Realizing the value of complex medical technology: Demonstrating cost-effectiveness is not enough.

The main factors driving the value of medical treatments are proven effectiveness and cost-effectiveness. This is different for complex medical technologies that combine scientific disciplines, functions or tools in a single solution-oriented method. This short communication provides three recommendations to realize the value of complex medical technologies. It is important to engage stakeholders before technology implementation to promote its relevance from multiple perspectives, to explore opportunities for professional development and collaboration, and to demonstrate the societal effects over the entire life-cycle.

Omega-3 fatty acids in heart disease-why accurately measured levels matter.

Current guidelines barely support marine omega­3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in cardiology, mainly because results of large trials were equivocal. Most large trials have tested EPA alone or EPA + DHA combined as a drug, thereby disregarding the relevance of their blood levels. These levels are frequently assessed with the Omega­3 Index (percentage of EPA + DHA in erythrocytes), which is determined using a specific standardised analytical procedure. EPA and DHA are present in every human being at unpredictable levels (even in the absence of intake), and their bioavailability is complex. Both facts need to be incorporated into trial design and should direct clinical use of EPA and DHA. An Omega­3 Index in the target range of 8-11% is associated with lower total mortality, fewer major adverse cardiac and other cardiovascular events. Moreover, functions of organs such as the brain benefit from an Omega­3 Index in the target range, while untoward effects, such as bleeding or atrial fibrillation, are minimised. In pertinent intervention trials, several organ functions were improved, with improvements correlating with the Omega­3 Index. Thus, the Omega­3 Index is relevant in trial design and clinical medicine, which calls for a widely available standardised analytical procedure and a discussion on possible reimbursement of this test.

Prevalence of Cardioprotective Medication Use in Coronary Heart Disease Patients in South America: Systematic review and Meta-Analysis.

Background: Coronary heart disease (CHD) is the most common cause of death globally, and clinical guidelines recommend cardioprotective medications for patients with established CHD. Suboptimal use of these medications has been reported, but information from South America is scarce. Methods: We conducted a systematic review on prevalence of secondary prevention medication in South America. We pooled prevalence estimates, analysed time-trends and guideline compliance, and identified factors associated with medication use with meta-regression models. Results: 73 publications were included. Medication prevalence varied by class: beta-blockers 73.4%(95%CI 66.8%-79.1%), ACEI/ARBs 55.8%(95%CI 49.7%-61.8), antiplatelets 84.6%(95%CI 79.6%-88.5%), aspirin 85.1%(95%CI 79.7%-89.3%) and statins 78.9%(95%CI 71.2%-84.9%). The use of beta-blockers, ACEI/ARBs and statins increased since 1993. Ten publications reported low medication use and nine reported adequate use. Medication use was lower in community, public and rehabilitation settings compared to tertiary centres. Conclusion: Cardioprotective medication use has increased, but could be further improved particularly in community settings.

Alcohol-attributable burden of cancer in Argentina.

INTRODUCTION: Alcohol consumption is a risk factor for several types of cancer. Alcohol consumption levels in Argentina are among the highest in the world, and malignant neoplasms are the second cause of death in the country. Public health strategies aimed at reducing alcohol consumption could possibly lead to a decrease in cancer burden. Alcohol-attributable burden has been estimated before in neighboring countries Chile and Brazil. We now aimed to quantify the burden for Argentina. METHODS: We obtained data on alcohol consumption levels from a national representative health survey and etiologic effect sizes for the association between alcohol and cancer from the most recent comprehensive meta-analysis. We estimated the number of alcohol-attributable cancer-related deaths and disability-adjusted life years (DALYs), stratified by consumption level (light (0.1-12.5 g/day), moderate (12.6-50 g/day), or heavy (> 50 g/day) drinking). We additionally explored which hypothetical scenario would achieve the highest reduction in alcohol-attributable cancer burden: 1) heavy drinkers shifting to moderate drinking or 2) moderate drinkers shifting to light drinking. RESULTS: In 2018, 53% of the Argentinean population consumed alcohol. In men 3.7% of all cancer deaths and DALYs were attributable to alcohol consumption, in women this was 0.8% of all cancer deaths and DALYs. When moderate drinkers would shift to light drinking, 46% of alcohol-attributable cancer deaths and DALYs would be prevented, opposed to only 24% when heavy drinkers would shift to moderate drinking. CONCLUSION: Most cancer deaths and DALYs were attributable to moderate alcohol consumption (50%). This calls for implementation of population-wide strategies-instead of targeting heavy drinking only-to effectively reduce harmful use of alcohol and its impact on disease burden.

