Showing papers by "Diederick E. Grobbee published in 2014"

2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD

Abstract: This is the second iteration of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) joining forces to write guidelines on the management of diabetes mellitus (DM), pre-diabetes, and cardiovascular disease (CVD), designed to assist clinicians and other healthcare workers to make evidence-based management decisions. The growing awareness of the strong biological relationship between DM and CVD rightly prompted these two large organizations to collaborate to generate guidelines relevant to their joint interests, the first of which were published in 2007. Some assert that too many guidelines are being produced but, in this burgeoning field, five years in the development of both basic and clinical science is a long time and major trials have reported in this period, making it necessary to update the previous Guidelines.

2013 ESH/ESC Practice guidelines for the management of arterial hypertension

Abstract: ABPMambulatory blood pressure monitoringACEangiotensin converting enzymeARBangiotensin receptor blockerA-Vatrio-ventricularBBbeta-blockerBPblood pressureCHDcoronary heart diseaseCKDchronic kidney d...

Follow-up of Blood-Pressure Lowering and Glucose Control in Type 2 Diabetes

Abstract: Background In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) factorial trial, the combination of perindopril and indapamide reduced mortality among patients with type 2 diabetes, but intensive glucose control, targeting a glycated hemoglobin level of less than 6.5%, did not. We now report results of the 6-year post-trial follow-up. Methods We invited surviving participants, who had previously been assigned to perindopril–indapamide or placebo and to intensive or standard glucose control (with the glucose-control comparison extending for an additional 6 months), to participate in a post-trial follow-up evaluation. The primary end points were death from any cause and major macrovascular events. Results The baseline characteristics were similar among the 11,140 patients who originally underwent randomization and the 8494 patients who participated in the post-trial follow-up for a median of 5.9 years (blood-pressure–lowering comparison) or ...

Effect of aleglitazar on cardiovascular outcomes after acute coronary syndrome in patients with type 2 diabetes mellitus: the AleCardio randomized clinical trial.

Abstract: Importance No therapy directed against diabetes has been shown to unequivocally reduce the excess risk of cardiovascular complications. Aleglitazar is a dual agonist of peroxisome proliferator–activated receptors with insulin-sensitizing and glucose-lowering actions and favorable effects on lipid profiles. Objective To determine whether the addition of aleglitazar to standard medical therapy reduces cardiovascular morbidity and mortality among patients with type 2 diabetes mellitus and a recent acute coronary syndrome (ACS). Design, Setting, and Participants AleCardio was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial conducted in 720 hospitals in 26 countries throughout North America, Latin America, Europe, and Asia-Pacific regions. The enrollment of 7226 patients hospitalized for ACS (myocardial infarction or unstable angina) with type 2 diabetes occurred between February 2010 and May 2012; treatment was planned to continue until patients were followed-up for at least 2.5 years and 950 primary end point events were positively adjudicated. Interventions Randomized in a 1:1 ratio to receive aleglitazar 150 µg or placebo daily. Main Outcomes and Measures The primary efficacy end point was time to cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Principal safety end points were hospitalization due to heart failure and changes in renal function. Results The trial was terminated on July 2, 2013, after a median follow-up of 104 weeks, upon recommendation of the data and safety monitoring board due to futility for efficacy at an unplanned interim analysis and increased rates of safety end points. A total of 3.1% of patients were lost to follow-up and 3.2% of patients withdrew consent. The primary end point occurred in 344 patients (9.5%) in the aleglitazar group and 360 patients (10.0%) in the placebo group (hazard ratio, 0.96 [95% CI, 0.83-1.11]; P = .57). Rates of serious adverse events, including heart failure (3.4% for aleglitazar vs 2.8% for placebo, P = .14), gastrointestinal hemorrhages (2.4% for aleglitazar vs 1.7% for placebo, P = .03), and renal dysfunction (7.4% for aleglitazar vs 2.7% for placebo, P Conclusions and Relevance Among patients with type 2 diabetes and recent ACS, use of aleglitazar did not reduce the risk of cardiovascular outcomes. These findings do not support the use of aleglitazar in this setting with a goal of reducing cardiovascular risk. Trial Registration clinicaltrials.gov Identifier:NCT01042769

