Oral free session: Evidence from clinical trials and big data
| Friday, November 29, 2024 |
| 2:10 PM - 3:10 PM |
| Blackwattle Bay Room 1 & 2, Level R |
Speaker
Assoc Prof Martin Schultz
Scientist
University of Tasmania
A hypertensive response to exercise relative-to-fitness in type 2 diabetes is associated with fatal and non-fatal cardiovascular events: results from the exercise stress test collaboration (EXERTION).
2:10 PM - 2:25 PMAbstract:
Background and aims. A hypertensive response to exercise (HRE) recorded during clinical exercise testing is independently associated with cardiovascular disease (CVD), but its interpretation may be clouded by functional capacity (fitness). Type-2 diabetes (T2DM) is associated with increased prevalence of HRE, but whether this confers additional CVD risk in T2DM when an HRE is considered relative-to-fitness has never been determined and was the aim of this study.
Methods. Clinical exercise test records were analysed from 12,742 people (aged 52.8±13.5 years, 58.9% male) who completed the Bruce treadmill protocol (stages 1-4, and peak) at 6 Australian hospitals. Records (including BP) were linked to administrative health datasets (hospital and emergency admissions, death register) to define clinical characteristics, classify T2DM (n=1,198) vs. no-T2DM (n=11,544) and determine the primary outcome of CVD events and death [n=1,349 events over 51 months (IQR 32-75 months) follow-up; analysis adjusted for age, sex and pre-exercise BP]. To consider exercise systolic BP relative to fitness, systolic BP was divided by peak metabolic equivalents (METs) and defined as HRE if values were ≥90th percentile for each exercise test stage. Competing risks regression compared events across strata of those with (+) and without (-) HRE and T2DM.
Results. Compared to HRE- and T2DM- (reference), there was a stepwise increase in risk of fatal and non-fatal CVD events across strata (HRE+ and T2DM-, HRE- and T2DM+, HRE+ and T2DM+), with those HRE+ and T2DM+ showing the highest risk at exercise test stage 1 (HR:2.89, 95%CI:2.29-3.65), stage 2 (HR:2.44, 95%CI:1.80-3.30), stage 3 (HR:2.11, 95%CI:1.34-3.32), and at peak exercise (HR:2.51, 95%CI:1.97-3.18). These associations were stronger than if HRE was not considered relative-to-fitness and persisted when the sample was restricted to those without a history of CVD at baseline (P<0.01 at stages 1-3 and peak).
Conclusions. When exercise systolic BP is considered relative-to-fitness, those with T2DM and an HRE are at high risk of CVD events and death compared to those without, or either condition alone. This suggests that clinicians supervising exercise testing should be alert to an HRE and impaired functional capacity in people with T2DM and optimise therapeutic interventions to lower CVD risk
Methods. Clinical exercise test records were analysed from 12,742 people (aged 52.8±13.5 years, 58.9% male) who completed the Bruce treadmill protocol (stages 1-4, and peak) at 6 Australian hospitals. Records (including BP) were linked to administrative health datasets (hospital and emergency admissions, death register) to define clinical characteristics, classify T2DM (n=1,198) vs. no-T2DM (n=11,544) and determine the primary outcome of CVD events and death [n=1,349 events over 51 months (IQR 32-75 months) follow-up; analysis adjusted for age, sex and pre-exercise BP]. To consider exercise systolic BP relative to fitness, systolic BP was divided by peak metabolic equivalents (METs) and defined as HRE if values were ≥90th percentile for each exercise test stage. Competing risks regression compared events across strata of those with (+) and without (-) HRE and T2DM.
Results. Compared to HRE- and T2DM- (reference), there was a stepwise increase in risk of fatal and non-fatal CVD events across strata (HRE+ and T2DM-, HRE- and T2DM+, HRE+ and T2DM+), with those HRE+ and T2DM+ showing the highest risk at exercise test stage 1 (HR:2.89, 95%CI:2.29-3.65), stage 2 (HR:2.44, 95%CI:1.80-3.30), stage 3 (HR:2.11, 95%CI:1.34-3.32), and at peak exercise (HR:2.51, 95%CI:1.97-3.18). These associations were stronger than if HRE was not considered relative-to-fitness and persisted when the sample was restricted to those without a history of CVD at baseline (P<0.01 at stages 1-3 and peak).
Conclusions. When exercise systolic BP is considered relative-to-fitness, those with T2DM and an HRE are at high risk of CVD events and death compared to those without, or either condition alone. This suggests that clinicians supervising exercise testing should be alert to an HRE and impaired functional capacity in people with T2DM and optimise therapeutic interventions to lower CVD risk
Biography
Associate Professor Martin Schultz is an accredited exercise physiologist (AEP) and principal research fellow at Menzies Institute for Medical Research. He leads a clinical research program with a focus on exercise and its role
in the identification of CVD risk, with a specific focus on exercise in the prevention, detection and treatment of high blood pressure..