Added value of computed tomography fractional flow reserve in the diagnosis of coronary artery disease.

Multiple non-invasive tests are performed to diagnose coronary artery disease (CAD), but all are limited to either anatomical or functional assessments. Computed tomography derived Fractional Flow Reserve (CT-FFR) based on patient-specific lumped parameter models is a new test combining both characteristics simulating invasive FFR. This study aims to evaluate the added value of CT-FFR over other non-invasive tests to diagnose CAD. Patients with clinical suspicion of angina pectoris between 2010 and 2011 were included in this cross-sectional study. All underwent stress electrocardiography (X-ECG), SPECT, CT coronary angiography (CCTA) and CT-FFR. Invasive coronary angiography (ICA) and FFR were used as reference standard. Five models mimicking the clinical workflow were fitted and the area under receiver operating characteristic (AUROC) curve was used for comparison. 44% of the patients included in the analysis had a FFR of ≤ 0.80. The basic model including pre-test-likelihood and X-ECG had an AUROC of 0.79. The SPECT-strategy had an AUROC of 0.90 (p = 0.008), CCTA-strategy of 0.88 (p < 0.001), 0.93 when adding CT-FFR (p = 0.40) compared to 0.94 when combining CCTA and SPECT. This study shows adding on-site CT-FFR based on patient-specific lumped parameter models leads to an increased AUROC compared to the basic model. It improves the diagnostic work-up beyond SPECT or CCTA and is non-inferior to the combined strategy of SPECT and CCTA in the diagnosis of hemodynamically relevant CAD.

Ideal Cardiovascular Health Index and Its Determinants in a Rural South African Population.

Background: The ideal cardiovascular health index (CVHI) is a measure to summarize cardiovascular (CV) health, and includes smoking, body-mass index, physical activity, blood pressure, glucose, total cholesterol, and diet. Objective: This study aimed to assess CV health using the CVHI and determinants on CV health in a rural African population, and correlate carotid intima-media thickness (CIMT), a surrogate marker for atherosclerosis, with CVHI. Methods: A cross-sectional analysis was performed on baseline data of the Ndlovu Cohort Study, located in rural South Africa. CVHI score (CVHIs) was calculated by the sum of favourable CVHI factors (range 0 to 7). Logistic regression was performed to examine the association of age, sex, HIV-status, education level, employment status, and income with good CV health (5-7 favourable health factors). Mean CIMT was displayed by poor, intermediate and good CV health. Results: The study included 1927 participants with a mean age of 38.7 years (SD ± 12.8). Of the factors contributing to the CVHI, glucose and total cholesterol scored best; diet least good. Average CVHIs for the population was 4.4 (SD ± 1.2) and 53% of the population had a good CV health. Determinants associated with good CV health were younger age, higher educational attainment, and HIV positivity. CVHIs showed good agreement with CIMT. Conclusion: CVHIs showed that more than half of the participants had a good CV health. Agreement between CVHIs and CIMT indicates potential use of CVHIs as a surrogate marker for CV risk. The study highlights the importance of education for health promotion; good CV health in HIV-positive participants may in part be attributed to more frequent health care contact and provision of chronic disease care. Highlights: Good cardiovascular health (CVH) was observed in 53% of the study population.In global comparison, rural African study participants showed a good CVH score.HIV positivity was associated with a good CVH score.CVH score showed good agreement with carotid intima-media thickness.

Cardiovascular disease risk and its determinants in people living with HIV across different settings in South Africa.

