Showing papers by "Diederick E. Grobbee published in 2021"

Primary prevention efforts are poorly developed in people at high cardiovascular risk: A report from the European Society of Cardiology EURObservational Research Programme EUROASPIRE V survey in 16 European countries:

Abstract: BackgroundEuropean Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) V in primary care was carried out by the European Society of Cardiology EURObservational ...

Associations between the built environment and obesity: an umbrella review

Abstract: In the past two decades, the built environment emerged as a conceptually important determinant of obesity As a result, an abundance of studies aiming to link environmental characteristics to weight-related outcomes have been published, and multiple reviews have attempted to summarise these studies under different scopes and domains We set out to summarise the accumulated evidence across domains by conducting a review of systematic reviews on associations between any aspect of the built environment and overweight or obesity Seven databases were searched for eligible publications from the year 2000 onwards We included systematic literature reviews, meta-analyses and pooled analyses of observational studies in the form of cross-sectional, case–control, longitudinal cohort, ecological, descriptive, intervention studies and natural experiments We assessed risk of bias and summarised results structured by built environmental themes such as food environment, physical activity environment, urban–rural disparity, socioeconomic status and air pollution From 1850 initial hits, 32 systematic reviews were included, most of which reported equivocal evidence for associations For food- and physical activity environments, associations were generally very small or absent, although some characteristics within these domains were consistently associated with weight status such as fast-food exposure, urbanisation, land use mix and urban sprawl Risks of bias were predominantly high Thus far, while most studies have not been able to confirm the assumed influence of built environments on weight, there is evidence for some obesogenic environmental characteristics Registration: This umbrella review was registered on PROSPERO under ID CRD42019135857

EAPC Core Curriculum for Preventive Cardiology

Abstract: Preventive cardiology encompasses the whole spectrum of cardiovascular disease (CVD) prevention, at individual and population level, through all stages of life This includes promotion of cardiovascular (CV) health, management of individuals at risk of developing CVD, and management of patients with established CVD, through interdisciplinary care in different settings Preventive cardiology addresses all aspects of CV health in the context of the social determinants of health, including physical activity, exercise, sports, nutrition, weight management, smoking cessation, psychosocial factors and behavioural change, environmental, genetic and biological risk factors, and CV protective medications This is the first European Core Curriculum for Preventive Cardiology, which will help to standardize, structure, deliver, and evaluate training in preventive cardiology across Europe It will be the basis for dedicated fellowship programmes and a European Society of Preventive Cardiology (EAPC) subspecialty certification for cardiologists, with the intention to improve quality and outcome in CVD prevention

Insights into therapeutic products, preclinical research models, and clinical trials in cardiac regenerative and reparative medicine: where are we now and the way ahead. Current opinion paper of the ESC Working Group on Cardiovascular Regenerative and Reparative Medicine.

Abstract: Great expectations have been set around the clinical potential of regenerative and reparative medicine in the treatment of cardiovascular diseases [i.e. in particular, heart failure (HF)]. Initial excitement, spurred by encouraging preclinical data, resulted in a rapid translation into clinical research. The sobering outcome of the resulting clinical trials suggests that preclinical testing may have been insufficient to predict clinical outcome. A number of barriers for clinical translation include the inherent variability of the biological products and difficulties to develop potency and quality assays, insufficient rigour of the preclinical research and reproducibility of the results, manufacturing challenges, and scientific irregularities reported in the last years. The failure to achieve clinical success led to an increased scrutiny and scepticism as to the clinical readiness of stem cells and gene therapy products among clinicians, industry stakeholders, and funding bodies. The present impasse has attracted the attention of some of the most active research groups in the field, which were then summoned to analyse the position of the field and tasked to develop a strategy, to re-visit the undoubtedly promising future of cardiovascular regenerative and reparative medicine, based on lessons learned over the past two decades. During the scientific retreat of the ESC Working Group on Cardiovascular Regenerative and Reparative Medicine (CARE) in November 2018, the most relevant and timely research aspects in regenerative and/or reparative medicine were presented and critically discussed, with the aim to lay out a strategy for the future development of the field. We report herein the main ideas and conclusions of that meeting.

Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose control.

