Protocol for the Metformin Aneurysm Trial (MAT): a placebo-controlled randomised trial testing whether metformin reduces the risk of serious complications of abdominal aortic aneurysm.

BACKGROUND: Multiple observational studies have associated metformin prescription with reduced progression of abdominal aortic aneurysm (AAA). The Metformin Aneurysm Trial (MAT) will test whether metformin reduces the risk of AAA rupture-related mortality or requirement for AAA surgery (AAA events) in people with asymptomatic aneurysms. METHODS: MAT is an international, multi-centre, prospective, parallel-group, randomised, placebo-controlled trial. Participants must have an asymptomatic AAA measuring at least 35 mm in maximum diameter, no diabetes, no contraindication to metformin and no current plans for surgical repair. The double-blind period is preceded by a 6-week, single-blind, active run-in phase in which all potential participants receive metformin. Only patients tolerating metformin by taking at least 80% of allocated medication will enter the trial and be randomised to 1500 mg of metformin XR or an identical placebo. The primary outcome is the proportion of AAA events defined as rupture-related mortality or need for surgical repair. Secondary outcomes include AAA growth, major adverse cardiovascular events and health-related quality of life. In order to test if metformin reduced the risk of AAA events by at least 25%, 616 primary outcome events will be required (power 90%, alpha 0.05). DISCUSSION: Currently, there is no drug therapy for AAA. Past trials have found no convincing evidence of the benefit of multiple blood pressure lowering, antibiotics, a mast cell inhibitor, an anti-platelet drug and a lipid-lowering medication on AAA growth. MAT is one of a number of trials now ongoing testing metformin for AAA. MAT, unlike these other trials, is designed to test the effect of metformin on AAA events. The international collaboration needed for MAT will be challenging to achieve given the current COVID-19 pandemic. If this challenge can be overcome, MAT will represent a trial unique within the AAA field in its large size and design. TRIAL REGISTRATION: Australian Clinical Trials ACTRN12618001707257 . Registered on 16 October 2018.

Effectiveness of a Sodium-Reduction Smartphone App and Reduced-Sodium Salt to Lower Sodium Intake in Adults With Hypertension: Findings From the Salt Alternatives Randomized Controlled Trial.

BACKGROUND: Even modest reductions in blood pressure (BP) can have an important impact on population-level morbidity and mortality from cardiovascular disease. There are 2 promising approaches: the SaltSwitch smartphone app, which enables users to scan the bar code of a packaged food using their smartphone camera and receive an immediate, interpretive traffic light nutrition label on-screen alongside a list of healthier, lower-salt options in the same food category; and reduced-sodium salts (RSSs), which are an alternative to regular table salt that are lower in sodium and higher in potassium but have a similar mouthfeel, taste, and flavor. OBJECTIVE: Our aim was to determine whether a 12-week intervention with a sodium-reduction package comprising the SaltSwitch smartphone app and an RSS could reduce urinary sodium excretion in adults with high BP. METHODS: A 2-arm parallel randomized controlled trial was conducted in New Zealand (target n=326). Following a 2-week baseline period, adults who owned a smartphone and had high BP (≥140/85 mm Hg) were randomized in a 1:1 ratio to the intervention (SaltSwitch smartphone app + RSS) or control (generic heart-healthy eating information from The Heart Foundation of New Zealand). The primary outcome was 24-hour urinary sodium excretion at 12 weeks estimated via spot urine. Secondary outcomes were urinary potassium excretion, BP, sodium content of food purchases, and intervention use and acceptability. Intervention effects were assessed blinded using intention-to-treat analyses with generalized linear regression adjusting for baseline outcome measures, age, and ethnicity. RESULTS: A total of 168 adults were randomized (n=84, 50% per group) between June 2019 and February 2020. Challenges associated with the COVID-19 pandemic and smartphone technology detrimentally affected recruitment. The adjusted mean difference between groups was 547 (95% CI -331 to 1424) mg for estimated 24-hour urinary sodium excretion, 132 (95% CI -1083 to 1347) mg for urinary potassium excretion, -0.66 (95% CI -3.48 to 2.16) mm Hg for systolic BP, and 73 (95% CI -21 to 168) mg per 100 g for the sodium content of food purchases. Most intervention participants reported using the SaltSwitch app (48/64, 75%) and RSS (60/64, 94%). SaltSwitch was used on 6 shopping occasions, and approximately 1/2 tsp per week of RSS was consumed per household during the intervention. CONCLUSIONS: In this randomized controlled trial of a salt-reduction package, we found no evidence that dietary sodium intake was reduced in adults with high BP. These negative findings may be owing to lower-than-anticipated engagement with the trial intervention package. However, implementation and COVID-19-related challenges meant that the trial was underpowered, and it is possible that a real effect may have been missed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12619000352101; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377044 and Universal Trial U1111-1225-4471.

