Primary Prevention Studies Research Articles

Relationship Between Brain Amyloid Deposition and Instrumental Activities of Daily Living in Older Adults: A Longitudinal Study from the Multidomain Alzheimer Prevention Trial.

To examine the evolution of instrumental activity of daily living (IADL) performance according to the presence of brain amyloid deposition. Longitudinal analysis of a randomized controlled trial. Neuroimaging ancillary study from the Multidomain Alzheimer Prevention Trial (MAPT). Community-dwelling individuals aged 70 and older without dementia (N = 269; 60% female, mean age 75±4). Linear mixed models were used to assess the 36-month evolution of the performance of an IADL questionnaire for primary prevention studies in dementia, the Activity of Daily Living Prevention Instrument (ADL-PI), according to the presence of amyloid deposition using florbetapir positron emission tomography (PET) (standardized uptake value≥1.17). Additional analyses were also conducted to examine the changes in specific domains of daily functioning with and without adjustment for age, sex, apolipoprotein E, randomization group, and time between baseline and PET examination. One hundred two (37.9%) participants were amyloid positive. Amyloid-negative participants had statistically significant improvement in ADL-PI total score between baseline and 36 months (p=.04). The difference after 3 years between amyloid-positive and -negative participants was not significant (β=-0.95±0.53 at 36 months, p=.08; adjusted models: β=-1.07±0.56, p=.06). Amyloid-negative participants also improved in memory-related IADLs (p<.001) throughout the study, unlike amyloid-positive participants. Amyloid-positive and -negative older adults are likely to have different trajectories in IADL performance. Future research is needed to better understand the relationship between amyloid plaques and functional limitations.

Legacy effects of statins on cardiovascular and all-cause mortality: a meta-analysis

ObjectivesTo assess evidence for ‘legacy’ (post-trial) effects on cardiovascular disease (CVD) mortality and all-cause mortality among adult participants of placebo-controlled randomised controlled trials (RCTs) of statins.DesignMeta-analysis of aggregate data.Setting/ParticipantsPlacebo-controlled statin...

Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial

The use of aspirin in the primary prevention of cardiovascular events remains controversial. We aimed to assess the efficacy and safety of aspirin versus placebo in patients with a moderate estimated risk of a first cardiovascular event. ARRIVE is a randomised, double-blind, placebo-controlled, multicentre study done in seven countries. Eligible patients were aged 55 years (men) or 60 years (women) and older and had an average cardiovascular risk, deemed to be moderate on the basis of the number of specific risk factors. We excluded patients at high risk of gastrointestinal bleeding or other bleeding, or diabetes. Patients were randomly assigned (1:1) with a computer-generated randomisation code to receive enteric-coated aspirin tablets (100 mg) or placebo tablets, once daily. Patients, investigators, and others involved in treatment or data analysis were masked to treatment allocation. The primary efficacy endpoint was a composite outcome of time to first occurrence of cardiovascular death, myocardial infarction, unstable angina, stroke, or transient ischaemic attack. Safety endpoints were haemorrhagic events and incidence of other adverse events, and were analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00501059. Between July 5, 2007, and Nov 15, 2016, 12 546 patients were enrolled and randomly assigned to receive aspirin (n=6270) or placebo (n=6276) at 501 study sites. Median follow-up was 60 months. In the intention-to-treat analysis, the primary endpoint occurred in 269 (4·29%) patients in the aspirin group versus 281 (4·48%) patients in the placebo group (hazard ratio [HR] 0·96; 95% CI 0·81-1·13; p=0·6038). Gastrointestinal bleeding events (mostly mild) occurred in 61 (0·97%) patients in the aspirin group versus 29 (0·46%) in the placebo group (HR 2·11; 95% CI 1·36-3·28; p=0·0007). The overall incidence rate of serious adverse events was similar in both treatment groups (n=1266 [20·19%] in the aspirin group vs n=1311 [20·89%] in the placebo group. The overall incidence of adverse events was similar in both treatment groups (n=5142 [82·01%] vs n=5129 [81·72%] in the placebo group). The overall incidence of treatment-related adverse events was low (n=1050 [16·75%] vs n=850 [13·54%] in the placebo group; p<0·0001). There were 321 documented deaths in the intention-to-treat population (n=160 [2·55%] vs n=161 [2·57%] of 6276 patients in the placebo group). The event rate was much lower than expected, which is probably reflective of contemporary risk management strategies, making the study more representative of a low-risk population. The role of aspirin in primary prevention among patients at moderate risk could therefore not be addressed. Nonetheless, the findings with respect to aspirin's effects are consistent with those observed in the previously published low-risk primary prevention studies. Bayer.

