Showing papers by "Diederick E. Grobbee published in 2020"

Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients

Abstract: Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. Results: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. Conclusions: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.

Association of Cardiovascular Risk Factors and Lifestyle Behaviors With Hypertension: A Mendelian Randomization Study.

Abstract: Hypertension is a major risk factor for cardiovascular disease and mortality. To identify targets for the prevention of hypertension and its associated disease burden, we used the 2-sample Mendelian randomization method to investigate the causal associations of 18 cardiovascular risk factors and lifestyle behaviors with hypertension. From European-descent genome-wide association studies, we selected genetic variants (P<5×10-8) for type 2 diabetes, fasting glucose, lipids, body mass index, smoking, alcohol and coffee consumption, physical activity, sleep duration, insomnia, and educational level. We extracted the genetic associations with hypertension from 2 European cohorts: the FinnGen Study (15 870 cases and 74 345 controls) and UK Biobank (54 358 cases and 408 652 controls). The inverse-variance weighted method was used as main analysis method. Genetically predicted triglycerides (pooled odds ratio [OR] per 1 SD, 1.17 [1.10-1.25]), body mass index (OR per 1 SD, 1.42 [1.37-1.48]), alcohol dependence (OR, 1.10 [1.06-1.13]), and insomnia (OR, 1.17 [1.13-1.20]) were associated with a higher odds of hypertension. Higher genetically predicted high-density lipoprotein cholesterol (OR per 1 SD, 0.88 [0.83-0.94]) and educational level (OR per 1 SD, 0.56 [0.54-0.59]) were associated with a lower odds of hypertension. Suggestive evidence was obtained for type 2 diabetes, smoking initiation and alcohol consumption with a higher hypertension odds, and longer sleep duration with a lower hypertension odds. This Mendelian randomization study identified high-density lipoprotein cholesterol, triglycerides, body mass index, alcohol dependence, insomnia, and educational level as causal risk factors for hypertension. This implicates that these modifiable risk factors are important targets in the prevention of hypertension.

World Heart Federation Briefing on Prevention: Coronavirus Disease 2019 (COVID-19) in Low-Income Countries.

Abstract: In December 2019, the novel coronavirus Coronavirus Disease 2019 (COVID-19) outbreak started in Wuhan, the capital of Hubei province in China. Since then it has spread to many other regions, including low-income countries.

Systematic review of prediction models for gestational hypertension and preeclampsia.

Abstract: Introduction Prediction models for gestational hypertension and preeclampsia have been developed with data and assumptions from developed countries. Their suitability and application for low resource settings have not been tested. This review aimed to identify and assess the methodological quality of prediction models for gestational hypertension and pre-eclampsia with reference to their application in low resource settings. Methods Using combinations of keywords for gestational hypertension, preeclampsia and prediction models seven databases were searched to identify prediction models developed with maternal data obtained before 20 weeks of pregnancy and including at least three predictors (Prospero registration CRD 42017078786). Prediction model characteristics and performance measures were extracted using the CHARMS, STROBE and TRIPOD checklists. The National Institute of Health quality assessment tools for observational cohort and cross-sectional studies were used for study quality appraisal. Results We retrieved 8,309 articles out of which 40 articles were eligible for review. Seventy-seven percent of all the prediction models combined biomarkers with maternal clinical characteristics. Biomarkers used as predictors in most models were pregnancy associated plasma protein-A (PAPP-A) and placental growth factor (PlGF). Only five studies were conducted in a low-and middle income country. Conclusions Most of the studies evaluated did not completely follow the CHARMS, TRIPOD and STROBE guidelines in prediction model development and reporting. Adherence to these guidelines will improve prediction modelling studies and subsequent application of prediction models in clinical practice. Prediction models using maternal characteristics, with good discrimination and calibration, should be externally validated for use in low and middle income countries where biomarker assays are not routinely available.

