Showing papers by "Bruce Neal published in 2012"

Association of HbA1c levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds

Abstract: Aims/hypothesis There is conflicting evidence regarding appropriate glycaemic targets for patients with type 2 diabetes. Here, we investigate the relationship between HbA1c and the risks of vascular complications and death in such patients.

Omega 3 Fatty Acids and Cardiovascular Outcomes Systematic Review and Meta-Analysis

Abstract: Background—Early trials evaluating the effect of omega 3 fatty acids (ω-3 FA) reported benefits for mortality and cardiovascular events but recent larger studies trials have variable findings. We assessed the effects of ω-3 FA on cardiovascular and other important clinical outcomes. Methods and Results—We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for all randomized studies using dietary supplements, dietary interventions, or both. The primary outcome was a composite of cardiovascular events (mostly myocardial infarction, stroke, and cardiovascular death). Secondary outcomes were arrhythmia, cerebrovascular events, hemorrhagic stroke, ischemic stroke, coronary revascularization, heart failure, total mortality, nonvascular mortality, and end-stage kidney disease. Twenty studies including 63030 participants were included. There was no overall effect of ω-3 FA on composite cardiovascular events (relative risk [RR]=0.96; 95% confidence interval [CI], 0.90–1.03; P=0.24) or...

International collaborative project to compare and monitor the nutritional composition of processed foods

Abstract: Background: Chronic diseases are the leading cause of premature death and disability in the world with overnutrition a primary cause of diet-related ill health. Excess energy intake, saturated fat, sugar, and salt derived from processed foods are a major cause of disease burden. Our objective is to compare the nutritional composition of processed foods between countries, between food companies, and over time. Design: Surveys of processed foods will be done in each participating country using a standardized methodology. Information on the nutrient composition for each product will be sought either through direct chemical analysis, from the product label, or from the manufacturer. Foods will be categorized into 14 groups and 45 categories for

The variability of reported salt levels in fast foods across six countries: opportunities for salt reduction

Abstract: Background: Several fast food companies have made commitments to reduce the levels of salt in the foods they serve, but technical issues are often cited as a barrier to achieving substantial reductions. Our objective was to examine the reported salt levels for products offered by leading multinational fast food chains. Methods: Data on salt content for products served by six fast food chains operating in Australia, Canada, France, New Zealand, the United Kingdom and the United States were collected by survey in April 2010. Mean salt contents (and their ranges) were calculated and compared within and between countries and companies. Results: We saw substantial variation in the mean salt content for different categories of products. For example, the salads we included in our survey contained 0.5 g of salt per 100 g, whereas the chicken products we included contained 1.6 g. We also saw variability between countries: chicken products from the UK contained 1.1 g of salt per 100 g, whereas chicken products from the US contained 1.8 g. Furthermore, the mean salt content of food categories varied between companies and between the same products in different countries (e.g., McDonald9s Chicken McNuggets contain 0.6 g of salt per 100 g in the UK, but 1.6 g of salt per 100 g in the US). Interpretation: The salt content of fast foods varies substantially, not only by type of food, but by company and country in which the food is produced. Although the reasons for this variation are not clear, the marked differences in salt content of very similar products suggest that technical reasons are not a primary explanation. In the right regulatory environment, it is likely that fast food companies could substantially reduce the salt in their products, translating to large gains for population health.

Socio-economic distribution of cardiovascular risk factors and knowledge in rural India

Abstract: 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.

Effects of SGLT2 inhibitors on cardiovascular outcomes.

Abstract: Glucose in the glomerular ultrafiltrate is actively reabsorbed by sodium glucose transporters (SGLT) in the proximal tubule. The SGLT2 protein is a high capacity molecule responsible for the majority of glucose reuptake with pharmacological inhibition, resulting in the loss of about 80g of glucose in the urine each day. About a dozen inhibitors of SGLT2 have entered clinical development, and the first has recently been submitted for registration with the United States Food and Drug Administration. The rationale for the clinical evaluation of these agents is their beneficial effects on glycaemia, blood pressure and body weight. No adequately powered trial has yet determined the effects of an SGLT2 inhibitor on either macrovascular or microvascular outcomes, although a number of large-scale trials are now ongoing. Evidence that will define the overall balance of benefits and risks of this new drug class is anticipated within the next 5 years.

