Risk of stroke and bleeding in relation to hypertension in anticoagulated patients with atrial fibrillation: a meta-analysis of randomised controlled trials.

Background and purpose Hypertension is common in patients with atrial fibrillation (AF) and carries an additional risk for complications, most notably stroke and bleeding. We assessed the history of hypertension, level of blood pressure control, and an interaction with the choice of oral anticoagulants on clinical outcomes. Methods We performed a systematic review and meta-analysis of studies that randomised patients to novel oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) and reported outcomes stratified by presence of hypertension. Collected outcomes were: ischaemic stroke or systemic embolism (SE), haemorrhagic stroke, intracranial haemorrhage and major bleeding. Log adjusted hazard ratios (HR) and corresponding standard error were calculated, and HRs were compared using Mantel-Haenszel random effects. Quality of the evidence was assessed with Cochrane risk of bias tool. Results Five high-quality studies were eligible, including 71.527 participants who received NOACs (apixaban, dabigatran, edoxaban, rivaroxaban) or VKAs, with median follow-up of 1.8-2.8 years. Compared with patients without hypertension, those with hypertension had higher adjusted risk for ischaemic stroke/SE (HR: 1.25, 95%-CI:1.09, 1.43) and haemorrhagic stroke (HR:1.98, 1.24-3.16). On a continuous scale, the risk of ischaemic stroke/SE increased 6-7% per 10 mmHg increase in systolic blood pressure. No interactions were found between the efficacy or safety of NOACs versus VKAs in the presence or absence of hypertension. In both groups, the use of NOACs led to a lower risk of ischaemic stroke/SE, haemorrhagic stroke and intracranial haemorrhage compared with patients that used VKAs. Conclusions Adequate blood pressure management is vital to optimally reduce the risk of stroke in patients with atrial fibrillation. The benefits of NOACs over VKAs, also apply to patients with elevated blood pressure

Validating risk models versus age alone for atrial fibrillation in a young Dutch population cohort:should atrial fibrillation risk prediction be expanded to younger community members?

BACKGROUND: Advancing age is the primary selection criterion for community screening for atrial fibrillation (AF), with selection often restricted to those aged ≥65 years. If multivariable models were shown to have considerable additional value over age alone in predicting AF risk among younger individuals, AF screening could be expanded to patients with lower age, but with high AF risk as per a validated risk model. METHODS: We validated risk models CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology model for AF) and FHS-AF (Framingham Heart Study model for AF), and risk scores CHA(2)DS(2)-VASc and CHA(2)DS(2)-VA, and presented their predictive abilities for 5-year and 10-year AF risk versus that of age alone in a young Dutch population cohort (PREVEND) free from AF at baseline. We assessed discrimination by the C-statistic and calibration by the calibration plot and stratified Kaplan-Meier plot using survey-weighted Cox models. RESULTS: During 5-year and 10-year follow-up there were n=98 (2.46/1000 person-years) and n=249 (3.29/1000 person-years) new AF cases, respectively, among 8265 participants with mean age 49±13 years. CHARGE-AF and FHS-AF both showed good discrimination for 5-year and 10-year AF (C-statistic range 0.83–0.86) with accurate calibration for 5-year AF, but overestimation of 10-year AF risk in highest-risk individuals. CHA(2)DS(2)-VASc and CHA(2)DS(2)-VA relatively underperformed. Age alone showed similar discrimination to that of CHARGE-AF and FHS-AF both in the overall, young PREVEND cohort and in subgroups for lower age and lower stroke risk. CONCLUSION: Multivariable models accurately discriminate for 5-year and 10-year AF risk among young European community-dwelling individuals. However, their additional discriminatory value over age alone was limited. Selection strategies for primary AF screening using multivariable models should not be expanded to younger individuals

Prediction models for atrial fibrillation applicable in the community:a systematic review and meta-analysis