OBJECTIVES: Socio-economic factors and lifestyle are known to differ across geographies and populations, which may result in distinct risk profiles for cardiovascular disease (CVD). This study assessed carotid intima-media thickness (CIMT), a proxy for CVD, and its determinants in two groups of people living with HIV (PLHIV) in two different settings in South Africa. METHODS: A cross-sectional analysis was conducted comparing data from the Ndlovu Cohort Study in the Limpopo Province (group 1) and from three clinical trials in Johannesburg (group 2). The association between demographics, conventional CVD risk factors, HIV-related factors and CIMT in groups 1 and 2 was analysed with two separate multivariable linear regression models. RESULTS: Group 1 consisted of 826 participants (mean age 42.2 years) and mean (± standard deviation) CIMT was 0.626 ± 0.128 mm. In this group, sex, age, body mass index (BMI), cholesterol, glucose and antiretroviral therapy (ART) duration (ß = 0.011 mm per 5 years; P = 0.02) were associated with higher CIMT. There were positive interactions between age and ART duration and age and cholesterol. Group 2 consisted of 382 participants (mean age 39.5 years) and mean (± standard deviation) CIMT was 0.560 ± 0.092 mm. In this group, only sex, education level, BMI and cholesterol were associated with higher CIMT, albeit with weaker associations than in group 1. CONCLUSIONS: Conventional CVD risk factors were the main drivers of CIMT. The impact of some of these risk factors appeared to increase with age. Differences in sample size, age and viral suppression might explain why an effect of ART was observed in group 1 but not in group 2.

A computerised decision support system for cardiovascular risk management 'live' in the electronic health record environment: development, validation and implementation-the Utrecht Cardiovascular Cohort Initiative.

PURPOSE: We set out to develop a real-time computerised decision support system (CDSS) embedded in the electronic health record (EHR) with information on risk factors, estimated risk, and guideline-based advice on treatment strategy in order to improve adherence to cardiovascular risk management (CVRM) guidelines with the ultimate aim of improving patient healthcare. METHODS: We defined a project plan including the scope and requirements, infrastructure and interface, data quality and study population, validation and evaluation of the CDSS. RESULTS: In collaboration with clinicians, data scientists, epidemiologists, ICT architects, and user experience and interface designers we developed a CDSS that provides 'live' information on CVRM within the environment of the EHR. The CDSS provides information on cardiovascular risk factors (age, sex, medical and family history, smoking, blood pressure, lipids, kidney function, and glucose intolerance measurements), estimated 10-year cardiovascular risk, guideline-compliant suggestions for both pharmacological and non-pharmacological treatment to optimise risk factors, and an estimate on the change in 10-year risk of cardiovascular disease if treatment goals are adhered to. Our pilot study identified a number of issues that needed to be addressed, such as missing data, rules and regulations, privacy, and patient participation. CONCLUSION: Development of a CDSS is complex and requires a multidisciplinary approach. We identified opportunities and challenges in our project developing a CDSS aimed at improving adherence to CVRM guidelines. The regulatory environment, including guidance on scientific evaluation, legislation, and privacy issues needs to evolve within this emerging field of eHealth.

Views and preferences of medical professionals and pregnant women about a novel primary prevention intervention for hypertensive disorders of pregnancy: a qualitative study.

BACKGROUND: Calcium and low-dose aspirin are two potential approaches for primary prevention of hypertensive disorders of pregnancy (HDP). This study aimed to explore the acceptability, views and preferences of pregnant women and primary healthcare providers for a fixed-dose combined preparation of aspirin and calcium (a polypill) as primary prevention of HDP in an unselected pregnant population. METHODS: In this qualitative study eight in-depth semi-structured interviews were conducted with Dutch primary care midwives and general practitioners. Seven focus group discussions were organised with women with low-risk pregnancies. Topics discussed were: perceptions of preeclampsia; information provision about preeclampsia and a polypill; views on the polypill concept; preferences and needs regarding implementation of a polypill. Thematic analysis of the data transcripts was carried out to identify emerging themes. RESULTS: Two major themes shaped medical professionals' and women's views on the polypill concept: 'Informed Choice' and 'Medicalisation'. Both could be divided into subthemes related to information provision, personal choice and discussions with regard to the balance between 'unnecessary medicalisation' and 'scientific progress'. CONCLUSIONS: In general, women and healthcare practitioners expressed a positive attitude towards a polypill intervention as primary prevention strategy with aspirin and calcium, providing some conditions are met. The most important conditions for implementation of such a strategy were safety, effectiveness and the possibility to make a well-informed autonomous decision.

Excess early postnatal weight gain and blood pressure in healthy young children.