Abstract: Type 2 diabetes increases the risk of cardiovascular and renal complications, but early risk prediction could lead to timely intervention and better outcomes. Genetic information can be used to enable early detection of risk. We developed a multi-polygenic risk score (multiPRS) that combines ten weighted PRSs (10 wPRS) composed of 598 SNPs associated with main risk factors and outcomes of type 2 diabetes, derived from summary statistics data of genome-wide association studies. The 10 wPRS, first principal component of ethnicity, sex, age at onset and diabetes duration were included into one logistic regression model to predict micro- and macrovascular outcomes in 4098 participants in the ADVANCE study and 17,604 individuals with type 2 diabetes in the UK Biobank study. The model showed a similar predictive performance for cardiovascular and renal complications in different cohorts. It identified the top 30% of ADVANCE participants with a mean of 3.1-fold increased risk of major micro- and macrovascular events (p = 6.3 × 10−21 and p = 9.6 × 10−31, respectively) and a 4.4-fold (p = 6.8 × 10−33) higher risk of cardiovascular death. While in ADVANCE overall, combined intensive blood pressure and glucose control decreased cardiovascular death by 24%, the model identified a high-risk group in whom it decreased the mortality rate by 47%, and a low-risk group in whom it had no discernible effect. High-risk individuals had the greatest absolute risk reduction with a number needed to treat of 12 to prevent one cardiovascular death over 5 years. This novel multiPRS model stratified individuals with type 2 diabetes according to risk of complications and helped to target earlier those who would receive greater benefit from intensive therapy.

Alcohol consumption in relation to cardiovascular diseases and mortality: a systematic review of Mendelian randomization studies

Abstract: The causal effects of alcohol-in-moderation on cardiometabolic health are continuously debated. Mendelian randomization (MR) is an established method to address causal questions in observational studies. We performed a systematic review of the current evidence from MR studies on the association between alcohol consumption and cardiometabolic diseases, all-cause mortality and cardiovascular risk factors. We performed a systematic search of the literature, including search terms on type of design and exposure. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions. We additionally looked at exploration of non-linearity. We reported the direction of the studied associations. Our search yielded 24 studies that were eligible for inclusion. A full instrumental variable analysis was performed in 17 studies (71%) and 13 out of 24 studies (54%) validated all three key assumptions. Five studies (21%) assessed potential non-linearity. In general, null associations were reported for genetically predicted alcohol consumption with the primary outcomes cardiovascular disease (67%) and diabetes (75%), while the only study on all-cause mortality reported a detrimental association. Considering the heterogeneity in methodological quality of the included MR studies, it is not yet possible to draw conclusions on the causal role of moderate alcohol consumption on cardiometabolic health. As MR is a rapidly evolving field, we expect that future MR studies, especially with recent developments regarding instrument selection and non-linearity methodology, will further substantiate this discussion.

Poor cardiovascular health is associated with subclinical atherosclerosis in apparently healthy sub-Saharan African populations: an H3Africa AWI-Gen study

Abstract: The cardiovascular health index (CVHI) introduced by the American Heart Association is a valid, accessible, simple, and translatable metric for monitoring cardiovascular health in a population. Components of the CVHI include the following seven cardiovascular risk factors (often captured as life’s simple 7): smoking, dietary intake, physical activity, body mass index, blood pressure, glucose, and total cholesterol. We sought to expand the evidence for its utility to under-studied populations in sub-Saharan Africa, by determining its association with common carotid intima-media thickness (CIMT). We conducted a cross-sectional study involving 9011 participants drawn from Burkina Faso, Ghana, Kenya, and South Africa. We assessed established classical cardiovascular risk factors and measured carotid intima-media thickness of the left and right common carotid arteries using B-mode ultrasonography. Adjusted multilevel mixed-effect linear regression was used to determine the association of CVHI with common CIMT. In the combined population, an individual participant data meta-analyses random-effects was used to conduct pooled comparative sub-group analyses for differences between countries, sex, and socio-economic status. The mean age of the study population was 51 ± 7 years and 51% were women, with a mean common CIMT of 637 ± 117 μm and CVHI score of 10.3 ± 2.0. Inverse associations were found between CVHI and common CIMT (β-coefficients [95% confidence interval]: Burkina Faso, − 6.51 [− 9.83, − 3.20] μm; Ghana, − 5.42 [− 8.90, − 1.95]; Kenya, − 6.58 [− 9.05, − 4.10]; and South Africa, − 7.85 [− 9.65, − 6.05]). Inverse relations were observed for women (− 4.44 [− 6.23, − 2.65]) and men (− 6.27 [− 7.91, − 4.64]) in the pooled sample. Smoking (p < 0.001), physical activity (p < 0.001), and hyperglycemia (p < 0.001) were related to CIMT in women only, while blood pressure and obesity were related to CIMT in both women and men (p < 0.001). This large pan-African population study demonstrates that CVHI is a strong marker of subclinical atherosclerosis, measured by common CIMT and importantly demonstrates that primary prevention of atherosclerotic cardiovascular disease in this understudied population should target physical activity, smoking, obesity, hypertension, and hyperglycemia.

