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Showing papers by "Bruce Neal published in 2019"


Journal ArticleDOI
TL;DR: In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years.
Abstract: Background Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium...

3,233 citations


Journal ArticleDOI
TL;DR: Evidence is provided that the proportional effect of SGLT2 inhibitors might attenuate with declining kidney function and there was clear, separate evidence of benefit for all eG FR subgroups, including for participants with a baseline eGFR 30-45 mL/min per 1·73 m2.

534 citations


Journal ArticleDOI
TL;DR: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as.
Abstract: Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as ...

185 citations


Journal ArticleDOI
TL;DR: A systematic review and meta‐analysis was performed to assess the efficacy and safety of SGLT2 inhibitors in patients with T2DM and CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2.
Abstract: AIM: The use of sodium glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has been limited, primarily because glycemic efficacy is dependent on kidney function. We performed a systematic review and meta-analysis to assess the efficacy and safety of SGLT2 inhibitors in patients with T2DM and CKD, defined as estimated glomerular filtration rate (eGFR) <60mL/min/1.73m2 . MATERIALS AND METHODS: We searched MEDLINE, EMBASE and the Cochrane Library to August 7, 2018, as well as the websites of the United States, European, and Japanese regulatory authorities to July 27, 2018 for data from randomized controlled trials of SGLT2 inhibitors that included reporting of effects on biomarkers, cardiovascular, renal, or safety outcomes in individuals with T2DM and CKD. Random effects models and inverse variance weighting were used to calculate relative risks with 95% confidence intervals. RESULTS: Data were obtained from 27 studies with up to 7,363 participants contributing. In patients with T2DM and CKD, SGLT2 inhibitors lowered glycated hemoglobin (-0.29%, 95% CI -0.39 to -0.19), as well as blood pressure, body weight, and albuminuria. SGLT2 inhibition reduced the risk of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (RR 0.81, 95% CI 0.70-0.94) and heart failure (RR 0.61, 95% CI 0.48-0.78), without a clear effect on all-cause mortality (HR 0.86, 95% CI 0.73-1.01). These agents also attenuated the annual decline in eGFR slope (placebo-subtracted difference of 1.35 mL/1.73m2 /year, 95% CI 0.78-1.93) and reduced the risk of the composite renal outcome (HR 0.71, 95% CI 0.53-0.95). There was no evidence of additional risks with SGLT2 inhibition in CKD beyond those already known for the class, although heterogeneity was observed across individual agents for some safety outcomes. CONCLUSION: Currently available data suggest that despite only modest reductions in glycated hemoglobin, SGLT2 inhibitors reduce the risk of cardiovascular and renal outcomes in patients with T2DM and CKD, without clear evidence of additional safety concerns. This article is protected by copyright. All rights reserved.

170 citations


Journal ArticleDOI
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations as discussed by the authors.

111 citations



Journal ArticleDOI
TL;DR: Key components of 31 FOP nutrition labelling regulations endorsed by governments up to June 2019 are evaluated to support policymakers to design and implement best-practice, evidence-informed regulation.
Abstract: Unhealthy diets are a leading cause of death and disability globally. The WHO recommends Member States implement front-of-pack (FOP) nutrition labels to guide consumers towards healthier food choices, as part of comprehensive strategies to prevent diet-related non-communicable diseases. Interest in FOP nutrition labelling is increasing, but there is limited guidance for policymakers developing regulations necessary for effective implementation. A rapidly evolving evidence base, limited regulatory capacity and possibility of legal challenge by affected food industry stakeholders can create ‘regulatory chill’, whereby governments are dissuaded from progressive public health policymaking. We use a framework for analysing public health law and available best-practice guidance to evaluate key components of 31 FOP nutrition labelling regulations endorsed by governments up to June 2019. Analysis of regulatory form shows recent rapid uptake of label formats that are easier for consumers to understand and increasing use of mandatory legislation. However, policymakers must decide much more than whether to apply ‘stars’, ‘traffic lights’ or ‘stop signs’. The substance of effective regulation must contain strategic regulatory objectives, clear specifications for displaying the label on pack, a valid scoring mechanism and a justified scope for including foods. While there are limited data on current practice, good governance of FOP nutrition labelling regulation also requires transparency and accountability in processes of label development, implementation, evaluation and enforcement to promote continuous improvement and withstand undue commercial interference. Whether developing new FOP nutrition labels or reforming existing ones, our findings support policymakers to design and implement best-practice, evidence-informed regulation.