Benefits and harms of high-dose haemodiafiltration versus high-flux haemodialysis: the comparison of high-dose haemodiafiltration with high-flux haemodialysis (CONVINCE) trial protocol

Abstract: Introduction End-stage kidney disease (ESKD) is a major public health problem affecting more than 2 million people worldwide. It is one of the most severe chronic non-communicable diseases. Haemodialysis (HD) is the most common therapeutic option but is also associated with a risk of cardiovascular events, hospitalisation and suboptimal quality of life. Over the past decades, haemodiafiltration (HDF) has become available. Although high-dose HDF has shown some promising survival advantage compared to conventional HD, the evidence remains controversial. A Cochrane systematic review found, in low-quality trials, with various convective forms of dialysis, a reduction in cardiovascular, but not all-cause mortality and the effects on non-fatal cardiovascular events and hospitalisation were uncertain. In contrast, an individual patient data analysis suggested that high-dose HDF reduced both all-cause and cardiovascular mortality compared to HD. In view of these discrepant results, a definitive trial is required to determine whether high-dose HDF is preferable to high-flux HD. The comparison of high-dose HDF with high-flux HD (CONVINCE) study will assess the benefits and harms of high-dose HDF versus a conventional high-flux HD in adults with ESKD. Methods and analysis This international, prospective, open label, randomised controlled trial aims to recruit 1800 ESKD adults treated with HD in nine European countries. Patients will be randomised 1:1 to high-dose HDF versus continuation of conventional high-flux HD. The primary outcome will be all-cause mortality at 3 years’ follow-up. Secondary outcomes will include cause-specific mortality, cardiovascular events, all-cause and infection-related hospitalisations, patient-reported outcomes (eg, health-related quality of life) and cost-effectiveness. Ethics and dissemination The CONVINCE study will address the question of benefits and harms of high-dose HDF compared to high-flux HD for kidney replacement therapy in patients with ESKD with a focus on survival, patient perspectives and cost-effectiveness. Trial registration number Netherlands National Trial Register (NTR 7138).

Virological suppression and clinical management in response to viremia in South African HIV treatment program: A multicenter cohort study.

Abstract: Author(s): Hermans, Lucas E; Carmona, Sergio; Nijhuis, Monique; Tempelman, Hugo A; Richman, Douglas D; Moorhouse, Michelle; Grobbee, Diederick E; Venter, Willem DF; Wensing, Annemarie MJ | Abstract: BACKGROUND:Uptake of antiretroviral treatment (ART) is expanding rapidly in low- and middle-income countries (LMIC). Monitoring of virological suppression is recommended at 6 months of treatment and annually thereafter. In case of confirmed virological failure, a switch to second-line ART is indicated. There is a paucity of data on virological suppression and clinical management of patients experiencing viremia in clinical practice in LMIC. We report a large-scale multicenter assessment of virological suppression over time and management of viremia under programmatic conditions. METHODS AND FINDINGS:Linked medical record and laboratory source data from adult patients on first-line ART at 52 South African centers between 1 January 2007 and 1 May 2018 were studied. Virological suppression, switch to second-line ART, death, and loss to follow-up were analyzed. Multistate models and Cox proportional hazard models were used to assess suppression over time and predictors of treatment outcomes. A total of 104,719 patients were included. Patients were predominantly female (67.6%). Median age was 35.7 years (interquartile range [IQR]: 29.9-43.0). In on-treatment analysis, suppression below 1,000 copies/mL was 89.0% at month 12 and 90.4% at month 72. Suppression below 50 copies/mL was 73.1% at month 12 and 77.5% at month 72. Intention-to-treat suppression was 75.0% and 64.3% below 1,000 and 50 copies/mL at month 72, respectively. Viremia occurred in 19.8% (20,766/104,719) of patients during a median follow-up of 152 (IQR: 61-265) weeks. Being male and below 35 years of age and having a CD4 count below 200 cells/μL prior to start of ART were risk factors for viremia. After detection of viremia, confirmatory testing took 29 weeks (IQR: 16-54). Viral resuppression to below 1,000 copies/mL without switch of ART occurred frequently (45.6%; 6,030/13,210) but was associated with renewed viral rebound and switch. Of patients with confirmed failure who remained in care, only 41.5% (1,872/4,510) were switched. The median time to switch was 68 weeks (IQR: 35-127), resulting in 12,325 person-years spent with a viral load above 1,000 copies/mL. Limitations of this study include potential missing data, which is in part addressed by the use of cross-matched laboratory source data, and the possibility of unmeasured confounding. CONCLUSIONS:In this study, 90% virological suppression below the threshold of 1,000 copies/mL was observed in on-treatment analysis. However, this target was not met at the 50-copies/mL threshold or in intention-to-treat analysis. Clinical management in response to viremia was profoundly delayed, prolonging the duration of viremia and potential for transmission. Diagnostic tools to establish the cause of viremia are urgently needed to accelerate clinical decision-making.