Electrocardiographic and echocardiographic abnormalities in urban African people living with HIV in South Africa.

Abstract: Background Studies from high income countries report that HIV-positive people have an impaired systolic and diastolic cardiac function compared to HIV-negative people It is unclear if results can be translated directly to the Sub-Saharan Africa context This study assesses electro- and echocardiographic characteristics in an urban African population, comparing HIV-positive people (treated and not yet treated) with HIV-negative controls Methods We conducted a cross-sectional study in Johannesburg, South Africa We enrolled HIV-positive participants from three randomized controlled trials that had recruited participants from routine HIV testing programs HIV-negative controls were recruited from the community Data were collected on demographics, cardiovascular risk factors, medical history and electrocardiographic and echocardiographic characteristics Results In total, 394 HIV-positive participants and 153 controls were enrolled The mean age of HIV-positive participants was 40±9 years (controls: 35±10 years), and 34% were male (controls: 50%) Of HIV-positive participants 36% were overweight or obese (controls: 44%), 23% had hypertension (controls: 28%) and 12% were current smoker (controls: 37%) Median time since HIV diagnosis was 60 years (IQR 23–100) and median treatment duration was 40 years (IQR 00–80), 50% had undetectable viral load The frequency of anatomical cardiac abnormalities was low and did not differ between people with and without HIV We observed no relation between HIV or anti-retroviral therapy (ART) and systolic or diastolic heart function There was an association between ART use and corrected QT interval: +118 ms compared to HIV-negative controls (p<001) and +189 ms compared to ART-naive participants (p = 001) We also observed a higher left ventricular mass index in participants on ART (+78 g/m2, p<001), but this association disappeared after adjusting for CD4 cell count, viral load and HIV-duration Conclusion The low number of major cardiac abnormalities in this relatively young, well managed urban African HIV-positive population is reassuring The increase in corrected QT interval and left ventricular mass may contribute to higher cardiac mortality and morbidity in people living with HIV in the long term

Temporal trends in heart failure medication prescription in a population-based cohort study.

Abstract: Objective We examined temporal heart failure (HF) prescription patterns in a large representative sample of real-world patients in the UK, using electronic health records (EHR). Methods From primary and secondary care EHR, we identified 85 732 patients with a HF diagnosis between 2002 and 2015. Almost 50% of patients with HF were women and the median age was 79.1 (IQR 70.2–85.7) years, with age at diagnosis increasing over time. Results We found several trends in pharmacological HF management, including increased beta blocker prescriptions over time (29% in 2002–2005 and 54% in 2013–2015), which was not observed for mineralocorticoid receptor-antagonists (MR-antagonists) (18% in 2002–2005 and 18% in 2013–2015); higher prescription rates of loop diuretics in women and elderly patients together with lower prescription rates of angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers, beta blockers or MR-antagonists in these patients; little change in medication prescription rates occurred after 6 months of HF diagnosis and, finally, patients hospitalised for HF who had no recorded follow-up in primary care had considerably lower prescription rates compared with patients with a HF diagnosis in primary care with or without HF hospitalisation. Conclusion In the general population, the use of MR-antagonists for HF remained low and did not change throughout 13 years of follow-up. For most patients, few changes were seen in pharmacological management of HF in the 6 months following diagnosis.