93 citations


Journal ArticleDOI
TL;DR: To accurately estimate usual dietary sodium at the individual level, at least 3 non‐consecutive complete 24‐hour urine collections obtained over a series of days that reflect the usual short‐term variations in dietary pattern were recommended.
Abstract: The International Consortium for Quality Research on Dietary Sodium/Salt (TRUE) is a coalition of intentional and national health and scientific organizations formed because of concerns low-quality research methods were creating controversy regarding dietary salt reduction. One of the main sources of controversy is believed related to errors in estimating sodium intake with urine studies. The recommendations and positions in this manuscript were generated following a series of systematic reviews and analyses by experts in hypertension, nutrition, statistics, and dietary sodium. To assess the population's current 24-hour dietary sodium ingestion, single complete 24-hour urine samples, collected over a series of days from a representative population sample, were recommended. To accurately estimate usual dietary sodium at the individual level, at least 3 non-consecutive complete 24-hour urine collections obtained over a series of days that reflect the usual short-term variations in dietary pattern were recommended. Multiple 24-hour urine collections over several years were recommended to estimate an individual's usual long-term sodium intake. The role of single spot or short duration timed urine collections in assessing population average sodium intake requires more research. Single or multiple spot or short duration timed urine collections are not recommended for assessing an individual's sodium intake especially in relationship to health outcomes. The recommendations should be applied by scientific review committees, granting agencies, editors and journal reviewers, investigators, policymakers, and those developing and creating dietary sodium recommendations. Low-quality research on dietary sodium/salt should not be funded, conducted, or published.

88 citations


Journal ArticleDOI
TL;DR: In this article, the Canagliflozin cardioVascular Assessment Study (CANVAS) Program showed that canaglifloclozin had a beneficial effect on cardiovascular and renal outcomes in people with type 2 diabetes at high cardiovascular risk, but also an unexpected increased risk of major or minor lower extremity amputation.
Abstract: The primary analysis of the Canagliflozin cardioVascular Assessment Study (CANVAS) Program showed canagliflozin to have a beneficial effect on cardiovascular and renal outcomes in people with type 2 diabetes at high cardiovascular risk, but also an unexpected increased risk of major or minor lower extremity amputation. These secondary analyses explore this finding in more detail. The effect of canagliflozin on amputation risk in the CANVAS Program was calculated for amputations of different types and proximate aetiologies and different canagliflozin doses. Univariate and multivariate associations of baseline characteristics with amputation risk were determined and proportional and absolute effects of canagliflozin were compared across subgroups. There were 187 (1.8%) participants with atraumatic lower extremity amputations (minor 71%, major 29%); as previously published, rates were 6.30 vs 3.37 per 1000 participant-years with canagliflozin vs placebo (HR 1.97 [95% CI 1.41, 2.75]). Risk was similar for ischaemic and infective aetiologies and for 100 mg and 300 mg doses. Overall amputation risk was strongly associated with baseline history of prior amputation (major or minor) (HR 21.31 [95% CI 15.40, 29.49]) and other established risk factors. No interactions between randomised treatment and participant characteristics explained the effect of canagliflozin on amputation risk. For every clinical subgroup studied, numbers of amputation events projected were smaller than numbers of major adverse cardiovascular events averted. The CANVAS Program demonstrated that canagliflozin increased the risk of amputation (mainly minor) in this study population. Anticipated risk factors for amputation were identified, such as prior history of amputation, peripheral vascular disease and neuropathy, but no specific aetiological mechanism or at-risk subgroup for canagliflozin was identified.