Household fuel use and adverse pregnancy outcomes in a Ghanaian cohort study

Abstract: Accruing epidemiological evidence suggests that prenatal exposure to emissions from cooking fuel is associated with increased risks of adverse maternal and perinatal outcomes including hypertensive disorders of pregnancy, low birth weight, stillbirth and infant mortality. We aimed to investigate the relationship between cooking fuel use and various pregnancy related outcomes in a cohort of urban women from the Accra region of Ghana. Self-reported cooking fuel use was divided into “polluting” (wood, charcoal, crop residue and kerosene) and “clean” fuels (liquid petroleum gas and electricity) to examine 12 obstetric outcomes in a prospective cohort of pregnant women (N = 1010) recruited at < 17 weeks of gestation from Accra, Ghana. Logistic and multivariate linear regression analyses adjusted for BMI, maternal age, maternal education and socio-economic status asset index was conducted. 34% (n = 279) of 819 women with outcome data available for analysis used polluting fuel as their main cooking fuel. Using polluting cooking fuels was associated with perinatal mortality (aOR: 7.6, 95%CI: 1.67–36.0) and an adverse Apgar score (< 7) at 5 min (aOR:3.83, 95%CI: (1.44–10.11). The other outcomes (miscarriage, post-partum hemorrhage, pre-term birth, low birthweight, caesarian section, hypertensive disorders of pregnancy, small for gestational age, and Apgar score at 1 min) had non-statistically significant findings. We report an increased likelihood of perinatal mortality, and adverse 5-min Apgar scores in association with polluting fuel use. Further research including details on extent of household fuel use exposure is recommended to better quantify the consequences of household fuel use. Ghana Service Ethical Review Committee (GHS-ERC #: 07–9-11).

Problems and Promises of Introducing the Magnetic Resonance Imaging Linear Accelerator Into Routine Care: The Case of Prostate Cancer.

Abstract: The new radiotherapy high field, 1.5 Tesla MRI-guided linear accelerator (MR-Linac) is being clinically introduced. Sensing and evaluating opportunities and barriers at an early stage will facilitate its eventual scale-up. This study investigates the opportunities and barriers to the implementation of MR-Linac into prostate cancer care based on 43 semi-structured interviews with Dutch oncology care professionals, hospital and division directors, patients, payers and industry. The analysis was guided by the Non-adoption, Abandonment, Scale-up, Spread, and Sustainability framework of new medical technologies and services. Opportunities included: the acquirement of (1) advanced MRI-guided radiotherapy technology with (2) the potential for improved patient outcomes and (3) economic benefits, as well as (4) professional development and (5) a higher hospital quality profile. Barriers included: (1) technical complexities, (2) substantial staffing and structural investments, (3) the current lack of empirical evidence of clinical benefits, (4) professional silos, and (5) the presence of patient referral patterns. While our study confirms the expected technical and clinical prospects from the literature, it also reveals economic, organizational, and socio-political challenges.

