australian New Zealand Clinical Trial Registry (ACTRN12618001087246).
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http://dx.doi.org/10.1136/bmjopen-2019-036366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661361PMC
November 2020

Vascular compression of the rostral ventrolateral medulla: a relevant indicator of sympathetically driven blood pressure variability?

J Hypertens 2020 12;38(12):2380-2381

Dobney Hypertension Centre, School of Medicine - Royal Perth Hospital Unit/Medical Research Foundation, University of Western Australia, Western Australia.

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http://dx.doi.org/10.1097/HJH.0000000000002646DOI Listing
December 2020

Interventional Approaches for Loin Pain Hematuria Syndrome and Kidney-Related Pain Syndromes.

Curr Hypertens Rep 2020 10 31;22(12):103. Epub 2020 Oct 31.

Dobney Hypertension Centre, School of Medicine - Royal Perth Hospital Unit, University of Western Australia, Level 3, MRF Building, Rear 50 Murray St, Perth, WA, 6000, Australia.

Purpose Of Review: Loin pain hematuria syndrome (LPHS) frequently presents with severe chronic pain that poses a clinical challenge. Current treatment approaches are mostly empirical and include a wide range of therapeutic strategies such as physical therapy, local and systemic analgesia, interventional and surgical approaches usually flanked by psycho-behavioral therapy, and other strategies. LPHS often impacts negatively on quality of life particularly in patients who are refractory to treatment.

Recent Findings: With recent advances in catheter-based treatment approaches and better understanding of the pathophysiology of LPHS, intraluminal renal denervation (RDN) has been proposed as a valuable treatment option for kidney-related pain syndromes. The present review provides a brief overview of the clinical challenges associated with LPHS, highlights recent insights into its underlying mechanisms, and summarizes currently available data on the use of RDN in the context of LPHS and kidney-related pain syndromes. Renal denervation via various approaches including surgical and catheter-based techniques has shown promise in alleviating kidney-related pain syndromes. Randomized controlled trials are now required to better define its role in the management of these conditions.
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http://dx.doi.org/10.1007/s11906-020-01110-9DOI Listing
October 2020

Delayed retinal vein recovery responses indicate both non-adaptation to stress as well as increased risk for stroke: the SABPA study.

Cardiovasc J Afr 2021 Jan-Feb 23;32(1):5-16. Epub 2020 Oct 26.

Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, South Africa.

Objectives: Low or high sympatho-adrenal-medullary axis (SAM) and hypothalamic-pituitary-adrenal axis (HPA) dysregulation reflect chronic stress. Retinal vessel dynamics may relate to SAM, HPA activity and stroke risk. Our objectives were therefore to assess the relationships between retinal vessel, SAM and HPA responses, and to determine stroke risk.

Methods: A prospective bi-ethnic gender cohort ( = 275, 45 ± 9 years) was included. Urine/serum/saliva samples for SAM [norepinephrine:creatinine ratio (u-NE)] and HPA [adrenocorticotrophic hormone (ACTH), cortisol] were obtained at baseline, three-year follow up and upon flicker light-induced provocation. Diastolic ocular perfusion pressure was measured as a marker of hypo-perfusion. Retinal arterial narrowing and venous widening calibres were quantified from digital images in the mydriatic eye. A validated stress and stroke risk score was applied.

Results: An interaction term was fitted for venous dilation in u-NE tertiles (p ≤ 0.05) and not in u-NE median/quartiles/quintiles. Independent of race or gender, tertile 1 (low u-NE) had a 112% increase in u-NE, decreases in cortisol, and no changes in ACTH over three years (positive feedback). Tertile 3 (high u-NE) contradictorily had decreases in u-NE and cortisol, and increases in ACTH (negative feedback). In tertile 1, reduced arterial dilation, and faster arterial vasoconstriction and narrowing were related to higher SAM activity and hypo-perfusion ( ≤ 0.05), whereas delayed venous dilation, recovery and widening were related to cortisol hypo-secretion ( ≤ 0.05). In tertile 1, delayed venous recovery responses predicted stress and stroke risk [odds ratio 4.8 (1.2-19.6); = 0.03]. These associations were not found in u-NE tertiles 2 and 3.