3136Incremental and synergistic prognostic value of exercise stress testing and standard risk factor assessment in asymptomatic executives: a primary prevention study

3136Incremental and synergistic prognostic value of exercise stress testing and standard risk factor assessment in asymptomatic executives: a primary prevention study

Wheeze trajectories are modifiable through early-lifeintervention and predict asthma in adolescence.

The objectives of this study were to identify developmental trajectories of wheezing using data-driven methodology, and to examine whether trajectory membership differentially impacts the effectiveness of primary preventive efforts that target modifiable asthma risk factors. Secondary analysis of the Canadian Asthma Primary Prevention Study (CAPPS), a multifaceted prenatal intervention among children at high risk of asthma, followed from birth to 15years. Wheezing trajectories were identified by latent class growth analysis. Predictors, intervention effects, and asthma diagnoses were examined between and within trajectory groups. Among 525 children, 3 wheeze trajectory groups were identified: Low-Progressive (365, 69%), Early-Transient (52, 10%), and Early-Persistent (108, 21%). The study intervention was associated with lower odds of Early-Transient and Early-Persistent wheezing (P<.01). Other predictors of wheeze trajectories included, maternal asthma, maternal education, city of residence, breastfeeding, household pets, infant sex and atopy at 12months. The odds of an asthma diagnosis were three-fold to six-fold higher in the Early-Persistent vs Low-Progressive group at all follow-up assessments (P=.03), whereas Early-Transient wheezing (limited to the first year) was not associated with asthma. In the Early-Persistent group, the odds of wheezing were lower among intervention than control children (adjusted odds ratio: 0.67; 95% CI: 0.48; 0.93) at 7years. Using data-driven methodology, children can be classified into clinically meaningful wheeze trajectory groups that appear to be programmed by modifiable and non-modifiable factors, and are useful for predicting asthma risk. Early-life interventions can alter some wheeze trajectories (ie, Early-Persistent) in infancy and reduce wheezing prevalence in mid-childhood.

Intensive Treat-to-Target Statin Therapy in High-Risk Japanese Patients With Hypercholesterolemia and Diabetic Retinopathy: Report of a Randomized Study.

Diabetes is associated with high risk of cardiovascular (CV) events, particularly in patients with dyslipidemia and diabetic complications. We investigated the incidence of CV events with intensive or standard lipid-lowering therapy in patients with hypercholesterolemia, diabetic retinopathy, and no history of coronary artery disease (treat-to-target approach). In this multicenter, prospective, randomized, open-label, blinded end point study, eligible patients were randomly assigned (1:1) to intensive statin therapy targeting LDL cholesterol (LDL-C) <70 mg/dL (n = 2,518) or standard statin therapy targeting LDL-C 100-120 mg/dL (n = 2,524). Mean follow-up was 37 ± 13 months. LDL-C at 36 months was 76.5 ± 21.6 mg/dL in the intensive group and 104.1 ± 22.1 mg/dL in the standard group (P < 0.001). The primary end point events occurred in 129 intensive group patients and 153 standard group patients (hazard ratio [HR] 0.84 [95% CI 0.67-1.07]; P = 0.15). The relationship between the LDL-C difference in the two groups and the event reduction rate was consistent with primary prevention studies in patients with diabetes. Exploratory findings showed significantly fewer cerebral events in the intensive group (HR 0.52 [95% CI 0.31-0.88]; P = 0.01). Safety did not differ significantly between the two groups. We found no significant decrease in CV events or CV-associated deaths with intensive therapy, possibly because our between-group difference of LDL-C was lower than expected (27.7 mg/dL at 36 months of treatment). The potential benefit of achieving LDL-C <70 mg/dL in a treat-to-target strategy in high-risk patients deserves further investigation.

