Prevalence, characteristics and additional stroke risk stratification: an analysis of the Atrial Fibrillation cohort within the REMEDY study

Background: Atrial fibrillation (AF) is the most common arrhythmia and may be complicated by embolic stroke. It is also associated with a significant risk of heart failure and mortality. The burden of rheumatic heart disease remains great in the developing world. The prevalence of AF in those with rheumatic heart disease is in the order of 20% with a resultant 17-fold increased risk of embolic stroke. Over time, many other risk factors for stroke in the AF population have been described. Stroke risk stratification tools such as the CHADS₂ (Congestive heart failure, hypertension, age of 75 or older, diabetes mellitus or stroke/TIA) and CHA₂DS₂VASc (with the addition of a second age category, female gender, and peripheral artery disease) scores have been developed. These are used to assess the need for anticoagulation and have been well validated. These scores have traditionally excluded those patients with valvular AF. Valvular AF has not been studied extensively in the contemporary era. Oral anticoagulation had previously been advised in all patients with valvular AF. Little is known however about outcomes for stroke and mortality in this cohort of patients. Furthermore, the utilization of the CHADS₂ and CHA₂DS₂VASc scores may provide incremental benefit in prognostication and resultantly, both more diligent prescription of anticoagulation and improved outcomes. Objectives: The objectives of this study were as follows - 1. To determine the prevalence of AF in the Global Rheumatic Heart Disease Registry (the REMEDY study) and in the Groote Schuur Hospital (GSH) cohort. 2. To assess the demographic, social and clinical characteristics of patients with AF in the REMEDY study and in the GSH cohort. 3. To assess the frequency of CHADS₂ and CHA₂DS₂VASc risk factors in the GSH cohort and to calculate a CHADS₂ and CHA₂DS₂VASc score on each of the patients with AF. 4. To establish whether CHADS₂ and CHA₂DS₂VASc scores further increase the risk of stroke and death in this cohort of patients with valvular AF. Methods: This is a substudy of the Global Rheumatic Heart Disease Registry (the REMEDY study). We assessed those with AF from the entire cohort for prevalence and outcome data. Patients with ECG or Holter proven AF from the GSH cohort were further risk stratified using the CHADS₂ and CHA₂DS₂Vasc scores. Clinical data was obtained from folder reviews and telephonic interviews. The CHADS₂ and CHA₂DS₂Vasc scores for each patient in the GSH cohort were calculated. Patients were followed up for 2 years and information pertaining to death and stroke were obtained from folder reviews. These were then correlated with the CHADS₂ and CHA₂DS₂Vasc scores. Results: A total of 2624 REMEDY patients were analysed. Of these, 22% in the total cohort (586 of 2684 patients) and 38.2% in the GSH cohort (187 of 489 patients) had AF. These patients were older (35 years vs. 25 years, p<0.0001), more likely to be female (73.1% vs. 65.6%, p=0.001) and more frequently had a history of congestive heart disease (41.0% vs. 33.3%, p=0.001) when compared to those in sinus rhythm. They also had significantly more strokes (13.8% vs. 5%, p<0.0001) and a poorer NYHA class (NYHA III& IV 30.8% vs. 25.2%, p=0.002). The cohort with AF had more severely impaired left ventricular (LV) function compared to those in sinus rhythm (Ejection fraction (EF) 57% vs. 61%. P<0.0001). The presence of a larger left atrial (LA) size, spontaneous echo contrast and LA thrombus was much greater in the AF cohort. Of those patients in AF, only 68% had received a prescription for warfarin. The GSH cohort was risk stratified using the CHADS₂ and CHA₂DS₂VASc scores. Twenty-three percent of patients had a CHADS₂ score of 0 and 27.7% of 1. When the same cohort was scored using the CHA₂DS₂VASc score, only 5.4% had a score of 0; this difference was mainly driven by the additional category of female gender. The patients in our cohort were young (median age 28 years) and had few comorbidities. Despite this, patients with AF did significantly worse than those in sinus rhythm, with a stroke rate of 4.6% and a mortality rate of 13.1% observed at 2 years (compared to a 1.5% stroke rate and 5.5% mortality rate for those in sinus rhythm). The presence of any additional comorbidities significantly reduced survival in both the short and long term. Greater CHA₂DS₂VASc score categories (CHA₂DS₂VASc 1 and CHA₂DS₂VASc 2 or more) conferred an incrementally higher risk of death. Conclusion: In a contemporary cohort of patients with rheumatic heart disease, AF is common with a prevalence of 22-39%. These patients were older and exhibited features of more advanced disease both clinically and on echo, compared to their sinus rhythm counterparts. The mortality and stroke rates in the AF group were high despite the relatively young age of this cohort. Mortality and stroke increased significantly and incrementally with each greater CHA₂DS₂VASc score category. Given the differences in chronicity between RHD in the developed world (i.e., disease of older people) and RHD in developing countries (i.e., disease of the young), these results cannot be extrapolated to those living in the first world

Low‐Density Lipoprotein Cholesterol Attributable Cardiovascular Disease Risk Is Sex Specific

