Publications by authors named "Bruce Neal"

402 Publications

Heart Failure Therapies for the Prevention of HER2-Monoclonal Antibody-Mediated Cardiotoxicity: A Systematic Review and Meta-Analysis of Randomized Trials.

Cancers (Basel) 2021 Nov 3;13(21). Epub 2021 Nov 3.

Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.

Monoclonal antibodies including trastuzumab, pertuzumab, and antibody-drug conjugates, form the backbone of HER2-positive breast cancer therapy. Unfortunately, an important adverse effect of these agents is cardiotoxicity, occurring in approximately 10% of patients. There is increasing published data regarding prevention strategies for cardiotoxicity, though seldom used in clinical practice. We performed a systematic review and meta-analysis of randomized-controlled trials to evaluate pharmacotherapy for the prevention of monoclonal HER2-directed antibody-induced cardiotoxicity in patients with breast cancer. Online databases were queried from their inception until October 2021. Effects were determined by calculating risk ratios (RRs) and 95% confidence intervals (CI) or mean differences (MD) using random-effects models. We identified five eligible trials. In the three trials ( = 952) reporting data on the primary outcome of cardiotoxicity, there was no clear effect for patients assigned active treatment compared to control (RR = 0.90, 95% CI 0.63 to 1.29, = 0.57). Effects were similar for ACE-I/ARB and beta-blockers ( homogeneity = 0.50). Active treatment reduced the risk of HER2 therapy interruptions (RR = 0.57, 95% CI 0.43 to 0.77, < 0.001) with similar findings for ACE-I/ARB and beta-blockers ( homogeneity = 0.97). Prophylactic treatment with ACE-I/ARB or beta-blocker therapy may be of value for cardio-protection in patients with breast cancer prescribed monoclonal antibodies. Further, adequately powered randomized trials are required to define the role of routine prophylactic treatment in this patient group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13215527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583665PMC
November 2021

Estimating the potential impact of the Australian government's reformulation targets on household sugar purchases.

Int J Behav Nutr Phys Act 2021 10 28;18(1):138. Epub 2021 Oct 28.

Faculty of Medicine, The George Institute for Global Health, UNSW Sydney, Level 5, 1 King St, Newtown, Australia.

Background: Countries around the world are putting in place sugar reformulation targets for packaged foods to reduce excess sugar consumption. The Australian government released its voluntary sugar reformulation targets for nine food categories in 2020. We estimated the potential impact of these targets on household sugar purchases and examined differences by income. For comparison, we also modelled the potential impact of the UK sugar reduction targets on per capita sugar purchases as the UK has one of the most comprehensive sugar reduction strategies in the world.

Methods: Grocery purchase data from a nationally representative consumer panel (n=7,188) in Australia was linked with a large database (FoodSwitch) with product-specific sugar content information for packaged foods (n=25,261); both datasets were collected in 2018. Potential reductions in per capita sugar purchases were calculated overall and by food category. Differences in sugar reduction across income level were assessed by analysis of variance.

Results: In 2018, the total sugar acquired from packaged food and beverage purchases consumed at-home was 56.1 g/day per capita. Australia's voluntary reformulation targets for sugar covered 2,471/25,261 (9.8%) unique products in the FoodSwitch dataset. Under the scenario that all food companies adhered to the voluntary targets, sugar purchases were estimated to be reduced by 0.9 g/day per capita, which represents a 1.5% reduction in sugar purchased from packaged foods. However, if Australia adopted the UK targets, over twice as many products would be covered (n=4,667), and this would result in a more than four times greater reduction in sugar purchases (4.1 g/day per capita). It was also estimated that if all food companies complied with Australia's voluntary sugar targets, reductions to sugar would be slightly greater in low-income households compared with high-income households by 0.3 g/day (95%CI 0.2 - 0.4 g/day, p<0.001).

Conclusions: Sugar-reduction policies have the potential to substantially reduce population sugar consumption and may help to reduce health inequalities related to excess sugar consumption. However, the current reformulation targets in Australia are estimated to achieve only a small reduction to sugar intakes, particularly in comparison to the UK's sugar reduction program.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12966-021-01208-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555094PMC
October 2021

The estimated health impact of sodium reduction through food reformulation in Australia: A modeling study.

PLoS Med 2021 Oct 26;18(10):e1003806. Epub 2021 Oct 26.

The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia.

Background: The Australian Government recently established sodium targets for packaged foods to encourage voluntary reformulation to reduce population sodium consumption and related diseases. We modeled the health impact of Australia's sodium reformulation targets and additional likely health gains if more ambitious, yet feasible sodium targets had been adopted instead.

Methods And Findings: Using comparative risk assessment models, we estimated the averted deaths, incidence, and disability-adjusted life years (DALYs) from cardiovascular disease (CVD), chronic kidney disease (CKD) and stomach cancer after implementation of (a) Australia's sodium targets (overall and by individual companies); (b) United Kingdom's targets (that covers more product categories); and (c) an optimistic scenario (sales-weighted 25th percentile sodium content for each food category included in the UK program). We used nationally representative data to estimate pre- and post-intervention sodium intake, and other key data sources from the Global Burden of Disease study. Full compliance with the Australian government's sodium targets could prevent approximately 510 deaths/year (95% UI, 335 to 757), corresponding to about 1% of CVD, CKD, and stomach cancer deaths, and prevent some 1,920 (1,274 to 2,600) new cases and 7,240 (5,138 to 10,008) DALYs/year attributable to these diseases. Over half (59%) of deaths prevented is attributed to reformulation by 5 market-dominant companies. Compliance with the UK and optimistic scenario could avert approximately an additional 660 (207 to 1,227) and 1,070 (511 to 1,856) deaths/year, respectively, compared to Australia's targets. The main limitation of this study (like other modeling studies) is that it does not prove that sodium reformulation programs will prevent deaths and disease events; rather, it provides the best quantitative estimates and the corresponding uncertainty of the potential effect of the different programs to guide the design of policies.

Conclusions: There is significant potential to strengthen Australia's sodium reformulation targets to improve its health impact. Promoting compliance by market-dominant food companies will be critical to achieving the potential health gains.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pmed.1003806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547659PMC
October 2021

The Role of Sodium Glucose Cotransporter-2 Inhibitors in Atherosclerotic Cardiovascular Disease: A Narrative Review of Potential Mechanisms.

Cells 2021 10 9;10(10). Epub 2021 Oct 9.

The George Institute for Global Health, University of New South Wales, Sydney, NSW 2042, Australia.

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of medication with broad cardiovascular benefits in those with type 2 diabetes, chronic kidney disease, and heart failure. These include reductions in major adverse cardiac events and cardiovascular death. The mechanisms that underlie their benefits in atherosclerotic cardiovascular disease (ASCVD) are not well understood, but they extend beyond glucose lowering. This narrative review summarises the ASCVD benefits of SGLT2 inhibitors seen in large human outcome trials, as well as the mechanisms of action explored in rodent and small human studies. Potential pathways include favourable alterations in lipid metabolism, inflammation, and endothelial function. These all require further investigation in large human clinical trials with mechanistic endpoints, to further elucidate the disease modifying benefits of this drug class and those who will benefit most from it.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cells10102699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534746PMC
October 2021

Barriers and Facilitators to Implementing Reduced-Sodium Salts as a Population-Level Intervention: A Qualitative Study.