Effects of Blood Pressure Lowering on Intracranial and Extracranial Bleeding in Patients on Antithrombotic Therapy The PROGRESS Trial

Abstract: Background and Purpose—Observational studies demonstrate strong associations between blood pressure and bleeding complications of antithrombotic therapy. The objective was to determine whether blood pressure lowering reduces risks of bleeding in patients on antithrombotic therapy. Methods—This is a subsidiary analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) trial, a randomized, placebo-controlled trial. A total of 6105 patients with cerebrovascular disease were randomly assigned to either active treatment (perindopril±indapamide) or placebo(s). The outcomes were intracranial and extracranial bleeding. Results—There were 4876 (80%) patients on antithrombotic therapy at baseline. Over a mean follow-up of 3.9 years, 119 intracranial and 123 extracranial bleeding events were observed. Among patients with and without antithrombotic therapy, active treatment lowered blood pressure by 8.9/4.0 and 9.3/3.8 mm Hg and reduced the risks of intracranial bleeding by 46% (95% CI, 7%–69%) ...

Earlier blood pressure-lowering and greater attenuation of hematoma growth in acute intracerebral hemorrhage: INTERACT pilot phase

Abstract: Background and Purpose—The INTEnsive blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT) pilot study showed that early intensive blood pressure-lowering can attenuate hematoma growth in acute intracerebral hemorrhage. The present analysis aimed to determine the treatment effects on hematoma growth by time from intracerebral hemorrhage onset to randomization. Methods—Patients (N=404) with acute intracerebral hemorrhage and elevated systolic blood pressure were randomly assigned to intensive or guideline-based blood pressure management. Baseline and repeat CT (24 and 72 hours) were performed and changes in hematoma volume were assessed using generalized estimating equations. Results—Among 296 patients with all 3 CT scans available for analysis, reductions in proportional hematoma growth produced by randomized intensive blood pressure-lowering treatment over 72 hours decreased progressively with delays in initiation of study treatment: 22%, 17%, 9%, and 3% for quartile groups defined by ti...

Sampling bias in an internet treatment trial for depression.

Abstract: Internet psychological interventions are efficacious and may reduce traditional access barriers. No studies have evaluated whether any sampling bias exists in these trials that may limit the translation of the results of these trials into real-world application. We identified 7999 potentially eligible trial participants from a community-based health cohort study and invited them to participate in a randomized controlled trial of an online cognitive behavioural therapy programme for people with depression. We compared those who consented to being assessed for trial inclusion with nonconsenters on demographic, clinical and behavioural indicators captured in the health study. Any potentially biasing factors were then assessed for their association with depression outcome among trial participants to evaluate the existence of sampling bias. Of the 35 health survey variables explored, only 4 were independently associated with higher likelihood of consenting—female sex (odds ratio (OR) 1.11, 95% confidence interval (CI) 1.05–1.19), speaking English at home (OR 1.48, 95% CI 1.15–1.90) higher education (OR 1.67, 95% CI 1.46–1.92) and a prior diagnosis of depression (OR 1.37, 95% CI 1.22–1.55). The multivariate model accounted for limited variance (C-statistic 0.6) in explaining participation. These four factors were not significantly associated with either the primary trial outcome measure or any differential impact by intervention arm. This demonstrates that, among eligible trial participants, few factors were associated with the consent to participate. There was no indication that such self-selection biased the trial results or would limit the generalizability and translation into a public or clinical setting.

The risk of cancer in people with diabetes and chronic kidney disease

Abstract: 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 <60 mL/min) compared to those without CKD at baseline. These results were robust to multiple methods and thresholds used to estimate CKD. Conclusions. Mild to moderate CKD does not increase the risk of cancer in people with Type 2 diabetes. ADVANCE is registered with ClincalTrial.gov (number NCT00145925).

Trials in Kidney Disease — Time to EVOLVE

Abstract: Patients with kidney disease face a substantially increased risk of cardiovascular events and death1 — one in five patients who are undergoing dialysis die each year in the United States2 Elevated parathyroid hormone levels are almost universal in persons with advanced kidney failure and have been associated with these risks3 Cinacalcet is an oral calcimimetic agent approved by the Food and Drug Administration (FDA) in 2004 for the treatment of secondary hyperparathyroidism in patients with dialysis-dependent kidney failure Early reports4,5 supported the possibility that cinacalcet conferred cardiovascular protection and reduced fracture risk, although the statistical power of these studies

Effects of additional blood pressure and lipid measurements on the prediction of cardiovascular risk

Abstract: 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...