Quality of intrapartum care: direct observations in a low-resource tertiary hospital

Abstract: The majority of the world’s perinatal deaths occur in low- and middle-income countries. A substantial proportion occurs intrapartum and is avoidable with better care. At a low-resource tertiary hospital, this study assessed the quality of intrapartum care and adherence to locally-tailored clinical guidelines. A non-participatory, structured, direct observation study was held at Mnazi Mmoja Hospital, Zanzibar, Tanzania, between October and November 2016. Women in active labour were followed and structure, processes of labour care and outcomes of care systematically recorded. Descriptive analyses were performed on the labour observations and compared to local guidelines and supplemented by qualitative findings. A Poisson regression analysis assessed factors affecting foetal heart rate monitoring (FHRM) guidelines adherence. 161 labouring women were observed. The nurse/midwife-to-labouring-women ratio of 1:4, resulted in doctors providing a significant part of intrapartum monitoring. Care during labour and two-thirds of deliveries was provided in a one-room labour ward with shared beds. Screening for privacy and communication of examination findings were done in 50 and 34%, respectively. For the majority, there was delayed recognition of labour progress and insufficient support in second stage of labour. While FHRM was generally performed suboptimally with a median interval of 105 (interquartile range 57–160) minutes, occurrence of an intrapartum risk event (non-reassuring FHR, oxytocin use or poor progress) increased assessment frequency significantly (rate ratio 1.32 (CI 1.09–1.58)). Neither international nor locally-adapted standards of intrapartum routine care were optimally achieved. This was most likely due to a grossly inadequate capacity of birth attendants; without whom innovative interventions at birth are unlikely to succeed. This calls for international and local stakeholders to address the root causes of unsafe intrafacility care in low-resource settings, including the number of skilled birth attendants required for safe and respectful births.

Implementing Fixed Dose Combination Medications for the Prevention and Control of Cardiovascular Diseases.

Abstract: Highlights: - Despite clinical evidence of its effectiveness in secondary prevention of cardiovascular disease, uptake of fixed dose combination therapy (FDCs) for CVD has been poor.- A symposium was held bringing together stakeholders on this issue, including from academia, government and NGOs.- The conclusion made was that what is now needed to improve implementation of FDCs is country-specific health systems analyses to design appropriate implementation strategies.- Implementation strategies must look beyond listing on the WHO Essential Medicines List to consider approaches to improving FDC availability, accessibility, affordability, and adherence.- Strategies might include incorporation of FDCs into the WHO HEARTS technical package, simplified treatment and monitoring algorithms, decentralisation of medicine dispensing and task-sharing for treatment management.

Plasma extracellular vesicle proteins are associated with stress-induced myocardial ischemia in women presenting with chest pain.

Abstract: Diagnosing stable ischemic heart disease (IHD) is challenging, especially in females. Currently, no blood test is available. Plasma extracellular vesicles (EV) are emerging as potential biomarker source. We therefore aimed to identify stress induced ischemia due to stable IHD with plasma extracellular vesicle protein levels in chest pain patients. We analyzed 450 patients suspected for stable IHD who were referred for 82Rb PET/CT in the outpatient clinic. Blood samples were collected before PET/CT and plasma EVs were isolated in 3 plasma subfractions named: TEX, HDL, LDL. In total 6 proteins were quantified in each of these subfractions using immuno-bead assays. CD14 and CystatinC protein levels were independent significant predictors of stress-induced ischemia in the LDL and the HDL subfraction and SerpinC1 and SerpinG1 protein levels in the HDL fraction. Subgroup-analysis on sex revealed that these associations were completely attributed to the associations in women. None of the significant EV proteins remained significant in men. Plasma EV proteins levels are associated with the presence of stable IHD in females presenting with chest pain. This finding, if confirmed in larger cohort studies could be a crucial step in improving diagnostic assessment of women with suspected IHD.

The Moderate Alcohol and Cardiovascular Health Trial (MACH15): Design and methods for a randomized trial of moderate alcohol consumption and cardiometabolic risk:

Abstract: BackgroundObservational studies have documented lower risks of coronary heart disease and diabetes among moderate alcohol consumers relative to abstainers, but only a randomized clinical trial can ...