Nutrients 2021 Sep 17;13(9). Epub 2021 Sep 17.

The George Institute for Global Health, University of New South Wales, Sydney, NSW 2050, Australia.

Widespread use of reduced-sodium salts can potentially lower excessive population-level dietary sodium intake. This study aimed to identify key barriers and facilitators to implementing reduced-sodium salt as a population level intervention. Semi-structured interviews were conducted with key informants from academia, the salt manufacturing industry, and government. We used the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework to inform our interview guides and data analysis. Eighteen key informants from nine countries across five World Health Organization regions participated in the study from January 2020 to July 2020. Participants were concerned about the lack of robust evidence on safety for specific populations such as those with renal impairment. Taste and price compared to regular salt and an understanding of the potential health benefits of reduced-sodium salt were identified as critical factors influencing the adoption of reduced-sodium salts. Higher production costs, low profit return, and reduced market demand for reduced-sodium salts were key barriers for industry in implementation. Participants provided recommendations as potential strategies to enhance the uptake. There are presently substantial barriers to the widespread use of reduced-sodium salt but there are also clear opportunities to take actions that would increase uptake.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13093225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471368PMC
September 2021

Initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy in patients with hypertension (QUARTET): a phase 3, randomised, double-blind, active-controlled trial.

Lancet 2021 09 29;398(10305):1043-1052. Epub 2021 Aug 29.

The George Institute for Global Health, UNSW, Sydney, NSW, Australia.

Background: Treatment inertia is a recognised barrier to blood pressure control, and simpler, more effective treatment strategies are needed. We hypothesised that a hypertension management strategy starting with a single pill containing ultra-low-dose quadruple combination therapy would be more effective than a strategy of starting with monotherapy.

Methods: QUARTET was a multicentre, double-blind, parallel-group, randomised, phase 3 trial among Australian adults (≥18 years) with hypertension, who were untreated or receiving monotherapy. Participants were randomly assigned to either treatment, that started with the quadpill (containing irbesartan at 37·5 mg, amlodipine at 1·25 mg, indapamide at 0·625 mg, and bisoprolol at 2·5 mg) or an indistinguishable monotherapy control (irbesartan 150 mg). If blood pressure was not at target, additional medications could be added in both groups, starting with amlodipine at 5 mg. Participants were randomly assigned using an online central randomisation service. There was a 1:1 allocation, stratified by site. Allocation was masked to all participants and study team members (including investigators and those assessing outcomes) except the manufacturer of the investigational product and one unmasked statistician. The primary outcome was difference in unattended office systolic blood pressure at 12 weeks. Secondary outcomes included blood pressure control (standard office blood pressure <140/90 mm Hg), safety, and tolerability. A subgroup continued randomly assigned allocation to 12 months to assess long-term effects. Analyses were per intention to treat. This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry, ACTRN12616001144404, and is now complete.

Findings: From June 8, 2017, to Aug 31, 2020, 591 participants were recruited, with 743 assessed for eligibility, 152 ineligible or declined, 300 participants randomly assigned to intervention of initial quadpill treatment, and 291 to control of initial standard dose monotherapy treatment. The mean age of the 591 participants was 59 years (SD 12); 356 (60%) were male and 235 (40%) were female; 483 (82%) were White, 70 (12%) were Asian, and 38 (6%) reported as other ethnicity; and baseline mean unattended office blood pressure was 141 mm Hg (SD 13)/85 mm Hg (SD 10). By 12 weeks, 44 (15%) of 300 participants had additional blood pressure medications in the intervention group compared with 115 (40%) of 291 participants in the control group. Systolic blood pressure was lower by 6·9 mm Hg (95% CI 4·9-8·9; p<0·0001) and blood pressure control rates were higher in the intervention group (76%) versus control group (58%; relative risk [RR] 1·30, 95% CI 1·15-1·47; p<0·0001). There was no difference in adverse event-related treatment withdrawals at 12 weeks (intervention 4·0% vs control 2·4%; p=0·27). Among the 417 patients who continued, uptitration occurred more frequently among control participants than intervention participants (p<0·0001). However, at 52 weeks mean unattended systolic blood pressure remained lower by 7·7 mm Hg (95% CI 5·2-10·3) and blood pressure control rates higher in the intervention group (81%) versus control group (62%; RR 1·32, 95% CI 1·16-1·50). In all randomly assigned participants up to 12 weeks, there were seven (3%) serious adverse events in the intervention group and three (1%) serious adverse events in the control group.

Interpretation: A strategy with early treatment of a fixed-dose quadruple quarter-dose combination achieved and maintained greater blood pressure lowering compared with the common strategy of starting monotherapy. This trial demonstrated the efficacy, tolerability, and simplicity of a quadpill-based strategy.

Funding: National Health and Medical Research Council, Australia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(21)01922-XDOI Listing
September 2021

Effect of Salt Substitution on Cardiovascular Events and Death.

N Engl J Med 2021 09 29;385(12):1067-1077. Epub 2021 Aug 29.

From the George Institute for Global Health (B.N., M.T., L.H., Y.L., X.Y., J.Y., K.-C.L., G.L.D.T., S. Stepien, S. Shan) and the Centre for Big Data Research in Health (S.-A.P.), University of New South Wales, and George Clinical (N.L.) - all in Sydney; the School of Public Health (B.N., K.-C.L., P.E.), the U.K. Dementia Research Institute (P.E.), the British Heart Foundation Centre for Research Excellence (P.E.), and the NIHR Imperial Biomedical Research Centre (P.E.), Imperial College London, Health Data Research (P.E.), the NIHR Health Protection Research Unit in Chemical and Radiation Threats and Hazards (P.E.), and the Medical Research Council Centre for Environment and Health (P.E.) - all in London; Peking University Clinical Research Center, Peking University (Y.W.), the George Institute for Global Health at Peking University Health Science Center (Y.W., M.T., Z.H., X.Z., L.L.Y.), and the Department of Cardiology, Peking University Third Hospital (J.Y.), Beijing, the School of Public Health, Changzhi Medical College, Changzhi (X.F., Z.L., P.D.), the School of Public Health, Xi'an Jiaotong University, Xi'an (R.Z., Y.Y.), the School of Public Health and Management, Ningxia Medical University, Yinchuan (Y. Zhang, Y. Zhao, F.W.), the Department of Evidence-Based Medicine, First Hospital of China Medical University, Shenyang (J. Shi, B.Z., B.M.), the Department of Noncommunicable Disease Prevention and Control, Center for Disease Control of Hebei Province, Shijiazhuang (J.Z., J. Sun, W.S.), the School of Public Health, Harbin Medical University, Harbin (M.T.), the Global Health Research Center, Duke Kunshan University, Kunshan (L.L.Y.), and the School of Health Sciences, Wuhan University, Wuhan (L.L.Y.) - all in China; and the Feinberg School of Medicine, Northwestern University, Chicago (D.L.).

Background: Salt substitutes with reduced sodium levels and increased potassium levels have been shown to lower blood pressure, but their effects on cardiovascular and safety outcomes are uncertain.