Prognostic accuracy of antenatal Doppler ultrasound for adverse perinatal outcomes in low-income and middle-income countries: a systematic review.

Abstract: Objectives This systematic review examined available literature on the prognostic accuracy of Doppler ultrasound for adverse perinatal outcomes in low/middle-income countries (LMIC). Design We searched PubMed, Embase, Cochrane Library and Scopus from inception to April 2020. Setting Observational or interventional studies from LMICs. Participants Singleton pregnancies of any risk profile. Interventions Umbilical artery (UA), middle cerebral artery (MCA), cerebroplacental ratio (CPR), uterine artery (UtA), fetal descending aorta (FDA), ductus venosus, umbilical vein and inferior vena cava. Primary and secondary outcome measures Perinatal death, stillbirth, neonatal death, expedited delivery for fetal distress, meconium-stained amniotic fluid, low birth weight, fetal growth restriction, admission to neonatal intensive care unit, neonatal acidosis, Apgar scores, preterm birth, fetal anaemia, respiratory distress syndrome, length of hospital stay, birth asphyxia and composite adverse perinatal outcomes (CAPO). Results We identified 2825 records, and 30 (including 4977 women) from Africa (40.0%, n=12), Asia (56.7%, n=17) and South America (3.3%, n=01) were included. Many individual studies reported associations and promising predictive values of UA Doppler for various adverse perinatal outcomes mostly in high-risk pregnancies, and moderate to high predictive values of MCA, CPR and UtA Dopplers for CAPO. A few studies suggested that the MCA and FDA may be potent predictors of fetal anaemia. No randomised clinical trial (RCT) was found. Most studies were of suboptimal quality, poorly powered and characterised by wide variations in outcome classifications, the timing for the Doppler tests and study populations. Conclusion Local evidence to guide how antenatal Doppler ultrasound should be used in LMIC is lacking. Well-designed studies, preferably RCTs, are required. Standardisation of practice and classification of perinatal outcomes across countries, following the international standards, is imperative. PROSPERO registration number CRD42019128546

Prevalence and determinants of chronic kidney disease in women with hypertensive disorders in pregnancy in Nigeria: a cohort study

Abstract: Worldwide, hypertensive disorders in pregnancy (HDPs) complicate between 5 and 10% of pregnancies. Sub-Saharan Africa (SSA) is disproportionately affected by a high burden of HDPs and chronic kidney disease (CKD). Despite mounting evidence associating HDPs with the development of CKD, data from SSA are scarce. Women with HDPs (n = 410) and normotensive women (n = 78) were recruited at delivery and prospectively followed-up at 9 weeks, 6 months and 1 year postpartum. Serum creatinine was measured at all time points and the estimated glomerular filtration rates (eGFR) using CKD-Epidemiology equation determined. CKD was defined as decreased eGFR< 60 mL/min/1.73m2 lasting for ≥ 3 months. Prevalence of CKD at 6 months and 1 year after delivery was estimated. Logistic regression analyses were conducted to evaluate risk factors for CKD at 6 months and 1 year postpartum. Within 24 h of delivery, 9 weeks, and 6 months postpartum, women with HDPs were more likely to have a decreased eGFR compared to normotensive women (12, 5.7, 4.3% versus 0, 2 and 2.4%, respectively). The prevalence of CKD in HDPs at 6 months and 1 year postpartum was 6.1 and 7.6%, respectively, as opposed to zero prevalence in the normotensive women for the corresponding periods. Proportions of decreased eGFR varied with HDP sub-types and intervening postpartum time since delivery, with pre-eclampsia/eclampsia showing higher prevalence than chronic and gestational hypertension. Only maternal age was independently shown to be a risk factor for decreased eGFR at 6 months postpartum (aOR = 1.18/year; 95%CI 1.04–1.34). Prior HDP was associated with risk of future CKD, with prior HDPs being more likely to experience evidence of CKD over periods of postpartum follow-up. Routine screening of women following HDP-complicated pregnancies should be part of a postpartum monitoring program to identify women at higher risk. Future research should report on both the eGFR and total urinary albumin excretion to enable detection of women at risk of future deterioration of renal function.

177Lu-PSMA for advanced prostate cancer: are we ready to play big?