Prof Markus Schlaich
Dobney Chair In Clinical Research
Royal Perth Hospital - University of Western Australia
Catheter-based renal denervation in patients with severe chronic kidney disease including dialysis: results from the Global SYMPLICITY Registry DEFINE
2:25 PM - 2:40 PMAbstract:
Background and Aims: There is paucity of data regarding the safety and efficacy of renal denervation (RDN) in patients with severe chronic kidney disease (CKD). This analysis from the Global SYMPLICITY Registry DEFINE assessed blood pressure (BP) and renal function in patients with uncontrolled hypertension treated with radiofrequency (RF) RDN.
Methods: BP and eGFR changes from baseline through 12 months were compared across three groups according to baseline eGFR (mL/min/1.73m2): eGFR <45, eGFR 45-59, and eGFR ≥60, adjusted for baseline BP. Furthermore, we assessed these changes among a subset of 36 patients with end-stage renal disease on dialysis.
Results: Baseline office SBP (OSBP) was similar between eGFR subgroups p=0.28), although ambulatory SBP (ASBP) was higher in those with eGFR<45 mL/min/1.73m2; (156 vs 153 vs 153mmHg; p=0.037). Patients in the <45 mL/min/1.73m2 eGFR subgroup were significantly older, were more likely to have ischemic heart disease, heart failure, or diabetes. At 12 months, each eGFR subgroup had clinically meaningful SBP drops from baseline for both office (-10.9 vs -10.5 vs -14.5mmHg) and ambulatory SBP (-5.7 vs -7.1 vs -8.5mmHg, respectively). At 12 months, eGFR remained stable in the two lower eGFR subgroups. Estimated GFR declined by 5.7±15.8 ml/min/1.73m2 in the eGFR ≥60 mL/min/1.73m2 subgroup. Patients on dialysis (72% on hemodialysis, 28% on peritoneal dialysis) had substantial drops in both OSBP and ASBP after RF RDN. Among the dialysis subgroup there were 2 deaths and 2 vascular complications not related to the procedure.
Conclusion: Patients with moderate to severe CKD including those requiring dialysis experienced significant OSBP and ASBP reductions from baseline through 12 months after RF RDN. The eGFR of patients with moderate to severe CKD remained stable through 12 months. There were no safety concerns. These findings suggest that RDN appears to be efficacious and safe for BP reduction in CKD, which needs to be confirmed in a prospective trial.
Methods: BP and eGFR changes from baseline through 12 months were compared across three groups according to baseline eGFR (mL/min/1.73m2): eGFR <45, eGFR 45-59, and eGFR ≥60, adjusted for baseline BP. Furthermore, we assessed these changes among a subset of 36 patients with end-stage renal disease on dialysis.
Results: Baseline office SBP (OSBP) was similar between eGFR subgroups p=0.28), although ambulatory SBP (ASBP) was higher in those with eGFR<45 mL/min/1.73m2; (156 vs 153 vs 153mmHg; p=0.037). Patients in the <45 mL/min/1.73m2 eGFR subgroup were significantly older, were more likely to have ischemic heart disease, heart failure, or diabetes. At 12 months, each eGFR subgroup had clinically meaningful SBP drops from baseline for both office (-10.9 vs -10.5 vs -14.5mmHg) and ambulatory SBP (-5.7 vs -7.1 vs -8.5mmHg, respectively). At 12 months, eGFR remained stable in the two lower eGFR subgroups. Estimated GFR declined by 5.7±15.8 ml/min/1.73m2 in the eGFR ≥60 mL/min/1.73m2 subgroup. Patients on dialysis (72% on hemodialysis, 28% on peritoneal dialysis) had substantial drops in both OSBP and ASBP after RF RDN. Among the dialysis subgroup there were 2 deaths and 2 vascular complications not related to the procedure.
Conclusion: Patients with moderate to severe CKD including those requiring dialysis experienced significant OSBP and ASBP reductions from baseline through 12 months after RF RDN. The eGFR of patients with moderate to severe CKD remained stable through 12 months. There were no safety concerns. These findings suggest that RDN appears to be efficacious and safe for BP reduction in CKD, which needs to be confirmed in a prospective trial.
Biography
Prof Markus Schlaich is a renal physician and a European Society of Hypertension (ESH) accredited hypertension specialist. Markus is Chair of Hypertension Australia and Co-Chair of the National Hypertension Taskforce. He has a strong background in clinical research with a focus on the pathophysiology of hypertension, the role of the sympathetic nervous system, involvement of the kidneys, and hypertension mediated organ damage. He has a specific interest in treatment modalities targeting the sympathetic nervous system and has been a pioneer of renal denervation and other interventional approaches. He has authored more than 475 articles in peer reviewed journals and serves on the Editorial Board of Hypertension, Journal of Hypertension, and Hypertension Research.