Individual and community determinants of neonatal mortality in Ghana: a multilevel analysis

Abstract: Neonatal mortality is a global challenge; identification of individual and community determinants associated with it are important for targeted interventions. However in most low and middle income countries (LMICs) including Ghana this problem has not been adequately investigated as the impact of contextual factors remains undetermined despite their significant influence on under-five mortality and morbidity. Based on a modified conceptual framework for child survival, hierarchical modelling was deployed to examine about 6,900 women, aged 15 – 49 years (level 1), nested within 412 communities (level 2) in Ghana by analysing combined data of the 2003 and 2008 Ghana Demographic and Health Survey. The aim was to identify individual (maternal, paternal, neonatal, antenatal, delivery and postnatal) and community (socioeconomic disadvantage communities) determinants associated with neonatal mortality. The results showed both individual and community characteristics to be associated with neonatal mortality. Infants of multiple-gestation [OR 5.30; P-value < 0.001; 95% CI 2.81 – 10.00], neonates with inadequate birth spacing [OR 3.47; P-value < 0.01; 95% CI 1.60 – 7.57] and low birth weight [OR 2.01; P-value < 0.01; 95% CI 1.23 – 3.30] had a lower chance of surviving the neonatal period. Similarly, infants of grand multiparous mothers [OR 2.59; P-value < 0.05; 95% CI 1.03 – 6.49] and non-breastfed infants [OR 142.31; P-value < 0.001; 95% CI 80.19 – 252.54] were more likely to die during neonatal life, whereas adequate utilization of antenatal, delivery and postnatal health services [OR 0.25; P-value < 0.001; 95% CI 0.13 – 0.46] reduced the likelihood of neonatal mortality. Dwelling in a neighbourhood with high socioeconomic deprivation was associated with increased neonatal mortality [OR 3.38; P-value < 0.01; 95% CI 1.42 – 8.04]. Both individual and community characteristics show a marked impact on neonatal survival. Implementation of community-based interventions addressing basic education, poverty alleviation, women empowerment and infrastructural development and an increased focus on the continuum-of-care approach in healthcare service will improve neonatal survival.

Contextual risk factors for low birth weight: a multilevel analysis.

Abstract: Background Low birth weight (LBW) remains to be a leading cause of neonatal death and a major contributor to infant and under-five mortality. Its prevalence has not declined in the last decade in sub-Saharan Africa (SSA) and Asia. Some individual level factors have been identified as risk factors for LBW but knowledge is limited on contextual risk factors for LBW especially in SSA. Methods Contextual risk factors for LBW in Ghana were identified by performing multivariable multilevel logistic regression analysis of 6,900 mothers dwelling in 412 communities that participated in the 2003 and 2008 Demographic and Health Surveys in Ghana. Results Contextual-level factors were significantly associated with LBW: Being a rural dweller increased the likelihood of having a LBW infant by 43% (OR 1.43; 95% CI 1.01–2.01; P-value <0.05) while living in poverty-concentrated communities increased the risk of having a LBW infant twofold (OR 2.16; 95% CI 1.29–3.61; P-value <0.01). In neighbourhoods with a high coverage of safe water supply the odds of having a LBW infant reduced by 28% (OR 0.74; 95% CI 0.57–0.96; P-value <0.05). Conclusion This study showed contextual risk factors to have independent effects on the prevalence of LBW infants. Being a rural dweller, living in a community with a high concentration of poverty and a low coverage of safe water supply were found to increase the prevalence of LBW infants. Implementing appropriate community-based intervention programmes will likely reduce the occurrence of LBW infants.