Longitudinal study of occupational noise exposure and joint effects with job strain and risk for coronary heart disease and stroke in Swedish men

ObjectivesThe aims were to investigate whether occupational noise increased the risk for coronary heart disease (CHD) and stroke and to elucidate interactions with stressful working conditions in a cohort of...

Abstract P144: Cardiovascular Risk Assessment in Western Honduras; An Epidemiological Perspective

Background: Cardiovascular Disease (CVD) epidemiology varies significantly among Low and Middle-Income Countries. Honduras is the Central American country with the highest ischemic heart disease and CVD mortality rates. The objective of this study is to provide an epidemiologic perspective of CVD in Western Honduras by analyzing cardiovascular (CV) risk in a population of Hispanics/mestizos and calculating their predicted CVD mortality using Cardiovascular Risk Assessment Scores (CVRAS) such as AHA/ACC Pooled-Cohort Equations (PCEs), Framingham Risk Score (FRS) and Multi-Ethnic Study on Atherosclerosis (MESA) Risk Score. Methods: Data was derived from Torres et al study, which was a cross-sectional, primary-prevention study, including 382 subjects between 45-75 years, in Copán, Honduras, between November 2016 and January 2017. Results: Out of 379 subjects meeting inclusion criteria, 38% (143 of 379) were male and 62% (237 of 379) were female. Age was 57 ± 8.2 for men and 58 ± 7.7 for women. Prevalence of hypertension was 49.7% (71 of 143) in men and 47.7% (113 of 237) in women; 91.3% (168 of 184) were being treated. DM was present in 19% (27 of 143) of men and 22.1% (52 of 237) of women; 96.2% (75 of 79) were being treated. Obesity was 24.5% (35 of 143) in men and 24.1% (57 of 237) in women. Total cholesterol was ≥ 200 mg/dl in 63.1% (239 of 379) of subjects, 21.8% (52 of 239) were taking lipid-lowering medications. For men and women respectively; AHA/ACC-PCEs was ≥7.5% (high-risk) in 62.2% (89 of 143) and 29.8% (71 of 237), FRS was ≥20% in 46.2% (66 of 143) and 15.2% (36 of 237), and MESA Risk Score was ≥7.5% in 70.6% (101 of 143) and 17.7% (42 of 237). Conclusions: After collecting anthropometric and laboratory data, calculation of CVRAS showed significantly elevated rates of high-CV risk patients according to all 3 scores. This is the first study of its type in Honduras. Efforts should be made to aggressively reduce CVD risk factors, and follow this cohort of subjects to better understand CVD morbidity and mortality in Western Honduras.

Is There a Sex Difference of Cardiovascular Risk Factors in Patients with Acute Myocardial Infarction?

Conventional cardiovascular risk factors, such as hypertension, diabetes, smoking, and dyslipidemia, increase the risk of developing acute myocardial infarction. Primary prevention studies have shown that early detection and aggressive treatment of risk factors prevent cardiovascular events. In women, coronary artery disease appears up to 10 years later in life than in men. We analyzed the presence of conventional risk factors in patients with acute myocardial infarction and compared findings according to sex. We observed that more than 90% of patients included in the study had at least one of these risk factors, hypertension and diabetes predominated in women and smoking was more frequent in men. Because many of these risk factors are modifiable and amenable to treatment, an early detection and aggressive treatment can prevent cardiovascular events.

Periodontal therapy for the management of cardiovascular disease in patients with chronic periodontitis.