Methods: We conducted an open-label, cluster-randomized trial involving persons from 600 villages in rural China. The participants had a history of stroke or were 60 years of age or older and had high blood pressure. The villages were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (75% sodium chloride and 25% potassium chloride by mass), or to the control group, in which the participants continued to use regular salt (100% sodium chloride). The primary outcome was stroke, the secondary outcomes were major adverse cardiovascular events and death from any cause, and the safety outcome was clinical hyperkalemia.

Results: A total of 20,995 persons were enrolled in the trial. The mean age of the participants was 65.4 years, and 49.5% were female, 72.6% had a history of stroke, and 88.4% a history of hypertension. The mean duration of follow-up was 4.74 years. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1000 person-years; rate ratio, 0.86; 95% confidence interval [CI], 0.77 to 0.96; P = 0.006), as were the rates of major cardiovascular events (49.09 events vs. 56.29 events per 1000 person-years; rate ratio, 0.87; 95% CI, 0.80 to 0.94; P<0.001) and death (39.28 events vs. 44.61 events per 1000 person-years; rate ratio, 0.88; 95% CI, 0.82 to 0.95; P<0.001). The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1000 person-years; rate ratio, 1.04; 95% CI, 0.80 to 1.37; P = 0.76).

Conclusions: Among persons who had a history of stroke or were 60 years of age or older and had high blood pressure, the rates of stroke, major cardiovascular events, and death from any cause were lower with the salt substitute than with regular salt. (Funded by the National Health and Medical Research Council of Australia; SSaSS ClinicalTrials.gov number, NCT02092090.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa2105675DOI Listing
September 2021

Effects of canagliflozin compared with placebo on major adverse cardiovascular and kidney events in patient groups with different baseline levels of HbA, disease duration and treatment intensity: results from the CANVAS Program.

Diabetologia 2021 Nov 26;64(11):2402-2414. Epub 2021 Aug 26.

The George Institute for Global Health, UNSW, Sydney, NSW, Australia.

Aims/hypothesis: Type 2 diabetes mellitus can manifest over a broad clinical range, although there is no clear consensus on the categorisation of disease complexity. We assessed the effects of canagliflozin, compared with placebo, on cardiovascular and kidney outcomes in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program over a range of type 2 diabetes mellitus complexity, defined separately by baseline intensity of treatment, duration of diabetes and glycaemic control.

Methods: We performed a post hoc analysis of the effects of canagliflozin on major adverse cardiovascular events (MACE) according to baseline glucose-lowering treatments (0 or 1, 2 or 3+ non-insulin glucose-lowering treatments, or insulin-based treatment), duration of diabetes (<10, 10 to 16, >16 years) and HbA (≤53.0 mmol/mol [<7.0%], >53.0 to 58.5 mmol/mol [>7.0% to 7.5%], >58.5 to 63.9 mmol/mol [>7.5 to 8.0%], >63.9 to 69.4 mmol/mol [8.0% to 8.5%], >69.4 to 74.9 mmol/mol [>8.5 to 9.0%] or >74.9 mmol/mol [>9.0%]). We analysed additional secondary endpoints for cardiovascular and kidney outcomes, including a combined kidney outcome of sustained 40% decline in eGFR, end-stage kidney disease or death due to kidney disease. We used Cox regression analyses and compared the constancy of HRs across subgroups by fitting an interaction term (p value for significance <0.05).

Results: At study initiation, 5095 (50%) CANVAS Program participants were treated with insulin, 2100 (21%) had an HbA > 74.9 mmol/mol (9.0%) and the median duration of diabetes was 12.6 years (interquartile interval 8.0-18 years). Canagliflozin reduced MACE (HR 0.86 [95% CI 0.75, 0.97]) with no evidence that the benefit differed between subgroups defined by the number of glucose-lowering treatments, the duration of diabetes or baseline HbA (all p-heterogeneity >0.17). Canagliflozin reduced MACE in participants receiving insulin with no evidence that the benefit differed from other participants in the trial (HR 0.85 [95% CI 0.72, 1.00]). Similar results were observed for other cardiovascular outcomes and for the combined kidney outcome (HR for combined kidney outcome 0.60 [95% CI 0.47, 0.77]), with all p-heterogeneity >0.37.

Conclusions/interpretation: In people with type 2 diabetes mellitus at high cardiovascular risk, there was no evidence that cardiovascular and renal protection with canagliflozin differed across subgroups defined by baseline treatment intensity, duration of diabetes or HbA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00125-021-05524-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494676PMC
November 2021

The Contribution of Major Food Categories and Companies to Household Purchases of Added Sugar in Australia.

J Acad Nutr Diet 2021 Aug 20. Epub 2021 Aug 20.

Background: The Australian Government will soon be releasing a series of sugar reformulation targets for packaged foods.

Objective: To estimate the amount of added sugar purchased from packaged food and beverages and the relative contribution that food categories and food companies made to these purchases in 2018. The secondary objective was to examine differences in purchases of added sugar across income levels.

Design: Cross-sectional study.

Participants/setting: We used 1 year of grocery purchase data from a nationally representative panel of Australian households (the NielsenIQ Homescan panel), combined with a packaged food and beverage database (FoodSwitch).

Main Outcome Measures: Added sugar purchases (grams per day per capita), purchase-weighted added sugar content (grams per 100 g) and total weight of products (with added sugar) purchased (grams per day per capita).

Statistical Analyses Performed: Food categories and food companies were ranked according to their contribution to added sugar purchases. Differences in added sugar purchases by income levels were assessed by 1-factor analysis of variance.

Results: Added sugar information was available from 7188 households and across 26,291 unique foods and beverages. On average, the amount of added sugar acquired from packaged foods and beverages was (mean ± SE) 35.9 ± 0.01 g/d per capita. Low-income households purchased 11.0 g/d (95% CI: 10.9-11.0 g/d, P < .001) more added sugar from packaged products than high-income households per capita. The top 10 food categories accounted for 82.2% of added sugar purchased, largely due to purchases of chocolate and sweets, soft drinks, and ice cream and edible ices. Out of 994 food companies, the top 10 companies contributed to 62.1% of added sugar purchases.

Conclusions: The Australian Government can strengthen their proposed sugar reduction program by adding further category-specific targets, prioritizing engagement with key food companies and considering a broader range of policies to reduce added sugar intakes across the Australian population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jand.2021.06.013DOI Listing
August 2021

Effects of canagliflozin on serum potassium in people with diabetes and chronic kidney disease: the CREDENCE trial.

Eur Heart J 2021 Aug 23. Epub 2021 Aug 23.

Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, PO Box 30001, 9700 AD Groningen, the Netherlands.

Aims: Hyperkalaemia is a common complication of type 2 diabetes mellitus (T2DM) and limits the optimal use of agents that block the renin-angiotensin-aldosterone system, particularly in patients with chronic kidney disease (CKD). In patients with CKD, sodium‒glucose cotransporter 2 (SGLT2) inhibitors provide cardiorenal protection, but whether they affect the risk of hyperkalaemia remains uncertain.