Common carotid intima-media thickness measurements do not improve cardiovascular risk prediction in individuals with elevated blood pressure: the USE-IMT collaboration

Abstract: Carotid intima-media thickness (CIMT) is a marker of cardiovascular risk. It is unclear whether measurement of mean common CIMT improves 10-year risk prediction of first-time myocardial infarction or stroke in individuals with elevated blood pressure. We performed an analysis among individuals with elevated blood pressure (ie, a systolic blood pressure ≥140 mm Hg and a diastolic blood pressure ≥ 90 mm Hg) in USE-IMT, a large ongoing individual participant data meta-analysis. We refitted the risk factors of the Framingham Risk Score on asymptomatic individuals (baseline model) and expanded this model with mean common CIMT (CIMT model) measurements. From both models, 10-year risks to develop a myocardial infarction or stroke were estimated. In individuals with elevated blood pressure, we compared discrimination and calibration of the 2 models and calculated the net reclassification improvement (NRI). We included 17 254 individuals with elevated blood pressure from 16 studies. During a median follow-up of 9.9 years, 2014 first-time myocardial infarctions or strokes occurred. The C-statistics of the baseline and CIMT models were similar (0.73). NRI with the addition of mean common CIMT was small and not significant (1.4%; 95% confidence intervals, −1.1 to 3.7). In those at intermediate risk (n=5008, 10-year absolute risk of 10% to 20%), the NRI was 5.6% (95% confidence intervals, 1.6–10.4). There is no added value of measurement of mean common CIMT in individuals with elevated blood pressure for improving cardiovascular risk prediction. For those at intermediate risk, the addition of mean common CIMT to an existing cardiovascular risk score is small but statistically significant.

Outcome in moderate haemophilia.

Abstract: BACKGROUND: Moderate haemophilia is the rarest form of haemophilia. This study aims to assess short- and long-term outcome, including its association with treatment, in patients with moderate haemophilia. MATERIAL AND METHODS: Seventy-five patients with moderate haemophilia (1-5% factor VIII/ factor IX activity), without a history of inhibitors, treated at the van Creveldkliniek, Utrecht (NL) were included in the study. Life-long data on bleeding and treatment were collected. Joints were evaluated using the Haemophilia Joint Health Score. Adults completed questionnaires on activity (HAL) and quality of life (SF-36, EQ5D). RESULTS: The median age of the patients was 37 years (IQR 23-52 years) and haemophilia A was diagnosed in 89%. Bleeding frequency was low: the median annual bleeding rate was 2.0 bleeds/ year (IQR 0.8-3.7 bleeds/year), including a median of 0 joint bleeds/year (IQR 0.8-3.7 bleeds/year). Joint function was good: 82% scored<10 out of 126 points of the Haemophilia Joint Health Score (HJHS). Nevertheless, 29% of patients with moderate haemophilia had a history of prophylaxis, because of a high bleeding frequency. Median age at first joint bleed was 4.8 years (IQR 3.5-8.5). Use of prophylaxis was more associated with age at first joint bleed (P<0.01) than with baseline factor activity (P=0.12). Most patients (52%) who suffered their first joint bleed before the age of 5 years required prophylaxis later in life. DISCUSSION: The majority of patients with moderate haemophilia have few bleeds and complications; however, a considerable subset of patients with a more severe bleeding pattern need prophylactic treatment. These latter patients may be identified by the onset of joint bleeding before the age of 5 years.

Ramadan fasting and newborn's birth weight in pregnant Muslim women in The Netherlands

Abstract: Many Muslim women worldwide are pregnant during Ramadan and adhere to Ramadan fasting during pregnancy. In the present study, we determined whether maternal adherence to Ramadan fasting during pregnancy has an impact on the birth weight of the newborn, and whether the effects differed according to trimester in which Ramadan fasting took place. A prospective cohort study was conducted in 130 pregnant Muslim women who attended antenatal care in Amsterdam and Zaanstad, The Netherlands. Data on adherence to Ramadan fasting during pregnancy and demographics were self-reported by pregnant women, and the outcome of the newborn was retrieved from medical records after delivery. The results showed that half of all the women adhered to Ramadan fasting. With strict adherence to Ramadan fasting in pregnancy, the birth weight of newborns tended to be lower than that of newborns of non-fasting mothers, although this was not statistically significant ( - 198 g, 95 % CI - 447, 51, P= 0·12). Children of mothers who fasted in the first trimester of pregnancy were lighter at birth than those whose mothers had not fasted ( - 272 g, 95 % CI - 547, 3, P= 0·05). There were no differences in birth weight between children whose mothers had or had not fasted if Ramadan fasting had taken place later in pregnancy. Ramadan fasting during early pregnancy may lead to lower birth weight of newborns. These findings call for further confirmation in larger studies that should also investigate potential implications for perinatal and long-term morbidity and mortality.

