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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 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.

Background 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 (RAAS), 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. Purpose We sought to assess the effect of canagliflozin on hyperkalaemia and other potassium-related outcomes in people with T2DM and CKD by conducting a post-hoc analysis of the CREDENCE trial. Methods 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 Results 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. Canagliflozin reduced the risk of investigator-reported hyperkalaemia or initiation of potassium binders (HR 0.78, 95% CI 0.64–0.95, p=0.014; Figure 1). The incidence of laboratory-determined hyperkalaemia was similarly reduced (HR 0.77, 95% CI 0.61–0.98, p=0.031; Figure 2); the risk of hypokalaemia (HR 0.92, 95% CI 0.71–1.20, p=0.53) was not increased. Mean serum potassium over time with canagliflozin was similar to that of placebo. Conclusion Among patients treated with RAAS inhibitors, SGLT2 inhibition with canagliflozin may reduce the risk of hyperkalaemia in people with T2DM and CKD without increasing the risk of hypokalaemia. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Background Front-of-pack nutrition labelling (FoPL) of packaged foods can promote healthier diets. Australia & New Zealand (NZ) adopted the voluntary Health Star Rating (HSR) scheme in 2014. We studied the impact of voluntary adoption of HSR on food reformulation overall, and for more- versus less-healthy foods. Methods Annual nutrition information panel data was collected for non-seasonal packaged foods sold in major supermarkets in Auckland from 2013-19, and Sydney from 2014-18. We used difference-in-differences to estimate reformulation associated with HSR adoption. Results Healthier products adopted HSR more than unhealthy products: 35% of products that achieved four or more stars displayed the label compared to 15% of products that achieved two stars or less. Products that adopted HSR were 6.5% & 10.7% more likely to increase their rating by ≥ 0.5 stars in Australia and NZ, respectively. Labelled products showed a -4.2% [95% CI -6.5% to -1.9%] relative decline in sodium content in NZ, but there was no sodium change in Australia. There was a -2.3% [-3.7% to -1.0 %] change in sugar content in NZ and a -1.1% [-2.2% to 0.0%] difference in Australia. Initially unhealthy products showed larger reformulation when adopting HSR than healthier products. Conclusions Overall, introduction of HSR had a small effect on product reformulation. The voluntary nature of the HSR program lowers effectiveness because labels were mostly placed on already healthy products. These already healthy products had limited scope for reformulation. Key messages HSR adoption by unhealthy products should be incentivized, or mandated, by governments to maximise reformulation

Background SGLT2 inhibitors have been shown to reduce hospitalization for heart failure (HHF). We sought to determine independent baseline predictors for HHF specifically in a population with type 2 diabetes and chronic kidney disease (CKD). Methods CREDENCE randomized 4401 participants with type 2 diabetes and CKD to canagliflozin 100 mg versus placebo. We evaluated the baseline clinical and demographic factors using multivariate regression modeling to identify the independent predictors of HHF. Results Overall, 230 participants (89 canagliflozin; 141 placebo) had at least 1 HHF event. Canagliflozin reduced the incidence of HHF compared with placebo (4.0% vs 6.4%; HR 0.61; 95% CI 0.47–0.80). Participants with HHF events postrandomization were older (65.8 vs 62.9 y), and had a longer duration of diabetes (17.4 vs 15.7 y), higher prevalence of prior HF (30.4% vs 14.0%), higher urinary albumin:creatinine ratio (1347 vs 904 mg/g), lower estimated glomerular filtration rate (51.5 vs 56.4 mL/min/1.73m2), and higher prevalence of prior cardiovascular disease (65.7% vs 49.6%) compared to those without HHF. Independent predictors of HHF are shown in the Table. Conclusions HHF is common in patients with type 2 diabetes and CKD. Canagliflozin reduces HHF by 39% compared with placebo. Higher urinary albumin:creatinine ratio was the most potent predictor of HHF and should be part of patient risk assessment. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Janssen Research & Development, LLC