Dr Yaxing Meng
Baker Heart And Diabetes Institute
Relative contribution of blood pressure in childhood, young-, and mid-adulthood with carotid plaque presence and area
2:40 PM - 2:55 PMAbstract:
Background
Blood pressure (BP) is a key modifiable risk factor for atherosclerosis. How BP across different life-stages associates with carotid plaque in mid-adulthood remains unclear.
Aim
To investigate the relative contribution of BP in childhood, young adulthood, and mid-adulthood with carotid plaque presence and area in mid-adulthood.
Methods
The sample included 1889 participants from the Cardiovascular Risk in Young Finns Study who had their BP measured in childhood (6-18 years), young adulthood (21-39 years), and mid-adulthood (40-56 years). Outcomes were the carotid plaque presence and area in mid-adulthood. A Bayesian relevant life-course exposure model was used to estimate the life-course association of BP with carotid plaque and determine the relative contributions attributed to each life-stage.
Results
After a 38-year follow-up, 745 participants (39.4%) developed carotid plaques. Cumulative systolic BP (SBP) from childhood, young-, and mid-adulthood was associated with carotid plaque presence in mid-adulthood [for each 1-standard deviation increase (~12 mmHg), relative risk (95% credible intervals): 1.22 (1.10-1.36)], with SBP at each life-stage contributing approximately equally (relative weights: childhood, 39.4%; young adulthood, 37.9%; mid-adulthood, 22.7%). Cumulative SBP was associated with carotid plaque areas [β (95% credible intervals), 0.16 (0.08-0.23)] mm², with mid-adulthood SBP showing a higher contribution (relative weights: childhood, 12.5%; young adulthood, 25.0%; mid-adulthood, 62.5%). Similar patterns were observed for diastolic BP, pulse pressure, and mean arterial pressure.
Conclusions
BP at each life-stage contributes equally to carotid plaque presence, with mid-adulthood BP associated with a greater contribution to plaque area. These findings underscore the importance of maintaining normal BP throughout life to reduce atherosclerosis risk and suggest that intensive BP management in mid-adulthood may help slow plaque progression.
Blood pressure (BP) is a key modifiable risk factor for atherosclerosis. How BP across different life-stages associates with carotid plaque in mid-adulthood remains unclear.
Aim
To investigate the relative contribution of BP in childhood, young adulthood, and mid-adulthood with carotid plaque presence and area in mid-adulthood.
Methods
The sample included 1889 participants from the Cardiovascular Risk in Young Finns Study who had their BP measured in childhood (6-18 years), young adulthood (21-39 years), and mid-adulthood (40-56 years). Outcomes were the carotid plaque presence and area in mid-adulthood. A Bayesian relevant life-course exposure model was used to estimate the life-course association of BP with carotid plaque and determine the relative contributions attributed to each life-stage.
Results
After a 38-year follow-up, 745 participants (39.4%) developed carotid plaques. Cumulative systolic BP (SBP) from childhood, young-, and mid-adulthood was associated with carotid plaque presence in mid-adulthood [for each 1-standard deviation increase (~12 mmHg), relative risk (95% credible intervals): 1.22 (1.10-1.36)], with SBP at each life-stage contributing approximately equally (relative weights: childhood, 39.4%; young adulthood, 37.9%; mid-adulthood, 22.7%). Cumulative SBP was associated with carotid plaque areas [β (95% credible intervals), 0.16 (0.08-0.23)] mm², with mid-adulthood SBP showing a higher contribution (relative weights: childhood, 12.5%; young adulthood, 25.0%; mid-adulthood, 62.5%). Similar patterns were observed for diastolic BP, pulse pressure, and mean arterial pressure.
Conclusions
BP at each life-stage contributes equally to carotid plaque presence, with mid-adulthood BP associated with a greater contribution to plaque area. These findings underscore the importance of maintaining normal BP throughout life to reduce atherosclerosis risk and suggest that intensive BP management in mid-adulthood may help slow plaque progression.
Biography
Yaxing Meng is a research officer at the Baker Heart and Diabetes Institute, where he is actively engaged in cutting-edge cardiovascular research. Yaxing's research focuses on life-course epidemiology, specifically examining how blood pressure across different life stages affects cardiovascular health. Her ongoing efforts aim to impact public health strategies and enhance the prevention and management of blood pressure and cardiovascular disease.