White rice and risk of type 2 diabetes.

Abstract: New study highlights old challenges of nutritional epidemiology A marked rise in the incidence of type 2 diabetes is a characteristic feature of populations that have undergone nutritional transition.1 First seen in the developed Western world, the same pattern is now being replicated in low income and middle income countries, where most new cases of diabetes now occur.2 The role of poor diet in the diabetes epidemic is undisputed, but the details have long been debated.3 Although overconsumption of energy and accumulation of excess body fat is a common cause of type 2 diabetes,4 diet almost certainly has other unknown effects, and specific foods with particular adverse effects may have a direct role in the development of type 2 diabetes. The linked paper by Hu and colleagues (doi:10.1136/bmj.e1454) sheds new light on the relation between diet and diabetes, and the authors bring a new level of rigour to efforts to answer the question of the possible effect of higher consumption of white rice.5 They systematically searched for …

1118 quantifying salt and potassium intake in victorian adults

Abstract: Background: Salt and potassium intake have not been quantified in a large sample of adults residing in the state of Victoria. Methods: Participants of the Victoria Health Monitor survey (2009/2010) were invited to take part in salt intake assessment. 30% of those invited expressed interest and 546 adults have provided 24-hour urine samples which were analysed for sodium (expressed as salt equivalents), potassium and creatinine. The mean age was 56.3(12.3)(SD) years (range 21 to 78), and 55% were women. Results: The salt intake of men (9.5 ± 0.2 grams/day) (± SEM) was higher than that of women (6.9 ± 0.2 grams/day) (p < 0.0001). 97% of men and 86% of women had salt intake levels above the 4 grams per day Suggested Dietary Target (SDT). Salt intake was lower in the older age groups: 21–39 years (9.2 ± 0.5 grams/day), 40–59 years (8.2 ± 0.2 grams/day) and 60–78 years (7.6 ± 0.2 grams/day) (ANOVA p = 0.002). There was no significant difference in the salt intake between non-urban (7.7 ± 0.3 grams/day) and urban (8.1 ± 0.2 grams/day) residents. Potassium intake for men (3346 ± 61 mg/day) was higher than that for women (2765 ± 51 mg/day) (p < 0.0001). The sodium to potassium ratio was also higher for men (1.99 ± 0.05) compared to women (1.78 ± 0.04) (p = 0.002). Conclusions: Victorian men and women have increased risk for high blood pressure and cardiovascular disease due to salt intake levels that are well above the SDT for health. Younger adults and men are more likely to have higher intakes of salt.

Sanguine about salt reduction.

Abstract: Salt has been much in the media these last few months and mostly for the wrong reasons. Poor-quality, underpowered research has been misinterpreted and afforded undue attention by media outlets looking for a story. It is refreshing to see this issue of the journal reporting a new aspect of the salt story that is worthy of the attention – new plans for objectively tracking commitments to improve the composition of the global food supply. This proposal for systematic monitoring of progress with efforts to reduce salt in processed foods will be a key step in delivering upon the enormous potential of salt reduction programmes. For the first time, industry and governments around the world will be held to account by objective, quantitative measures of progress. While the true standardization of data collection across countries will doubtless be difficult to achieve, the pragmatic approach taken should add substantially to the public health armamentarium. For most of human evolution, man existed on a diet very different to that consumed now. Food contained just traces of sodium and only with the discovery that salt could preserve food did salt consumption levels start to rise. Now, some 6000 years on, average salt intake in most populations is much greater than is required to support normal physiology. With processed and fast foods now so widespread, it’s very hard to find a population that illustrates what can be achieved with consumption of a diet congruent with physiological needs. A good historical example is the Yanomamo Indians of the Amazon basin. When first studied by Western society in the 1950s, the Yanomamo were still consuming an unacculturated diet – low in fat and supplying just a fraction of a gram of salt each day. A striking consequence of the Yanomamo lifestyle was that blood pressure in old age was the same as in adolescence – an observation substantively attributable to lifetime consumption of sodium at normal physiological levels. Having the right concept of ‘normal’ is key to understanding the potential offered by salt reduction. Jointly, the anthropological, physiological, and epidemiological evidence suggests that ‘normal’ salt intake for most of human evolution was a gram or less a day. Correspondingly, for blood pressure, the consensus is now that normal adult systolic blood pressure is not ‘100mmHg plus age’, but about 100mmHg throughout the lifecourse. Maximum recommended daily salt consumption levels of 5–6 g represent a pragmatic compromise between the current consumption levels of most countries and achievable short-term targets, not a target for normalization of consumption. Likewise, being ‘non-hypertensive’ in old age is much better than being ‘hypertensive’, but having a blood pressure well below the 140mmHg threshold will confer a substantial further survival advantage. The downside of re-defining normal in this way is that it means that almost the entire global population is eating more salt than required and has a blood pressure above the optimum – with some adverse consequence for vascular risk in most. Defining normal systolic blood pressure as about 100mmHg is also the reason why blood pressure is the greatest cause of premature death and disability in the world – small increments in risks for huge numbers producing an enormous total disease burden. The upside of this equation is the potential for prevention – almost the entire global population stands to gain from a reduced salt intake and a lower blood pressure. And the potential benefits from population-wide programmes targeting these exposures are therefore enormous. While the reductions in risk for most individuals will be fairly small, the accumulation of these small reductions across the entire community translates into very large numbers of events that could be averted. Furthermore, because centrally implemented programmes targeting salt in the food supply require

