Farhan Shahid

Hypertension and Atrial Fibrillation: An Intimate Association of Epidemiology, Pathophysiology, and Outcomes.

Atrial fibrillation (AF) is the most prevalent sustained arrhythmia found in clinical practice. AF rarely exists as a single entity but rather as part of a diverse clinical spectrum of cardiovascular diseases, related to structural and electrical remodeling within the left atrium, leading to AF onset, perpetuation, and progression. Due to the high overall prevalence within the AF population arterial hypertension plays a significant role in the pathogenesis of AF and its complications. Fibroblast proliferation, apoptosis of cardiomyocytes, gap junction remodeling, accumulation of collagen both in atrial and ventricular myocardium all accompany ageing-related structural remodeling with impact on electrical activity. The presence of hypertension also stimulates oxidative stress, systemic inflammation, rennin-angiotensin-aldosterone and sympathetic activation, which further drives the remodeling process in AF. Importantly, both hypertension and AF independently increase the risk of cardiovascular and cerebrovascular events, e.g., stroke and myocardial infarction. Given that both AF and hypertension often present with limited on patient wellbeing, treatment may be delayed resulting in development of complications as the first clinical manifestation of the disease. Antithrombotic prevention in AF combined with strict blood pressure control is of primary importance, since stroke risk and bleeding risk are both greater with underlying hypertension.

Risk Stratification Models in Atrial Fibrillation.

Abstract Atrial fibrillation (AF) is associated with an increased risk of stroke compared with the general population. AF‐related stroke confers a higher mortality and morbidity risk, and thus, early detection and assessment for the initiation of effective stroke prevention with oral anticoagulation are crucial. Simple and practical risk assessment tools are essential to facilitate stroke and bleeding risk assessment in busy clinics and wards to aid decision making. At present, the CHA2DS2VASc score is recommended by guidelines as the most simple and practical method of assessing stroke risk in AF patients. Alongside this, the use of the HAS‐BLED score aims to identify patients at high risk of bleeding for more regular review and follow‐up, and draws attention to potentially reversible bleeding risk factors. The aim of this review article is to summarize the current risk scores available for both stroke and bleeding in AF patients, and the recommendations for their use.

Prognostic and therapeutic implications of vascular disease in patients with atrial fibrillation

&NA; Atrial fibrillation (AF) is associated with a 5‐fold increase in the risk of ischemic stroke, and AF‐related stroke patients have a higher mortality and greater morbidity than patients with non‐AF related stroke. AF and vascular disease share a close relationship, with the concomitant presence of both disease states leading to a dramatic rise in future cardiovascular events. Indeed, the presence of peripheral artery disease independently predicts stroke in patients with AF. Myocardial infarction (MI) is another well‐established risk factor for the development of AF; however, the role of pre‐existing AF in MI is less well evidenced, with recent studies showing that this population more frequently develops coronary ischaemic events and has a higher risk of mortality than sinus rhythm patients. Finally, complex aortic plaque is associated with heightened thromboembolic risk in AF patients. Recent data from clinical trials with non‐vitamin K antagonist oral anticoagulants (NOACs) provided new insights on the prognostic implications of vascular disease coexistence in AF patients, and randomised trials testing a combination of NOAC with antiplatelet agents are ongoing. This review article provides an overview of recent data linking adverse outcomes in concomitant AF and vascular disease and the clinical trial evidence for possible therapeutic targets. Graphical abstract Figure. No caption available.

Renin–angiotensin blockade in atrial fibrillation: where are we now?