Methods And Results: The CREDENCE trial randomized 4401 participants with T2DM and CKD to the SGLT2 inhibitor canagliflozin or matching placebo. In this post hoc analysis using an intention-to-treat approach, we assessed the effect of canagliflozin on a composite outcome of time to either investigator-reported hyperkalaemia or the initiation of potassium binders. We also analysed effects on central laboratory-determined hyper- and hypokalaemia (serum potassium ≥6.0 and <3.5 mmol/L, respectively) and change in serum potassium. At baseline, the mean serum potassium in canagliflozin and placebo arms was 4.5 mmol/L; 4395 (99.9%) participants were receiving renin-angiotensin system blockade. The incidence of investigator-reported hyperkalaemia or initiation of potassium binders was lower with canagliflozin than with placebo [occurring in 32.7 vs. 41.9 participants per 1000 patient-years; hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.64-0.95, P = 0.014]. Canagliflozin similarly reduced the incidence of laboratory-determined hyperkalaemia (HR 0.77, 95% CI 0.61-0.98, P = 0.031), with no effect on the risk of hypokalaemia (HR 0.92, 95% CI 0.71-1.20, P = 0.53). The mean serum potassium over time with canagliflozin was similar to that of placebo.

Conclusion: Among patients treated with renin-angiotensin-aldosterone system inhibitors, SGLT2 inhibition with canagliflozin may reduce the risk of hyperkalaemia in people with T2DM and CKD without increasing the risk of hypokalaemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehab497DOI Listing
August 2021

Effects of the SGLT2 inhibitor canagliflozin on plasma biomarkers TNFR-1, TNFR-2 and KIM-1 in the CANVAS trial.

Diabetologia 2021 Oct 20;64(10):2147-2158. Epub 2021 Aug 20.

Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, the Netherlands.

Aims/hypothesis: Higher plasma concentrations of tumour necrosis factor receptor (TNFR)-1, TNFR-2 and kidney injury molecule-1 (KIM-1) have been found to be associated with higher risk of kidney failure in individuals with type 2 diabetes in previous studies. Whether drugs can reduce these biomarkers is not well established. We measured these biomarkers in samples of the CANVAS study and examined the effect of the sodium-glucose cotransporter 2 inhibitor canagliflozin on these biomarkers and assessed whether the early change in these biomarkers predict cardiovascular and kidney outcomes in individuals with type 2 diabetes in the CANagliflozin cardioVascular Assessment Study (CANVAS).

Methods: Biomarkers were measured with immunoassays (proprietary multiplex assay performed by RenalytixAI, New York, NY, USA) at baseline and years 1, 3 and 6. Mixed-effects models for repeated measures assessed the effect of canagliflozin vs placebo on the biomarkers. Associations of baseline levels and the early change (baseline to year 1) for each biomarker with the kidney outcome were assessed using multivariable-adjusted Cox regression.

Results: In total, 3523/4330 (81.4%) of the CANVAS participants had available samples at baseline. Each doubling in baseline TNFR-1, TNFR-2 and KIM-1 was associated with a higher risk of kidney outcomes, with corresponding HRs of 3.7 (95% CI 2.3, 6.1; p < 0.01), 2.7 (95% CI 2.0, 3.6; p < 0.01) and 1.5 (95% CI 1.2, 1.8; p < 0.01), respectively. Canagliflozin reduced the level of the plasma biomarkers with differences in TNFR-1, TNFR-2 and KIM-1 between canagliflozin and placebo during follow-up of 2.8% (95% CI 3.4%, 1.3%; p < 0.01), 1.9% (95% CI 3.5%, 0.2%; p = 0.03) and 26.7% (95% CI 30.7%, 22.7%; p < 0.01), respectively. Within the canagliflozin treatment group, each 10% reduction in TNFR-1 and TNFR-2 at year 1 was associated with a lower risk of the kidney outcome (HR 0.8 [95% CI 0.7, 1.0; p = 0.02] and 0.9 [95% CI 0.9, 1.0; p < 0.01] respectively), independent of other patient characteristics. The baseline and 1 year change in biomarkers did not associate with cardiovascular or heart failure outcomes.

Conclusions/interpretation: Canagliflozin decreased KIM-1 and modestly reduced TNFR-1 and TNFR-2 compared with placebo in individuals with type 2 diabetes in CANVAS. Early decreases in TNFR-1 and TNFR-2 during canagliflozin treatment were independently associated with a lower risk of kidney disease progression, suggesting that TNFR-1 and TNFR-2 have the potential to be pharmacodynamic markers of response to canagliflozin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00125-021-05512-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423682PMC
October 2021

Reasons for hospitalizations in patients with type 2 diabetes in the CANVAS programme: A secondary analysis.

Diabetes Obes Metab 2021 Dec 23;23(12):2707-2715. Epub 2021 Aug 23.

Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, California, USA.

Aim: To determine the reasons for hospitalizations in the CANagliflozin cardioVascular Assessment Study (CANVAS) programme and the effects of the sodium-glucose co-transporter-2 inhibitor canagliflozin on hospitalization.

Materials And Methods: A secondary analysis was performed on the CANVAS programme that included 10 142 participants with type 2 diabetes randomized to canagliflozin or placebo. The primary outcome was the rate of total (first plus all recurrent) all-cause hospitalizations (ACH). Secondary outcomes were total hospitalizations categorized by the Medical Dictionary for Regulatory Activities hierarchy at the system organ class level, reported by investigators at each centre. Outcomes were assessed using negative binomial models.

Results: Of the 7115 hospitalizations reported, the most common reasons were cardiac disorders (23.7%), infections and infestations (15.0%), and nervous system disorders (9.0%). The rate of total ACH was lower in the canagliflozin group (n = 5795) compared with the placebo group (n = 4347): 197.9 versus 215.8 participants per 1000 patient-years, respectively (rate ratio [RR] 0.92; 95% confidence interval [CI] 0.86, 0.98). Canagliflozin reduced the rate of total hospitalizations because of cardiac disorders (RR 0.81; 95% CI 0.75, 0.88). There was no significant difference between the canagliflozin and placebo groups in the rates of total hospitalizations because of infections and infestations (RR 0.96; 95% CI 0.86, 1.02) or nervous system disorders (RR 0.96; 95% CI 0.88, 1.05).

Conclusions: In the CANVAS programme, the most common reasons for hospitalization were cardiac disorders, infections and infestations, and nervous system disorders. Canagliflozin, compared with placebo, reduced the rate of total ACH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dom.14525DOI Listing
December 2021

Vital Signs During the COVID-19 Outbreak: A Retrospective Analysis of 19,960 Participants in Wuhan and Four Nearby Capital Cities in China.

Glob Heart 2021 13;16(1):47. Epub 2021 Jul 13.

The George Institute for Global Health, Faculty of Medicine, University of New South Wales, NSW, Sydney, AU.

Background: The implications of city lockdown on vital signs during the COVID-19 outbreak are unknown.

Objective: We longitudinally tracked vital signs using data from wearable sensors and determined associations with anxiety and depression.

Methods: We selected all participants in the HUAWEI Heart Study from Wuhan and four nearby large provincial capital cities (Guangzhou, Chongqing, Hangzhou, Zhengzhou) and extracted all data from 26 December 2019 (one month before city lockdown) to 21 February 2020. Sleep duration and quality, daily steps, oxygen saturation and heart rate were collected on a daily basis. We compared the vital signs before and after the lockdown using segmented regression analysis of the interrupted time series. The depression and anxiety cases were defined as scores ≥8 on the Hospital Anxiety and Depression Scale depression and anxiety subscales [HADS-D and HADS-A] in 727 participants who finished the survey.