Prevalence of chronic kidney disease and risk factors in North-Central Nigeria: a population-based survey

Abstract: Chronic kidney disease (CKD) is a growing challenge in low- and middle-income countries, particularly in sub-Saharan Africa. There is insufficient population-based data on CKD in Nigeria that is required to estimate its true burden, and to design prevention and management strategies. The study aims to determine the prevalence of CKD and its risk factors in Nigeria. We studied 8 urban communities in Kwara State, North-Central zone of Nigeria. Blood pressure, fasting blood sugar, urinalysis, weight, height, waist circumference and hip circumference were obtained. Albuminuria and kidney length were measured by ultrasound while estimated glomerular filtration rate (eGFR) was derived from serum creatinine, using chronic disease epidemiology collaboration (CKD-EPI) equation. Associations of risk factors with CKD were determined by multivariate logistic regression and expressed as adjusted odds ratio (aOR) with corresponding 95% confidence intervals. One thousand three hundred and fifty-three adults ≥18 years (44% males) with mean age of 44.3 ± 14.4 years, were screened. Mean kidney lengths were: right, 93.5 ± 7.0 cm and left, 93.4 ± 7.5 cm. The age-adjusted prevalence of hypertension was 24%; diabetes 4%; obesity 8.7%; albuminuria of > 30 mg/L 7%; and dipstick proteinuria 13%. The age-adjusted prevalence of CKD by estimated GFR < 60 ml/min/1.73m2 and/or Proteinuria was 12%. Diabetes (aOR 6.41, 95%CI = 3.50–11.73, P = 0.001), obesity (aOR 1.50, 95%CI = 1.10–2.05, P = 0.011), proteinuria (aOR 2.07, 95%CI = 1.05–4.08, P = 0.035); female sex (aOR 1.67, 95%CI = 1.47–1.89, P = 0.001); and age (aOR 1.89, 95%CI = 1.13–3.17, P = 0.015) were the identified predictors of CKD. CKD and its risk factors are prevalent among middle-aged urban populations in North-Central Nigeria. It is common among women, fueled by diabetes, ageing, obesity, and albuminuria. These data add to existing regional studies of burden of CKD that may serve as template for a national prevention framework for CKD in Nigeria. One of the limitations of the study is that the participants were voluntary community dwellers and as such not representative for the community. The sample may thus have been subjected to selection bias possibly resulting in overestimation of CKD risk factors.

Cardiovascular Disease Burden in Rural Africa: Does HIV and Antiretroviral Treatment Play a Role?: Baseline Analysis of the Ndlovu Cohort Study.

Abstract: Background HIV is associated with an increased risk of cardiovascular disease (CVD) in high‐income countries. Little is known about the CVD burden in sub‐Saharan Africa, where 70% of the world's HI...

Elevated Lp(a) (Lipoprotein[a]) Levels Increase Risk of 30-Day Major Adverse Cardiovascular Events in Patients Following Carotid Endarterectomy.

Abstract: Background and Purpose: General population studies have shown that elevated Lp(a) (lipoprotein[a]) levels are an emerging risk factor for cardiovascular disease and subsequent cardiovascular events...

Extracellular vesicle Cystatin C and CD14 are associated with both renal dysfunction and heart failure