There is an association between chronic periodontitis and cardiovascular disease (CVD). However, it is not known whether periodontal therapy could prevent or manage CVD in patients with chronic periodontitis. The objective of this systematic review was to investigate the effects of periodontal therapy in preventing the occurrence of, and management or recurrence of, CVD in patients with chronic periodontitis. Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 31 August 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2017, Issue 7), MEDLINE Ovid (1946 to 31 August 2017), Embase Ovid (1980 to 31 August 2017) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL EBSCO) (1937 to 31 August 2017) . The US National Institutes of Health Trials Registry (ClinicalTrials.gov), the World Health Organization International Clinical Trials Registry Platform and Open Grey were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases.We also searched the Chinese BioMedical Literature Database (1978 to 27 August 2017), the China National Knowledge Infrastructure (1994 to 27 August 2017), the VIP database (1989 to 27 August 2017) and Sciencepaper Online (2003 to 27 August 2017). Randomised controlled trials (RCTs) and quasi-RCTs were considered eligible. Studies were selected if they included patients with a diagnosis of chronic periodontitis and previous CVD (secondary prevention studies) or no CVD (primary prevention studies); patients in the intervention group received active periodontal therapy compared to maintenance therapy, no periodontal treatment or another kind of periodontal treatment in the control group. Two review authors carried out the study identification, data extraction and risk of bias assessment independently and in duplicate. Any discrepancies between the two authors were resolved by discussion or with a third review author. A formal pilot-tested data extraction form was adopted for the data extraction, and the Cochrane tool for risk of bias assessment was used for the critical appraisal of the literature. No studies were identified that assessed primary prevention of CVD in people with periodontitis. One study involving 303 participants with ≥ 50% blockage of one coronary artery or a coronary event within three years, but not the three months prior, was included. The study was at high risk of bias due to deviation from the protocol treatment allocation and lack of follow-up data. The trial compared scaling and root planing (SRP) with community care for a follow-up period of six to 25 months. No data on deaths (all-cause or CVD-related) were reported. There was insufficient evidence to determine the effect of SRP and community care in reducing the risk of CVD recurrence in patients with chronic periodontitis (risk ratio (RR) 0.72; 95% confidence interval (CI) 0.23 to 2.22; very low quality evidence). The effects of SRP compared with community care on high-sensitivity C-reactive protein (hs-CRP) (mean difference (MD) 0.62; -1.45 to 2.69), the number of patients with high hs-CRP (RR 0.77; 95% CI 0.32 to 1.85) and adverse events (RR 9.06; 95% CI 0.49 to 166.82) were also not statistically significant. The study did not assess modifiable cardiovascular risk factors, other blood test results, heart function parameters or revascularisation procedures. We found very low quality evidence that was insufficient to support or refute whether periodontal therapy can prevent the recurrence of CVD in the long term in patients with chronic periodontitis. No evidence on primary prevention was found.

Reduced risk of peanut sensitization following exposure through breast-feeding and early peanut introduction

Recent trials have shown that avoiding peanuts during infancy increases the risk of peanut allergy; however, these studies did not address maternal peanut consumption. We sought to investigate the relationship between maternal peanut consumption while breast-feeding, timing of direct peanut introduction, and peanut sensitization at age 7years. Secondary analysis of a nested cohort within the 1995 Canadian Asthma Primary Prevention Study intervention study was performed. Breast-feeding and maternal and infant peanut consumption were captured by repeated questionnaires during infancy. Skin prick testing for peanut sensitization was performed at age 7 years. Overall, 58.2% of mothers consumed peanuts while breast-feeding and 22.5% directly introduced peanuts to their infant by 12months. At 7years, 9.4% of children were sensitized to peanuts. The lowest incidence (1.7%) was observed among children whose mothers consumed peanuts while breast-feeding and directly introduced peanuts before 12months. Incidence was significantly higher (P<.05) if mothers consumed peanuts while breast-feeding but delayed introducing peanuts to their infant beyond 12months (15.1%), or if mothers avoided peanuts themselves but directly introduced peanuts by 12months (17.6%). Interaction analyses controlling for study group and maternal atopy confirmed that maternal peanut consumption while breast-feeding and infant peanut consumption by 12months were protective in combination, whereas either exposure in isolation was associated with an increased risk of sensitization (P interaction=.003). In this secondary analysis, maternal peanut consumption while breast-feeding paired with direct introduction of peanuts in the first year of life was associated with the lowest risk of peanut sensitization, compared with all other combinations of maternal and infant peanut consumption.