Incidental Imaging Findings from Routine Chest CT Used to Identify Subjects at High Risk of Future Cardiovascular Events

Abstract: Using radiologic information may complement standard clinical strategies in cardiovascular risk screening and help to improve timely installment of cardiovascular risk management in eligible patients.

Quantifying the validity of routine neonatal healthcare data in the Greater Accra Region, Ghana.

Abstract: OBJECTIVES The District Health Information Management System-2 (DHIMS-2) is the database for storing health service data in Ghana, and similar to other low and middle income countries, paper-based data collection is being used by the Ghana Health Service. As the DHIMS-2 database has not been validated before this study aimed to evaluate its validity. METHODS Seven out of ten districts in the Greater Accra Region were randomly sampled; the district hospital and a polyclinic in each district were recruited for validation. Seven pre-specified neonatal health indicators were considered for validation: antenatal registrants, deliveries, total births, live birth, stillbirth, low birthweight, and neonatal death. Data were extracted on these health indicators from the primary data (hospital paper-registers) recorded from January to March 2012. We examined all the data captured during this period as these data have been uploaded to the DHIMS-2 database. The differences between the values of the health indicators obtained from the primary data and that of the facility and DHIMS-2 database were used to assess the accuracy of the database while its completeness was estimated by the percentage of missing data in the primary data. RESULTS About 41,000 data were assessed and in almost all the districts, the error rates of the DHIMS-2 data were less than 2.1% while the percentages of missing data were below 2%. At the regional level, almost all the health indicators had an error rate below 1% while the overall error rate of the DHIMS-2 database was 0.68% (95% C I = 0.61-0.75) and the percentage of missing data was 3.1% (95% C I = 2.96-3.24). CONCLUSION This study demonstrated that the percentage of missing data in the DHIMS-2 database was negligible while its accuracy was close to the acceptable range for high quality data.

Effect of including nonfatal events in cardiovascular risk estimation, illustrated with data from The Netherlands

Abstract: Aims: European physicians use SCORE risk charts to predict a patient’s 10-year risk of cardiovascular diseases (CVD) mortality. We examined whether the inclusion of nonfatal events improved risk estimation and the identification of high-risk persons. Methods and results: In the EPIC-NL cohort, risk factor data were collected between 1993 and 1997 in 6772 men and 9108 women aged 35–65 years. During 10 years of follow up, 540 total (fatal + nonfatal) CVD events occurred, of which 122 (23%) were fatal. Risk equations were developed using Cox proportional hazard models. Discriminating ability and hazard ratios for CVD risk factors did not differ between the two endpoints. Absolute risks for total CVD were approximately 4-fold higher than for CVD mortality. Using the current 5% CVD mortality threshold or the 22% total CVD threshold for identification of high-risk persons leaves more than 84% of all male and 98% of all female future cases untreated. Of those exceeding these thresholds, 20% and 27% of the men, respectively, and 16% and 19% of women will get a CVD event in the next 10 years. Cut-off points of 2% for CVD mortality, corresponding to 10% for total CVD, will identify high-risk persons of whom approximately 10% will get an event in the next 10 years. Conclusion: CVD mortality comprises a quarter of all total CVD events. Risk functions and the discriminating ability did not differ between the two endpoints. Cut-off points of 2% for CVD mortality or 10% for total CVD could be considered to identify high-risk persons.

Intakes of Potassium, Magnesium, and Calcium and Risk of Stroke

Abstract: Background and Purpose—We aimed to investigate the associations of dietary and total potassium, magnesium, and calcium intakes with stroke occurrence. Methods—A prospective cohort study was conducted among 36 094 participants aged 21 to 70 years. Dietary intake was assessed with a food frequency questionnaire. Results—During 12 years of follow-up, 631 strokes occurred. After adjustment for confounders, magnesium intake was associated with reduced stroke risk (hazard ratio [95% confidence interval] per 100 mg/d, 0.80 [0.67–0.97] dietary magnesium; 0.78 [0.65–0.93] total magnesium). Potassium and calcium intakes were not associated with stroke. Conclusions—This study supports an association between high magnesium intake and a reduced stroke risk.