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

[This corrects the article DOI: 10.5334/gh.913.].

Mediators of the Effects of Canagliflozin (CANA) on Heart Failure (HF) and CV Death in Patients with Type 2 Diabetes (T2D) and Chronic Kidney Disease (CKD)

The benefits of CANA for HF in people with T2D at CV risk appeared to be statistically mediated by erythrocyte concentration, serum urate, and urinary albumin:creatinine ratio (UACR) in the CANVAS Program. CANA reduced the risk of HF in patients with T2D and CKD in CREDENCE. We explored potential mediators of CANA's effects on the composite of hospitalized HF (HHF) and CV death. Mediation analyses are hypothesis-generating observational analyses that calculate the effect of selected biomarkers on the overall treatment effect using time-varying Cox regression. We compared hazard ratios for the effect of randomized treatment from an unadjusted model versus a model adjusted for the average post-randomization level of the biomarker of interest. 62 routine clinical biomarkers and vital sign indicators were collected on all participants and tested as potential mediators. When multiple potential mediators represented a single pathway, those with the strongest univariable mediation were tested in multivariable models. 12 biomarkers, including 3 markers of volume/erythropoiesis (hematocrit [24%], hemoglobin [32%], erythrocytes [27%]), 2 markers of kidney function (UACR [28%], eGFR from wk 3 [7.4%]), and serum albumin (39%), serum protein (24%), lactate dehydrogenase (13%), systolic BP (10%), urine pH (8%), serum urate (7%) and gamma glutamyltransferase (4%), mediated the effect of CANA on HHF/CV death in univariable models. In the multivariable model, hemoglobin, UACR, serum urate and systolic BP maximized cumulative mediation (74%). A diverse set of potential mediators of CANA's effect on HHF/CV death were identified with serum albumin, hemoglobin (or its analogues) and UACR being the most important. The extent to which these mediators reflect underlying inflammatory, nutritional, volume-related or cardiorenal pathways is unclear and underscores the need for further research into the mechanisms of benefit of SGLT2 inhibitors. Disclosure: J. Li: Employee;Self;George Institute. B. Neal: Research Support;Self;Janssen Research & Development, LLC, Merck Schering Plough, Roche Pharma, Servier, Zydus Pharmaceuticals, Inc. Other Relationship;Self;Abbott, Janssen, Novartis, Pfizer, Roche, and Servier. H.L. Heerspink: Consultant;Self;AbbVie Inc., AstraZeneca, Boehringer Ingelheim International GmbH, CSL Behring, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Mundipharma International, Retrophin, Inc. C. Arnott: Employee;Self;George Institute for Global Health. C. Cannon: None. R. Agarwal: Other Relationship;Self;AbbVie Inc., Akebia Therapeutics, Amgen, AstraZeneca, Bayer Inc., Bird Rock Bio, Boehringer Ingelheim Pharmaceuticals, Inc., Celgene, Daiichi Sankyo, Eli