Abstract: Aims: Extracellular vesicles (EVs) are small double-membrane plasma vesicles that play key roles in cellular crosstalk and mechanisms such as inflammation. The role of EVs in combined organ failure such as cardiorenal syndrome has not been investigated. The aim of this study is to identify EV proteins that are associated with renal dysfunction, heart failure, and their combination in dyspnoeic patients. Methods and results: Blood samples were prospectively collected in 404 patients presenting with breathlessness at the emergency department at National University Hospital, Singapore. Renal dysfunction was defined as estimated glomerular filtration rate ' 60 mL/min/1.73 m2. The presence of heart failure was independently adjudicated by two clinicians on the basis of the criteria of the European Society of Cardiology guidelines. Protein levels of SerpinG1, SerpinF2, Cystatin C, and CD14 were measured with a quantitative immune assay within three EV sub-fractions and in plasma and were tested for their associations with renal dysfunction, heart failure, and the concurrence of both conditions using multinomial regression analysis, thereby correcting for confounders such as age, gender, ethnicity, and co-morbidities. Renal dysfunction was found in 92 patients (23%), while heart failure was present in 141 (35%). In total, 58 patients (14%) were diagnosed with both renal dysfunction and heart failure. Regression analysis showed that Cystatin C was associated with renal dysfunction, heart failure, and their combination in all three EV sub-fractions and in plasma. CD14 was associated with both renal dysfunction and the combined renal dysfunction and heart failure in all EV sub-fractions, and with presence of heart failure in the high density lipoprotein sub-fraction. SerpinG1 and SerpinF2 were associated with heart failure in, respectively, two and one out of three EV sub-fractions and in plasma, but not with renal dysfunction. Conclusions: We provide the first data showing that Cystatin C and CD14 in circulating EVs are associated with both renal dysfunction and heart failure in patients presenting with acute dyspnoea. This suggests that EV proteins may be involved in the combined organ failure of the cardiorenal syndrome and may represent possible targets for prevention or treatment.

The effect of non-organophosphate household pesticides exposure during pregnancy on infants birth sizes and growth rate: a cohort study

Abstract: To date, there is limited evidence on the effect of antenatal exposure to non-organophosphate household pesticides on infant health. Our hypothesis is that antenatal exposure to non-organophosphate household pesticides will be associated with birth sizes and infant growth rate. In this prospective cohort study, 284 mother-infant pairs were studied. Mothers were recruited at the third trimester in two primary care centers and one private hospital in Jakarta, Indonesia. Mothers filled out questionnaires about exposure to non-organophosphate household pesticides at the 3rd trimester of pregnancy. Birth weight and length were measured at birth. Afterwards, the weight, height, and head circumference (HC) were measured at 7 days, 1, 2, 4, and 6 months of age. Linear mixed modeling and linear regression was performed to calculate growth rate of each infant. Multivariable linear regression adjusted for confounders was used to assess the association between household pesticides exposure and birth sizes and infant growth rate. Based on self-report questionnaires, 133 (46.8%) mothers were exposed to household pesticides during pregnancy. The mean HC at day 7 in the exposed group was − 7.1 mm (95%CI -13.1;-1.2) lower than in the non-exposed group. The difference was more prominent in the non-mosquito pesticide group (linear regression coefficient: − 22.1 mm, 95%CI -36.5;-7.6). No material associations were found between antenatal exposure to household pesticides with other growth measures, including weight gain, length gain, HC increment and weight-to-length gain rates. No modification of effects by breastfeeding was found. Our findings suggest that antenatal exposure to household non-organophosphate pesticides is associated with smaller head circumference at birth.

Association of Factor V Leiden with Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data

Abstract: Background: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given t...

Heart Rate Variability, HIV and the Risk of Cardiovascular Diseases in Rural South Africa.