Results: We included 19,960 participants (mean age 36 yrs, 90% men). Compared with pre-lockdown, resting heart rate dropped immediately by 1.1 bpm after city lockdown (95% confidence interval [CI]: -1.8, -0.4). Sleep duration increased by 0.5 hour (95% CI: 0.3, 0.8) but deep sleep ratio decreased by 0.9% (95% CI: -1.2, -0.6). Daily steps decreased by 3352 steps (95% CI: -4333, -2370). Anxiety and depression existed in 26% and 17% among 727 available participants, respectively, and associated with longer sleep duration (0.2 and 0.1 hour, both p < 0.001).

Conclusions: Lockdown of Wuhan in China was associated with an adverse vital signs profile (reduced physical activity, heart rate, and sleep quality, but increased sleep duration). Wearable devices in combination with mobile-based apps may be useful to monitor both physical and mental health.

Clinical Trial Registration: The trial is registered at Chinese Clinical Trial Registry (ChiCTR) website (ChiCTR-OOC-17014138).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5334/gh.913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284499PMC
August 2021

Estimating the potential impact of Australia's reformulation programme on households' sodium purchases.

BMJ Nutr Prev Health 2021 12;4(1):49-58. Epub 2021 Jan 12.

Faculty of Medicine, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.

Background: On average, Australian adults consume 3500 mg sodium per day, almost twice the recommended maximum level of intake. The Australian government through the Healthy Food Partnership initiative has developed a voluntary reformulation programme with sodium targets for 27 food categories. We estimated the potential impact of this programme on household sodium purchases (mg/day per capita) and examined potential differences by income level. We also modelled and compared the effects of applying the existing UK reformulation programme targets in Australia.

Methods: This study used 1 year of grocery purchase data (2018) from a nationally representative consumer panel of Australian households (Nielsen Homescan) that was linked with a packaged food and beverage database (FoodSwitch) that contains product-specific sodium information. Potential reductions in per capita sodium purchases were calculated and differences across income level were assessed by analysis of variance. All analyses were modelled to the Australian population in 2018.

Results: A total of 7188 households were included in the analyses. The Healthy Food Partnership targets covered 4307/26 728 (16.1%) unique products, which represented 22.3% of all packaged foods purchased by Australian households in 2018. Under the scenario that food manufacturers complied completely with the targets, sodium purchases will be reduced by 50 mg/day per capita, equivalent to 3.5% of sodium currently purchased from packaged foods. Reductions will be greater in low-income households compared with high-income households (mean difference -7 mg/day, 95% CI -4 to -11 mg/day, p<0.001). If Australia had adopted the UK sodium targets, this would have covered 9927 unique products, resulting in a reduction in per capita sodium purchases by 110 mg/day.

Conclusion: The Healthy Food Partnership reformulation programme is estimated to result in a very small reduction to sodium purchases. There are opportunities to improve the programme considerably through greater coverage and more stringent targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjnph-2020-000173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258059PMC
January 2021

Measuring the Healthiness of Ready-to-Eat Child-Targeted Cereals: Evaluation of the FoodSwitch Platform in Sweden.

JMIR Mhealth Uhealth 2021 07 22;9(7):e17780. Epub 2021 Jul 22.

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

Background: Childhood obesity is a major public health issue. The increase in the consumption of foods with poor nutritional value, such as processed foods, contributes to this. Breakfast cereals are often advertised as a healthy way to start the day, but the healthiness of these products varies greatly.

Objective: Our main objective was to gather information about the nutritional characteristics of ready-to-eat breakfast cereals in Sweden and to investigate the healthiness of products targeted at children compared to other cereals by use of the FoodSwitch platform. A secondary objective was to evaluate the alignment between the Keyhole symbol and the Health Star Rating.

Methods: The FoodSwitch app is a mobile health (mHealth) tool used to present nutrition data and healthier alternative products to consumers. Ready-to-eat breakfast cereals from the largest Swedish grocery retailers were collected using the FoodSwitch platform. Products were defined as targeting children if they presented features addressing children on the package.

Results: Overall, information on 261 ready-to-eat cereals was examined. Of this total, 8% (n=21) were targeted at children. Child-targeted cereals were higher in sugar (22.3 g/100 g vs 12.8 g/100 g, P<.001) and lower in fiber (6.2 g/100 g vs 9.8 g/100 g, P<.001) and protein (8.1 g/100 g vs 10.5 g/100 g, P<.001). Total fat (3 g/100 g vs 10.5 g/100 g, P<.001) and saturated fat (0.8 g/100 g vs 2.6 g/100 g, P<.001) were also lower. No difference was found in salt content (P=.61). Fewer child-targeted breakfast cereals displayed an on-pack Keyhole label (n=1, 5% vs n=53, 22%; P=.06), and the mean Health Star Rating value was 3.5 for child-targeted cereals compared to others (mean 3.8, P=.07). A correlation was found between the Keyhole symbol and the Health Star Rating.

Conclusions: Ready-to-eat breakfast cereals targeted at children were less healthy in terms of sugar and fiber content compared to products not targeted at children. There is a need to improve the nutritional quality of child-targeted cereals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/17780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367182PMC
July 2021

Protocol for the economic evaluation of the China Salt Substitute and Stroke Study (SSaSS).

BMJ Open 2021 07 20;11(7):e045929. Epub 2021 Jul 20.

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

Introduction: Cardiovascular diseases (CVDs) are the leading causes of death and disability worldwide. Reducing dietary salt consumption is a potentially cost-effective way to reduce blood pressure and the burden of CVD. To date, economic evidence has focused on sodium reduction in food industry or processed food with blood pressure as the primary outcome. This study protocol describes the planned within-trial economic evaluation of a low-sodium salt substitute intervention designed to reduce the risk of stroke in China.

Methods And Analyses: The economic evaluation will be conducted alongside the Salt Substitute and Stroke Study: a 5-year large scale, cluster randomised controlled trial. The outcomes of interest are quality of life measured using the EuroQol-5-Dimensions and major adverse cardiovascular events. Costs will be estimated from a healthcare system perspective and will be sought from the routinely collected data available within the New Rural Cooperative Medical Scheme. Cost-effectiveness and cost-utility analyses will be conducted, resulting in the incremental cost-effectiveness ratio expressed as cost per cardiovascular event averted and cost per quality-adjusted life year gained, respectively.

Ethics And Dissemination: The trial received ethics approval from the University of Sydney Ethics Committee (2013/888) and Peking University Institutional Review Board (IRB00001052-13069). Informed consent was obtained from each study participant. Findings of the economic evaluation will be published in a peer-reviewed journal and presented at international conferences.

Trial Registration Number: ClinicalTrials.gov Registry (NCT02092090).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-045929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292808PMC
July 2021

Canagliflozin, serum magnesium and cardiovascular outcomes-Analysis from the CANVAS Program.

Endocrinol Diabetes Metab 2021 Jul 13;4(3):e00247. Epub 2021 Mar 13.

Division of Nephrology Stanford University School of Medicine Stanford CA USA.

Background: Patients with type 2 diabetes (T2D) are predisposed to derangements in serum Magnesium (Mg), which may have implications for cardiometabolic events and outcomes. In clinical trials, participants with T2D randomized to sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown mild to moderate increases in serum Mg from baseline levels. This post hoc analysis assesses the relation between serum Mg with cardiovascular outcomes in 10,140 participants of the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program.