Blood pressure (BP) tracks from childhood to adulthood, and early BP trajectories predict cardiovascular disease risk later in life. Excess postnatal weight gain is associated with vascular changes early in life. However, to what extent it is associated with children's BP is largely unknown. In 853 healthy 5-year-old children of the Wheezing-Illnesses-Study-Leidsche-Rijn (WHISTLER) birth cohort, systolic (SBP) and diastolic BP (DBP) were measured, and z scores of individual weight gain rates adjusted for length gain rates were calculated using at least two weight and length measurements from birth until 3 months of age. Linear regression analyses were conducted to investigate the association between weight gain rates adjusted for length gain rates and BP adjusted for sex and ethnicity. Each standard deviation increase in weight gain rates adjusted for length gain rates was associated with 0.9 mmHg (95% CI 0.3, 1.5) higher sitting SBP after adjustment for confounders. Particularly in children in the lowest birth size decile, high excess weight gain was associated with higher sitting SBP values compared to children with low weight gain rates adjusted for length gain rates. BMI and visceral adipose tissue partly explained the association between excess weight gain and sitting SBP (ß 0.5 mmHg, 95% CI -0.3, 1.3). Weight gain rates adjusted for length gain rates were not associated with supine SBP or DBP. Children with excess weight gain, properly adjusted for length gain, in the first three months of life, particularly those with a small birth size, showed higher sitting systolic BP at the age of 5 years.

The impact of 13-valent pneumococcal conjugate vaccination on virus-associated community-acquired pneumonia in elderly: Exploratory analysis of the CAPiTA trial.

OBJECTIVES: Our objective was to evaluate whether vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) prevents the incidence of community-acquired pneumonia (CAP) caused by influenza (influenza-associated CAP, IA-CAP) or other respiratory viruses in the elderly. METHODS: This analysis was part of the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA); a double blind, randomized, placebo-controlled trial in 84 496 immunocompetent individuals aged ≥65 years. CAP was defined by clinical and radiological criteria, and oropharyngeal swabs were collected from all individuals referred to a sentinel centre with a clinical suspicion of pneumonia. Presence of influenza A and B, parainfluenza 1, 2, 3 and 4, human adeno-, boca-, corona-, metapneumo-, rhino- and respiratory syncytial viruses was determined by real-time PCR. RESULTS: Of 3209 episodes of suspected pneumonia, viral aetiology was tested in 2917 and proportions with influenza virus, human metapneumovirus and respiratory syncytial virus were 4.6%, 2.5% and 3.1%, respectively. There were 1653 oropharyngeal swabs for PCR testing available from 1814 episodes that fulfilled criteria for CAP, yielding 23 first episodes of IA-CAP in the PCV13 and 35 in the in placebo group-vaccine efficacy for IA-CAP of 34.4% (95% CI -11.1% to 61.2%; p 0.117). Annual influenza vaccination was received by 672 (87.2%) in the PCV13 group and 719 (87.7%) in the placebo group of the confirmed CAP cases. CONCLUSION: In a randomized study of 84 496 elderly individuals with a high uptake of influenza vaccination, PCV13 was not associated with a statistically significant reduction of influenza or virus-associated CAP. Overall incidence of non-influenza viral pneumonia was low.

Risk of death from cardiovascular disease following breast cancer: a systematic review.

PURPOSE: Breast cancer incidence and survival is high, which results in high prevalence of breast cancer survivors. The risk of (death from) cardiovascular disease (CVD) is higher in patients exposed to cardiotoxic treatments, in particular if they have pre-existing CVD risk factors. This study systematically summarized the risk of death from CVD following breast cancer. METHODS: Databases of Medline, Embase, and the Cochrane Library were systematically searched using the following terms and synonyms: breast cancer, cardiovascular disease, and cause of death. Articles reporting on both risk and risk factors of CVD mortality following breast cancer were eligible for inclusion. The methodological quality of each article was assessed using the Newcastle Ottawa quality assessment scale for cohort studies. RESULTS: Fourteen articles were included assessing the risk of CVD mortality among 1,217,910 women with breast cancer. The methodological quality was high for the majority of the studies. Studies were heterogeneous in design, study population, length of follow-up, CVD outcomes, and risk factors. 1.6-10.4% of all women with breast cancer died of CVD. Women with breast cancer had a higher risk of CVD mortality than women from the general population. The risk of CVD mortality was higher among women with breast cancer with older age at diagnosis, left-sided tumor, diagnosis in an earlier calendar period, and black ethnic origin. CONCLUSIONS: CVD is an important cause of death following breast cancer. Identification of patients at high risk of CVD is important to optimize CVD prevention and tailor breast cancer treatment.