Lilly and Company, GlaxoSmithKline plc., Ironwood Pharmaceuticals, Johnson & Johnson, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, OPKO Health, Inc., Reata, Relypsa, Inc., Sandoz, Sanofi, Takeda Pharmaceutical Company Limited, ZS Pharma. G. Bakris: Consultant;Self;Alnylam, Merck & Co., Inc., Relypsa, Inc., Teijin Pharma Limited. Other Relationship;Self;Bayer AG, Novo Nordisk Inc., Vascular Dynamics. D.M. Charytan: Advisory Panel;Self;Allena Pharmaceuticals, AstraZeneca, Merck & Co., Inc., PLC Medical. Employee;Self;BAIM Institute. Research Support;Self;Janssen Pharmaceuticals, Inc. Other Relationship;Self;Baim, Amgen, Medtronic/Covidien, Zoll, Fresenius, Daiichi Sankyo, Douglas and London, Eli Lilly, Merck, Gilead, and Novo Nordisk. D. de Zeeuw: Advisory Panel;Self;AbbVie Inc., Bayer AG, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. T. Greene: Other Relationship;Self;Janssen, Durect, and Pfizer. A. Levin: Consultant;Self;Janssen Pharmaceuticals, Inc. Research Support;Self;AstraZeneca K.K., Boehringer Ingelheim Pharmaceuticals, Inc., Gilead Sciences, Inc. R. Oh: Employee;Self;Janssen Pharmaceuticals, Inc. C.A. Pollock: Advisory Panel;Self;AstraZeneca, Boehringer Ingelheim Pharma euticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Otsuka Pharmaceutical Co., Ltd., Vifor Pharma Group. Research Support;Self;Diabetes Australia. Speaker's Bureau;Self;AstraZeneca, Cipla Inc., MedErgy, Medscape, Mitsubishi Tanabe Pharma Corporation, Novartis AG, Otsuka Pharmaceutical Co., Ltd., Vifor Pharma Group. Other Relationship;Self;Amgen, George Institute for Global Health, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc. D.C. Wheeler: Advisory Panel;Self;Boehringer Ingelheim Pharmaceuticals, Inc., Reata. Consultant;Self;AstraZeneca, Bayer AG, GlaxoSmithKline, Janssen Pharmaceuticals, Inc. Speaker's Bureau;Self;Amgen, Astellas Pharma Inc., Mundipharma International, Napp Pharmaceuticals. Y. Yavin: Employee;Self;Janssen Research & Development, LLC. H. Zhang: Employee;Self;Renal Division of Peking University First Hospital. B. Zinman: Advisory Panel;Self;Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. G. Di Tanna: Employee;Self;George Institute for Global Health. V. Perkovic: Other Relationship;Self;See Other Relationship field. K.W. Mahaffey: Consultant;Self;Medscape, Mitsubishi, Myokardia, NIH, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, UCSF. Research Support;Self;Afferent, Amgen, Apple, Inc, AstraZeneca, Cardiva Medical, Inc, Daiichi, Ferring, Google (Verily), Johnson & Johnson, Luitpold, Medtronic, Merck, NIH, Novartis, Sanofi, St. Jude, Tenax. M. Jardine: Other Relationship;Self;See Other Relationship field. Funding: Janssen Research & Development, LLC [ABSTRACT FROM AUTHOR] Copyright of Diabetes is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Effect of Canagliflozin on Total Hospitalization for Heart Failure Events in Patients with Type 2 Diabetes and Chronic Kidney Disease