Background Nutrient Profiling Systems (NPSs), including the UK Food Standards Agency NPS and its variants are used to classify foods according to their nutritional composition for nutrition policies. The prospective validity of these NPSs requires however further investigation. The study investigates the associations of the original Food Standards Agency (FSA)-NPS and three variants - the Food Standards Australia New Zealand Nutrient Profiling Scoring Criterion (NPSC), the Health Star Rating (HSR) system NPS and the French NPS (HCSP-NPS) -, which are used as a basis for nutrition policies, with weight status. Methods Dietary indices based on each of the four investigated NPSs applied at the food level were computed at the individual level to characterize the diet quality of 71,178 French individuals from the NutriNet-Santé cohort. Associations of these Dietary Indices (DIs) (as tertiles) with weight gain were assessed using multivariable mixed models, and with overweight and obesity risks using multivariable Cox models. Results For the four NPSs, participants with a lower diet nutritional quality were more likely to have an increase in body mass index over time (median follow-up of 3.14 ± 2.76 years, beta coefficients positive, all p ≤ 0.0001), and an increased risk of overweight (HRT3vs.T1=1.27 [1.17-1.37] for the HCSP-DI, followed by the original FSA-DI with HRT3vs.T1=1.18 [1.09-1.28], the NPSC-DI with HRT3vs.T1=1.14 [1.06-1.24] and the HSR-DI, HRT3vs.T1=1.12 [1.04-1.21]). Whilst differences were small, the HCSP-DI appeared to show significantly greater association with risk of overweight compared to other NPS. Conclusions Less healthy diets defined using the Food Standards Agency-NPS and related systems were all associated with weight gain and overweight risk. Demonstrating this association with health outcomes is an important indicator of one validity dimension of NPSs and supports their use in public policies for the prevention of diet-related chronic diseases. Key messages Nutrient profile models of foods and beverages allow capturing the nutritional quality of diets and are prospectively associated with weight gain and obesity. The French NPS which underpins the front-of-pack Nutri-Score appeared to have a small but significant higher performance.

Background and Aims To describe genital mycotic infections (GMI) and urinary tract infections (UTI) in the CREDENCE trial, determine whether canagliflozin increased the risk of these infections overall and in subgroups, and describe predictors of risk for genital mycotic infections. Method The CREDENCE trial randomised people with type 2 diabetes and albuminuric stage 2 and 3 chronic kidney disease to canagliflozin 100mg daily or placebo. We analysed the risk of GMI and UTI with canagliflozin compared to placebo overall and in patient subgroups. The primary analysis was conducted in the on-treatment population, as the more conservative approach with sensitivity analyses conducted using an intention-to-treat population. When canagliflozin increased risk, we determined patient risk factors for GMIs using multivariable Cox regression models adjusting for age, gender, race, markers of disease severity (body mass index (BMI), haemoglobin A1c, diabetes duration, other glucose lowering medications at baseline and kidney function). Results Overall 31/2905 (1.1%) men and 32/1492 (2.1%) women experienced 91 GMIs and 166/2905 (5.7%) men and 300/1492 (20.1%) women experienced 669 UTIs. Canagliflozin increased the risk of GMI (HR 3.83 [95% CI 2.08-7.06] p Conclusion Canagliflozin increased the risk of genital mycotic infections but not urinary tract infections. The risk of genital mycotic infections from canagliflozin over placebo was higher in men and those with higher BMI. In those treated with canagliflozin, higher BMI and longer diabetes duration independently predicted infection. Most participants continued treatment following their first infection with similar recurrence rates in the canagliflozin and placebo groups.These findings will be useful in clinical care, and help identify those at greatest risk for genital infections with canagliflozin treatment.

Background and Aims Patient with type 2 diabetes mellitus (T2DM) included in trials of sodium-glucose cotransporter 2 inhibitors are heterogeneous in terms of disease severity. We assessed the effects of canagliflozin compared to placebo on cardiovascular and renal outcomes in the CANVAS program according to severity of T2DM as indicated by intensity of treatment, duration of diabetes and glycaemic control. Method We compared effects on major adverse cardiovascular events ([MACE], defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) according to three indicators of T2DM severity at study baseline: number of oral glucose lowering treatments or insulin therapy (0-1, 2, 3+, insulin), duration of diabetes (16 years) and HbA1c (9.0%). We also assessed effects on other pre-specified cardiovascular outcomes, and an adjudicated composite of end-stage kidney disease, renal death or sustained 40% decline in estimated glomerular filtration rate. We assessed for constancy of hazard ratios across subgroups by fitting an interaction term that tested for linear trend. Results Of 10,142 participants in the CANVAS Program, 1011 experienced a MACE during a mean follow-up of 3.6 years. Event rates for MACE were higher in those with longer duration of diabetes and higher HbA1c at baseline. The effect of canagliflozin on MACE in the overall population (HR 0.86, 95 % CI 0.75-0.97) was consistent irrespective of the number of glucose lowering treatments (p=0.509), duration of diabetes (p=0.174) and baseline HbA1c (p =0.314). Effects were also consistent across different levels of T2DM disease severity for all other outcomes studied. Conclusion Higher event rates were observed in those with longer disease duration and higher HbA1c. The proportional risk reductions achieved with canagliflozin were comparable regardless of diabetes duration, number of therapies or HbA1C at baseline.