AIMS: Atrial fibrillation (AF) is a common arrhythmia associated with an increased stroke risk. The use of multivariable prediction models could result in more efficient primary AF screening by selecting at-risk individuals. We aimed to determine which model may be best suitable for increasing efficiency of future primary AF screening efforts. METHODS AND RESULTS: We performed a systematic review on multivariable models derived, validated, and/or augmented for AF prediction in community cohorts using Pubmed, Embase, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) through 1 August 2019. We performed meta-analysis of model discrimination with the summary C-statistic as the primary expression of associations using a random effects model. In case of high heterogeneity, we calculated a 95% prediction interval. We used the CHARMS (Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies) checklist for risk of bias assessment. We included 27 studies with a total of 2 978 659 unique participants among 20 cohorts with mean age ranging from 42 to 76 years. We identified 21 risk models used for incident AF risk in community cohorts. Three models showed significant summary discrimination despite high heterogeneity: CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology) [summary C-statistic 0.71; 95% confidence interval (95% CI) 0.66-0.76], FHS-AF (Framingham Heart Study risk score for AF) (summary C-statistic 0.70; 95% CI 0.64-0.76), and CHA2DS2-VASc (summary C-statistic 0.69; 95% CI 0.64-0.74). Of these, CHARGE-AF and FHS-AF had originally been derived for AF incidence prediction. Only CHARGE-AF, which comprises easily obtainable measurements and medical history elements, showed significant summary discrimination among cohorts that had applied a uniform (5-year) risk prediction window. CONCLUSION: CHARGE-AF appeared most suitable for primary screening purposes in terms of performance and applicability in older community cohorts of predominantly European descent

The COVID-19 pandemic and temporal change in metabolic risk factors for cardiovascular disease: A natural experiment within the HELIUS study

The coronavirus disease 2019 (COVID-19) pandemic, including the restrictive measures taken to reduce the spread of the virus, negatively affected people's health behavior. We explored whether the pandemic also had an effect on metabolic risk factors for cardiovascular disease (CVD) in women and men. We conducted a natural experiment, using data from 6962 participants without CVD at baseline (2011–2015) of six ethnic groups of the HELIUS study in Amsterdam, the Netherlands. We studied whether participants whose follow-up measurements were taken within the 11 months before the pandemic (control group) differed from those whose measurements were taken taken within 6 months after the first lockdown (exposed group). Using sex-stratified linear regressions with inverse probability weighting, we compared changes in baseline- and follow-up data between the control and exposed group in six metabolic risk factors: systolic and diastolic blood pressure (SBP, DBP), total cholesterol (TC), fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and estimated glomerular filtration rate (eGFR). Next, we explored the mediating effect of changes in body-mass index (BMI), alcohol, smoking, depressive symptoms and negative life events at follow-up. We observed less favorable changes in SBP (+1.12mmHg for women, +1.38mmHg for men), DBP (+0.85mmHg, +0.80mmHg) and FPG (only in women, +0.12 mmol/L) over time in the exposed group relative to the control group. Conversely, changes in HbA1c (−0.65 mmol/mol, −0.84 mmol/mol) and eGFR (+1.06 mL/min, +1.04 mL/min) were more favorable in the exposed compared to the control group, respectively. Changes in SBP, DBP, and FPG were partially mediated by changes in behavioral factors, in particular BMI and alcohol consumption. Concluding, the COVID-19 pandemic, in particular behavioral changes associated with restrictive lockdown measures, may have negatively affected several CVD risk factors, in both women and men

Optimal Antithrombotic Regimens for Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention An Updated Network Meta-analysis