Predicting functional decline in older patients undergoing cardiac surgery

Abstract: Background: a growing number of older patients undergo cardiac surgery. Some of these patients are at increased risk of post-operative functional decline, potentially leading to reduced quality of life and autonomy, and other negative health outcomes. First step in prevention is to identify patients at risk of functional decline. There are no current published tools available to predict functional decline following cardiac surgery. Objective: to validate the identification of seniors at risk—hospitalised patients (ISAR-HP), in older patients undergoing cardiac surgery. Design and methods: a multicenter cohort study in cardiac surgery wards of two university hospitals with follow-up 3 months after hospital admission. Inclusion criteria: consecutive cardiac surgery patients, aged ≥65. Functional decline was defined as a decline of at least one point on the Katz ADL Index at follow-up compared with preadmission status. Results: 475 patients were included, 16% of all patients and 20% of patients ≥70+ suffered functional decline. The amended prediction model predicted functional decline using four criteria: preadmission need for daily assistance in instrumental activities of daily living, use of a walking device, need for assistance in travelling and no education after age 14. Area under the receiver operating curve for patients ≥70 it was 0.73. For the amended ISAR-HP sensitivity, specificity, positive and negative predictive values were 85, 48, 29 and 93%, respectively. Conclusions: the amended ISAR-HP used in older cardiac surgery patients showed good discriminative values at score ≥1, supporting the generalisability of this prediction model for this patient group.

Prevention of functional decline in older hospitalized patients: nurses should play a key role in safe and adequate care.

Abstract: This paper presents a discussion of knowledge and awareness regarding prevention of functional decline in older hospitalized patients. Functional decline is experienced by 30–60% of the older hospitalized patients, resulting in decreased independence and other adverse health outcomes. One literature study and four cohort studies (total n = 1628) were conducted to develop and validate an instrument to identify older hospitalized patients at risk for functional decline. An evidence-based best practice was developed to improve the quality of care for older patients. This paper shows the relevance and the complexity of this problem and shows that patients at risk can be recognized by four simple questions. Due to their ability to observe and guide patients and their 24-h patient supervision, nurses should play a key role in strategies to prevent functional decline. Nurses should assess the geriatric needs in patients at risk and based on these initiate and coordinate multi-professional interventions. Given the growing number of older people in western society and the growing need for care, action to prevent functional decline cannot be withheld. Knowledge of the ageing process, implementation of an evidence-based programme and a multidisciplinary approach is a basic ingredient to prevent functional decline.

Abstract P381: Impact Of Switching From Different Treatment Regimens To A Fixed-dose Combination Pill (Polypill) In Patients With Cardiovascular Disease Or Similarly High Risk