Background and Aims The skin’s hypertonic microenvironment has a hypothesized protective antimicrobial function that may be disrupted by SGLT2i. The association between sodium glucose cotransporter inhibitors (SGLT2i) and genital mycotic infections is well established, but it is not known if these agents increase the risk of other skin and soft tissue infections (SSTI). We aimed to describe SSTI in the CREDENCE trial, and determine whether canagliflozin affects the risk of skin and soft tissue infections (SSTIs) overall and in subgroups. Method We performed a post-hoc analysis of the CREDENCE trial that randomised people with type 2 diabetes and albuminuric stage 2 and 3 chronic kidney disease to either canagliflozin 100mg daily or placebo. Infections reported as adverse events were assessed by two blinded authors following predetermined criteria for SSTI with discrepancies resolved by consensus. We analysed the risks of SSTIs in the on-treatment population as the more conservative approach, with a sensitivity analysis conducted in the intention-to-treat population. Univariable time-to first-event regression models were assessed. Results Overall 373/4397 (8.5%) participants experienced 478 events comprising 252 bacterial skin infections (including 2 episodes of necrotising fasciitis), 94 fungal skin infections, 109 other skin infections and 23 soft tissue infections. Of these, 136/478 (28%) were serious. Drug was continued in 290/373 (78%) of first events, with similar frequency of subsequent events between groups (31/133 (23%) and 33/157 (21%) for those continuing canagliflozin and placebo respectively). In both cases of necrotising fasciitis, drug was withdrawn and the participants recovered.Canagliflozin did not increase the risk of SSTI (HR 0.85 [95% Confidence Interval (CI) 0.69-1.04] p=0.11) (Figure 1). Results were similar in the intention-to-treat population (HR 0.88 [95% CI 0.73-1.07] p=0.20), in analyses confined to serious SSTI (HR 0.83 [95% CI 0.58-1.21] p=0.33), and in the predefined subgroups. Conclusion Although other studies suggest that SGLT2i may reduce the sodium content of the skin, we found that canagliflozin does not increase the risk of skin and soft tissue infections, overall or in any subgroup, in people with type 2 diabetes mellitus and albuminuric chronic kidney disease.

Excess salt intake contributes to hypertension and increased cardiovascular disease risk. Efforts to implement effective salt-reduction strategies require accurate data on the sources of salt consumption. We therefore performed a systematic review to identify the sources of dietary salt around the world. We systematically searched peer-reviewed and gray literature databases for studies that quantified discretionary (salt added during cooking or at the table) and nondiscretionary sources of salt and those that provided information about the food groups contributing to dietary salt intake. Exploratory linear regression analysis was also conducted to assess whether the proportion of discretionary salt intake is related to the gross domestic product (GDP) per capita of a country. We identified 80 studies conducted in 34 countries between 1975 and 2018. The majority (n = 44, 55%) collected data on dietary salt sources within the past 10 y and were deemed to have a low or moderate risk of bias (n = 75, 94%). Thirty-two (40%) studies were judged to be nationally representative. Populations in Brazil, China, Costa Rica, Guatemala, India, Japan, Mozambique, and Romania received more than half of their daily salt intake from discretionary sources. A significant inverse correlation between discretionary salt intake and a country's per capita GDP was observed (P

Background SaltSwitch is an innovative smartphone application (app) that enables shoppers to scan the barcode of a packaged food and receive an immediate, interpretive, traffic light nutrition label on the screen, along with suggestions for lower salt alternatives. Our aim was to determine the effectiveness of SaltSwitch to support people with cardiovascular disease to make lower salt food choices. Design Six-week, two-arm, parallel, randomised controlled trial in Auckland, New Zealand (2 weeks baseline and 4 weeks intervention). Methods Sixty-six adults with diagnosed cardiovascular disease (mean (SD) age 64 (7) years) were randomly assigned in a 1:1 ratio to either the SaltSwitch smartphone app or control (usual care). The primary outcome was the salt content of household packaged food purchases during the 4-week intervention (g/MJ). Secondary outcomes were the saturated fat content (g/MJ), energy content (kJ/kg) and expenditure (NZ$) of household food purchases; systolic blood pressure (mmHg), urinary sodium (mg) and use and acceptability of the SaltSwitch app. Results Thirty-three participants with cardiovascular disease were allocated to the SaltSwitch intervention, and 33 to the control group. A significant reduction in mean household purchases of salt was observed (mean difference (95% confidence interval), -0.30 (-0.58 to -0.03) g/MJ), equating to a reduction of ∼0.7 g of salt per person per day during the 4-week intervention phase. There were no significant between-group differences in any secondary outcomes (all P > 0.05). Conclusions The SaltSwitch smartphone app is effective in supporting people with cardiovascular disease to make lower salt food purchases. A larger trial with longer follow-up is warranted to determine the effects on blood pressure. Trial registration Australian New Zealand Clinical Trials Registry https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365784&isReview=true ACTRN12614000206628.