85 citations


Journal ArticleDOI
TL;DR: The proportional effects of canagliflozin on renal and cardiovascular outcomes are mostly consistent across patients with different levels of albuminuria, but absolute benefits are greatest among those with severely increasedalbuminuria.
Abstract: BACKGROUND If SGLT2 inhibitors protect the kidneys by reducing albuminuria as hypothesized, people with type 2 diabetes mellitus (T2DM) with higher albuminuria should benefit more. METHODS We conducted a post-hoc analysis of data from the CANagliflozin cardioVascular Assessment Study (CANVAS) Program, which randomized 10,142 participants with T2DM and high cardiovascular risk to canagliflozin or placebo. We assessed effects of canagliflozin on renal, cardiovascular, and safety outcomes by baseline albuminuria. The trial included 2266 participants (22.3%) with moderately increased albuminuria (urinary albumin/creatinine ratio [UACR] 30-300 mg/g) and 760 (7.5%) with severely increased albuminuria (UACR >300 mg/g) at baseline. RESULTS Canagliflozin lowered albuminuria with greater proportional reductions in those with moderately and severely increased albuminuria (P heterogeneity<0.001). After week 13, canagliflozin slowed the annual loss of kidney function across albuminuria subgroups, with greater absolute reductions in participants with severely increased albuminuria (placebo-subtracted difference 3.01 ml/min per 1.73 m2 per year; P heterogeneity<0.001). Heterogeneity for the renal composite outcome of 40% reduction in eGFR, ESKD, or renal-related death was driven by lesser effects in participants with moderately increased albuminuria (P heterogeneity=0.03), but no effect modification was observed when albuminuria was fitted as a continuous variable (P heterogeneity=0.94). Cardiovascular and safety outcomes were mostly consistent across albuminuria levels including increased risks for amputation across albuminuria subgroups (P heterogeneity=0.66). Greater absolute risk reductions in the renal composite outcome were observed in participants with severely increased albuminuria (P heterogeneity=0.004). CONCLUSIONS The proportional effects of canagliflozin on renal and cardiovascular outcomes are mostly consistent across patients with different levels of albuminuria, but absolute benefits are greatest among those with severely increased albuminuria.

83 citations


01 Jan 2019
TL;DR: The International Consortium for Quality Research on Dietary Sodium/ Salt (TRUE) is a coalition of intentional and national health and scientific organizations formed because of concerns low-quality research methods were creating controversy regarding dietary salt reduction as mentioned in this paper.
Abstract: The International Consortium for Quality Research on Dietary Sodium/Salt (TRUE) is a coalition of intentional and national health and scientific organizations formed because of concerns low-quality research methods were creating controversy regarding dietary salt reduction. One of the main sources of controversy is believed related to errors in estimating sodium intake with urine studies. The recommendations and positions in this manuscript were generated following a series of systematic reviews and analyses by experts in hypertension, nutrition, statistics, and dietary sodium. To assess the population's current 24-hour dietary sodium ingestion, single complete 24-hour urine samples, collected over a series of days from a representative population sample, were recommended. To accurately estimate usual dietary sodium at the individual level, at least 3 non-consecutive complete 24-hour urine collections obtained over a series of days that reflect the usual short-term variations in dietary pattern were recommended. Multiple 24-hour urine collections over several years were recommended to estimate an individual's usual long-term sodium intake. The role of single spot or short duration timed urine collections in assessing population average sodium intake requires more research. Single or multiple spot or short duration timed urine collections are not recommended for assessing an individual's sodium intake especially in relationship to health outcomes. The recommendations should be applied by scientific review committees, granting agencies, editors and journal reviewers, investigators, policymakers, and those developing and creating dietary sodium recommendations. Low-quality research on dietary sodium/salt should not be funded, conducted, or published.

Journal ArticleDOI
01 Feb 2019-Stroke
TL;DR: There were too few events in the CANVAS Program to separately define the effects of canagliflozin on stroke, but benefit is more likely than harm.
Abstract: Background and Purpose— This study reports the detailed effects of canagliflozin on stroke, stroke subtypes, and vascular outcomes in participants with and without cerebrovascular disease (stroke o...