Background: The sodium glucose co-transporter 2 inhibitor canagliflozin reduced the risk of first hospitalization for heart failure (HHF) in the CREDENCE trial. The prevention of recurrent events is important to patients, clinicians and payers. In this post-hoc analysis, we evaluated the effect of canagliflozin on total HHF events. Methods: The CREDENCE trial compared canagliflozin or matching placebo and followed patients for a median of 2.6 years. The study included 4401 participants with type 2 diabetes, substantial albuminuria and estimated glomerular filtration rate (eGFR) 30 to <90 ml/min/1.73 m2 receiving renin-angiotensin system blockade. Negative binomial regression models were performed to assess the effect of canagliflozin on the total number of HHF events. Results: The mean age of participants was 63 years, with a mean eGFR of 56.3 ml/min/1.73 m2, while 50% had a history of previous cardiovascular disease and 15% had a history of heart failure. During the trial, 230 people experienced 326 total HHF events, with 166 having 1 event, 43 having 2 events, 15 having 3 events, and 6 having ≥4 events;thus, 42% of those experiencing at least 1 event went on to suffer a recurrent event during the follow up. Canagliflozin reduced first HHF events by 39% (hazard ratio [HR], 0.61;95% confidence interval [CI] 0.47-0.80;P <0.001;number needed to treat [NNT], 46;95% CI 29-124) and total HHF events by 36% (event rates of 22.0 and 34.8 participants with an event/1000 patient-years with canagliflozin and placebo, respectively;incidence rate ratio [RR], 0.64;95% CI 0.56-0.73;P <0.001). Conclusions: Canagliflozin significantly reduced first and recurrent HHF events. These findings provide further support for the benefit of continuing canagliflozin therapy after an index heart failure presentation to prevent recurrent HHF events. Disclosure: J. Li: Employee;Self;George Institute. M.J. Jardine: Other Relationship;Self;See Other Relationship field. B. Neal: Research Support;Self;Janssen Research & Development, LLC, Merck Schering Plough, Roche Pharma, Servier, Zydus Pharmaceuticals, Inc. Other Relationship;Self;Abbott, Janssen, Novartis, Pfizer, Roche, and Servier. H.L. Heerspink: Consultant;Self;AbbVie Inc., AstraZeneca, Boehringer Ingelheim International GmbH, CSL Behring, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Mundipharma International, Retrophin, Inc. C. Cannon: None. R. Agarwal: Other Relationship;Self;AbbVie Inc., Akebia Therapeutics, Amgen, AstraZeneca, Bayer Inc., Bird Rock Bio, Boehringer Ingelheim Pharmaceuticals, Inc., Celgene, Daiichi Sankyo, Eli Lilly and Company, GlaxoSmithKline plc., Ironwood Pharmaceuticals, Johnson & Johnson, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, OPKO Health, Inc., Reata, Relypsa, Inc., Sandoz, Sanofi, Takeda Pharmaceutical Company Limited, ZS Pharma. G. Bakris: Consultant;Self;Alnylam, Merck & Co., Inc., Relypsa, Inc., Teijin Pharma Limited. Other Relationship;Self;Bayer AG, Novo Nordisk Inc., Vascular Dynamics. D.M. Charytan: Advisory Panel;Self;Allena Pharmaceuticals, AstraZeneca, Merck & Co., Inc., PLC Medical. Employee;Self;BAIM Institute. Research Support;Self;Janssen Pharmaceuticals, Inc. Other Relationship;Self;Baim, Amgen, Medtronic/Covidien, Zoll, Fresenius, Daiichi Sankyo, Douglas and London, Eli Lilly, Merck, Gilead, and Novo Nordisk. D. de Zeeuw: Advisory Panel;Self;AbbVie Inc., Bayer AG, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. R. Edwards: Employee;Self;Janssen. T. Greene: Other Relationship;Self;Janssen, Durect, and Pfizer. A. Levin: Consultant;Self;Janssen Pharmaceuticals, Inc. Research Support;Self;AstraZeneca K.K., Boehringer Ingelheim Pharmaceuticals, Inc., Gilead Sciences, Inc. C.A. Pollock: Advisory Panel;Self;AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Otsuka Pharmaceutical Co., Ltd., Vifor Pharma Group. Research Support;Self;Diabetes Australia. Speaker's Bureau;Self;AstraZeneca, Cipla Inc., MedErgy, Medscape, Mitsubishi Tanabe Pharma Corporation, Novartis AG, Otsuka Pharmaceutical Co., Ltd., Vifor Pharma Group. Other Relationship;Self;Amgen, George Institute for Global Health, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc. N. Rosenthal: None. D.C. Wheeler: Advisory Panel;Self;Boehringer Ingelheim Pharmaceuticals, Inc., Reata. Consultant;Self;AstraZeneca, Bayer AG, GlaxoSmithKline, Janssen Pharmaceuticals, Inc. Speaker's Bureau;Self;Amgen, Astellas Pharma Inc., Mundipharma International, Napp Pharmaceuticals. H. Zhang: Employee;Self;Renal Division of Peking University First Hospital. B. Zinman: Advisory Panel;Self;Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. V. Perkovic: Other Relationship;Self;See Other Relationship field. K.W. Mahaffey: Consultant;Self;Medscape, Mitsubishi, Myokardia, NIH, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, UCSF. Research Support;Self;Afferent, Amgen, Apple, Inc, AstraZeneca, Cardiva Medical, Inc, Daiichi, Ferring, Google (Verily), Johnson & Johnson, Luitpold, Medtronic, Merck, NIH, Novartis, Sanofi, St. Jude, Tenax. C. Arnott: Employee;Self;George Institute for Global Health. Funding: Janssen Research & Development, LLC [ABSTRACT FROM AUTHOR] Copyright of Diabetes is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Acute Declines in EGFR during Treatment with Canagliflozin and Its Implications for Clinical Practice: Insights from CREDENCE