Conclusions: In response to low norepinephrine, a reflex increase in SAM activity occurred, enhancing arterial vasoconstriction and hypo-perfusion. Concomitant HPA dysregulation attenuated retinal vein vasoactivity and tone, reflecting delayed vein recovery responses and non-adaptation to stress. These constrained vein recovery responses are indicative of increased chronic stress and stroke risk.
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http://dx.doi.org/10.5830/CVJA-2020-031DOI Listing
October 2020

The role of selective imidazoline receptor agonists in modern hypertension management: an international real-world survey (STRAIGHT).

Curr Med Res Opin 2020 Dec 23;36(12):1939-1945. Epub 2020 Oct 23.

Hypertension in Africa Research Team, MRC Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa.

Background: Multiple pharmacologic strategies are currently available to lower blood pressure (BP). Renin-angiotensin system (RAS)-inhibitors, calcium channel blockers and diuretics are widely recommended as first line therapies. Sympathetic activation is an important contributor to BP elevation but remains unopposed or is even increased by some of these drug classes. Selective imidazoline receptor agonists (SIRAs) reduce increased central sympathetic outflow and are considered as add-on therapy in most guidelines. We conducted an international survey to evaluate contemporary hypertension management strategies in countries with high prescription rates of SIRAs to better understand the rationale and practical indications for their use in a real-world setting.

Methods: Physicians from seven countries (India, Jordan, Lebanon, Russia, Saudi Arabia, South Africa, United Arab Emirates) were asked to complete a web-based questionnaire and comment on clinical case scenarios to provide information on their current practice regarding antihypertension strategies, underlying rationale for their choices, and adherence to relevant guidelines.

Results: 281 physicians completed the questionnaire including mainly cardiologists (35%) and general practitioners (32%). 96% reported using European (60%) or local (56%) guidelines in their daily practices. The majority of responding physicians (83%) had knowledge of SIRAs and 70% prescribed SIRAs regularly typically as a third line antihypertensive strategy (63%). The preferred combination partners for SIRAs were RAS-inhibitors (72%).

Conclusions: Contemporary hypertension management varies between countries and therapeutic approaches in a real-world setting are not always in line with recommendations from available guidelines. In the countries selected for this survey prescription of SIRAs was common and appeared to be guided predominantly by considerations relating to the underlying pathophysiologic mechanism of sympathetic inhibition.
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http://dx.doi.org/10.1080/03007995.2020.1835852DOI Listing
December 2020

Nocturnal hypertension: a common phenotype in a tertiary clinical setting associated with increased arterial stiffness and central blood pressure.

J Hypertens 2021 Feb;39(2):250-258

Dobney Hypertension Centre, School of Medicine - Royal Perth Hospital Unit, University of Western Australia.

Objective: Although the detrimental effect of increased mean blood pressure (BP) is well established, the role of the dynamic and circadian features of BP is less well defined but may be similarly important. In this prospective analysis of hypertensive patients from a tertiary hospital hypertension clinic, we investigated whether the presence of night-time systolic hypertension is associated with more pronounced end-organ damage as assessed by measures of pulse wave analysis (PWA) and pulse wave velocity (PWV).

Methods: A cohort of 222 consecutive hypertensive patients underwent ambulatory blood pressure measurements, PWA, PWV testing and collection of routine clinical data. Group differences and group-effects of daytime and night-time hypertension on target organ damage and cardiovascular risk parameters were analysed.

Results: Nocturnal hypertension was evident in more than half of the study population. PWV, central systolic, mean arterial and pulse pressure were higher in patients with nocturnal hypertension. Stratification into four groups according to daytime and night-time hypertension status revealed group differences in all outcome parameters. Posthoc testing for individual group differences demonstrated significant differences between fully controlled individuals and the group with high daytime and night-time BP. In a regression analysis for independent effects of categorical night-time and daytime hypertension, nocturnal hypertension was a significant predictor for all PWA and PWV outcomes.