Background: Epidemiological studies show that women are generally at lower risk for cardiovascular disease than men. Here, we investigated the sex‐specific differential effect of genetically increased low‐density lipoprotein cholesterol (LDL‐C) on cardiovascular disease (CVD) and other lipid‐associated diseases. Methods and Results: This is a 2‐sample Mendelian randomization study that uses individual participant data from 425 043 participants from the UK Biobank, including 229 279 female participants. An 80‐variant LDL‐C weighted genetic score was generated. Linear and logistic regression models with interactions were used to identify differences between sex‐specific LDL‐C effects on lipids, carotid‐intima media thickness, and multiple cardiovascular outcomes such as CVD, ischemic heart disease, peripheral artery disease, heart failure, aortic valve disease, type 2 diabetes, atrial fibrillation, and aortic aneurysm and dissection. After correction for multiple testing, we observed that the genetically increased LDL‐C effect on CVD events was sex specific: per SD genetically increased LDL‐C, female participants had a higher LDL‐C increase but an attenuated CVD risk increase compared with male participants (LDL‐C: female participants 0.71 mmol/L, 95% CI, 0.70–0.72 and male participants 0.57 mmol/L, 95% CI, 0.56–0.59. P for interaction: 5.03×10−60; CVD: female participants: odds ratio [OR], 1.32; 95% CI 1.24–1.40 and male participants: OR, 1.52; 95% CI, 1.46–1.58. P for interaction: 9.88×10−5). We also observed attenuated risks for ischemic heart disease and (nominally for) heart failure in female participants, and genetically increased LDL‐C results in higher risk for aortic valve disease in female participants compared with male participants. Genetically increased LDL‐C was also associated with an attenuated carotid‐intima media thickness increase in female participants. We did not observe other significant attenuations. Sensitivity analyses with an unweighted genetic score and sex‐specific weighted genetic scores showed similar results. Conclusions: We found that genetically increased LDL‐C has a sex‐specific differential effect on the risk for cardiovascular disease, ischemic heart disease, heart failure, and aortic valve stenosis. Our observations provide evidence that LDL‐C might be a less important determinant of CVD in women compared with men, suggesting that male patients might benefit more from LDL‐C targeted therapies for CVD management than female patients and warranting investigations into the sex‐specific relative contribution of risk factors for CVD

Genetically Predicted Neutrophil-to-Lymphocyte Ratio and Coronary Artery Disease: Evidence From Mendelian Randomization.

Inflammation contributes to atherosclerosis and coronary artery disease (CAD). In order to help identify therapeutic targets, it is important to ascertain whether biomarkers associated with CAD risk are causal. In a recent meta-analysis of clinical trials, neutrophil-to lymphocyte ratio (NLR) was associated with increased cardiovascular risk 1 . We investigate a potential causal nature of this relationship by performing Mendelian randomization (MR) analyse

An approach to the diagnosis and management of valvular heart disease

Valvular heart disease poses a common yet difficult problem in everyday clinical practice. A thorough clinical evaluation with basic commoninvestigations such as an electrocardiogram (ECG) and a chest radiograph (CXR) remains the cornerstone of diagnosis. Echocardiographyand more invasive testing, if needed, are usually performed at specialist level to confirm the diagnosis, assess severity and assist in definitivedecision-making.The causes and clinical, ECG and CXR features of the common valve lesions are described. Patients with symptomatic valve lesions shouldbe referred for specialist assessment. In most cases, medical therapy serves as a bridge to definitive mechanical or surgical therapy

Spatial distribution of low-energy plasma around 2 comet 67P/CG from Rosetta measurements

International audienceWe use measurements from the Rosetta plasma consortium (RPC) Langmuir probe (LAP) and mutual impedance probe (MIP) to study the spatial distribution of low-energy plasma in the near-nucleus coma of comet 67P/Churyumov-Gerasimenko. The spatial distribution is highly structured with the highest density in the summer hemisphere and above the region connecting the two main lobes of the comet, i.e. the neck region. There is a clear correlation with the neutral density and the plasma to neutral density ratio is found to be ∼1-2·10 −6 , at a cometocentric distance of 10 km and at 3.1 AU from the sun. A clear 6.2 h modulation of the plasma is seen as the neck is exposed twice per rotation. The electron density of the collisonless plasma within 260 km from the nucleus falls of with radial distance as ∼1/r. The spatial structure indicates that local ionization of neutral gas is the dominant source of low-energy plasma around the comet

Dissecting the IL-6 pathway in cardiometabolic disease: A Mendelian randomization study on both IL6 and IL6R

Aims: Chronic inflammation is a risk factor for cardiovascular disease (CVD). IL-6 signalling perturbation through IL-6 or IL-6R blockade may have potential benefit on cardiovascular risk. It is unknown whether targeting either IL-6 or IL-6 receptor may result in similar effects on CVD and adverse events. We compared the anticipated effects of targeting IL-6 and IL-6 receptor on cardiometabolic risk and potential side effects. // Methods: We constructed four instruments: two main instruments with genetic variants in the IL6 and IL6R loci weighted for their association with CRP, and two after firstly filtering variants for their association with IL-6 or IL-6R expression. Analyses were performed for coronary artery disease (CAD), ischemic stroke, atrial fibrillation (AF), heart failure, type 2 diabetes (T2D), rheumatoid arthritis (RA), infection endpoints, and quantitative haematological, metabolic and anthropometric parameters. // Results: A 1 mg/L lower CRP by the IL6 instrument was associated with lower CAD (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.77;0.96), AF and T2D risk. A 1 mg/L lower CRP by the IL6R instrument was associated with lower CAD (OR 0.90, 95% CI 0.86;0.95), any stroke and ischemic stroke, AF, RA risk and higher pneumonia risk. The eQTL-filtered results were in concordance with the main results, but with wider confidence intervals. // Conclusions: IL-6 signalling perturbation by either IL6 or IL6R genetic instruments is associated with a similar risk reduction for multiple cardiometabolic diseases, suggesting that both IL-6 and IL-6R are potential therapeutic targets to lower CVD. Moreover, IL-6 rather than IL-6R inhibition might have a more favourable pneumonia risk