Background: Canagliflozin (CANA) slows progression of chronic kidney disease (CKD) in people with type 2 diabetes. CANA also induces a reversible acute decline in estimated glomerular filtration rate (eGFR), which is believed to be a hemodynamic effect. Predictors of the initial decline and its association with long-term eGFR trajectories and safety outcomes are unknown. Methods: This post-hoc study of the CREDENCE trial included 4289 patients with type 2 diabetes and CKD who had eGFR measured at both baseline and week 3. Participants were categorized by percentage decline in eGFR at week 3: >10%, ≤10% to >0%, and ≤0%. Baseline characteristics associated with acute eGFR declines >10% were evaluated using logistic regression. Long-term eGFR decline and safety outcomes were estimated in each eGFR decline category by linear mixed effects models and Cox regression after adjustment for laboratory measures and medication use. Results: More participants in the CANA (956 [45%]) versus placebo (PBO) group (450 [21%]) had an acute eGFR decline >10% (p<0.001). A >30% decline occurred infrequently (89 [4%] with CANA and 39 [2%] with PBO;p<0.001). In the CANA but not in the PBO group, older age (OR CANA 1.17, 95% CI 1.05-1.31;per 10 years) and history of heart failure (OR CANA 0.77, 0.59-0.99) were associated with a higher and lower likelihood of an acute eGFR decline >10%, respectively (both p for interaction <0.05). Following the initial eGFR change, long-term eGFR trajectories as well as overall safety profiles were similar across eGFR decline categories (all p values >0.05). Results were consistent when other decline thresholds (>20%) were used and in subgroup analysis by baseline eGFR (30-<45, 45-<60, and 60-<90 ml/min/1.73 m2). Conclusions: Although acute eGFR declines >10% occurred in nearly half of all patients following initiation of CANA, the benefit of CANA compared with placebo was observed regardless of the acute eGFR decline and safety profiles were similar. Disclosure: M. Oshima: Research Support;Self;Japan Society for the Promotion of Science Program for Fostering Globally Talented Researchers. M.J. Jardine: Other Relationship;Self;See Other Relationship field. R. Agarwal: Other Relationship;Self;AbbVie Inc., Akebia Therapeutics, Amgen, AstraZeneca, Bayer Inc., Bird Rock Bio, Boehringer Ingelheim Pharmaceuticals, Inc., Celgene, Daiichi Sankyo, Eli Lilly and Company, GlaxoSmithKline plc., Ironwood Pharmaceuticals, Johnson & Johnson, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, OPKO Health, Inc., Reata, Relypsa, Inc., Sandoz, Sanofi, Takeda Pharmaceutical Company Limited, ZS Pharma. G. Bakris: Consultant;Self;Alnylam, Merck & Co., Inc., Relypsa, Inc., Teijin Pharma Limited. Other Relationship;Self;Bayer AG, Novo Nordisk Inc., Vascular Dynamics. C. Cannon: None. D.M. Charytan: Advisory Panel;Self;Allena Pharmaceuticals, AstraZeneca, Merck & Co., Inc., PLC Medical. Employee;Self;BAIM Institute. Research Support;Self;Janssen Pharmaceuticals, Inc. Other Relationship;Self;Baim, Amgen, Medtronic/Covidien, Zoll, Fresenius, Daiichi Sankyo, Douglas and London, Eli Lilly, Merck, Gilead, and Novo Nordisk. D. de Zeeuw: Advisory Panel;Self;AbbVie Inc., Bayer AG, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. R. Edwards: Employee;Self;Janssen. T. Greene: Other Relationship;Self;Janssen, Durect, and Pfizer. A. Levin: Consultant;Self;Janssen Pharmaceuticals, Inc. Research Support;Self;AstraZeneca K.K., Boehringer Ingelheim Pharmaceuticals, Inc., Gilead Sciences, Inc. K.W. Mahaffey: Consultant;Self;Medscape, Mitsubishi, Myokardia, NIH, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, UCSF. Research Support;Self;Afferent, Amgen, Apple, Inc, AstraZeneca, Cardiva Medical, Inc, Daiichi, Ferring, Google (Verily), Johnson & Johnson, Luitpold, Medtronic, Merck, NIH, Novartis, Sanofi, St. Jude, Tenax. B. Neal: Research Support;Self;Janssen Research & Development LLC, Merck Schering Plough, Roche Pharma, Servier, Zydus Pharmaceuticals, Inc. Other Relationship;Self;Abbott, Janssen, Novartis, Pfizer, Roche, and Servier. C.A. Pollock: Advisory Panel;Self;AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Otsuka Pharmaceutical Co., Ltd., Vifor Pharma Group. Research Support;Self;Diabetes Australia. Speaker's Bureau;Self;AstraZeneca, Cipla Inc., MedErgy, Medscape, Mitsubishi Tanabe Pharma Corporation, Novartis AG, Otsuka Pharmaceutical Co., Ltd., Vifor Pharma Group. Other Relationship;Self;Amgen, George Institute for Global Health, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc. N. Rosenthal: None. D.C. Wheeler: Advisory Panel;Self;Boehringer Ingelheim Pharmaceuticals, Inc., Reata. Consultant;Self;AstraZeneca, Bayer AG, GlaxoSmithKline, Janssen Pharmaceuticals, Inc. Speaker's Bureau;Self;Amgen, Astellas Pharma Inc., Mundipharma International, Napp Pharmaceuticals. H. Zhang: Employee;Self;Renal Division of Peking University First Hospital. B. Zinman: Advisory Panel;Self;Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. V. Perkovic: Other Relationship;Self;See Other Relationship field. H.L. Heerspink: Consultant;Self;AbbVie Inc., AstraZeneca, Boehringer Ingelheim International GmbH, CSL Behring, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Mundipharma International, Retrophin, Inc. Funding: Janssen Research & Development, LLC [ABSTRACT FROM AUTHOR] Copyright of Diabetes is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Effect of Salt Substitution on Cardiovascular Events and Death.