Risk of death from cardiovascular disease following breast cancer in Southeast Asia: a prospective cohort study.

Breast cancer incidence and survival is high in Southeast Asia. As such, many women diagnosed with breast cancer are at risk of dying of other causes. Given the increased risk of cardiotoxicity induced by breast cancer treatments, it is important to identify patients at high risk of cardiovascular disease (CVD) mortality. The aim of this study was to investigate if this risk varies by age and ethnicity. Patient details were obtained from 5,868 Chinese, Malay, and Indian women diagnosed with in situ or non-metastasized invasive breast cancer at the National University Hospital of Singapore and KK Women's and Children's Hospital in Singapore. Death causes were obtained from the National Registry of Births and Deaths. Flexible parametric survival models estimated CVD mortality rates and hazard ratios. During a median follow-up of six years, 1,010 deaths occurred of which 6.8% were due to CVD. CVD mortality rates of older women peaked within the first year following diagnosis and increased over time since diagnosis. Indian had more than double the risk of CVD mortality than Chinese, independent of age at diagnosis and stage. Taking ethnicity and age into account may promote CVD risk stratification and management in (Southeast Asian) women with breast cancer.

No psychological distress in sportsmen aged 45 years and older after cardiovascular screening, including cardiac CT: The Measuring Athlete's Risk of Cardiovascular events (MARC) study.

BACKGROUND: Psychological distress caused by cardiovascular pre-participation screening (PPS) may be a reason not to implement a PPS program. We assessed the psychological impact of PPS, including cardiac computed tomography (CT), in 318 asymptomatic sportsmen aged ≥45 years. METHODS: Coronary artery disease (CAD) was defined as a coronary artery calcium score ≥100 Agatson units and/or ≥50% luminal stenosis on contrast-enhanced cardiac CT. Psychological impact was measured with the Impact of Event Scale (IES) (seven items) on a six-point scale (grade 0-5). A sum score ≥19 indicates clinically relevant psychological distress. A Likert scale was used to assess overall experiences and impact on sports and lifestyle. RESULTS: A total of 275 participants (86.5% response rate, 95% CI 83-90%) with a mean age of 54.5 ± 6.4 years completed the questionnaires, 48 (17.5%, 95% CI 13-22%) of whom had CAD. The median IES score was 1 (IQR 0-2, [0-23]). IES was slightly higher in those with CAD (mean rank 175 vs. 130, p < 0.001). One participant (with CAD) experienced clinically relevant psychological distress (IES = 23). Participants reported numerous benefits, including feeling safer exercising (58.6%, 95% CI 53-65%) and positive lifestyle changes, especially in those with CAD (17.2 vs. 52.1%, p < 0.001). The majority were satisfied with their participation (93.8%, 95% CI 91-97%). CONCLUSION: Cardiovascular PPS, including cardiac CT, causes no relevant psychological distress in older sportsmen. Psychological distress should not be a reason to forego screening in sportsmen.

Prevention of Hypertensive Disorders of Pregnancy: a Novel Application of the Polypill Concept.

Nearly all of the annual 287,000 global maternal deaths are preventable. Hypertensive disorders of pregnancy (HDP) are among the major causes. A novel fixed-dose combination pill or polypill to prevent cardiovascular disease is a promising strategy for prevention of HDP. The aim of this study was to identify eligible candidates for a polypill for the prevention of HDP. A comprehensive review of systematic reviews on drug and dietary interventions to prevent HDP was conducted. Interventions were evaluated based on efficacy, dose, route of administration, and side effects. Fourteen interventions were assessed. Low-dose aspirin and calcium were identified as candidates for a polypill, with risk reduction estimations for pregnancy-induced hypertension and preeclampsia ranging between 10 and 62 %, depending on patient population characteristics including a priori risk, and gestation age at start of intervention. Their effect may be augmented through the addition of vitamin D, vitamin B12, and folic acid. The effect and optimal composition needs to be evaluated in future trials. Given the persistent burden of maternal and perinatal mortality associated with HDP, prevention of these disorders is key-especially in low-resource settings. The polypill approach with a combination of aspirin, calcium, vitamin D, vitamin B12, and folic acid is a promising strategy to improve maternal and perinatal health outcomes.