1119 correlation of salt intake with knowledge, attitudes and behaviours in australian adults

Abstract: Background: Salt reduction efforts usually have a strong focus on consumer education. Understanding the association between salt consumption levels and knowledge, attitudes and behaviours (KAB) towards salt will provide insight into the likely effects of educating people. Methods: 1,970 eligible individuals from a regional town in Australia were randomly selected from the 2009 Federal electoral roll and invited to participate. 306 (response rate 16%) provided a 24hr urine sample and completed a questionnaire describing KAB. Results: The mean age of participants was 58 years, 47% were men and the overall mean 24hr urinary salt excretion was 9.0 g/d. There was no difference in salt excretion between persons who indicated an education level of secondary or below (8.8 ± 0.3 g/d), tertiary (9.2 ± 0.4 g/d) or post graduate (8.3 ± 0.7 g/d) (p = 0.66). Nor was there a difference between those who did (9 ± 0.2 g/d) and did not (8.3 ± 0.4 g/d) understand that a diet high in salt causes high blood pressure (p = 0.18). Likewise, people who believed they consumed “too much” (8.8 ± 0.4 g/d) “just the right amount” (8.8 ± 0.3 g/d) or “too little salt” (9.1 ± 0.4 g/d) did not actually have different consumption levels (p = 0.82). Individuals who reported they controlled their salt intake (9 ± 0.3 g/d) did not have lower salt intake than individuals who did not (8.5 ± 0.4 g/d) (p = 0.44). Conclusion: The absence of a clear association between KAB and salt consumption levels suggest that interventions targeting KAB individuals may be of limited efficacy. Strategies such as sector-wide food reformulation programs are likely to be an important part of salt reduction programs.

434 earlier blood pressure lowering and greater attenuation of haematoma growth in acute intracerebral haemorrhage: interact pilot phase

Abstract: Background: The INTERACT pilot study showed that early intensive blood pressure lowering can attenuate haematoma growth in acute intracerebral haemorrhage (ICH). The present analysis aimed to determine the treatment effects on haematoma growth by time from ICH onset to randomisation. Design and methods: Patients (N = 404) with acute ICH and elevated systolic blood pressure were randomly assigned to intensive or guideline-based blood pressure management. Baseline and repeat CT (24 and 72 hours) were performed and absolute and proportional changes in haematoma volume were assessed as repeat measures using generalized estimating equations. Results: Among 296 patients with all 3 CT scans available for analysis, reductions in proportional haematoma growth produced by randomised intensive blood pressure lowering treatment over 72 hours decreased progressively with delays in initiation of study treatment: 22%, 17%, 9% and 3% for quartile groups defined by time from onset to randomisation of <2.9, 2.9–3.6, 3.7–4.8 and ≥4.9 hours, respectively (P trend = 0.001). There were also smaller absolute reductions in haematoma growth with delays in initiation of study treatment (6.5 ml, 3.2 ml, 0.9 ml and 0.6 ml) although the trend did not reach statistical significance (P trend = 0.12). Conclusion: Earlier initiation of intensive blood pressure lowering treatment is likely to provide greater protection against haematoma growth in acute ICH.