Conclusion: Nocturnal hypertension was a highly prevalent phenotype in this population and associated with increased central BP and more pronounced target organ damage as indicated by elevated PWV. Regression analysis confirmed the role of night-time hypertension as an independent explanatory variable for elevated PWV.
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http://dx.doi.org/10.1097/HJH.0000000000002620DOI Listing
February 2021

Reply.

J Hypertens 2020 11;38(11):2339-2340

CARIM - School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.

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http://dx.doi.org/10.1097/HJH.0000000000002612DOI Listing
November 2020

Sympathetic hyperactivity after coronary artery bypass graft surgery: an important player in the development of postoperative atrial fibrillation?

Europace 2021 Jan;23(1):158

Dobney Hypertension Centre, School of Medicine, Royal Perth Hospital Unit/Medical Research Foundation, University of Western Australia, Level 3, MRF Building, Rear 50 Murray St, Perth, WA 6000, Australia.

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http://dx.doi.org/10.1093/europace/euaa285DOI Listing
January 2021

Contribution of the Renal Nerves to Hypertension in a Rabbit Model of Chronic Kidney Disease.

Hypertension 2020 11 8;76(5):1470-1479. Epub 2020 Sep 8.

From the Neuropharmacology Laboratory (Y.S., S.L.B., C.G., K.L., K.L.J., G.A.H.), Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

Overactivity of the sympathetic nervous system and high blood pressure are implicated in the development and progression of chronic kidney disease (CKD) and independently predict cardiovascular events in end-stage renal disease. To assess the role of renal nerves, we determined whether renal denervation (RDN) altered the hypertension and sympathoexcitation associated with a rabbit model of CKD. The model involves glomerular layer lesioning and uninephrectomy, resulting in renal function reduced by one-third and diuresis. After 3-week CKD, blood pressure was 13±2 mm Hg higher than at baseline (<0.001), and compared with sham control rabbits, renal sympathetic nerve activity was 1.2±0.5 normalized units greater (=0.01). The depressor response to ganglion blockade was also +8.0±3 mm Hg greater, but total norepinephrine spillover was 8.7±3.7 ng/min lower (both <0.05). RDN CKD rabbits only increased blood pressure by 8.0±1.5 mm Hg. Renal sympathetic activity, the response to ganglion blockade and diuresis were similar to sham denervated rabbits (non-CKD). CKD rabbits had intact renal sympathetic baroreflex gain and range, as well as normal sympathetic responses to airjet stress. However, hypoxia-induced sympathoexcitation was reduced by -9±0.4 normalized units. RDN did not alter the sympathetic response to hypoxia or airjet stress. CKD increased oxidative stress markers Nox5 and MCP-1 (monocyte chemoattractant protein-1) in the kidney, but RDN had no effect on these measures. Thus, RDN is an effective treatment for hypertension in this model of CKD without further impairing renal function or altering the normal sympathetic reflex responses to various environmental stimuli.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15769DOI Listing
November 2020

May Measurement Month 2018: an analysis of blood pressure screening results from Australia.

Eur Heart J Suppl 2020 Aug 28;22(Suppl H):H17-H19. Epub 2020 Aug 28.

Dobney Hypertension Centre, School of Medicine - Royal Perth Hospital Unit, University of Western Australia, Level 3, MRF Building, Rear 50 Murray St, Perth, WA, 6000, Australia.