Journal ArticleDOI
TL;DR: The recently reported null result for fracture in the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial suggests that the observed association in CANVAS is likely to be a chance finding, although an unidentified fall-related mechanism remains a possibility.
Abstract: An increased risk of fracture with canagliflozin vs placebo was reported from the CANagliflozin cardioVascular Assessment Study (CANVAS) Program, with heterogeneity of findings identified between the two trials that comprise the CANVAS Program, CANVAS and CANVAS-R. The objective of these analyses was to identify reasons for the possibly different effects on fracture observed between CANVAS and CANVAS-R. This study was an analysis of two highly similar trials, CANVAS and CANVAS-R, conducted in 10,142 individuals with type 2 diabetes and history or high risk of cardiovascular disease who received canagliflozin (pooled 100/300 mg once daily) or placebo. Outcomes assessed in this analysis were effects on adjudicated fractures overall and by type, location, association with a fall, dose and follow-up time. A total of 496 participants recorded ≥1 fracture event during follow-up (15.40 vs 11.93 per 1000 patient-years with canagliflozin vs placebo; HR 1.26 [95% CI 1.04, 1.52]). There was significant heterogeneity in the effects on fracture (p = 0.005) between CANVAS (n = 4330: HR 1.55 [95% CI 1.21, 1.97]) and CANVAS-R (n = 5812: HR 0.86 [95% CI 0.62, 1.19]). The between-study heterogeneity in fracture risk was not clearly explained by differences in baseline characteristics, interactions of randomised treatment with participant characteristics, dose effects, duration of follow-up, metabolic effects, adverse events related to falls or adverse events possibly causing falls. There was no evidence to explain clearly the fracture risk observed in the CANVAS Program or the heterogeneity in fracture risk between the two studies. The recently reported null result for fracture in the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial suggests that the observed association in CANVAS is likely to be a chance finding, although an unidentified fall-related mechanism remains a possibility. ClinicalTrials.gov NCT01032629, NCT01989754.

Journal ArticleDOI
TL;DR: The continuation of angiotensin-converting enzyme inhibitor-based therapy reduced the long-term risk of major clinical outcomes, irrespective of acute increase in creatinine, in diabetes mellitus patients randomly assigned to perindopril-indapamide or placebo.
Abstract: Discontinuation of angiotensin-converting enzyme (ACE) inhibitor is recommended if patients experience ≥30% acute increase in serum creatinine after starting this therapy. However, the long-term ef...

Journal ArticleDOI
01 Jan 2019-Heart
TL;DR: Polypill-based therapy significantly improved the achievement of all three ESC targets for blood pressure, low-density lipoprotein (LDL) cholesterol and antiplatelet therapy compared with usual care, particularly among those undertreated at baseline.
Abstract: Objective The aim of this study was to determine the effect of polypill-based care on the achievement of 2016 European Society of Cardiology (ESC) guideline targets for blood pressure (BP), low-density lipoprotein (LDL) cholesterol and antiplatelet therapy. Methods We conducted an individual participant data meta-analysis of three randomised clinical trials that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior cardiovascular disease (CVD) event or who were at high risk of their first event. Overall, the trials included 3140 patients from Australia, England, India, Ireland, the Netherlands and New Zealand (75% male, mean age 62 years and 76% with a prior CVD event). The primary outcome for this study was the proportion of people achieving ESC guideline targets for BP, LDL and antiplatelet therapy. Results Those randomised to polypill-based care were more likely than those receiving usual care to achieve recommended targets for BP (62% vs 58%, risk ratio (RR) 1.08, 95% CI 1.02 to 1.15), LDL (39% vs 34%, RR 1.13, 95% CI 1.02 to 1.25) and all three targets for BP, LDL and adherence to antiplatelet therapy (the latter only applicable to those with a prior CVD event) simultaneously (24% vs 19%, RR 1.27, 95% CI 1.10 to 1.47) at 12 months. There was no difference between groups in antiplatelet adherence (96% vs 96%, RR 1.00, 95% CI 0.98 to 1.01). There was heterogeneity by baseline treatment intensity such that treatment effects increased with the fewer the number of treatments being taken at baseline: for patients taking 3, 2 and 0–1 treatment modalities the RRs for reaching all three guideline goals simultaneously were 1.10 (95% CI 0.94 to 1.30, 22% vs 20%), 1.62 (95% CI 1.09 to 2.42, 27% vs 17%) and 3.07 (95% CI 1.77 to 5.33, 35% vs 11%), respectively. Conclusions Polypill-based therapy significantly improved the achievement of all three ESC targets for BP, LDL and antiplatelet therapy compared with usual care, particularly among those undertreated at baseline.