Abstract: Prostate cancer is the second most common cancer among men [1, 2]. Although patients with localized prostate cancer receive treatment with curative intent, a significant proportion of patients will nonetheless progress to advanced metastatic disease [1, 3]. The interest in Lutetium-177 labeled, prostate specific membrane antigen (Lu-PSMA) targeted radioligand therapy for the treatment of advanced prostate cancer is growing: it generally appears well-tolerated and has a potential low toxicity as well as a beneficial efficacy profile [4–8]. Nevertheless, empirical evidence of clinical effectiveness is still limited to a number of retrospective studies and at best a phase II trial [7, 9]. Ongoing trials registered on ClinicalTrials.gov include three phase I and five phase II studies. In May 2018, the first phase III study, so-called VISION (ClinicalTrials.gov: NCT03511664), started, investigating Lu-PSMA treatment safety and effectiveness against the current standard treatments for patients with progressive PSMA-positive, castration-resistant, postchemotherapy metastatic prostate cancer [3, 6, 10]. The primary endpoint is survival and the first data of this study are expected in 2021 [3]. When trials prove positive, the demand for Lu-PSMA therapy is might dramatically increase at short notice. Global supply must anticipate; however, a precise forecast of the expected therapeutic isotope production capacity for the next 10 years is not yet available. To date, most of Lu is produced in Europe, in six nuclear reactors, one of which is located in Petten, the Netherlands [11, 12]. Two of these facilities (aged over 45 years) require renovation or new construction investments in the coming 15 years [11]. The Dutch demand for Lu is expected to increase with 7% per year, which will lead to shortages within 5 years [11]. In the Netherlands alone, with an estimated number of 4500 eligible patients per year and an anticipated 4–6 Lu-PSMA treatment cycles per patient, this means that a number of 18,000– 27,000 Lu-PSMA treatments need to be accommodated per year. This would be a volume increase without parallel in the history of nuclear medicine, and it is at best questionable whether existing production facilities can produce the Lu necessary. However, the hitherto inconceivable patient volume is just one of a multitude of issues that need to be dealt with. Other obstacles are the lack of empirical evidence of clinical effectiveness, the limited hospital capacity (e.g., appropriate facilities, resources, and staffing), and appropriate regulations that limit the introduction of radioligand therapy in today’s healthcare systems [13]. Lu-PSMA is a radiopharmaceutical agent with a mechanism of action that is far more a form of radiation therapy than a conventional pharmaceutical treatment. Nonetheless, it is strongly regulated like a conventional pharmaceutical, while it differs markedly from conventional oncological therapies. This in turn has a number of strong implications for its clinical introduction. Thus far, no directives have yet been developed for Lu-PSMA’s introduction into routine care. Along the lines of implementation challenges, we here propose an agenda to promote optimal introduction and implementation of Lu-PSMA. The implementation of Lu-PSMA into routine care, like other new treatments, typically is multifaceted [14]. It includes provider behavior and preference, care organization, and environmental, ethical, and policy considerations [15–17]. The Non-adoption, Abandonment, Scale-up, Spread and Sustainability (NASSS) framework of new medical technologies and services points to the fundamental elements/aspects This article is part of the Topical Collection on Oncology – General

Adherence to Guidelines in Postpartum Management of Hypertensive Disorders in Pregnancy in Tertiary Health Facilities in Nigeria: A Multi-centre Study.

Abstract: Hypertensive disorders in pregnancy (HDPs) are a leading cause of maternal morbidity and mortality. Available guidelines for their postpartum management are expected to be optimally utilized. This study aimed to determine adherence to guidelines in selected Nigerian tertiary hospitals. It was nested in a cohort of women with HDPs who delivered in eight facilities between October 2017 and June 2018. Nine weeks after delivery, their cases were evaluated on prespecified indicators and supplemented with interviews. The level of adherence to the guidelines was determined using descriptive analyses, including frequencies, percentages, means, and standard deviations, as well as charts. Of the 366 participants, 33 (9%), 75 (20%), 200 (55%), and 58 (16%) had chronic hypertension, gestational hypertension, preeclampsia, and eclampsia, respectively. Only about a third had their blood pressure measured between postpartum days three and five. Similarly, a third of those with persistent hypertension (≥140/90 mmHg) were not on antihypertensive medications within the first week postpartum. In addition, 37% and 42% of participants were not counseled on contraceptives and early subsequent antenatal visits, respectively. Among those with preeclampsia/eclampsia, 93% were not offered postpartum screening for thromboprophylaxis. Although all women with preeclampsia/eclampsia remained hypertensive two weeks after discharge, only 24% had medical reviews. Overall, only 58% and 44% of indicators were adhered to among all HDPs and preeclampsia/eclampsia-specific indicators, respectively. Level of adherence to guidelines on postpartum management of HDPs in Nigerian tertiary hospitals is poor. It is recommended that institutionalization of guidelines be prioritized and linked to the entire continuum from preconception through longer term postpartum care.