May Measurement Month (MMM), originally initiated as a temporary solution to address the lack of blood pressure (BP) screening programs worldwide, emerged as an effective annual campaign to increase the awareness of hypertension. MMM18, a cross-sectional survey of volunteers aged ≥18 years was carried out during May 2018 predominantly in capital cities across Australia following the standard MMM protocol. Blood pressure screening along with additional information including anthropometric data and responses to questionnaires on demographic, lifestyle, and environmental factors were collected from 3 352 individuals across Australia. After multiple imputation, 1 026 (30.6%) adult Australians had hypertension. Of the 2 936 individuals not on antihypertensive treatment, 610 (20.8%) were hypertensive, and 237 (57.1%) of the 416 individuals receiving antihypertensive treatment had uncontrolled BP. In line with MMM17 results and other previous surveys, MMM18 revealed that close to one-third of the screened population (30.6%) had hypertension, 57.1% of individuals treated with BP-lowering medication remained uncontrolled indicating suboptimal management of the condition in the majority of patients. Most importantly, only 49.0% of those with hypertension were aware of their elevated BP, highlighting lack of awareness of elevated BP in nearly half of the affected population. Elevated BP was directly associated with alcohol consumption, overweight, and obesity. Our findings demonstrate the need for (i) continued efforts to increase BP awareness in the population, (ii) optimization of BP management strategies, and (iii) tackling some of the major contributors to BP elevation, including alcohol consumption and obesity.
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http://dx.doi.org/10.1093/eurheartj/suaa018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455264PMC
August 2020

The Influence of Hypertensive Therapies on Circulating Factors: Clinical Implications for SCFAs, FGF21, TNFSF14 and TNF-α.

J Clin Med 2020 Aug 26;9(9). Epub 2020 Aug 26.

Dobney Hypertension Centre, School of Biomedical Science-Royal Perth Hospital Unit, University of Western Australia, Crawley, WA 6009, Australia.

Studying the role of circulatory factors in the pathogenesis of diseases has been key to the development of effective therapies. We sought to examine the effect of antihypertensive therapies on numerous circulatory factors including short chain fatty acids and growth factors in a human cohort. A subset of participants from an earlier study was characterized by their hypertensive and/or treatment status and separated into three groups: (i) normotensives; (ii) untreated hypertensive and (iii) treated hypertensive subjects. Circulating levels of short chain fatty acids, FGF21 and TNF superfamily members were measured as part of this study. Both F2-isoprostane and circulating lipid levels were reanalysed as part of this current study. We found that antihypertensive treatment increased butyrate levels and decreased acetate levels to levels similar to normotensives. We also found that antihypertensive treatments reduced levels of circulating FGF21, TNFSF14 and TNF-α. In conclusion, we identified several circulatory factors that are altered in hypertension.
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http://dx.doi.org/10.3390/jcm9092764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576485PMC
August 2020

Differential sympathetic response to lesion-induced chronic kidney disease in rabbits.

Kidney Int 2020 10 25;98(4):906-917. Epub 2020 Apr 25.

Neuropharmacology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Department of Pharmacology, Monash University, Melbourne, Victoria, Australia. Electronic address:

Chronic kidney disease (CKD) is associated with greater sympathetic nerve activity but it is unclear if this is a kidney-specific response or due to generalized stimulation of sympathetic nervous system activity. To determine this, we used a rabbit model of CKD in which quantitative comparisons with control rabbits could be made of kidney sympathetic nerve activity and whole-body norepinephrine spillover. Rabbits either had surgery to lesion 5/6 of the cortex of one kidney by electro-lesioning and two weeks later removal of the contralateral kidney, or sham lesioning and sham nephrectomy. After three weeks, the blood pressure was statistically significantly 20% higher in conscious rabbits with CKD compared to rabbits with a sham operation, but their heart rate was similar. Strikingly, kidney nerve activity was 37% greater than in controls, with greater burst height and frequency. Total norepinephrine spillover was statistically significantly lower by 34%, and kidney baroreflex curves were shifted to the right in rabbits with CKD. Plasma creatinine and urine output were elevated by 38% and 131%, respectively, and the glomerular filtration rate was 37% lower than in sham-operated animals (all statistically significant). Kidney gene expression of fibronectin, transforming growth factor-β, monocyte chemotactic protein1, Nox4 and Nox5 was two- to eight-fold greater in rabbits with CKD than in control rabbits. Overall, the glomerular layer lesioning model in conscious rabbits produced a moderate, stable degree of CKD characterized by elevated blood pressure and increased kidney sympathetic nerve activity. Thus, our findings, together with that of a reduction in total norepinephrine spillover, suggest that kidney denervation, rather than generalized sympatholytic treatments, may represent a preferable management for CKD associated hypertension.
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http://dx.doi.org/10.1016/j.kint.2020.03.039DOI Listing
October 2020

Cardiovascular disease and COVID-19: Australian and New Zealand consensus statement.