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.).

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

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).

Impact of salt substitute and stepwise reduction of salt supply on blood pressure in residents in senior residential facilities: Design and rationale of the DECIDE-Salt trial.

BACKGROUND: High sodium intake has been considered as the leading dietary risk factor for deaths and disability-adjusted life-years among older adults. High-quality randomized trials to evaluate the effects of practical sodium reduction strategies are needed. METHODS: The study is a cluster randomized trial with a 2 × 2 factorial design conducted in 48 senior residential facilities in northern China. These facilities are randomly assigned (1:1:1:1) to 1 of 4 groups: stepwise salt supply control (SSSC) in which 5%-10% of the study salt supply in the institutional kitchens will be reduced every 3 months, replacing normal salt with salt substitute (SS); SSSC only; SS only; or neither SSSC nor SS. The interventions last for 2 years with follow-up every 6 months. The primary outcome is the change in systolic blood pressure from baseline to 24 months. Secondary outcomes include the incidence of hyperkalemia, hyponatremia, cardiovascular events, and death. CURRENT STATUS: The study has recruited and randomized 48 senior residential facilities with 1,606 participants. Mean age at baseline was 71 years, and 76% are male. Both types of salt intervention were initiated in the study facilities between January and April 2018. CONCLUSION: The study is well placed to define the effects of 2 practical and scalable sodium reduction strategies for blood pressure reduction and will provide important new data about safety of these strategies among older adults in China.

The impact of 2019 novel coronavirus on heart injury: A Systematic review and Meta-analysis.

BACKGROUND: Evidence about COVID-19 on cardiac injury is inconsistent. OBJECTIVES: We aimed to summarize available data on severity differences in acute cardiac injury and acute cardiac injury with mortality during the COVID-19 outbreak. METHODS: We performed a systematic literature search across Pubmed, Embase and pre-print from December 1, 2019 to March 27, 2020, to identify all observational studies that reported cardiac specific biomarkers (troponin, creatine kinase-MB fraction, myoglobin, or NT-proBNP) during COVID-19 infection. We extracted data on patient demographics, infection severity, comorbidity history, and biomarkers during COVID-19 infection. Where possible, data were pooled for meta-analysis with standard (SMD) or weighted (WMD) mean difference and corresponding 95% confidence intervals (CI). RESULTS: We included 4189 confirmed COVID-19 infected patients from 28 studies. More severe COVID-19 infection is associated with higher mean troponin (SMD 0.53, 95% CI 0.30 to 0.75, p < 0.001), with a similar trend for creatine kinase-MB, myoglobin, and NT-proBNP. Acute cardiac injury was more frequent in those with severe, compared to milder, disease (risk ratio 5.99, 3.04 to 11.80; p < 0.001). Meta regression suggested that cardiac injury biomarker differences of severity are related to history of hypertension (p = 0.030). Also COVID19-related cardiac injury is associated with higher mortality (summary risk ratio 3.85, 2.13 to 6.96; p < 0.001). hsTnI and NT-proBNP levels increased during the course of hospitalization only in non-survivors. CONCLUSION: The severity of COVID-19 is associated with acute cardiac injury, and acute cardiac injury is associated with death. Cardiac injury biomarkers mainly increase in non-survivors. This highlights the need to effectively monitor heart health to prevent myocarditis in patients infected with COVID-19.