Methods: We evaluated the association of baseline serum Mg with the primary composite end point of death from cardiovascular causes, non-fatal myocardial infarction, and non-fatal stroke, and tested whether this association is modified by baseline serum Mg. Using mediation analysis, we determined whether change in serum Mg post-randomization mediates the beneficial effect of canagliflozin on cardiovascular outcomes.

Results: Mean serum Mg levels at baseline were 0.77 ± 0.09 mmol/L in both canagliflozin group and placebo groups. The canagliflozin group experienced an average increase in serum Mg by 0.07 mmol/L (95% CI, 0.065-0.072 mmol/L;  < .001) for the duration of the trial. We found no association between baseline serum Mg levels and the primary composite end point, and no evidence of effect modification by baseline Mg levels. Change in serum Mg post-randomization was not a mediator of the effects of canagliflozin on cardiovascular outcomes.

Conclusions: In participants of the CANVAS Program, baseline and post-randomization serum Mg levels are not associated with cardiovascular outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/edm2.247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279612PMC
July 2021

Deconstructing the Supermarket: Systematic Ingredient Disaggregation and the Association between Ingredient Usage and Product Health Indicators for 24,229 Australian Foods and Beverages.

Nutrients 2021 May 31;13(6). Epub 2021 May 31.

Department of Epidemiology and Biostatistics, Faculty of Medicine, School of Public Health, Imperial College London, London SW7 2AZ, UK.

Unhealthy diets are underpinned by the over-consumption of packaged products. Data describing the ingredient composition of these products is limited. We sought to define the ingredients used in Australian packaged foods and beverages and assess associations between the number of ingredients and existing health indicators. Statements of ingredients were disaggregated, creating separate fields for each ingredient and sub-ingredient. Ingredients were categorised and the average number of ingredients per product was calculated. Associations between number of ingredients and both the nutrient-based Health Star Rating (HSR) and the NOVA level-of-processing classification were assessed. A total of 24,229 products, listing 233,113 ingredients, were included. Products had between 1 and 62 ingredients (median (Interquartile range (IQR)): 8 (3-14)). We identified 915 unique ingredients, which we organised into 17 major and 138 minor categories. 'Additives' were contained in the largest proportion of products (64.6%, (15,652/24,229)). The median number of ingredients per product was significantly lower in products with the optimum 5-star HSR (when compared to all other HSR score groups, -value < 0.001) and significantly higher in products classified as ultra-processed (when compared to all other NOVA classification groups, -value < 0.001). There is a strong relationship between the number of ingredients in a product and indicators of nutritional quality and level of processing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13061882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228782PMC
May 2021

The adaptation, validation, and application of a methodology for estimating the added sugar content of packaged food products when total and added sugar labels are not mandatory.

Food Res Int 2021 06 22;144:110329. Epub 2021 Mar 22.

Nutrition Postgraduate Program, Nutrition in Foodservice Research Centre (NUPPRE), Federal University of Santa Catarina (UFSC), Campus Universitário Reitor João David Ferreira Lima, Florianópolis, Santa Catarina 88040-970, Brazil. Electronic address:

Nutrition policies recommend limiting the intake of added sugars. Information about added sugar content is not provided on packaged foods in Brazil, and even total sugar content information is often absent. This study aimed to (i) adapt a systematic methodology for estimating added sugar content in packaged foods when information on total and added sugar contents is not mandatory on labels, (ii) apply the adapted methodology to a Brazilian food composition database to estimate the extent of added sugar content in the national food supply, and (iii) assess the validity of the adapted methodology. We developed an 8-step protocol to estimate added sugar content using information provided on food labels. These steps included objective and subjective estimation procedures. Mean, median, and quartiles of the added sugar content of 4,805 Brazilian foods were determined and presented by food categories. Validity was assessed using a US database containing values of added sugar as displayed on the product labels. Objective estimation of added sugar content could be conducted for 3,119 products (64.9%), with the remainder 1,686 (35.1%) being assessed using subjective estimation. We found that 3,093 (64.4%) foods contained added sugar ingredients and the overall estimated median added sugar content was 4.7 g (interquartile range 0-29.3) per 100 g or 100 ml. The validity testing on US data for products with known added sugar values showed excellent agreement between estimated and reported added sugar values (ICC = 0.98). This new methodology is a useful approach for estimating the added sugar content of products in countries where both added and total sugar information are not mandated on food labels. The method can be used to monitor added sugar levels and support interventions aimed at limiting added sugar intake.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodres.2021.110329DOI Listing
June 2021

Canagliflozin and Kidney-Related Adverse Events in Type 2 Diabetes and CKD: Findings From the Randomized CREDENCE Trial.

Am J Kidney Dis 2021 May 23. Epub 2021 May 23.

The George Institute for Global Health, UNSW Sydney, Sydney, Australia; Concord Repatriation General Hospital, Sydney, Australia.

Rationale & Objective: Canagliflozin reduced the risk of kidney failure and related outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial. This analysis of CREDENCE trial data examines the effect of canagliflozin on the incidence of kidney-related adverse events (AEs).

Study Design: A randomized, double-blind, placebo-controlled, multicenter international trial.

Setting & Participants: 4,401 trial participants with T2DM, CKD, and urinary albumin-creatinine ratio >300-5,000 mg/g.

Interventions: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.

Outcomes: Rates of kidney-related AEs were analyzed using an on-treatment approach, overall and by screening estimated glomerular filtration rate (eGFR) strata (30-<45, 45-<60, and 60-<90 mL/min/1.73 m).

Results: Canagliflozin was associated with a reduction in the overall incidence rate of kidney-related AEs (60.2 vs 84.0 per 1,000 patient-years; hazard ratio [HR], 0.71 [95% CI, 0.61-0.82]; P < 0.001), with consistent results for serious kidney-related AEs (HR, 0.72 [95% CI, 0.51-1.00]; P = 0.05) and acute kidney injury (AKI; HR, 0.85 [95% CI, 0.64-1.13]; P = 0.3). The rates of kidney-related AEs were lower with canagliflozin relative to placebo across the 3 eGFR strata (HRs of 0.73, 0.60, and 0.81 for eGFR 30-<45, 45-<60, and 60-<90 mL/min/1.73 m, respectively; P = 0.3 for interaction), with similar results for AKI (P = 0.9 for interaction). Full recovery of kidney function within 30 days after an AKI event occurred more frequently with canagliflozin versus placebo (53.1% vs 35.4%; odds ratio, 2.2 [95% CI, 1.0-4.7]; P = 0.04).

Limitations: Kidney-related AEs including AKI were investigator-reported and collected without central adjudication. Biomarkers of AKI and structural tubular damage were not measured, and creatinine data after an AKI event were not available for all participants.

Conclusions: Compared with placebo, canagliflozin was associated with a reduced incidence of serious and nonserious kidney-related AEs in patients with T2DM and CKD. These results highlight the safety of canagliflozin with regard to adverse kidney-related AEs.

Funding: The CREDENCE trial and this analysis were funded by Janssen Research & Development, LLC, and were conducted as a collaboration between the funder, an academic steering committee, and an academic research organization, George Clinical.