Atrial fibrillation (AF) is associated with a fivefold increase in the risk of stroke, with AF-related stroke patients having a higher mortality and greater morbidity than patients with non-AF-related stroke. Between 14–17 million patients will be diagnosed with this most prevalent arrhythmia within the European Union by 2030. The use of oral anticoagulant therapy, whether with the vitamin K antagonists (for example, warfarin) or more recently, the non-VKA oral anticoagulants, results in a marked reduction in stroke and all-cause mortality. At present, a focus on preventing AF-related stroke is the mainstay of medical management. However, prevention of AF occurrence and reduction of AF burden at the population level offers major advantages for both reduction of health care cost, longevity and quality of life. Activation of the renin–angiotensin system (RAS) is closely linked to the development of AF, especially in hypertensive patients. It promotes fibrotic changes in the atria, which subsequently leads to the pro-arrhythmogenic electrophysiological abnormalities. This favours the onset and perpetuation of AF. Multiple mechanisms have been identified to mediate the activation of RAS and initiation of AF. For example, angiotensin II activates the profibrotic pathways by the triggering differentiation of atrial fibroblasts into myofibroblasts that have an adverse effect on atrial remodelling. The subsequent release of proinflammatory cytokines, such as transforming growth factor β-1, modulates the electrical properties of atrial myocytes. Also, by blocking the action of angiotensin II, angiotensin-converting enzyme inhibitors reduce cardiac sympathetic activity, a contributor to AF development. Of note, recent studies have found a lower incidence of AF in hypertensive patients receiving RAS inhibitors compared to controls. A causative role for aldosterone in the pathogenesis of AF is supported by findings from large retrospective cohort studies in patients with primary aldosteronism who were compared to matched patients with essential hypertension. The mechanisms behind the increased risk of AF in subjects with high aldosterone production is multifactorial. The process of left atrial dilatation, along with enhanced deposition of the extracellular matrix all conform to the end results of myocardial fibrosis. This manifests itself clinically as diastolic dysfunction, left ventricular hypertrophy and eventual remodelling of the left ventricle. In theory, all anti-hypertensive medications may be effective in reducing the incidence of AF by preventing diastolic dysfunction, atrial dilatation and to some extent fibrosis. Nonetheless, there have been conflicting results as to whether RAS blockade provides superior efficacy in this regard, with a meta-analysis showing a 28% relative risk reduction in preventing AF. The Losartan Intervention For End Point Reduction in Hypertension study which compared the efficacy of losartan to atenolol in 8300 hypertensive patients, found a marked reduction of new-onset AF in the losartan group (6.8 vs 10.1 per 1000 person-years, relative risk 0.67, 95% confidence interval 0.55–0.83, Po0.001) despite similar reductions in blood pressure. Benefits of losartan in this cohort may be due to the more favourable effect on atrial remodelling, both due to improved haemodynamics and inhibition of collagen deposition, thereby reducing the stimuli for onset AF. However, similar rates of AF occurrence were observed in the ACEI and conventional therapy arms in the Captopril Prevention Project and the Swedish Trial in Old Patients with Hypertension. The differences in study findings may be explained by the fact that the Losartan Intervention For End Point Reduction in Hypertension study enrolled patients with left ventricular hypertrophy, which in itself has a strong association with increased left atrial size and likely more cardiac fibrosis. However, methodology of AF recording could also affect how complete these data were, a particularly important issue given that AF is often ‘silent’. In this issue of the Journal of Human Hypertension, Takeshi et al. present results of an observational study aiming to provide further insight into the potential benefits of RAS blockade in the prevention of new-onset AF in hypertensive subjects. A total of 964 eligible patients were enrolled in the study and observed for over 4-year medium duration. Only patients taking an angiotensin-converting enzyme inhibitor or angiotensin receptor

Recent advances in the understanding and management of atrial fibrillation: a focus on stroke prevention.

Atrial fibrillation (AF) is associated with an increased risk of stroke compared with the general population. It is anticipated that by 2030 an estimated 14–17 million patients will be diagnosed with this most prevalent arrhythmia within the European Union. AF-related stroke confers a higher mortality and morbidity risk, and thus early detection and assessment for the initiation of effective stroke prevention with oral anticoagulation (OAC) is crucial. Recent guidelines point to the use of non-vitamin K antagonist OACs (NOACs) where appropriate in stroke prevention of patients with non-valvular AF. At present, there are four NOACS available, with no direct head-to-head comparisons to suggest the superiority of one drug over another. Simple and practical risk assessment tools have evolved over the years to facilitate stroke and bleeding risk assessment in busy clinics and wards to aid decision-making. At present, the CHA 2DS 2VASc (congestive heart failure, hypertension, age 65–74/>75, diabetes mellitus, stroke/transient ischemic attack/thromboembolism, vascular disease, female sex) score is recommended by many international guidelines as a simple and practical method of assessing stroke risk in such patients. Alongside this, use of the HAS BLED (hypertension systolic blood pressure >160 mmHg, abnormal liver/renal function [with creatinine ≥200 μmol/L], stroke, bleeding history or predisposition, labile international normalized ratio [range <60% of the time], elderly [>65], concomitant drugs/alcohol) score aims to identify patients at high risk of bleeding for more regular review and follow-up and draws attention to potentially reversible bleeding risk factors. The aim of this review article is to provide an overview of recent advances in the understanding and management of AF with a focus on stroke prevention.