Vitamin D supplementation in primary allergy prevention: Systematic review of randomized and non‐randomized studies

To date, a systematic review of the evidence regarding the association between vitamin D and allergic diseases development has not yet been undertaken. To review the efficacy and safety of vitamin D supplementation when compared to no supplementation in pregnant women, breastfeeding women, infants, and children for the prevention of allergies. Three databases were searched through January 30, 2016, including randomized (RCT) and nonrandomized studies (NRS). Two reviewers independently extracted data and assessed the certainty in the body of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Among the 1932 articles identified, one RCT and four NRS were eligible. Very low certainty in the body of evidence across examined studies suggests that vitamin D supplementation for pregnant women, breastfeeding women, and infants may not decrease the risk of developing allergic diseases such as atopic dermatitis (in pregnant women), allergic rhinitis (in pregnant women and infants), asthma and/or wheezing (in pregnant women, breastfeeding women, and infants), or food allergies (in pregnant women). We found no studies of primary prevention of allergic diseases in children. Limited information is available addressing primary prevention of allergic diseases after vitamin D supplementation, and its potential impact remains uncertain.

High-Sensitivity Cardiac Troponin Concentration and Risk of First-Ever Cardiovascular Outcomes in 154,052 Participants

BackgroundHigh-sensitivity assays can quantify cardiac troponins I and T (hs-cTnI, hs-cTnT) in individuals with no clinically manifest myocardial injury. ObjectivesThe goal of this study was to assess associations of cardiac troponin concentration with cardiovascular disease (CVD) outcomes in primary prevention studies. MethodsA search was conducted of PubMed, Web of Science, and EMBASE for prospective studies published up to September 2016, reporting on associations of cardiac troponin concentration with first-ever CVD outcomes (i.e., coronary heart disease [CHD], stroke, or the combination of both). Study-specific estimates, adjusted for conventional risk factors, were extracted by 2 independent reviewers, supplemented with de novo data from PROSPER (Pravastatin in Elderly Individuals at Risk of Vascular Disease Study), then pooled by using random effects meta-analysis. ResultsA total of 28 relevant studies were identified involving 154,052 participants. Cardiac troponin was detectable in 80.0% (hs-cTnI: 82.6%; hs-cTnT: 69.7%). In PROSPER, positive associations of log-linear shape were observed between hs-cTnT and CVD outcomes. In the meta-analysis, the relative risks comparing the top versus the bottom troponin third were 1.43 (95% confidence interval [CI]: 1.31 to 1.56) for CVD (11,763 events), 1.67 (95% CI: 1.50 to 1.86) for fatal CVD (7,775 events), 1.59 (95% CI: 1.38 to 1.83) for CHD (7,061 events), and 1.35 (95% CI: 1.23 to 1.48) for stroke (2,526 events). For fatal CVD, associations were stronger in North American studies (p = 0.010) and those measuring hs-cTnT rather than hs-cTnI (p = 0.027). ConclusionsIn the general population, high cardiac troponin concentration within the normal range is associated with increased CVD risk. This association is independent of conventional risk factors, strongest for fatal CVD, and applies to both CHD and stroke.

Chocolate Consumption and Risk of Coronary Heart Disease, Stroke, and Diabetes: A Meta-Analysis of Prospective Studies.

Although epidemiological studies have examined the role of chocolate in preventing cardiometabolic disease, the results remain inconsistent. Herein, we conducted a meta-analysis of prospective studies to determine the association between chocolate intake and risk of coronary heart disease (CHD), stroke, and diabetes. A systematical search in PubMed and Embase through March 2017, together with reference scrutiny of relevant literatures, was performed to identify eligible studies. Relative risks (RRs) and 95% confidence intervals (CIs) were pooled using random effect models. Fourteen prospective studies of primary prevention with 508,705 participants were finally included, with follow-up durations ranging from 5 to 16 years. The summary RRs for the highest versus lowest chocolate consumption were 0.90 (95% CI: 0.82–0.97; n = 6) for CHD, 0.84 (95% CI: 0.78–0.90; n = 7) for stroke, and 0.82 (95% CI: 0.70–0.96; n = 5) for diabetes. Dose–response meta-analysis suggested a nonlinear association of chocolate consumption with all outcomes. For both CHD and stroke, there was little additional risk reduction when consuming chocolate ≥3 servings/week (one serving was defined as 30 g of chocolate). For diabetes, the peak protective effect of chocolate emerged at 2 servings/week (RR: 0.75, 95% CI: 0.63–0.89), with no benefit observed when increasing consumption above 6 servings/week. In conclusion, chocolate intake is associated with decreased risks of CHD, stroke, and diabetes. Consuming chocolate in moderation (≤6 servings/week) may be optimal for preventing these disorders.