Background 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. Purpose To understand the effect of dietary salt reduction on blood pressure and the impact of intervention duration. Methods 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. Results 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 ( Figure 1 Conclusions 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. Acknowledgement/Funding None

OBJECTIVES: Population-level replacement of discretionary (i.e, table/cooking) salt with potassium-enriched salt substitutes is a promising strategy to reduce blood pressure (BP) and prevent cardiovascular disease (CVD). This may be particularly impactful in countries like China where sodium intake is high, mainly from discretionary salt use, and where potassium intake low. However, hyperkalemia resulting from potassium-enriched substitutes and its adverse CVD consequences are of concern for those with chronic kidney disease (CKD). We aimed to estimate the benefits and risks of nationwide replacement of discretionary salt with potassium-enriched salt substitute on CVD mortality in Chinese CKD patients. METHODS: We used a comparative risk assessment framework and incorporated existing data and corresponding uncertainties from randomized trials, the China National Survey of CKD, the Global Burden of Disease study, and the CKD Prognosis Consortium. We estimated averted CVD mortality from reduced BP subsequent to salt substitution in CKD patients (defined as estimated glomerular filtration rate

Aim The aim of this study was to investigate whether polypill-based care for the prevention of cardiovascular disease (CVD) is associated with a change in lifestyle risk factors when compared with usual care, among patients with CVD or high calculated cardiovascular risk. Methods We conducted an individual participant data meta-analysis of three trials including patients from Australia, England, India, Ireland, the Netherlands and New Zealand that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior CVD event or who were at high risk of their first event. Analyses investigated any differential effect on anthropometric measures and self-reported lifestyle behaviours. Results Among 3140 patients (75% male, mean age 62 years and 76% with a prior CVD event) there was no difference in lifestyle risk factors in those randomised to polypill-based care compared with usual care over a median of 15 months, either across all participants combined, or in a range of subgroups. Furthermore, narrow confidence intervals (CIs) excluded any major effect; for example differences between the groups in body mass index was -0.1 (95% CI -0.2 to 0.1) kg/m2, in weekly duration of moderate intensity physical activity was -2 (-26 to 23) minutes and the proportion of smokers was 16% vs 17% (RR 0.98, 0.84 to 1.15) at the end of trial. Discussion This analysis allays concern that polypill-based care may lead to neglect of lifestyle risk factors, at least among high-risk patients. Maximally effective preventive approaches should address lifestyle factors alongside pharmaceutical interventions, as recommended by major international guidelines.

Background Estimating equations based on spot urine samples have been identified as a possible alternative approach to 24-h urine collections for determining mean population salt intake. This review compares estimates of mean population salt intake based upon spot and 24-h urine samples. Methods We systematically searched for all studies that reported estimates of daily salt intake based upon both spot and 24-h urine samples for the same population. The associations between the two were quantified and compared overall and in subsets of studies. Results A total of 538 records were identified, 108 were assessed as full text and 29 were included. The included studies involved 10,414 participants from 34 countries and made 71 comparisons available for the primary analysis. Overall average population salt intake estimated from 24-h urine samples was 9.3 g/day compared with 9.0 g/day estimated from the spot urine samples. Estimates based upon spot urine samples had excellent sensitivity (97%) and specificity (100%) at classifying mean population salt intake as above or below the World Health Organization maximum target of 5 g/day. Compared with the 24-h samples, estimates based upon spot urine overestimated intake at lower levels of consumption and underestimated intake at higher levels of consumption. Conclusions Estimates of mean population salt intake based upon spot urine samples can provide countries with a good indication of mean population salt intake and whether action on salt consumption is required.