Abstract: Background: Antiretroviral therapy (ART) transformed human immunodeficiency virus (HIV) infection into a chronic disease. Possible HIV-associated complications have emerged including cardiovascular diseases (CVD). Objectives: This study aims to determine the heart rate variability (HRV) distribution and association between HRV and HIV treated with ART in a rural African population. Methods: This cross-sectional study included 325 participants of the Ndlovu Cohort Study, South Africa. HRV was measured using a standardized five-minute resting ECG and assessed by the standard deviation of normal RR intervals (SDNN), root of mean squares of successive RR differences (RMSSD), percentage of RR intervals greater than 50 milliseconds different from its predecessor (pNN50), total-, low- and high-frequency power. CVD risk factors were assessed using measurements (blood pressure, anthropometry, cholesterol) and questionnaires (e.g. socio-demographics, alcohol, smoking, physical activity, age, diabetes). We used a Wilcoxon rank test to assess differences in medians between HIV-infected and HIV-uninfected participants and multivariable linear regression to investigate associations between HRV and HIV treated with ART. Conclusions: Of the participants, 196 (61.4%) were HIV-infected treated with ART and 123 (38.6%) were HIV-uninfected. HIV-infected consumed less alcohol, 52% versus 35%, smoked less, were less physically active, more often attained lower education, 26% versus 14%, and had lower systolic blood pressure, 134 mmHg versus 140 mmHg, compared to HIV-uninfected. Medians of all HRV parameters were lower for HIV-infected participants. The model fully adjusted for CVD risk factors showed a significant inverse association between HIV treated with ART and log RMSSD (–0.16) and log pnn50 (–0.61). Although HIV-infected participants treated with ART presented with less CVD risk factors they had a lower HRV indicating an increased risk of CVD. Highlights – African HIV-infected participants on ART had less conventional CVD risk factors than HIV-uninfected. – However, HIV-infected participants had lower HRV than HIV-uninfected participants. – Lower HRV of the HIV-infected participants indicates that they are at a higher risk for CVD.

Extracellular Vesicle cystatin c is associated with unstable angina in troponin negative patients with acute chest pain.

Abstract: Background Despite the use of high-sensitive cardiac troponin there remains a group of high-sensitive cardiac troponin negative patients with unstable angina with a non-neglectable risk for future adverse cardiovascular events, emphasising the need for additional risk stratification. Plasma extracellular vesicles are small bilayer membrane vesicles known for their potential role as biomarker source. Their role in unstable angina remains unexplored. We investigate if extracellular vesicle proteins are associated with unstable angina in patients with chest pain and low high-sensitive cardiac troponin. Methods The MINERVA study included patients presenting with acute chest pain but no acute coronary syndrome. We performed an exploratory retrospective case-control analysis among 269 patients. Cases were defined as patients with low high-sensitive cardiac troponin and proven ischemia. Patients without ischemia were selected as controls. Blood samples were fractionated to analyse the EV proteins in three plasma-subfractions: TEX, HDL and LDL. Protein levels were quantified using electrochemiluminescence immunoassay. Results Lower levels of (adjusted) EV cystatin c in the TEX subfraction were associated with having unstable angina (OR 0.93 95% CI 0.88–0.99). Conclusion In patients with acute chest pain but low high-sensitive cardiac troponin, lower levels of plasma extracellular vesicle cystatin c are associated with having unstable angina. This finding is hypothesis generating only considering the small sample size and needs to be confirmed in larger cohort studies, but still identifies extracellular vesicle proteins as source for additional risk stratification.

2019 Рекомендации ЕSC/EASD по сахарному диабету, предиабету и сердечно-сосудистым заболеваниям

Abstract: The Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD)

Sex differences in flow cytometry-based platelet reactivity in stable outpatients suspected of myocardial ischemia.

Abstract: Background: Antiplatelet therapy is the mainstay of secondary prevention of cardiovascular events. Studies suggest that women do not obtain equal therapeutic benefit from antiplatelet therapy compared with men. The link between sex differences in platelet biology and response to antiplatelet therapies is unclear. We therefore investigated the role of sex differences in platelet reactivity in a cohort of outpatients with chest pain, in response to treatment with antiplatelet agents. Methods: Platelet reactivity was measured in 382 randomly selected patients participating in the Myocardial Ischemia Detection by Circulating Biomarkers (MYOMARKER) study, an observational cohort study of outpatients suspected of myocardial ischemia. In all patients, blood was collected during diagnostic workup, and platelet reactivity was assessed with a flow cytometry–based platelet activation test that quantifies both platelet degranulation (P-selectin expression) and platelet aggregation (fibrinogen binding to integrin αIIbβ3) in whole blood. Results: Platelet reactivity was higher in women compared with men when activated with protease activating receptor 1–activating peptide SFLLRN (PAR1-AP) and adenosine 5′-phosphate (ADP), independent of age, basal activation status, estimated glomerular filtration rate < 60, platelet count, statin use, the use of P2Y12 inhibitors, or the use of aspirin. P2Y12 inhibitor use strongly reduced fibrinogen binding after stimulation with PAR1-AP, but only slightly reduced platelet P-selectin expression. Calculation of the relative inhibition in P2Y12 users indicated 62% inhibition of the response toward ADP. Stratified analysis showed that women (n = 14) using P2Y12 inhibitors showed less inhibition of fibrinogen binding after PAR1-AP stimulation than men (n = 38) using P2Y12 inhibitors. Conclusions: These findings call for further study of differential effects of P2Y12 inhibitors in women with suspected myocardial ischemia.