Journal ArticleDOI
TL;DR: Clinical practice should focus less on pretreatment BP levels, which rarely predict future untreated BP levels or rule out capacity to benefit from BP lowering in high cardiovascular risk patients, and instead focus on prompt, empirical treatment to maintain lower BP for those with high BP and/or high risk.
Abstract: Objective:To assess the clinical relevance of regression to the mean for clinical trials and clinical practice.Methods:MEDLINE was searched until February 2018 for randomized trials of BP lowering with over 1000 patient-years follow-up per group. We estimated baseline mean BP, follow-up mean (usual)

Journal ArticleDOI
TL;DR: The wide variability in healthfulness and level of processing demonstrates that opportunities exist, through reformulation or replacement, for large-scale improvements to the healthfulness of the US packaged food and beverage supply.
Abstract: The US food supply is dominated by highly-processed packaged food and beverage products that are high in energy, saturated fat, sugar, and salt. We report results of a cross-sectional assessment of the 2018 US packaged food and beverage supply by nutritional composition and indicators of healthfulness and level of processing. Data were obtained through Label Insight’s Open Data database, which represents >80% of all food and beverage products sold in the US over the past three years. Healthfulness and the level of processing, measured by the Health Star Rating (HSR) system and the NOVA classification framework, respectively, were compared across product categories and leading manufacturers. Among 230,156 food and beverage products, the mean HSR was 2.7 (standard deviation (SD) 1.4) from a possible maximum rating of 5.0, and 71% of products were classified as ultra-processed. Healthfulness and level of processing varied substantially by category (range: HSR 1.1–3.9; 0–100% ultra-processed) and manufacturer (range: HSR 0.9–4.6; 26–100% ultra-processed). The US packaged food and beverage supply is large, heterogeneous, highly processed, and generally unhealthy. The wide variability in healthfulness and level of processing demonstrates that opportunities exist, through reformulation or replacement, for large-scale improvements to the healthfulness of the US packaged food and beverage supply.

Journal ArticleDOI
01 Dec 2019
TL;DR: Compared with placebo, canagliflozin reduced serum urate concentration and also reduced events related to gout flare among patients with type 2 diabetes.
Abstract: Summary Background Sodium glucose co-transporter 2 inhibitors have been shown to reduce serum urate concentration. The Canagliflozin Cardiovascular Assessment Study (CANVAS) Program integrated data from two similarly designed, randomised, double-blind, placebo-controlled trials (CANVAS and CANVAS-Renal) assessing the cardiovascular and renal safety of canagliflozin compared with placebo in patients with type 2 diabetes. In this post-hoc analysis, we aimed to investigate the effect of canagliflozin compared with placebo on gout in the CANVAS Program. Methods In the CANVAS Program, individuals with type 2 diabetes and an elevated risk of cardiovascular disease were randomly assigned to receive either canagliflozin (100 or 300 mg) or placebo. In this post-hoc analysis, we assessed the effects of canagliflozin versus placebo on serum urate concentration using mixed linear models and the occurrence of either an adverse event attributed to gout flare or the commencement of a drug for gout using Kaplan-Meier analysis with Cox proportional hazards models to determine a hazard ratio (HR) and 95% CIs. All analyses were done according to the principle of intention to treat, and there was no imputation for missing data. Findings 10 142 participants were included in analyses. At baseline, mean age was 63 years (SD 8), 3633 (36%) participants were female, mean serum urate concentration was 348·9 μmol/L (95·5), and 471 (5%) of participants had a history of gout. Mean follow-up was 3·6 years (SD 2·0) and mean serum urate concentration was −23·3 μmol/L (95% CI −25·4 to −21·3) lower in participants treated with canagliflozin than in those who received placebo, equating to a 6·7% reduction in serum urate (percentage difference −6·7%, 95% CI −7·3 to −6·1). During follow-up, 80 individuals reported an episode of gout flare and 147 commenced a drug for gout. The occurrence of gout flare or the need for treatment for gout was lower in participants treated with canagliflozin than in those who received placebo (HR 0·53, 95% CI 0·40–0·71; p Interpretation In this post-hoc analysis, compared with placebo, canagliflozin reduced serum urate concentration and also reduced events related to gout flare among patients with type 2 diabetes. A trial explicitly designed to test the effects of sodium glucose co-transporter 2 inhibition on gout is required to confirm these observations. Funding Janssen Research & Development.