Background: The capacity of spot urine samples for detecting changes in dietary sodium and potassium intake is unclear. Methods: Changes in sodium and potassium intake, over a 6-month to 2-year interval, were measured from 24-hour urine samples and estimated from spot urine samples using several published methods in 3270 Chinese. Additional estimates were made by multiplying individual spot sodium and potassium concentrations by a single estimated 24-hour urine volume derived from external data. Results: The measured difference in 24-hour intake between intervention and control groups was -0.35g (95%CI: -0.68 to -0.02g; p=0.039) for sodium and 0.66g (95%CI: 0.52 to 0.80g; p0.10). The estimates were -0.65g for sodium and 1.11g for potassium using individual spot urine concentrations and an externally derived standard urine volume (both p Conclusions: The published equations were unable to detect the differences in sodium intake measured by 24-hour urine samples in our study. A simpler method based upon spot urine electrolyte concentrations and a standard urine volume may offer an alternative approach to measuring differences in sodium and potassium intakes between population groups without requiring 24-hour urine, but will need further investigation.

Background As a public health intervention, front-of-pack labels (FoPLs) have the potential to reach large numbers of consumers and promote healthier food choices. Of the different FoPLs, those that summarize a product's overall nutritional profile tend to be most effective in guiding healthier choices. However, information is lacking as to whether FoPLs are as effective when nutrient or health claims also appear on-pack. Objective The aim of this study was to examine how the choice of foods of varying levels of healthfulness (less healthy, moderately healthy, and healthier) is affected by the appearance of various FoPLs (Daily Intake Guide, Multiple Traffic Lights, Health Star Rating) when shown in combination with different claim conditions (no claim, nutrient claim, general-level health claim, and higher-level health claim). Design Adults and children (n = 2069) completed a discrete-choice experiment online. Respondents were shown 8 choice sets, each containing 4 alternatives of the same food type (cookies, cornflakes, pizza, or yogurt) of varying levels of healthfulness and were asked which product they would likely purchase (or they could select none). Respondents were randomly assigned to view 1 of the 3 FoPLs across all choice sets. Claim type and healthfulness varied within choice sets in accordance with a D-efficient design. Results The probability of choosing a healthy product and avoiding an unhealthy product was greatest when only an FoPL (especially the Health Star Rating) appeared on-pack. The addition of a nutrient or health claim did not affect the likelihood of picking healthier products but did increase the likelihood of selecting less healthy foods across all FoPL conditions. Conclusions FoPLs are most effective in helping consumers make better food choices when nutrient and health claims are not present. Policies are required to control how nutrient and health claims are applied to less healthy foods. This trial was registered as ACTRN12617000015347 (www.anzctr.org.au/Trial/Resgistration/TrialReview.aspx?id=372055&isReview=true).

The Sleep Apnea cardioVascular Endpoints (SAVE) study is an ongoing investigator-initiated and conducted, international, multicenter, open, blinded endpoint, randomized controlled trial that was designed to determine whether treatment of obstructive sleep apnea (OSA) with continuous positive airways pressure (CPAP) can reduce the risk of serious cardiovascular (CV) events in patients with established CV disease (clinical trial registration NCT00738179). The results of this study will have important implications for the provision of health care to patients with sleep apnea around the world. The SAVE study has brought together respiratory, sleep, CV and stroke clinicians-scientists in an interdisciplinary collaboration with industry and government sponsorship to conduct an ambitious clinical trial. Following its launch in Australia and China in late 2008, the recruitment network expanded across 89 sites that included New Zealand, India, Spain, USA, and Brazil for a total of 2,717 patients randomized by December 2013. These patients are being followed until December 2015 so that the average length of follow-up of the cohort will be over 4 y. This article describes the rationale for the SAVE study, considerations given to the design including how various cultural and ethical challenges were addressed, and progress in establishing and maintaining the recruitment network, patient follow-up, and adherence to CPAP and procedures. The assumptions underlying the original trial sample size calculation and why this was revised downward in 2012 are also discussed. Clinical trials registration number NCT00738179. Australia new zealand clinical trials registry number ACTRN12608000409370.

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Most individuals at high cardiovascular disease (CVD) risk worldwide do not receive any or optimal preventive drugs. We aimed to determine whether fixed dose combinations of generic drugs ('polypills') would promote use of such medications.We conducted a randomized, open-label trial involving 623 participants from Australian general practices. Participants had established CVD or an estimated five-year CVD risk of ≥15%, with indications for antiplatelet, statin and ≥2 blood pressure lowering drugs ('combination treatment'). Participants randomized to the 'polypill-based strategy' received a polypill containing aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg. Participants randomized to 'usual care' continued with separate medications and doses as prescribed by their doctor. Primary outcomes were self-reported combination treatment use, systolic blood pressure and total cholesterol.After a median of 18 months, the polypill-based strategy was associated with greater use of combination treatment (70% vs. 47%; relative risk 1.49, (95% confidence interval (CI) 1.30 to 1.72) p 0.0001; number needed to treat = 4.4 (3.3 to 6.6)) without differences in systolic blood pressure (-1.5 mmHg (95% CI -4.0 to 1.0) p = 0.24) or total cholesterol (0.08 mmol/l (95% CI -0.06 to 0.22) p = 0.26). At study end, 17% and 67% of participants in polypill and usual care groups, respectively, were taking atorvastatin or rosuvastatin.Provision of a polypill improved self-reported use of indicated preventive treatments. The lack of differences in blood pressure and cholesterol may reflect limited study power, although for cholesterol, improved statin use in the polypill group counter-balanced use of more potent statins with usual care.