Abstract: Aims: Cardiovascular fixed-dose combination (FDC) pills, or polypills, may help address the large treatment gaps that exist among patients with cardiovascular disease or similarly high risk. Initiation of polypill-based care in this group typically entails switching from current separately taken medications. Given the heterogeneity in usual care, there is interest in the impact of polypill treatment across different prior medication regimens. Methods: This abstract describes effects of a polypill-based treatment strategy, according to baseline anti platelet, statin and blood pressure (BP)-lowering therapy, in a randomized clinical trial among 2004 participants from India and Europe. The main eligibility criteria were established cardiovascular disease or estimated five year cardiovascular risk of ≥15%. Participants were randomly assigned to a polypill-based treatment strategy or usual care. In the polypill group, physicians could use a polypill that contained aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg. Baseline medication was reviewed and coded into categories. Statin therapy was defined as less potent than the polypill if estimated LDL-cholesterol reduction was 40%. Estimated cardiovascular risk reduction was calculated by combining risk factor changes with results seen in meta-analyses of previous randomized trials. Results: The effect of the polypill at twelve months was relatable to baseline statin usage, with LDL differences of -0.37, -0.22, -0.14 and -0.07 mmol/L compared to continuing usual care among patients taking no statin, less potent, equipotent and more potent statin at baseline, respectively. Similarly there were differences in systolic BP of -5.4, -6.2, -3.3 and -1.8 mmHg among patients taking 0, 1, 2 or ≥3 BP-lowering agents. Among patients taking more potent statins at baseline, there was no significant difference in LDL-cholesterol but there were benefits for BP and aspirin adherence. Similarly, among patients taking ≥3 BP-lowering agents, there were no differences in BP, but benefits for LDL-cholesterol and aspirin adherence. As a result, there were estimated cardiovascular relative risk reductions across all subgroups defined by baseline medication usage. Conclusion: Adherence benefits from switching to a polypill resulted in risk factor changes that were at least as good as usual care, even when usual care involved more potent regimens. More importantly, switching to a polypill-based strategy resulted in estimated cardiovascular relative risk reductions across a wide range of usual care patterns of antiplatelet, statin and BP-lowering therapy prescribing.

A novel approach for establishing cardiovascular drug efficacy

Abstract: Gaining an early understanding of the likely ultimate efficacy of drugs is crucial for the pharmaceutical industry, as lack of efficacy remains a major reason for attrition in the later stages of drug development (Phase II and Phase III attrition rates 2011–2012. Nature Rev. Drug Discov. 12, 569; 2013)1. Drug development for cardiovascular and/ or renal diseases is currently often based on the modification of a single risk factor, such as blood pressure or lipid profiles, with the expectation that this will decrease the long-term risk of morbidity or mortality. Thus, the risk factor serves as a surrogate for the intended effect. To confirm that the drug effect on the risk factor indeed leads to the expected long-term efficacy and safety, short-term trials focused on effects on the risk factor are (or should be) followed by one or more (post-registration) trials evaluating clinically meaningful outcomes, such as reduction in cardiovascular events, which are typically large, complex and expensive. In parallel to this process to investigate efficacy, the safety of the drug is established by monitoring a mostly fixed set of parameters in all efficacy trials.

Improving clinical trial efficiency by biomarker-guided patient selection

Abstract: Background: In many therapeutic areas, individual patient markers have been identified that are associated with differential treatment response. These markers include both baseline characteristics, as well as short-term changes following treatment. Using such predictive markers to select subjects for inclusion in randomized clinical trials could potentially result in more targeted studies and reduce the number of subjects to recruit. Methods: This study compared three trial designs on the sample size needed to establish treatment efficacy across a range of realistic scenarios. A conventional parallel group design served as the point of reference, while the alternative designs selected subjects on either a baseline characteristic or an early improvement after a short active run-in phase. Data were generated using a model that characterized the effect of treatment on survival as a combination of a primary effect, an interaction with a baseline marker and/or an early marker improvement. A representative scenario derived from empirical data was also evaluated. Results: Simulations showed that an active run-in design could substantially reduce the number of subjects to recruit when improvement during active run-in was a reliable predictor of differential treatment response. In this case, the baseline selection design was also more efficient than the parallel group design, but less efficient than the active run-in design with an equally restricted population. For most scenarios, however, the advantage of the baseline selection design was limited. Conclusions: An active run-in design could substantially reduce the number of subjects to recruit in a randomized clinical trial. However, just as with the baseline selection design, generalizability of results may be limited and implementation could be difficult.