Dr Matthew Snelson
Researcher
Monash University
Temporal microbial volatility remains unchanged with dietary fibre intervention and does not distinguish between responders and non-responders to fibre's blood pressure-lowering effects
2:55 PM - 3:10 PMAbstract:
Background and Aim:
Increased temporal variability in the gut microbiome is associated with intestinal conditions such as ulcerative colitis and Crohn's disease, leading to the recently established concept of microbial volatility. The gut microbiota influences hypertension, and high-fibre intake reduces blood pressure (BP). However, not all individuals exhibit a response to these fibre-based dietary changes, and it is unknown if dietary fibre intake impacts microbial volatility. Similarly, it is unknown whether the degree of stability of the gut microbiota consortium could be a determining factor in individual responsiveness to dietary interventions. Here, we aimed to identify: i) whether gut microbiome volatility differs between dietary fibre and placebo interventions, and ii) whether microbiome volatility discriminates between BP responders and non-responders to a high fibre intervention.
Methods:
Twenty treatment-naive participants with hypertension received either placebo or 40g per day of prebiotic acetylated and butyrylated high amylose maize starch (HAMSAB) supplementation for 3 weeks in a phase II randomized cross-over double-blind placebo-controlled trial. Blood pressure was monitored at baseline and each endpoint by 24-hour ambulatory BP monitoring, with those experiencing a reduction between timepoints of ≥ 2 mmHg classified as responders. Baseline stool samples were collected, and the V4 region of the 16S gene was sequenced. Taxonomy was assigned by reference to the SILVA database. Microbial volatility between timepoints (e.g. pre- and post-intervention) was calculated as the Euclidian distance of centered log-ratio transformed genera counts (Aitchison distance).
Results:
No difference was observed in microbial volatility between individuals when they received the dietary fibre intervention or the placebo (21.5 ± 5.5 vs 20.5 ± 7.7, p = 0.51). There was no significant difference between microbial volatility on the dietary intervention between responders and non-responders (21.8 ± 4.9 vs 20.9 ± 7.2, p = 0.84). There was no association between the change in BP during intervention and microbial volatility during intervention (r2 = -0.09, p = 0.72).
Conclusion:
These data suggest that temporal volatility of the gut microbiota does not change with fibre intake or contribute to the BP response to dietary fibre intervention trials in people with hypertension.
Increased temporal variability in the gut microbiome is associated with intestinal conditions such as ulcerative colitis and Crohn's disease, leading to the recently established concept of microbial volatility. The gut microbiota influences hypertension, and high-fibre intake reduces blood pressure (BP). However, not all individuals exhibit a response to these fibre-based dietary changes, and it is unknown if dietary fibre intake impacts microbial volatility. Similarly, it is unknown whether the degree of stability of the gut microbiota consortium could be a determining factor in individual responsiveness to dietary interventions. Here, we aimed to identify: i) whether gut microbiome volatility differs between dietary fibre and placebo interventions, and ii) whether microbiome volatility discriminates between BP responders and non-responders to a high fibre intervention.
Methods:
Twenty treatment-naive participants with hypertension received either placebo or 40g per day of prebiotic acetylated and butyrylated high amylose maize starch (HAMSAB) supplementation for 3 weeks in a phase II randomized cross-over double-blind placebo-controlled trial. Blood pressure was monitored at baseline and each endpoint by 24-hour ambulatory BP monitoring, with those experiencing a reduction between timepoints of ≥ 2 mmHg classified as responders. Baseline stool samples were collected, and the V4 region of the 16S gene was sequenced. Taxonomy was assigned by reference to the SILVA database. Microbial volatility between timepoints (e.g. pre- and post-intervention) was calculated as the Euclidian distance of centered log-ratio transformed genera counts (Aitchison distance).
Results:
No difference was observed in microbial volatility between individuals when they received the dietary fibre intervention or the placebo (21.5 ± 5.5 vs 20.5 ± 7.7, p = 0.51). There was no significant difference between microbial volatility on the dietary intervention between responders and non-responders (21.8 ± 4.9 vs 20.9 ± 7.2, p = 0.84). There was no association between the change in BP during intervention and microbial volatility during intervention (r2 = -0.09, p = 0.72).
Conclusion:
These data suggest that temporal volatility of the gut microbiota does not change with fibre intake or contribute to the BP response to dietary fibre intervention trials in people with hypertension.
Biography
Dr. Matthew Snelson an advanced Accredited Practising Dietitian and a Heart Foundation Postdoctoral Fellow in the Hypertension Research Laboratory at Monash University, where he is the group leader of the Gut Permeability research theme. His research investigates the role of diet in altering hypertension through the modulation of the gut microbiota and intestinal homeostasis. He is the immediate past president of the Australasian Human Microbiome Research Network.