Journal ArticleDOI
TL;DR: The finding that packaged foods and beverages are less healthy in middle‐income countries such as China and India suggests that nutrient profiling is an important tool to enable policymakers and industry actors to reformulate products available in the marketplace to reduce the risk of obesity and NCDs among populations.
Abstract: We compared the healthiness of packaged foods and beverages between selected countries using the Health Star Rating (HSR) nutrient profiling system. Packaged food and beverage data collected 2013-2018 were obtained for Australia, Canada, Chile, China, India, Hong Kong, Mexico, New Zealand, Slovenia, South Africa, the UK, and USA. Each product was assigned to a food or beverage category and mean HSR was calculated overall by category and by country. Median energy density (kJ/100 g), saturated fat (g/100 g), total sugars (g/100 g) and sodium (mg/100 g) contents were calculated. Countries were ranked by mean HSR and median nutrient levels. Mean HSR for all products (n = 394,815) was 2.73 (SD 1.38) out of 5.0 (healthiest profile). The UK, USA, Australia and Canada ranked highest for overall nutrient profile (HSR 2.74-2.83) and India, Hong Kong, China and Chile ranked lowest (HSR 2.27-2.44). Countries with higher overall HSR generally ranked better with respect to nutrient levels. India ranked consistently in the least healthy third for all measures. There is considerable variability in the healthiness of packaged foods and beverages in different countries. The finding that packaged foods and beverages are less healthy in middle-income countries such as China and India suggests that nutrient profiling is an important tool to enable policymakers and industry actors to reformulate products available in the marketplace to reduce the risk of obesity and NCDs among populations.

Journal ArticleDOI
TL;DR: Urgent action is needed to implement a program to achieve the WHO salt reduction target of a 30% reduction by 2025, and the focus needs to be on changing consumer behavior combined with low sodium, salt substitution.
Abstract: Recent data on salt intake levels in India show consumption is around 11 g per day, higher than the World Health Organization’s (WHO) recommended intake of 5 g per day. However, high-quality data on sources of salt in diets to inform a salt reduction strategy are mostly absent. A cross-sectional survey of 1283 participants was undertaken in rural, urban, and slum areas in North (n = 526) and South (n = 757) India using an age-, area-, and sex-stratified sampling strategy. Data from two 24-h dietary recall surveys were transcribed into a purpose-built nutrient database. Weighted salt intake was estimated from the average of the two recall surveys, and major contributors to salt intake were identified. Added salt contributed the most to total salt intake, with proportions of 87.7% in South India and 83.5% in North India (p < 0.001). The main food sources of salt in the south were from meat, poultry, and eggs (6.3%), followed by dairy and dairy products (2.6%), and fish and seafood (1.6%). In the north, the main sources were dairy and dairy products (6.4%), followed by bread and bakery products (3.3%), and fruits and vegetables (2.1%). Salt intake in India is high, and this research confirms it comes mainly from added salt. Urgent action is needed to implement a program to achieve the WHO salt reduction target of a 30% reduction by 2025. The data here suggest the focus needs to be on changing consumer behavior combined with low sodium, salt substitution.



Journal ArticleDOI
TL;DR: A cap on single serve SSB could be an effective part of a suite of obesity prevention and sugar reduction interventions in high income countries.