Patterns of Immune Activation in HIV and Non HIV Subjects and Its Relation to Cardiovascular Disease Risk.

Abstract: Introduction: Insight into inflammation patterns is needed to understand the pathophysiology of HIV and related cardiovascular disease (CVD). We assessed patterns of inflammation related to HIV infection and CVD risk assessed with carotid intima media thickness (CIMT). Methods: A cross-sectional study was performed in Johannesburg, South Africa, including participants with HIV who were virally suppressed on anti-retroviral therapy (ART) as well as HIV-negative participants who were family members or friends to the HIV-positive participants. Information was collected on CVD risk factors and CIMT. Inflammation was measured with the Olink panel ‘inflammation’, allowing to simultaneously assess 92 inflammation markers. Differences in inflammation patterns between HIV-positive and HIV-negative participants were explored using a principal component analysis (PCA) and ANCOVA. The impact of differentiating immune markers, as identified by ANCOVA, on CIMT was assessed using linear regression while adjusting for classic CVD risk factors. Results: In total, 185 HIV-positive and 104 HIV negative participants, 63% females, median age 40.7 years (IQR 35.4 – 47.7) were included. HIV-positive individuals were older (+6 years, p <0.01) and had a higher CIMT (p <0.01). No clear patterns of inflammation were identified by use of PCA. Following ANCOVA, nine immune markers differed significantly between HIV-positive and HIV-negative participants, including PDL1. PDL1 was independently associated with CIMT, but upon stratification this effect remained for HIV-negative individuals only. Conclusion: HIV positive patients on stable ART and HIV negative controls had similar immune activation patterns. CVD risk in HIV-positive participants was mediated by inflammation markers included in this study.

Predictors of impaired pulmonary function in people living with HIV in an urban African setting.

Abstract: Background: Studies have associated HIV with an increased risk of obstructive lung disease (OLD). Objectives: We aimed to identify the predictive factors for impaired lung function in an urban, African, HIV-positive population. Method: A cross-sectional study was performed in Johannesburg, South Africa, from July 2016 to November 2017. A questionnaire was administered and pre- and post-bronchodilator spirometry conducted. The predictors investigated included age, sex, antiretroviral treatment (ART) duration, body mass index, history of tuberculosis (TB) or pneumonia, occupational exposure, environmental exposure, smoking and symptoms of OLD (cough, wheeze, mucus and dyspnoea). Impaired lung function was defined as a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of < 0.70, or below the 20th percentile of normal. Results: The 98 ART-naive participants (mean age = 34.0, standard deviation [s.d.] = 8.2), 85 participants on first-line ART (mean age = 36.9, s.d. = 6.6) and 189 participants on second-line ART (mean age = 43.5, s.d. = 7.9) were predominantly female (65.6%). Of the participants, 64 (17.2%) had impaired lung function and 308 had normal lung function. Linear regression identified age (β = –0.003, P < 0.01), male sex (β = –0.016, P = 0.03) and history of TB or pneumonia (β = –0.024, P < 0.01) as independent predictors of a lower FEV1/FVC ratio. Following logistic regression, only a history of TB or pneumonia (odds ratio = 2.58, 95% confidence interval = 1.47–4.52) was significantly related to impaired lung function (area under the receiver operating characteristic curve = 0.64). Conclusion: Our data show that a history of TB or pneumonia predicts impaired lung function. In order to improve timely access to spirometry, clinicians should be alert to the possibility of impaired lung function in people with a history of TB or pneumonia.