Determinants of Mortality from Cardiovascular Disease in the Slums of Nairobi, Kenya

Abstract: Background: Cardiovascular diseases (CVD) comprise eighty percent of non-communicable disease (NCD) burden in low- and middle-income countries and are increasingly impacting the poor inequitably. Traditional and socioeconomic factors were analyzed for their association with CVD mortality over 10 years of baseline assessment in an urban slum of Nairobi, Kenya. Methods and results: A 2008 survey on CVD risk factors was linked to cause of death data collected between 2008 and 2018. Cox proportional hazards on relative risk of dying from CVD over a 10-year period following the assessment of cardiovascular disease risk factors were computed. Population attributable fraction (PAF) of incident CVD death was estimated for key risk factors. In total, 4,290 individuals, 44.0% female, mean age 48.4 years in 2008 were included in the analysis. Diabetes and hypertension were 7.8% and 24.9% respectively in 2008. Of 385 deaths recorded between 2008 and 2018, 101 (26%) were caused by CVD. Age (hazard ratio (HR) 1.11; 95% confidence interval (CI) 1.03–1.20, p = 0.005) and hypertension (HR 2.19, 95% CI 1.44–3.33, p Conclusions: A holistic approach in addressing socioeconomic factors in the broader context of social determinants of health at the policy, population and individual level will enhance prevention and treatment-adherence for CVD in underserved settings.

Urinary Ethyl Glucuronide as Measure of Alcohol Consumption and Risk of Cardiovascular Disease : A Population-Based Cohort Study

Abstract: Background Moderate alcohol consumption has been associated with a lower risk of cardiovascular disease (CVD) and all-cause mortality compared with heavy drinkers and abstainers. To date, studies have relied on self-reported consumption, which may be prone to misclassification. Urinary ethyl glucuronide (EtG) is an alcohol metabolite and validated biomarker for recent alcohol consumption. We aimed to examine and compare the associations of self-reported alcohol consumption and EtG with CVD and all-cause mortality. Methods and Results In 5676 participants of the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study cohort, EtG was measured in 24-hour urine samples and alcohol consumption questionnaires were administered. Participants were followed up for occurrence of first CVD and all-cause mortality. Cox proportional hazards regression models, adjusted for age, sex, and CVD risk factors, were fitted for self-reported consumption, divided into 5 categories: abstention, 1 to 4 units/month (reference), 2 to 7 units/week, 1 to 3 units/day, and ≥4 units/day. Similar models were fitted for EtG, analyzed as both continuous and categorical variables. Follow-up times differed for CVD (8 years; 385 CVD events) and all-cause mortality (14 years; 724 deaths). For both self-reported alcohol consumption and EtG, nonsignificant trends were found toward J-shaped associations between alcohol consumption and CVD, with higher risk in the lowest (hazard ratio for abstention versus 1-4 units/month, 1.42; 95% CI, 1.02-1.98) and highest drinking categories (hazard ratio for ≥4 units/day versus 1-4 units/month, 1.11; 95% CI, 0.68-1.84). Neither self-report nor EtG was associated with all-cause mortality. Conclusions Comparable associations with CVD events and all-cause mortality were found for self-report and EtG. This argues for the validity of self-reported alcohol consumption in epidemiologic research.