Atrial fibrillation and its complications: a focus on identifying risk factors and risk stratification

This editorial refers to ‘Risk factor changes and incident atrial fibrillation among middle-aged men in the Malmo Preventive Project cohort’, by L.S.B. Johnson et al ., on page 81. Although traditionally described as a diagnosis of the elderly, a growing population with high prevalence of cardiovascular risk factors and overt cardiovascular disorders makes the problem of atrial fibrillation (AF) highly relevant.1 Therefore, early risk assessment and management of cardiovascular risk factors are of primary importance in improving cardiovascular health and reducing the incidence of AF. Despite a clear association between AF and various risk factors such as hypertension, diabetes mellitus, and heart failure, very few AF patients simply fall into a simple, single homogeneous category with respect to predisposing factors for developing AF or its complications. In this issue of European Heart Journal: Cardiovascular Pharmacology , Johnson et al . report an observational study on the relationship between …

Treatment of Atrial Fibrillation in Patients With Chronic Kidney Disease: Is Stroke Prevention Worth the Risk?

Atrial fibrillation (AF) and chronic kidney disease (CKD) commonly coexist in the same patient, and presence of AF does increase the relative risk of stroke in patients with CKD at least to the same extent as in those with normal renal function. Based on these considerations, stroke prevention with oral anticoagulation (OAC) appears essential in patients with AF and CKD. However, patients with CKD also have a higher risk of both intracranial and extracranial haemorrhage. A delicate balance is therefore needed to shift the overall risk-to-benefit ratio toward stroke prevention

Prognostic implication of monocytes in atrial fibrillation: The West Birmingham Atrial Fibrillation Project

Background and objectives High monocyte counts are related to adverse outcomes in cardiovascular disease. Their role in prognostication in patients with atrial fibrillation (AF) is unknown. We investigated whether monocyte counts are useful as a marker of prognosis in patients with AF. Methods Monocyte counts were obtained from blood samples in 881 AF patients. Study outcomes were (i) all-cause death; (ii) major adverse cardiovascular events; (iii) stroke, TIA or other systemic embolism (SSE); and (iv) major bleeding. Results Median follow up was 7.2 years; 44% of patients died, 48% developed MACE; 9% had SSE and 5% had major bleeding. On Cox regression, after adjustment for CHA2DS2-VASc score, the highest quartile of monocyte counts (i.e., ≥580 μL vs. other quartiles) was associated with increased risk of death (hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.31–2.05, p<0.001) and MACE (HR 1.58, 95% CI 1.28–1.96, p<0.001). Persistent monocyte levels ≥580 per μL during follow up were associated with further increase in risk of death (HR 1.52, 95% CI 1.10–2.11, p = 0.01) and MACE (HR 1.54, 95% CI 1.13–2.09, p = 0.006). Persistent monocyte levels ≥580 per μL during were associated with a significant increase in major bleeding events (HR 2.77, 95% CI 1.36–5.67, p = 0.005, after adjustment for HAS-BLED score). Conclusion High monocyte counts independently predict the occurrence of MACE, major bleeding and mortality, but not SSE. Understanding the pathophysiological mechanisms involved would help understand the relationships between monocytes, and adverse thrombotic and bleeding outcomes in AF patients.

Role of Monocytes in Heart Failure and Atrial Fibrillation

Heart failure (HF) is a culmination of pathological processes presenting with debilitating symptoms that highlight a complex interplay between immunological, hormonal, and metabolic systems resulting in impaired cardiac function. HF has a major impact on the quality of life and longevity of the

Use of non‐vitamin K antagonist oral anticoagulants in patients with heart failure and atrial fibrillation: does concomitant kidney disease change our practice?

Heart failure (HF) and chronic kidney disease (CKD) are closely related, with CKD being an established independent marker of poor prognosis in patients diagnosed with HF.1 In the Acute Decompensated Heart Failure Registry (ADHERE), for example, 30% of the hospitalized patients had renal insufficiency;1 of this cohort, 21% had serum creatinine levels >2.0 mg/dL, 9% had serum creatinine >3.0 mg/dL, with 5% on dialysis. Thus, the term ‘cardio-renal syndrome’ has been coined to describe this close relationship between the heart and the kidney, where patients with established LV dysfunction develop glomerular hypoperfusion and subsequent impairment in renal function.2 Similarly, AF and CKD commonly co-exist in the same patient, and the presence of AF increases the relative risk of stroke in subjects with CKD at least to the same extent as in AF populations with normal renal function.3,4 Although CKD is a significant risk factor for stroke and major bleeding, CKD per se does not improve the predictive ability of the CHA2DS2-VASc score for high-risk patients, given that CKD is associated with its risk factor components.5 Furthermore, based on these considerations, stroke prevention with oral anticoagulation (OAC) remains essential in AF patients with CKD, with evidence of a clear positive net clinical benefit in such patients.6 However, patients with CKD still have a higher risk of both intracranial and extracranial haemorrhage.7 A fine balance is therefore needed to shift the overall risk-to-benefit ratio towards stroke prevention with minimal