Quality of life from a randomized trial of open and endovascular repair for abdominal aortic aneurysm.

BACKGROUND: Long-term survival is similar after open or endovascular repair of abdominal aortic aneurysm. Few data exist on the effect of either procedure on long-term health-related quality of life (HRQoL) and health status. METHODS: Patients enrolled in a multicentre randomized clinical trial (DREAM trial; 2000-2003) in Europe of open repair versus endovascular repair (EVAR) of abdominal aortic aneurysm were asked to complete questionnaires on health status and HRQoL. HRQoL scores were assessed at baseline and at 13 time points thereafter, using generic tools, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36®) and EuroQol 5D (EQ-5D™). Physical (PCS) and mental component summary scores were also calculated. Follow-up was 5 years. RESULTS: Some 332 of 351 patients enrolled in the trial returned questionnaires. More than 70 per cent of questionnaires were returned at each time point. Both surgical interventions had a short-term negative effect on HRQoL and health status. This was less severe in the EVAR group than in the open repair group. In the longer term the physical domains of SF-36® favoured open repair: mean difference in PCS score between open repair and EVAR -1·98 (95 per cent c.i. -3·56 to -0·41). EQ-5D™ descriptive and EQ-5D™ visual analogue scale scores for open repair were also superior to those for EVAR after the initial 6-week interval: mean difference -0·06 (-0·10 to -0·02) and -4·09 (-6·91 to -1·27) respectively. CONCLUSION: In this study EVAR appeared to be associated with less severe disruption to HRQoL and health status in the short term. However, during longer-term follow-up to 5 years, patients receiving open repair appeared to have improved quality of life and health status.

Multifactorial Prevention of Cardiovascular Disease in Patients with Hypertension: the Cardiovascular Polypill.

Hypertension is a major, if not the most important, contributor to the disease burden and premature death globally which is largely related to cardiovascular disease. In both the primary and the secondary preventions of cardiovascular disease, blood pressure (BP) targets are often not achieved which is similar to achievement of cholesterol goals. Combining aspirin, cholesterol and blood pressure-lowering agents into a fixed-dose combination pill called the cardiovascular polypill has been proposed as complementary care in the prevention of cardiovascular diseases in both the primary and secondary preventions of cardiovascular disease. This review article focuses on the potential role of fixed-dose combination therapy in the treatment of hypertension, outlines the pros and cons of combination therapy and emphasizes the rationale for trialling their use. Current and planned future cardiovascular polypill trials are summarized, and the prerequisites for implementation of the polypill strategy are described.

Perinatal outcomes after hypertensive disorders in pregnancy in a low resource setting.

OBJECTIVE: The objective of this study was to evaluate perinatal outcomes of pregnancies complicated by hypertensive disorders in pregnancy in an urban sub-Saharan African setting. METHODS: A prospective cohort study of 1010 women of less than 17 weeks of gestation was conducted at two antenatal clinics in Accra, Ghana, between July 2012 and March 2014. Information about hypertensive disorders was available for analysis on 789 pregnancies. The main outcomes were pre-term birth, birthweight, Apgar scores, small for gestational age and mortality. Relative risk (RR, 95% confidence interval (CI)) for the association between hypertensive disorders of pregnancy and perinatal outcomes was assessed using logistic regression adjusting for potential confounders. RESULTS: A total of 88.7% of women remained normotensive, 7.5% developed pregnancy-induced hypertension, 2.0% had chronic hypertension, and 1.7% developed (pre-)eclampsia. No adverse effects were observed in women with pregnancy-induced hypertension. Women with chronic hypertension were more likely to have a lower gestational age at delivery (38.0 ± 2.3 weeks vs. 39.0 ± 1.9 weeks, P = 0.04) and higher risk of pre-term delivery (aRR 4.63, 95% CI 1.35-15.91). Women with pre-eclampsia had emergency Caesarean section significantly more often (88.9% vs. 50%, P = 0.04), with a higher risk for low birthweight infants (aRR 7.95, 95% CI 1.41-44.80) and a higher risk of neonatal death (aRR 18.41, 95% CI 1.20-283.22). CONCLUSION: Comparable to high-income countries, in Accra hypertensive disorders during pregnancy were associated with increased risk of adverse perinatal outcomes necessitating maternal and newborn care.