11 Nov 2019
TL;DR: In this article, the authors proposed that there would be similar benefits on cardiovascular and renal endpoints regardless of baseline HbA1c, including those with Hb1c < 7%.
Abstract: Traditional management of diabetes mellitus has focused on glycemic control, beginning with lifestyle changes, followed by metformin, and then other classes of antiglycemic agents.1 Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce cardiovascular (CV) events, including CV death, myocardial infarction (MI) and heart failure, and slow progression of renal dysfunction, including prevention of end-stage kidney disease (ESKD).2-3 Because initial clinical trials included mostly patients with baseline HbA1c >7%, current guidelines have recommended this class as add-on therapy for patients whose HbA1c is not at goal, typically ≥7%.1 We hypothesized that there would be similar benefits on CV and renal endpoints regardless of baseline HbA1c, including those with HbA1c <7%.

Journal ArticleDOI
TL;DR: Dietary sodium reduction was associated with significantly lower uACR and less albuminuria after 18 months, and whether CKD progression can be slowed by dietary sodium reduction should be a global research priority.

Journal ArticleDOI
TL;DR: Observed variation likely reflects real differences in patient characteristics and physician management practices across regions and specialities but may also reflect differences in patients selection and errors in estimation of catchment population across participating centres.
Abstract: Objective:We evaluated the characteristics of patients with treatment-resistant hypertension (TRH) and the prevalence of TRH in a large multicountry sample of specialist tertiary centres.Methods:The Survey of PatIents with treatment ResIstant hyperTension (SPIRIT) study was a retrospective review of



Journal ArticleDOI
TL;DR: It is shown that sodium reduction could reduce blood pressure in all adult populations regardless of age, sex and race and there is not enough evidence to show the impact of intervention duration.
Abstract: Authoritative medical and public health agencies in most countries advise to reduce population dietary salt intake to under 5–6 g/day as a strategy for preventing high blood pressure and cardiovascular disease. However, there is still dispute about whether salt reduction should be adopted by all populations. In addition, the effect of duration of dietary salt reduction has not been sufficiently investigated. To understand the effect of dietary salt reduction on blood pressure and the impact of intervention duration. A systematic review and meta-analysis was conducted. Randomized controlled trials that allocated participants to low and high salt intake, without confounding from unequal concomitant interventions, were included. We excluded studies done in individuals younger than 18 years, pregnant women, individuals with renal disease or heart failure, and studies with sodium excretion estimated from spot urine. Random effect meta-analysis was used to generate pooled estimates of the effect on 24-hour urinary sodium excretion, systolic and diastolic blood pressure. Multivariate meta-regression was used to quantify the dose response effect of dietary salt on blood pressure change and to understand the impact of the intervention duration. 125 studies were included with 162 data points extracted. Ninety-nine data points (61%) had interventions under 4 weeks. Overall, 24-hour urinary sodium excretion changed by −141 mmol (95% CI: −156; −126), systolic blood pressure changed by −4.4 mm Hg (95% CI: −5.2; −3.7) and diastolic blood pressure changed by −2.4 mm Hg (95% CI: −2.9; −1.9). Sodium reduction resulted in a significant decrease of systolic blood pressure in all subgroups except in participants with low baseline sodium intake (<109 mmol) (Figure 1). Each 100 mmol reduction of sodium was associated with 2.7 mm Hg (95% CI: 1.0; 4.4; p=0.002) reduction of systolic blood pressure and 1.2 mm Hg (95% CI: 0.0; 2.4; p=0.046) reduction of diastolic blood pressure after adjusting for intervention duration, age, sex, race, baseline blood pressure, baseline sodium intake and interaction between age and baseline blood pressure. For the same amount of salt reduction, a 10 mm Hg higher baseline systolic blood pressure would result in 2.5 mm Hg greater reduction of systolic blood pressure. There is not enough evidence to show the impact of intervention duration. Figure 1 Our meta-analysis showed that sodium reduction could reduce blood pressure in all adult populations regardless of age, sex and race. The effect of salt reduction on systolic blood pressure increases with higher baseline blood pressure. Further studies, designed to investigate the impact of intervention duration, are needed to understand the significance of the duration. None