Med J Aust 2020 08 31;213(4):182-187. Epub 2020 Jul 31.

Royal North Shore Hospital, Sydney, NSW.

Introduction: The coronavirus 2019 disease (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pre-existing cardiovascular disease (CVD) increases the morbidity and mortality of COVID-19, and COVID-19 itself causes serious cardiac sequelae. Strategies to minimise the risk of viral transmission to health care workers and uninfected cardiac patients while prioritising high quality cardiac care are urgently needed. We conducted a rapid literature appraisal and review of key documents identified by the Cardiac Society of Australia and New Zealand Board and Council members, the Australian and New Zealand Society of Cardiac and Thoracic Surgeons, and key cardiology, surgical and public health opinion leaders.

Main Recommendations: Common acute cardiac manifestations of COVID-19 include left ventricular dysfunction, heart failure, arrhythmias and acute coronary syndromes. The presence of underlying CVD confers a five- to tenfold higher case fatality rate with COVID-19 disease. Special precautions are needed to avoid viral transmission to this population at risk. Adaptive health care delivery models and resource allocation are required throughout the health care system to address this need.

Changes In Management As A Result Of This Statement: Cardiovascular health services and cardiovascular health care providers need to recognise the increased risk of COVID-19 among CVD patients, upskill in the management of COVID-19 cardiac manifestations, and reorganise and innovate in service delivery models to meet demands. This consensus statement, endorsed by the Cardiac Society of Australia and New Zealand, the Australian and New Zealand Society of Cardiac and Thoracic Surgeons, the National Heart Foundation of Australia and the High Blood Pressure Research Council of Australia summarises important issues and proposes practical approaches to cardiovascular health care delivery to patients with and without SARS-CoV-2 infection.
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http://dx.doi.org/10.5694/mja2.50714DOI Listing
August 2020

Renal denervation as a synergistic tool for the treatment of polymorphic ventricular ectopic beats: A case report.

Medicine (Baltimore) 2020 Jul;99(29):e21098

Dobney Hypertension Centre, School of Medicine - Royal Perth Hospital Unit/Medical Research Foundation, University of Western Australia, Crawley, Australia.

Introduction: Ventricular ectopic beats (VEBs) are very common and often occur in hypertensive or obese individuals, as well as in patients presenting with either sleep apnea or structural cardiac disease. Sympathetic overactivity plays a crucial role in the development, continuation, and exacerbation of ventricular arrhythmias. Recent studies have reported the relevance of sympathetic activation in patients with ventricular arrhythmias and suggested a potential role for catheter-based renal denervation (RDN) in reducing the arrhythmic burden.

Patient Concerns: We describe a 38-year-old female symptomatic patient that at the time of presentation was complaining of fatigue in response to minor and medium efforts and not tolerating any physical activity, and episodes of tachycardia associated with dyspnoea, pre-syncope, and syncope.

Diagnosis: She had a high incidence of polymorphic VEBs on 24-hour-Holter monitoring who also presented with left ventricular (LV) hypertrophy for which she was treated with bisoprolol 10 mg/d. The 24-hour-Holter on bisoprolol at baseline showed sinus rhythm with an average heart rate of 92 bpm. There were 44,743 isolated VEBs. A total of 2538 nonsustained ventricular tachycardia events were registered. Her cardiac magnetic resonance imaging showed an increase in LV diastolic diameter and impairment of the right ventricle.