Adiposity Phenotypes and Subclinical Atherosclerosis in Adults from Sub-Saharan Africa: An H3Africa AWI-Gen Study.

Abstract: Background: Obesity and adipose tissue distribution contribute to an increased risk of cardiovascular disease (CVD) by promoting atherosclerosis. This association has been poorly studied in sub–Saharan Africa (SSA) despite the rising prevalence of cardiovascular disease. Objectives: We determined the association between various adiposity phenotypes and carotid intima–media thickness (CIMT), a proxy of subclinical atherosclerosis, in a large SSA population. Methods: A population–based cross–sectional study was performed from 2013–2016 in Burkina Faso, Ghana, Kenya and South Africa. Body mass index (BMI), waist (WC), hip circumferences (HC), visceral (VAT) and subcutaneous adipose tissue (SCAT) using B-mode ultrasound were measured. Ultrasonography of left and right far wall CIMT of the common carotid artery was used as an indicator of subclinical atherosclerosis. Individual participant data meta–analyses were used to determine the associations between adiposity phenotypes and CIMT in the pooled sample while adjusted multivariable linear regression analyses were used for site specific analyses. Results: Data were obtained from 9,010 adults (50.3% women and a mean age of 50± 6years). Men had higher levels of visceral fat than women while women had higher BMI, waist and hip circumference and subcutaneous fat than men at all sites except Burkina Faso. In the pooled analyses, BMI (â–value [95% CIs]: 19.5 [16.8, 22.3] im) showed the strongest relationship with CIMT followed by VAT (5.86 [4.65, 7.07] im), SCAT (5.00 [2.85, 7.15] im), WC (1.27 [1.09, 1.44] im) and HC (1.23 [1.04, 1.42] im). Stronger associations were observed in men than in women. Conclusion: Obesity within SSA will likely result in higher levels of atherosclerosis and promote the occurrence of cardio- and cerebrovascular events, especially in males, unless addressed through primary prevention of obesity in both rural and urban communities across Africa. The inverse association of VAT with CIMT in Burkina Faso and Ghana requires further investigation. Highlights All adiposity phenotypes were positively associated with common carotid intima–media thickness (CIMT) in the entire cohort (pooled analyses). BMI had the strongest association with CIMT compared to other phenotypes. The magnitude of association between adiposity phenotypes and CIMT was higher in men than in women. Subcutaneous adipose tissue was inversely associated with CIMT only in women. An unexpected finding was the inverse association of visceral adipose tissue with CIMT in Burkina Faso and Ghana.

Research within international non-governmental organisation programmes in low and middle-income countries: challenges amid opportunities.

Abstract: ### Summary box Over the past decades, enormous efforts have gone into improving access to quality health services in low and middle-income countries (LMICs) through the activities of international non-governmental organisations (INGOs).1 However, for most of these INGO-implemented interventions, responding to health research needs of these populations is not a priority, with a few exceptions.2 In instances where research is of interest, the capacities to generate valid evidence are limited.3 This is compounded by the limited number of academic research institutions with the capacity to conduct the required research in many LMICs despite the urgent need for locally led research efforts.3 4 Although there has been an expansion in INGO-led implementation science programmes recently in many LMICs, they are mainly motivated by the need to bridging the ‘know-do-gaps’, rather than providing answers to emerging health research questions based on implementation research principles.5 Without rigorous research methods, concepts and methods of current implementation science programmes in both high-income countries (HIC) and LMICs cannot …

Generalisability of Randomised Controlled Trials in Heart Failure with Reduced Ejection Fraction.