Rationale and design of the Measuring Athlete's Risk of Cardiovascular events (MARC) study : The role of coronary CT in the cardiovascular evaluation of middle-aged sportsmen.

BACKGROUND: More than 90 % of exercise-related cardiac arrests occur in men, predominantly those aged 45 years and older with coronary artery disease (CAD) as the main cause. The current sports medical evaluation (SME) of middle-aged recreational athletes consists of a medical history, physical examination, and resting and exercise electrocardiography. Coronary CT (CCT) provides a minimally invasive low radiation dose opportunity to image the coronary arteries. We present the study protocol of the Measuring Athlete's Risk of Cardiovascular events (MARC) study. MARC aims to assess the additional value of CCT to a routine SME in asymptomatic sportsmen ≥45 years without known CAD. DESIGN: MARC is a prospective study of 300 asymptomatic sportsmen ≥45 years who will undergo CCT if the SME does not reveal any cardiac abnormalities. The prevalence and determinants of CAD (coronary artery calcium score ≥100 Agatston Units (AU) or ≥50 % luminal stenosis) will be reported. The number needed to screen to prevent the occurrence of one cardiovascular event in the next 5 years, conditional to adequate treatment, will be estimated. DISCUSSION: We aim to determine the prevalence and severity of CAD and the additional value of CCT in asymptomatic middle-aged (≥45 years) sportsmen whose routine SME revealed no cardiac abnormalities.

Comparison of a morning polypill, evening polypill and individual pills on LDL-cholesterol, ambulatory blood pressure and adherence in high-risk patients; a randomized crossover trial.

AIMS: Cardiovascular polypills are a novel strategy in the prevention of cardiovascular disease. Based on considerations about the effectiveness, the individual pills of a polypill are taken at different times of the day. This study aimed therefore to compare the use of a polypill in the morning, in the evening or the individual components taken at their usual times on cardiovascular risk factors and patient acceptability. METHODS: The study was a randomized three-period crossover trial. Seventy-eight patients with established cardiovascular disease were randomly allocated to the use of polypill (aspirin 75 mg, simvastatin 40 mg, lisinopril 10mg and hydrochlorothiazide 12.5mg) in the morning, in the evening or use of the individual agents taken at different time points (Trial: NCT01506505). RESULTS: Using the polypill in the evening resulted in a 0.2 mmol/L (95%-confidence interval (CI): 0.1 to 0.3) lower fasting LDL-cholesterol compared to the use in the morning, and not statistically significantly different mean 24-hour systolic BP (mean difference: 0.7 mmHg; 95%-CI; -2.1 to 3.4). Compared to the use of the individual agents, the mean LDL-cholesterol was 0.2 mmol/L (95%-CI: 0.1 to 0.3) higher when using the polypill in the morning, but not statistically significantly different when used in the evening (mean difference: -0.1 mmol/L; 95%-CI: -0.1 to 0.0). Furthermore, there were no differences in mean 24-hour systolic BP with morning use (mean difference: 0.4 mmHg; 95%-CI; -1.5 to 2.3) or evening use (mean difference: 1.0mmHg; 95%-CI; -0.8 to 2.8) of the polypill compared to the individual agents. The adherence was 5.2% (95%-CI: 1.4 to 9.1) higher with morning use of the polypill and 5.0% (95%-CI: 1.5 to 8.5) higher with evening use compared to the individual agents. Treatment with the polypill was preferred by 92% of the participants. CONCLUSION: The use of a polypill in the evening was more effective in lowering LDL-cholesterol, and resulted in not statistically significantly different ambulatory BP levels compared to the use of a polypill in the morning. Therapy with a polypill was associated with an increased adherence. The polypill is highly preferred by patients, demonstrating a potential role for the polypill in the prevention of cardiovascular disease.