Interventions: The patient underwent endocardial ablation of the right ventricular outflow tract and the LV free lateral wall, and concomitantly underwent bilateral RDN.

Outcomes: Three months post-procedure, her 24-hour-Holter off medication demonstrated an average heart rate 72 bpm and a substantially reduced number of 2823 isolated monomorphic VEBs. Thus far, 18-months follow-up, she has been asymptomatic and doing physical exercises.

Conclusion: In our current patient, we used RDN as a synergistic method to attenuate the sympathetic overactivity, which is narrowly linked to VEBs appearance. Our case report highlighted that RDN may become a potential adjuvant treatment for VEBs in the future.
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http://dx.doi.org/10.1097/MD.0000000000021098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373520PMC
July 2020

Sodium glucose co-transporter 2 inhibition reduces succinate levels in diabetic mice.

World J Gastroenterol 2020 Jun;26(23):3225-3235

School of Biomedical Sciences, Dobney Hypertension Centre, Royal Perth Hospital Unit, University of Western Australia, Perth 6000, Australia.

Background: Type 1 diabetes (T1D) is associated with major chronic microvascular complications which contribute significantly to diabetes associated morbidity. The protein primarily responsible for glucose reabsorption in the kidney is sodium glucose co-transporter 2 (SGLT2). Presently, SGLT2 inhibitors are widely used in diabetic patients to improve blood glucose levels and prevent cardiovascular and renal complications. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may exert its protective effects alterations of the gut microbiome and tested this in a type 1 diabetic mouse model of diabetic retinopathy.

Aim: To determine whether the treatment with two independent SGLT2 inhibitors affects gut health in a type 1 diabetic mouse model.

Methods: The SGLT2 inhibitors empagliflozin or dapagliflozin (25 mg/kg/d) or vehicle dimethylsulfoxide (DMSO) were administered to C57BL/6J, Akita, Kimba and Akimba mice at 10 wk of age for 8 wk their drinking water. Serum samples were collected and the concentration of succinate and the short chain fatty acid (SCFA) butyric acid was measured using gas chromatography-mass spectrometry. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the concentration of insulin and leptin. Furthermore, the norepinephrine content in kidney tissue was determined using ELISA. Pancreatic tissue was collected and stained with haematoxylin and eosin and analysed using brightfield microscopy.

Results: Due to the presence of the Akita allele, both Akita and Akimba mice showed a reduction in insulin production compared to C57BL/6J and Kimba mice. Furthermore, Akita mice also showed the presence of apoptotic bodies within the pancreatic islets. The acinar cells of Akita and Akimba mice showed swelling which is indicative of acute injury or pancreatitis. After 8 wk of SGLT2 inhibition with dapagliflozin, the intermediate metabolite of gut metabolism known as succinate was significantly reduced in Akimba mice when compared to DMSO treated mice. In addition, empagliflozin resulted in suppression of succinate levels in Akimba mice. The beneficial SCFA known as butyric acid was significantly increased in Akita mice after treatment with dapagliflozin when compared to vehicle treated mice. The norepinephrine content in the kidney was significantly reduced with both dapagliflozin and empagliflozin therapy in Akita mice and was significantly reduced in Akimba mice treated with empagliflozin. In non-diabetic C57BL/6J and Kimba mice, serum leptin levels were significantly reduced after dapagliflozin therapy.

Conclusion: The inhibition of SGLT2 reduces the intermediate metabolite succinate, increases SCFA butyric acid levels and reduces norepinephrine content in mouse models of T1D. Collectively, these improvements may represent an important mechanism underlying the potential benefits of SGLT2 inhibition in T1D and its complications.
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http://dx.doi.org/10.3748/wjg.v26.i23.3225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336319PMC
June 2020

White Coat Hypertension-A Case for Assessing Vascular Age?

Am J Hypertens 2020 07;33(7):599-601

Iverson Health Innovation Research Institute, Swinburne University of Technology, Hawthorn, Australia.

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http://dx.doi.org/10.1093/ajh/hpaa061DOI Listing
July 2020