Evolving Concepts in Atopic Dermatitis.

Tremendous advances have been made in the field of atopic dermatitis in the past 5years. We will explore developments in burden of disease, co-morbidities, pathogenesis, prevention, and management. The tremendous burden moderate to severe atopic dermatitis (AD) places on families from a medical, psychosocial, and financial perspective has been characterized. Epidemiologic studies have identified intriguing new associations beyond the well-characterized "atopic march" of food allergies, asthma, and hay fever. Studies of primary prevention have gained traction including the remarkable impacts of early emollient therapy. Basic advances have simultaneously elucidated the nature of atopic inflammation, setting the stage for an explosion of new potential therapeutic targets. After a fallow period of nearly 15years without a substantial therapeutic advance, this year has already seen two new FDA-approved treatments for AD. AD has a tremendous impact on quality of life with an underappreciated burden of disease; there are important newly described co-morbidities including ADHD and anemia; new insights into etio-pathogenesis have paved the way for novel topical therapies like crisaborole, and new systemic interventions like dupilumab.

Treatment of Hypercholesterolemia in 2015.

Randomized, double-blind, placebo-controlled secondary prevention and primary prevention studies and observational studies have documented that statins reduce cardiovascular events in high-risk patients with hypercholesterolemia. The 2013 American College of Cardiology/American Heart Association guidelines on treatment of hypercholesterolemia support the use of statins in 4 major groups that will be discussed. The Expert Panel of these guidelines could find no data supporting the routine use of nonstatin drugs combined with statins to further reduce cardiovascular events. Since these guidelines were published, a double-blind randomized trial of 18,144 patients with an acute coronary syndrome demonstrated at a 7-year follow-up that the incidence of cardiovascular events was 34.7% in patients randomized to simvastatin plus placebo versus 32.7% in patients randomized to simvastatin plus ezetimibe (hazard ratio = 0.936; P = 0.016). Proprotein convertase subtilisin/kexin type 9 inhibitors further lower serum low-density lipoprotein cholesterol by 50%-70% in patients treated with statins and 4 phase 3 trials including more than 70,000 patients are investigating whether these monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 will lower cardiovascular events.

Procalcitonin and Midregional Proatrial Natriuretic Peptide as Biomarkers of Subclinical Cerebrovascular Damage: The Northern Manhattan Study.

Chronic infections and cardiac dysfunction are risk factors for stroke. We hypothesized that blood biomarkers of infection (procalcitonin) and cardiac dysfunction (midregional proatrial natriuretic peptide [MR-proANP]), previously associated with small vessel stroke and cardioembolic stroke are also associated with subclinical cerebrovascular damage, including silent brain infarcts and white matter hyperintensity volume. The NOMAS (Northern Manhattan Study) was designed to assess risk factors for incident vascular disease in a multiethnic cohort. A subsample underwent brain magnetic resonance imaging and had blood samples available for biomarker measurement (n=1178). We used logistic regression models to estimate the odds ratios and 95% confidence intervals (95% CIs) for the association of these biomarkers with silent brain infarcts after adjusting for demographic, behavioral, and medical risk factors. We used linear regression to assess associations with log-white matter hyperintensity volume. Mean age was 70±9 years; 60% were women, 66% Hispanic, 17% black, and 15% were white. After adjusting for risk factors, subjects with procalcitonin or MR-proANP in the top quartile, compared with the lowest quartile were more likely to have silent brain infarcts (adjusted odds ratio for procalcitonin, 2.2; 95% CI, 1.3-3.7 and for MR-proANP, 3.3; 95% CI, 1.7-6.3) and increased white matter hyperintensity volume (adjusted mean change in log-white matter hyperintensity volume for procalcitonin, 0.29; 95% CI, 0.13-0.44 and for MR-proANP, 0.18; 95% CI, 0.004-0.36). Higher concentrations of procalcitonin, a marker of infection, and MR-proANP, a marker of cardiac dysfunction, are independently associated with subclinical cerebrovascular damage. If further studies demonstrate an incremental value for risk stratification, biomarker-guided primary prevention studies may lead to new approaches to prevent cerebrovascular disease.