Background: Nutrition labeling is a prominent policy to promote healthy eating. Objective: We aimed to evaluate the effects of 2 interpretive nutrition labels compared with a noninterpretive label on consumer food purchases. Design: In this parallel-group randomized controlled trial, we enrolled household shoppers across New Zealand who owned smartphones and were aged ≥18 y. Eligible participants were randomly assigned (1:1:1) to receive either traffic light labels (TLLs), Health Star Rating labels (HSRs), or a control [nutrition information panel (NIP)]. Smartphone technology allowed participants to scan barcodes of packaged foods and to receive allocated labels on their smartphone screens. The primary outcome was the mean healthiness of all packaged food purchases over the 4-wk intervention period, which was measured by using the Food Standards Australia New Zealand Nutrient Profiling Scoring Criterion (NPSC). Results: Between October 2014 and November 2015, 1357 eligible shoppers were randomly assigned to TLL (n = 459), HSR (n = 443), or NIP (n = 455) labels. Overall difference in the mean transformed NPSC score for the TLL group compared with the NIP group was −0.20 (95% CI: −0.94, 0.54; P = 0.60). The corresponding difference for HSR compared with NIP was −0.60 (95% CI: −1.35, 0.15; P = 0.12). In an exploratory per-protocol analysis of participants who used the labeling intervention more often than average (n = 423, 31%), those who were assigned to TLL and HSR had significantly better NPSC scores [TLL compared with NIP: −1.33 (95% CI: −2.63, −0.04; P = 0.04); HSR compared with NIP: −1.70 (95% CI: −2.97, −0.43; P = 0.01)]. Shoppers who were randomly assigned to HSR and TLL also found the labels significantly more useful and easy to understand than the NIP (all P values

Background. Diabetes and chronic kidney disease (CKD) are both associated with an increased risk of cancer but it is unclear whether diabetes complicated by CKD further augments an individual’s cancer risk. The aim of our study was to determine the association of CKD [defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min] with the overall and site-specific risks of incident cancers among individuals with Type 2 diabetes. Methods. Cox proportional hazard regression models and competing risk analyses were used to examine the univariate and multivariate adjusted associations between reduced kidney function and the overall and site-specific risks of cancer in participants enrolled in the Action in Diabetes and Vascular disease: Preterax and Diamicron MR controlled evaluation (ADVANCE) trial. Results. Over a median follow-up of 5.0 years, 700 malignant neoplasms occurred in the 11 140 (6.4%) participants. There was no increase in overall cancer risk [adjusted hazard ratio: 1.07 (95% confidence interval: 0.89–1.29, P ¼ 0.50)] or site-specific cancer risk for individuals with CKD (defined as eGFR

Background To investigate the prevalence, screening and knowledge of cardiovascular risk factors (CVRFs) by socio-economic position (SEP) in rural India. Methods An age- and sex-stratified random sample of 4535 adults was recruited from rural Andhra Pradesh and a questionnaire was administered to assess prevalence, screening and knowledge of CVRFs and record recent attempts to modify behaviour. Education, income and occupation were used to measure SEP. Results Lower fruit intake and higher tobacco and alcohol use were found in those with lower SEP. Overweight, physical inactivity, diabetes, hypertension, family history of cardiovascular disease (CVD) and previous CVD (men only) were greater in higher SEP participants. Lower SEP participants had less blood pressure, glucose or cholesterol screening and less knowledge of nine CVRFs. Regardless of SEP, participants knowledgeable of the harms of a CVRF were more likely to have attempted to modify behaviour. For example, knowledge of benefits of smoking cessation was associated with an increased odds ratio (OR) for attempting to quit: in educated participants-OR 3.67, 95% confidence interval (CI) 2.10-6.42; in participants with no education-OR 3.98, 95% CI 2.27-6.97. Conclusions Some biological CVRFs were worse in higher SEP participants while some behavioural risk factors were worse in lower SEP participants. Lower SEP participants had less CVRF screening and knowledge of CVRFs. Those with knowledge of CVRFs were more likely to make healthy behavioural changes. Our findings suggest equipping rural Indians with knowledge about CVRFs may ameliorate projected future increases in CVD.