Importance: Antithrombotic treatment in patients with atrial fibrillation (AF) and percutaneous coronary intervention (PCI) presents a balancing act with regard to bleeding and ischemic risks. Objectives: To evaluate the safety and efficacy of 4 antithrombotic regimens by conducting an up-to-date network meta-analysis and to identify the optimal treatment for patients with AF undergoing PCI. Data Sources: Online computerized database (MEDLINE). Study Selection: Five randomized studies were included (N = 11542; WOEST, PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, ENTRUST-AF PCI). Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used in this network meta-analysis, in which bayesian random-effects models were applied. The data were analyzed from September 9 to 29, 2019. Main Outcomes and Measures: The primary safety outcome was thrombolysis in myocardial infarction (TIMI) major bleeding and the primary efficacy outcome was trial-defined major adverse cardiovascular events (MACE). Results: The total number of participants included in the study was 11 532. The mean age of the participants ranged from 70 to 72 years, 69% to 83% were male, 20% to 26% were female, and the participants were predominantly white (>90%). Compared with vitamin K antagonists (VKA) plus dual antiplatelet therapy (DAPT) (reference), the odds ratios (ORs) (95% credible intervals) for TIMI major bleeding were 0.57 (0.31-1.00) for VKA plus P2Y12 inhibitor, 0.69 (0.40-1.16) for non-VKA oral anticoagulant (NOAC) plus DAPT, and 0.52 (0.35-0.79) for NOAC plus P2Y12 inhibitor. For MACE, using VKA plus DAPT as reference, the ORs (95% credible intervals) were 0.97 (0.64-1.42) for VKA plus P2Y12 inhibitor, 0.95 (0.64-1.39) for NOAC plus DAPT, and 1.03 (0.77-1.38) for NOAC plus P2Y12 inhibitor. Conclusions and Relevance: The findings of this study suggest that an antithrombotic regimen of VKA plus DAPT should generally be avoided, because regimens in which aspirin is discontinued may lead to lower bleeding risk and no difference in antithrombotic effectiveness. The use of a NOAC plus a P2Y12 inhibitor without aspirin may be the most favorable treatment option and the preferred antithrombotic regimen for most patients with AF undergoing PCI

Adding ethnicity to cardiovascular risk prediction: External validation and model updating of SCORE2 using data from the HELIUS population cohort

BACKGROUND: Current prediction models for mainland Europe do not include ethnicity, despite ethnic disparities in cardiovascular disease (CVD) risk. SCORE2 performance was evaluated across the largest ethnic groups in the Netherlands and ethnic backgrounds were added to the model. METHODS: 11,614 participants, aged between 40 and 70 years without CVD, from the population-based multi-ethnic HELIUS study were included. Fine and Gray models were used to calculate sub-distribution hazard ratios (SHR) for South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin groups, representing their CVD risk relative to the Dutch group, on top of individual SCORE2 risk predictions. Model performance was evaluated by discrimination, calibration and net reclassification index (NRI). RESULTS: Overall, 274 fatal and non-fatal CVD events, and 146 non-cardiovascular deaths were observed during a median of 7.8 years follow-up (IQR 6.8-8.8). SHRs for CVD events were 1.86 (95 % CI 1.31-2.65) for the South-Asian Surinamese, 1.09 (95 % CI 0.76-1.56) for the African-Surinamese, 1.48 (95 % CI 0.94-2.31) for the Ghanaian, 1.63 (95 % CI 1.09-2.44) for the Turkish, and 0.67 (95 % CI 0.39-1.18) for the Moroccan origin groups. Adding ethnicity to SCORE2 yielded comparable calibration and discrimination [0.764 (95 % CI 0.735-0.792) vs. 0.769 (95 % CI 0.740-0.797)]. The NRI for adding ethnicity to SCORE2 was 0.24 (95 % CI 0.18-0.31) for events and - 0.12 (95 % CI -0.13-0.12) for non-events. CONCLUSIONS: Adding ethnicity to the SCORE2 risk prediction model in a middle-aged, multi-ethnic Dutch population did not improve overall discrimination but improved risk classification, potentially helping to address CVD disparities through timely treatment

Electrocardiographic screening in primary care for cardiovascular disease risk and atrial fibrillation

Electrocardiograms (ECGs) are frequently recorded in primary care for screening purposes. An ECG is essential in diagnosing atrial fibrillation, and ECG abnormalities are associated with cardiovascular events. While recent studies show that ECGs adequately reclassify a proportion of patients based on the clinical risk score calculations, there are no data to support that this also results in improved health outcomes. When applied for screening for atrial fibrillation, more cases are found with routine care, but this would be undone when physicians would perform systematic pulse palpation. In most studies, the harms of routine ECG use (such as unnecessary diagnostic testing, emotional distress, increased health expenses) were poorly documented. As such, the routine performing of ECGs in asymptomatic primary care patients, whether it is for cardiovascular disease risk assessment or atrial fibrillation, cannot be recommended