Trial Registration: The CREDENCE trial was registered at ClinicalTrials.gov with identifier number NCT02065791.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.ajkd.2021.05.005DOI Listing
May 2021

Healthy Food Prescription Programs and their Impact on Dietary Behavior and Cardiometabolic Risk Factors: A Systematic Review and Meta-Analysis.

Adv Nutr 2021 10;12(5):1944-1956

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

The enormous burden of diet-related chronic diseases has prompted interest in healthy food prescription programs. Yet, the impact of such programs remains unclear. The aim of this study was to conduct a systematic review of healthy food prescription programs and evaluate their impact on dietary behavior and cardiometabolic parameters by meta-analysis. A systematic search was carried out in Medline, Embase, Scopus, and Cochrane Central Register of Controlled Trials databases since their inception to 3 January, 2020 without language restriction. A systematic search of interventional studies investigating the effect of healthy food prescription on diet quality and/or cardiometabolic risk factors including BMI, systolic (SBP) and diastolic blood pressure (DBP), glycated hemoglobin (HbA1c), or blood lipids was carried out. Thirteen studies were identified for inclusion, most of which were quasi-experimental (pre/post) interventions without a control group (n = 9). Pooled estimates revealed a 22% (95% CI: 12, 32; n = 5 studies, n = 1039 participants; I2 = 97%) increase in fruit and vegetable consumption, corresponding to 0.8 higher daily servings (95% CI: 0.2, 1.4; I2 = 96%). BMI decreased by 0.6 kg/m2 (95% CI: 0.2, 1.1; I2 = 6.4%) and HbA1c by 0.8% (95% CI: 0.1, 1.6; I2 = 92%). No significant change was observed in other cardiometabolic parameters. These findings should be interpreted with caution in light of considerable heterogeneity, methodological limitations of the included studies, and moderate to very low certainty of evidence. Our results support the need for well-designed, large, randomized controlled trials in various settings to further establish the efficacy of healthy food prescription programs on diet quality and cardiometabolic health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/advances/nmab039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483962PMC
October 2021

Availability, Formulation, Labeling, and Price of Low-sodium Salt Worldwide: Environmental Scan.

JMIR Public Health Surveill 2021 07 14;7(7):e27423. Epub 2021 Jul 14.

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

Background: Regular salt is about 100% sodium chloride. Low-sodium salts have reduced sodium chloride content, most commonly through substitution with potassium chloride. Low-sodium salts have a potential role in reducing the population's sodium intake levels and blood pressure, but their availability in the global market is unknown.

Objective: The aim of this study is to assess the availability, formulation, labeling, and price of low-sodium salts currently available to consumers worldwide.

Methods: Low-sodium salts were identified through a systematic literature review, Google search, online shopping site searches, and inquiry of key informants. The keywords "salt substitute," "low-sodium salt," "potassium salt," "mineral salt," and "sodium reduced salt" in six official languages of the United Nations were used for the search. Information about the brand, formula, labeling, and price was extracted and analyzed.

Results: A total of 87 low-sodium salts were available in 47 out of 195 (24%) countries worldwide, including 28 high-income countries, 13 upper-middle-income countries, and 6 lower-middle-income countries. The proportion of sodium chloride varied from 0% (sodium-free) to 88% (as percent of weight; regular salt is 100% sodium chloride). Potassium chloride was the most frequent component with levels ranging from 0% to 100% (potassium chloride salt). A total of 43 (49%) low-sodium salts had labels with the potential health risks, and 33 (38%) had labels with the potential health benefits. The median price of low-sodium salts in high-income, upper-middle-income, and lower-middle-income countries was US $15.00/kg (IQR 6.4-22.5), US $2.70/kg (IQR 1.7-5.5), and US $2.90/kg (IQR 0.50-22.2), respectively. The price of low-sodium salts was between 1.1 and 14.6 times that of regular salts.

Conclusions: Low-sodium salts are not widely available and are commonly more expensive than regular salts. Policies that promote the availability, affordability, and labeling of low-sodium salts should increase uptake, helping populations reduce blood pressure and prevent cardiovascular diseases.

International Registered Report Identifier (irrid): RR2-10.1111/jch.14054.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/27423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319774PMC
July 2021

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis.

Stroke 2021 May 20;52(5):1545-1556. Epub 2021 Apr 20.

Westmead Applied Research Centre, University of Sydney, Sydney, Australia (R.I.L.).

Background And Purpose: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.

Methods: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.

Results: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HR, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HR, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HR, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HR, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HR, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (=0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m]) subgroup (HR, 0.50 [95% CI, 0.31-0.79]).

Conclusions: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.120.031623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078131PMC
May 2021

Sodium, Blood Pressure, and the Likely Massive Avoidable Burden of Cardiovascular Disease.

Authors:
Bruce Neal Jason Wu

Circulation 2021 Apr 19;143(16):1568-1570. Epub 2021 Apr 19.

The George Institute for Global Health, UNSW Sydney, New South Wales, Australia (B.N., J.W.).

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052654DOI Listing
April 2021

Effects of canagliflozin on myocardial infarction: a post hoc analysis of the CANVAS Program and CREDENCE trial.

Cardiovasc Res 2021 Apr 7. Epub 2021 Apr 7.

The George Institute for Global Health, UNSW Sydney, Sydney, Australia.

Aims: Given the benefits of sodium glucose co-transporter 2 inhibition (SGLT2i) in protecting against heart failure in diabetic patients, we sought to explore the potential impact of SGLT2i on the clinical features of patients presenting with myocardial infarction (MI) through a post-hoc analysis of CANVAS Program and CREDENCE trial.

Methods And Results: Individuals with type 2 diabetes and history or high risk of cardiovascular disease (CANVAS Program) or type 2 diabetes and chronic kidney disease (CREDENCE) were included. The intervention was Canagliflozin 100 or 300 mg (combined in the analysis) or placebo. MI events were adjudicated as ST-elevation myocardial infarction (STEMI), non-STEMI as well as type 1 MI or type 2 MI. 421 first MI events in the CANVAS Program and 178 first MI events in the CREDENCE trial were recorded (83 fatal, 128 STEMI, 431 non-STEMI, and 40 unknown). No benefit of canagliflozin compared with placebo on time to first MI event was observed (HR 0.89; 95% CI 0.75, 1.05). Canagliflozin was associated with lower risk for non-STEMI (HR 0.78; 95% CI 0.65, 0.95) but suggested a possible increase in STEMI (HR 1.55; 95% CI 1.06, 2.27), with no difference in risk of type 1 or type 2 MI. There was no change in fatal MI (HR 1.22, 95% CI 0.78, 1.93).

Conclusions: Canagliflozin was not associated with a reduction in overall MI in the pooled CANVAS Program and CREDENCE trial population. The possible differential effect on STEMI and Non-STEMI observed in the CANVAS cohort warrants further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cvr/cvab128DOI Listing
April 2021

Effects of a reduced-sodium added-potassium salt substitute on blood pressure in rural Indian hypertensive patients: a randomized, double-blind, controlled trial.

Am J Clin Nutr 2021 07;114(1):185-193

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

Background: High salt intake is a major modifiable risk factor of hypertension which is prevalent in India. It is not yet clear if salt substitutes reduce blood pressure (BP) among Indian hypertensive patients.

Objectives: Examine the acceptability, usage, and BP effects of a reduced-sodium and added-potassium salt substitute among hypertensive patients.