Background: Current guidelines recommend that decisions to start preventative therapy for cardiovascular disease (CVD) should be based on absolute risk; however, current risk equations are based on single measurements of risk factors. We aimed to assess whether two measurements of blood pressure and lipids improves the prediction of cardiovascular risk compared to one measurement.Methods and results: We used sex-specific Cox proportional hazards models to evaluate the risk of first CVD event in 2385 participants of the Framingham Offspring Study attending both the second and third visits. We estimated the effects on risk prediction of using the average of two measurements of blood pressure, total cholesterol, and HDL cholesterol compared to using one measurement of the risk factors. We found that these risk factors were each markedly more predictive of CVD when the average of two measurements was used rather than one measurement and age was less predictive of CVD. There were small improvements in the overall model fit, discrimination, and calibration. Reclassification also showed small improvements across the risk spectrum (net reclassification information, NRI, for women 3.0%, 95% CI -0.9 to 24.8%; NRI for men 4.0%, 95% CI -2.2 to 14.1%) and possibly greater improvements for intermediate-risk individuals (NRI for women 32.3%, 95% CI -21.9 to 46.8%; NRI for men 16.0%, 95% CI -3.3 to 43%).Conclusions: Averaging two measurements of blood pressure and lipids results in marked increases in the predictiveness of these risk factors and smaller improvements in the overall prediction of cardiovascular risk including reclassification. © 2011 The European Society of Cardiology.

Background: Australians currently consume too much salt causing adverse consequences for health. The media play an important role in the provision of nutrition advice to consumers. Previous research shows that many foods advertized in consumer magazines are high in salt, but little research has examined magazine recipes in this context. The aim of this project was to summarize directions for salt use in recipes in leading Australian magazines. Methods: In August 2007 and 2008, the top 10 magazines by circulation that included at least five recipes, were examined. Standardized information was collected about directions for salt use in recipes. Results: Three hundred and thirty recipes were identified in 2007 and 417 in 2008. About 68% of recipes included high-salt ingredients, 37% instructed to season with salt, 10% instructed to add a specific quantity of salt and 15% recommended selection of low-salt ingredients. There was substantial variability in directions for salt use in recipes between magazines, but no clear differences between 2007 and 2008. Conclusion: Many recipes advised to add salt in direct contradiction to national dietary guidelines. There is clear potential for editorial guidelines on salt use in recipes to play a role in advancing public health efforts in Australia and other such nations. Refereed/Peer-reviewed

Introduction: India is undergoing rapid epidemiological transition as a consequence of economic and social change. The pattern of mortality is a key indicator of the consequent health effects but up-to-date, precise, and reliable statistics are few, particularly in rural areas. Methods: Deaths occurring in 45 villages (population 180 162) were documented during a 12-month period in 2003-04 by multipurpose primary healthcare workers trained in the use of a verbal autopsy tool. Algorithms were used to define causes of death according to a limited list derived from the international classification of disease version 10. Causes were assigned by two independent physicians with disagreements resolved by a third. Results: A total of 1354 deaths were recorded with verbal autopsies completed for 98%. A specific underlying cause of death was assigned for 82% of all verbal autopsies done. The crude death rate was 7.5/1000 (95% confidence interval, 7.1-7.9). Diseases of the circulatory system were the leading causes of mortality (32%), with similar proportions of deaths attributable to ischaemic heart disease and stroke. Second was injury and external causes of mortality (13%) with one-third of these deaths attributable to deliberate self harm. Third were infectious and parasitic diseases (12%). Tuberculosis and intestinal conditions each caused one-third of deaths within this category. HIV was assigned as the cause for 2% of all deaths. The fourth and fifth leading causes of death were neoplasms (7%) and diseases of the respiratory system (5%). Conclusion: Non-communicable and chronic diseases are the leading causes of death in this part of rural India. The observed pattern of death is unlikely to be unique to these villages and provides new insight into the rapid progression of epidemiological transition in rural India.