ASPREE-NEURO study protocol: A randomized controlled trial to determine the effect of low-dose aspirin on cerebral microbleeds, white matter hyperintensities, cognition, and stroke in the healthy elderly.

Rationale Cerebral microbleeds seen on brain magnetic resonance imaging are markers of small vessel disease, linked to cognitive dysfunction and increased ischemic and hemorrhagic stroke risk. Observational studies suggest that aspirin use may induce cerebral microbleeds, and associated overt intracranial hemorrhage, but this has not been definitively resolved. Aims ASPREE-NEURO will determine the effect of aspirin on cerebral microbleed development over three years in healthy adults aged 70 years and over, participating in the larger 'ASPirin in Reducing Events in the Elderly (ASPREE)' primary prevention study of aspirin. Sample size Five hundred and fifty-nine participants provide 75% power (two-sided p value of 0.05) to determine an average difference of 0.5 cerebral microbleed per person after three years. Methods and design A multi-center, randomized placebo-controlled trial of 100 mg daily aspirin in participants who have brain magnetic resonance imaging at study entry, one and three years after randomization and who undergo cognitive testing at the same time points. Study outcomes The primary outcome is the number of new cerebral microbleeds on magnetic resonance imaging after three years. Secondary outcomes are the number of new cerebral microbleeds after one year, change in volume of white matter hyperintensity, cognitive function, and stroke. Discussion ASPREE-NEURO will resolve whether aspirin affects the presence and number of cerebral microbleeds, their relationship with cognitive performance, and indicate whether consideration of cerebral microbleeds alters the risk-benefit profile of aspirin in primary prevention for older people. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12613001313729.

A systematic review of published interventions for primary and secondary prevention of ischaemic heart disease (IHD) in rural populations of Australia.

BackgroundRural Australians are known to experience a higher burden of ischaemic heart disease (IHD) than their metropolitan counterparts and the reasons for this appear to be highly complex and not well understood. It is not clear what interventions and prevention efforts have occurred specifically in rural Australia in terms of IHD. A summary of this evidence could have implications for future action and research in improving the health of rural communities. The aim of this study was to review all published interventions conducted in rural Australia that were aimed at the primary and/or secondary prevention of ischaemic heart disease (IHD) in adults.MethodsSystematic review of the peer-reviewed literature published between January 1990 and December 2015. Search terms were derived from four major topics: (1) rural; (2) ischaemic heart disease; (3) Australia and; (4) intervention/prevention. Terms were adapted for six databases and three independent researchers screened results. Studies were included if the published work described an intervention focussed on the prevention or reduction of IHD or risk factors, specifically in a rural population of Australia, with outcomes specific to participants including, but not limited to, changes in diet, exercise, cholesterol or blood pressure levels.ResultsOf 791 papers identified in the search, seven studies met the inclusion criteria, and one further study was retrieved from searching reference lists of screened abstracts. Typically, excluded studies focused on cardiovascular diseases without specific reference to IHD, or presented intervention results without stratification by rurality. Larger trials that included metropolitan residents without stratification were excluded due to differences in the specific needs, characteristics and health service access challenges of rural populations. Six interventions were primary prevention studies, one was secondary prevention only and one included both primary and secondary intervention strategies. Two interventions were focussed exclusively on Aboriginal and Torres Strait Islander (Australian Indigenous) populations.ConclusionsFew interventions were identified that exclusively focussed on IHD prevention in rural communities, despite these populations being at increased risk of IHD in Australia, and this is consistent with comparable countries, internationally. Although limited, available evidence shows that primary and secondary interventions targeted at IHD and related risk factors can be effective in a rural setting.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-016-3548-1) contains supplementary material, which is available to authorized users.

Aspirin for Primary and Secondary Prevention of Cardiovascular Disease.

The first reported use of salicylate-rich plants as an analgesic and anti-inflammatory agent comes from the Ebers Papyrus, an Egyptian medical text from ca. 1,543 bc.1 It wasn't until the mid-1800s that silicon was isolated as the active component from willow tree bark extract, and then purified to acetylsalicylic acid. Bayer patented the compound in 1900, after the German chemist Felix Hoffmann's successful use of it to treat his father's severe arthritis. Finally, in 1950, the physician Lawrence Craven recognized that aspirin reduced the risk of heart attacks in men.2