Abstract: BACKGROUND Heart failure (HF) trials have stringent in- and ex- clusion criteria, but limited data exists regarding generalisability of trials. We compared patient characteristics and outcomes between patients with HF and reduced ejection fraction (HFrEF) in trials and observational registries. METHODS AND RESULTS Individual patient data for 16922 patients from five randomised clinical trials and 46914 patients from two HF registries were included. The registry patients were categorised into trial-eligible and non-eligible groups using the most commonly used in- and ex-clusion criteria. A total of 26104 (56%) registry patients fulfilled the eligibility criteria. Unadjusted all-cause mortality rates at one year were lowest in the trial population (7%), followed by trial-eligible patients (12%) and trial-non-eligible registry patients (26%). After adjustment for age and sex, all-cause mortality rates were similar between trial participants and trial-eligible registry patients (standardised mortality ratio (SMR) 0.97; 95% confidence interval (CI) 0.92 -1.03) but cardiovascular mortality was higher in trial participants (SMR 1.19; 1.12 -1.27). After full case-mix adjustment, the SMR for cardiovascular mortality remained higher in the trials at 1.28 (1.20- 1.37) compared to RCT-eligible registry patients. CONCLUSION In contemporary HF registries, over half of HFrEF patients would have been eligible for trial enrolment. Crude clinical event rates were lower in the trials, but, after adjustment for case-mix, trial participants had similar rates of survival as registries. Despite this, they had about 30% higher cardiovascular mortality rates. Age and sex were the main drivers of differences in clinical outcomes between HF trials and observational HF registries.

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

Abstract: 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.

Adherence to Drinking Guidelines and Reasons for Alcohol Consumption Cessation in the Southern Cone of Latin America – Findings from the CESCAS Study

Abstract: Introduction: Alcohol consumption is a risk factor for morbidity and mortality globally. Consumption levels in Southern Latin America are among the highest in the world. Objectives: To describe consumption patterns and adherence to guidelines in the general adult population of Southern Latin America, as well as exploration of reasons for alcohol cessation and the advising role of the health worker in this decision. Methods: In 7,520 participants from the Centro de Excelencia en Salud Cardiovascular para el America del Sur (CESCAS) cohort, consumption patterns were described and the proportion excessive drinkers (i.e. >7 units/week for women and >14 for men or binge drinking: >4 (women) or >5 (men) units at a single occasion) was calculated. Former drinkers were asked if they had quit alcohol consumption on the advice of a health worker and/or because of health reasons. Furthermore, among former drinkers, multivariable logistic regression analysis was performed to assess which participant characteristics were independently associated with the chance of quitting consumption on a health worker’s advice. Results: Mean age was 54.8 years (SD = 10.8), 42% was male. Current drinking was reported by 44.6%, excessive drinking by 8.5% of the population. In former drinkers, 23% had quit alcohol consumption because of health reasons, half of them had additionally quit on the advice of a health worker. The majority of former drinkers however had other, unknown, reasons. When alcohol cessation was based on a health worker’s advice, sex, country of residence, educational status and frequency of visiting a physician were independent predictors. Conclusion: In this Southern American population-based sample, most participants adhered to the alcohol consumption guidelines. The advising role of the health worker in quitting alcohol consumption was only modest and the motivation for the majority of former drinkers remains unknown. A more detailed assessment of actual advice rates and exploration of additional reasons for alcohol cessation might be valuable for alcohol policy making.

Diagnostic performance and clinical implications for enhancing a hybrid quantitative flow ratio-FFR revascularization decision-making strategy.

Abstract: Invasive fractional flow reserve (FFR) adoption remains low mainly due to procedural and operator related factors as well as costs. Alternatively, quantitative flow ratio (QFR) achieves a high accuracy mainly outside the intermediate zone without the need for hyperaemia and wire-use. We aimed to determine the diagnostic performance of QFR and to evaluate a QFR-FFR hybrid strategy in which FFR is measured only in the intermediate zone. This retrospective study included 289 consecutive patients who underwent invasive coronary angiography and FFR. QFR was calculated for all vessels in which FFR was measured. The QFR-FFR hybrid approach was modelled using the intermediate zone of 0.77-0.87 in which FFR-measurements are recommended. The sensitivity, specificity, and accuracy on a per vessel-based analysis were 84.6%, 86.3% and 85.6% for QFR and 88.0%, 92.9% and 90.3% for the QFR-FFR hybrid approach. The diagnostic accuracy of QFR-FFR hybrid strategy with invasive FFR measurement was 93.4% and resulted in a 56.7% reduction in the need for FFR. QFR has a good correlation and agreement with invasive FFR. A hybrid QFR-FFR approach could extend the use of QFR and reduces the proportion of invasive FFR-measurements needed while improving accuracy.