Sources of heterogeneity in case–control studies on associations between statins, ACE-inhibitors, and proton pump inhibitors and risk of pneumonia

Abstract: The heterogeneity in case–control studies on the associations between community-acquired pneumonia (CAP) and ACE-inhibitors (ACEi), statins, and proton pump inhibitors (PPI) hampers translation to clinical practice. Our objective is to explore sources of this heterogeneity by applying a common protocol in different data settings. We conducted ten case–control studies using data from five different health care databases. Databases varied on type of patients (hospitalised vs. GP), level of case validity, and mode of exposure ascertainment (prescription or dispensing based). Identified CAP patients and controls were matched on age, gender, and calendar year. Conditional logistic regression was used to calculate odds ratios (OR) for the associations between the drugs of interest and CAP. Associations were adjusted by a common set of potential confounders. Data of 38,742 cases and 118,019 controls were studied. Comparable patterns of variation between case–control studies were observed for ACEi, statins and PPI use and pneumonia risk with adjusted ORs varying from 1.04 to 1.49, 0.82 to 1.50 and 1.16 to 2.71, respectively. Overall, higher ORs were found for hospitalised CAP patients matched to population controls versus GP CAP patients matched to population controls. Prevalence of drug exposure was higher in dispensing data versus prescription data. We show that case–control selection and methods of exposure ascertainment induce bias that cannot be adjusted for and to a considerable extent explain the heterogeneity in results obtained in case–control studies on statins, ACEi and PPIs and CAP. The common protocol approach helps to better understand sources of variation in observational studies.

The Evening versus Morning Polypill Utilization Study: the TEMPUS rationale and design

Abstract: Background and rationaleIn clinical practice, blood pressure (BP)-lowering agents are generally prescribed for use in the morning, whereas (short-acting) statins are recommended for use in the evening. There is evidence that the reduction in LDL cholesterol (LDL-c) achieved with short-acting statins is superior when taken in the evening and reported improvement in BP control when aspirin and BP-lowering agents are taken in the evening. However, it is unclear whether the additional reduction in LDL-c and BP is offset by a reduction in adherence, given that taking medication in the evening may be less typical or convenient. There is therefore uncertainty concerning the best timing of administration of a cardiovascular combination pill such as the polypill.AimThe aim of TEMPUS (NCT01506505), a prospective randomized open blinded endpoint (PROBE) crossover trial, is to evaluate whether there is a difference in LDL-c levels or 24-hour ambulatory BP in individuals at increased risk of cardiovascular disease whe...

Sex disparities in risk and risk factors for ischemic heart disease in the Asia-Pacific region.

Abstract: BackgroundIschemic heart disease (IHD) is the leading cause of death and disability worldwide, with higher rates among men than women. Relatively few studies on risk factor associations are availab...

109913-valent Pneumococcal Conjugate Vaccine Efficacy is Declining with Old Age: Results from an Exploratory Analysis of the CAPiTA Trial

Abstract: Old Age: Results from an Exploratory Analysis of the CAPiTA Trial Cornelis H VanWerkhoven, MD; Susanne MHuijts, MD; Marieke Bolkenbaas, MD; Chris Webber, MD, PhD; Beate Schmoele-Thoma, MD; Scott D. Patterson, PhD; William Gruber, MD; Diederick E. Grobbee, MD, PhD; Marc Bonten, MD PhD; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; Pfizer Vaccine Clinical Research, Maidenhead, United Kingdom; Pfizer Pharma GmbH, Berlin, Germany; Pfizer Vaccine Clinical Research, Collegeville, PA; Pfizer Vaccine Clinical Research, Pearl River, NY; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands

Abstract P445: A Randomized Controlled Trial Of A Cardiovascular Fixed-dose Combination Pill (polypill) Treatment Strategy Compared With Usual Care On Carotid Intima Media Thickness Progression In Individuals At High Risk Of Cardiovascular Disease

Abstract: Aim: The use of fixed-dose combination (FDC) pills, frequently called polypills, containing aspirin, a statin and blood pressure (BP) lowering medication may improve medication adherence and consequently reduce cardiovascular risk. Carotid intima-media thickness (CIMT) and CIMT progression have been used as surrogate measures of cardiovascular risk. This study evaluated the effect of a polypill-based treatment strategy compared to usual care on CIMT progression. Methods: A study nested within the UMPIRE trial was performed to assess whether a polypill-based treatment strategy reduces CIMT progression compared to usual care. The study was a randomized, open label, blinded endpoint clinical trial in participants with established cardiovascular disease or at equivalent high risk (estimated five year cardiovascular risk of ≥15%). Two versions of the polypill were available. These contained aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide. The choices of polyp...