Methods: We enrolled 502 participants with hypertension (aged 61.6 ± 12.0 y, 58.8% women) from 7 villages in rural India. Participants were randomly assigned to receive either regular salt (100% sodium chloride) or the salt substitute (70% sodium chloride/30% potassium chloride blend), and advised to replace all home salt use. The primary outcome was the change in systolic BP (SBP) from baseline to 3 mo comparing the salt substitute and regular salt groups. Secondary outcomes included the change in diastolic BP (DBP), 24-h urinary biomarkers, and self-reported use and satisfaction with the study salt provided.

Results: A total of 494 (98%) participants completed 1 mo and 476 (95%) participants completed the 3-mo follow-up. At 3 mo, the salt substitute intervention significantly decreased the average SBP by 4.6 mmHg (95% CI: 3.0, 6.2, P < 0.001) and DBP by 1.1 mmHg (95% CI: 0.2, 2.1 mmHg, P = 0.02). There was a significant increase in 24-h urinary potassium excretion in the salt substitute group by 0.24 g/d (95% CI: 0.12, 0.35 g/d, P < 0.001) and a decrease in the urinary sodium to potassium ratio by 0.71 (95% CI: 0.55, 0.87, P < 0.0001) compared with the control group. Participants reported that they used the study salt nearly every day of the week (mean ± SD, 6.3 ± 1.8 d) and rated the taste of the study salts similarly.

Conclusion: The reduced-sodium added-potassium salt led to a substantial reduction in SBP in hypertensive patients, supporting salt substitution as an effective, low-cost intervention for BP lowering in rural India. This trial was registered at clinicaltrials.gov as NCT03909659.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqab054DOI Listing
July 2021

The effects of canagliflozin on heart failure and cardiovascular death by baseline participant characteristics: Analysis of the CREDENCE trial.

Diabetes Obes Metab 2021 07 16;23(7):1652-1659. Epub 2021 Apr 16.

Janssen Research & Development, LLC, Raritan, New Jersey, USA.

Heart failure is prevalent in those with type 2 diabetes and chronic kidney disease, and is associated with significant mortality and morbidity. In the CREDENCE trial, canagliflozin reduced the risk of hospitalization for heart failure (HHF) or cardiovascular (CV) death by 31%. In the current analysis we sought to determine whether the effect of canagliflozin on HHF/CV death differed in subgroups defined by key baseline participant characteristics. Cox regression models were used to estimate hazard ratios and 95% confidence intervals. Canagliflozin was associated with a reduction in the relative risk of HHF/CV death regardless of age, sex, history of heart failure or CV disease, and the use of loop diuretics or glucagon-like peptide-1 receptor agonists (all p  > .114). The absolute benefit of canagliflozin was greater in those at highest baseline risk, such as those with CV disease (50 fewer events/1000 patients treated over 2.5 years vs. 20 fewer events in those without CV disease) or advanced kidney disease (estimated glomerular filtration rate [eGFR] 30-45 mL/min/1.73m : 61 events prevented/1000 patients treated over 2.5 years vs. 23 events in eGFR 60-90 mL/min/1.73m ). Canagliflozin consistently reduces the proportional risk of HHF/CV death across a broad range of subgroups with greater absolute benefits in those at highest baseline risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dom.14386DOI Listing
July 2021

A Systematic Review of Salt Reduction Initiatives Around the World: A Midterm Evaluation of Progress Towards the 2025 Global Non-Communicable Diseases Salt Reduction Target.

Adv Nutr 2021 10;12(5):1768-1780

The George Institute for Global Health, University of New South Wales, Newtown, NSW, Australia.

In 2013, the WHO recommended that all member states aim to reduce population salt intake by 30% by 2025. The year 2019 represents the midpoint, making it a critical time to assess countries' progress towards this target. This review aims to identify all national salt reduction initiatives around the world in 2019, and to quantify countries' progress in achieving the salt reduction target. Relevant data were identified through searches of peer-reviewed and gray literature, supplemented with responses from prefilled country questionnaires sent to known country leads of salt reduction or salt champions, WHO regional representatives, and international experts to request further information. Core characteristics of each country's strategy, including evaluations of program impact, were extracted and summarized. A total of 96 national salt reduction initiatives were identified, representing a 28% increase in the number reported in 2014. About 90% of the initiatives were multifaceted in approach, and 60% had a regulatory component. Approaches include interventions in settings (n= 74), food reformulation (n = 68), consumer education (n = 50), front-of-pack labeling (n = 48), and salt taxation (n = 5). Since 2014, there has been an increase in the number of countries implementing each of the approaches, except consumer education. Data on program impact were limited. There were 3 countries that reported a substantial decrease (>2 g/day), 9 that reported a moderate decrease (1-2 g/day), and 5 that reported a slight decrease (<1 g/day) in the mean salt intake over time, but none have yet met the targeted 30% relative reduction in salt intake from baseline. In summary, there has been an increase in the number of salt reduction initiatives around the world since 2014. More countries are now opting for structural or regulatory approaches. However, efforts must be urgently accelerated and replicated in other countries and more rigorous monitoring and evaluation of strategies is needed to achieve the salt reduction target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/advances/nmab008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483946PMC
October 2021

The impact of baseline potassium intake on the dose-response relation between sodium reduction and blood pressure change: systematic review and meta-analysis of randomized trials.

J Hum Hypertens 2021 Nov 5;35(11):946-957. Epub 2021 Mar 5.

The George Institute for Global Health, UNSW Sydney, Sydney, NSW, Australia.

Sodium and potassium appear to interact with each other in their effects on blood pressure with potassium supplementation having a greater blood pressure lowering-effect when sodium intake is high. Whether the effect of sodium reduction on blood pressure varies according to potassium intake levels is unclear. We carried out a systematic review and meta-analysis to examine the impact of baseline potassium intake on blood pressure response to sodium reduction in randomized trials in adult populations, with sodium and potassium intake estimated from 24-h urine samples. We included 68 studies involving 5708 participants and conducted univariable and multivariable meta-regression. The median intake of baseline potassium was 67.7 mmol (Interquartile range: 54.6-76.4 mmol), and the mean reduction in sodium intake was 128 mmol (95% CI: 107-148). Multivariable meta-regression that included baseline 24-h urinary potassium excretion, age, ethnicity, baseline blood pressure, change in 24-h urinary sodium excretion, as well as the interaction between baseline 24-h urinary potassium excretion and change in 24-h urinary sodium excretion did not identify a significant association of baseline potassium intake levels with the blood pressure reduction achieved with a 50 mmol lowering of sodium intake (p > 0.05 for both systolic and diastolic blood pressure). A higher starting level of blood pressure was consistently associated with a greater blood pressure reduction from reduced sodium consumption. However, the nonsignificant findings may subject to the limitations of the data available. Additional studies with more varied potassium intake levels would allow a more confident exclusion of an interaction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41371-021-00510-xDOI Listing
November 2021

Association of Baseline Diuretic Use With Cardiovascular Outcomes in Patients With Heart Failure With Preserved Ejection Fraction: A Secondary Analysis From TOPCAT.

J Card Fail 2021 07 24;27(7):816-818. Epub 2021 Feb 24.

Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cardfail.2021.02.010DOI Listing
July 2021
-->