Vascular mortality is increasing in economically developing countries such as Thailand but reliable data about the determinants of these changes are few.In 1985, male and female employees of the Electricity Generating Authority of Thailand took part in a cardiovascular risk factor survey. In 1997, a follow-up survey was conducted and causes of death were determined for those subjects known to have died. Changes in levels of vascular risk factors over 12 years, and the associations of baseline risk factors with vascular mortality, were calculated.The 1985 survey recruited 3499 volunteers (average age 43 years) of whom 23% were female. In 1997, vital status was determined for 3318 (95%) and 2967 (85%) of the study participants were resurveyed. Mean levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP), body mass index, total cholesterol and high density lipoprotein (HDL) cholesterol all increased over the 12-year follow-up period. Over the same time, the prevalence of diabetes also rose but the proportion of current smokers decreased. Vascular diseases were the most frequent cause of death during follow-up (n = 46), were positively associated with baseline age, SBP, DBP, smoking, diabetes, male sex, and total cholesterol, and were negatively associated with HDL cholesterol.Levels of most vascular risk factors worsened over the 12-year period between 1985 and 1997. The associations between baseline risk factor levels and vascular mortality were consistent with those observed in other populations. Interventions that control vascular risk factors have the potential to avert much premature vascular disease in Thailand.

Aims To determine the effects on homocysteine levels of two doses of folic acid compared to placebo, where the high dose is typical of that provided by pharmacological intervention and the low dose approximates that provided by dietary supplementation. Methods and results The PACIFIC study was a double-blind, placebo-controlled, factorial randomized trial. Seven hundred and twenty-three individuals with a history of myocardial infarction or unstable angina were recruited from 28 clinical cardiology centres in Australia and New Zealand and randomized to folic acid 2.0 mg daily, folic acid 0.2 mg daily or placebo. The primary outcome, homocysteine, was measured using a fluorescence polarization immunoassay. Compared to placebo, 2.0 mg folic acid reduced homo-cysteine by 1.8 micromol x 1(-1) [95% confidence interval (CI) 1.3-2.3] and 0.2 mg reduced homocysteine by 1.2 micromol x 1(-1) [95% CI 0.8-1.7). The higher dose reduced homocysteine significantly more than the lower dose (P=001). Conclusions Both doses of folic acid reduced homocysteine, but the effects of the 2.0 mg dose were about one third greater than the 0.2 mg dose. Fortification of foods with folic acid should result in population-wide lower levels of homocysteine but high-dose pharmacological supplementation would produce greater reductions for high-risk individuals.

There is a large and increasing global burden of cardiovascular disease. Approximately 14 million individuals died of cardiovascular disease in 1990, and this is projected to rise to about 25 million by 2020. In large part, this increase can be explained on the basis of major ongoing sociodemographic changes in developing countries, and associated effects on the numbers of individuals at risk and the levels of cardiovascular risk factors. Developing countries now experience a much greater burden of cardiovascular disease than do developed countries. In addition, developing countries are expected to experience the greatest rise in cardiovascular disease burden over the next few years. Cardiovascular disease prevention programmes designed and implemented primarily in developed countries have most likely averted much premature cardiovascular disease in those countries over the past few decades. However, cardiovascular disease prevention programmes designed for developed countries are unlikely to be directly transferable to developing countries. Reliable information to inform the design and implementation of cardiovascular disease prevention programmes, tailored to the socioeconomic circumstances of developing countries, is now required. Such programmes have great potential to impact on the current and projected global epidemic of cardiovascular disease.

Background Spot urine samples are easier to collect than 24-h urine samples and have been used with estimating equations to derive the mean daily salt intake of a population. Whether equations using data from spot urine samples can also be used to estimate change in mean daily population salt intake over time is unknown. We compared estimates of change in mean daily population salt intake based upon 24-h urine collections with estimates derived using equations based on spot urine samples. Methods Paired and unpaired 24-h urine samples and spot urine samples were collected from individuals in two Australian populations, in 2011 and 2014. Estimates of change in daily mean population salt intake between 2011 and 2014 were obtained directly from the 24-h urine samples and by applying established estimating equations (Kawasaki, Tanaka, Mage, Toft, INTERSALT) to the data from spot urine samples. Differences between 2011 and 2014 were calculated using mixed models. Results A total of 1000 participants provided a 24-h urine sample and a spot urine sample in 2011, and 1012 did so in 2014 (paired samples n = 870; unpaired samples n = 1142). The participants were community-dwelling individuals living in the State of Victoria or the town of Lithgow in the State of New South Wales, Australia, with a mean age of 55 years in 2011. The mean (95% confidence interval) difference in population salt intake between 2011 and 2014 determined from the 24-h urine samples was –0.48g/day (–0.74 to –0.21; P 0.058). Separate analysis of the unpaired and paired data showed that detection of change by the estimating equations was observed only in the paired data. Conclusions All the estimating equations based upon spot urine samples identified a similar change in daily salt intake to that detected by the 24-h urine samples. Methods based upon spot urine samples may provide an approach to measuring change in mean population salt intake, although further investigation in larger and more diverse population groups is required.