Risk of Cerebrovascular Events in Intracerebral Hemorrhage Survivors With Atrial Fibrillation: A Nationwide Cohort Study.

BACKGROUND: In patients with intracerebral hemorrhage (ICH) and prevalent atrial fibrillation (AF), the optimal stroke prevention strategy is unclear. We sought to estimate the risk of cerebrovascular events among ICH survivors with AF. METHODS: We used the Danish Stroke Registry to identify patients with incident ICH and prevalent AF between 2003 and 2018. Key inclusion/exclusion criteria of the PRESTIGE-AF (Prevention of Stroke in Intracerebral hemorrhage Survivors With Atrial Fibrillation) trial were applied. Cumulative incidence of recurrent ICH, cerebrovascular ischemic event, and all-cause death were investigated after one year. RESULTS: A total of 1885 patients (median age 80.0 years; 47.6% females) were included in the study. We observed 191 cerebrovascular events and 650 all-cause deaths, and more cerebrovascular ischemic events (N=63) than recurrent ICH events (N=40). Risks of recurrent ICH, cerebrovascular ischemic event, and all-cause death were 1.5%, 3.2%, and 30.3%, respectively, among patients not exposed to OAC during follow-up. The cumulative incidences were 2.8% for recurrent ICH, 3.2% for cerebrovascular ischemic events, and 22.0% for all-cause death among patients initiating/resuming OAC during follow-up. CONCLUSIONS: We observed a high risk of cerebrovascular ischemic events and a very high risk of all-cause death at one year after the incident ICH. The results of ongoing clinical trials are warranted to determine optimal stroke prevention treatment among ICH survivors with concomitant AF.

Effectiveness and Safety of NOAC Versus Warfarin in Patients With Atrial Fibrillation and Aortic Stenosis.

Background Guideline recommendations on the use of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with aortic stenosis are based on studies including a low number of patients with aortic stenosis. The aim of this study was to estimate the effects of NOAC versus warfarin on thromboembolism and major bleeding among AF patients with aortic stenosis. Methods and Results We emulated a target trial using observational data from Danish nationwide registries between 2013 and 2018. Thromboembolism was defined as a hospital diagnosis of ischemic stroke and/or systemic embolism, and major bleeding was defined as a hospital diagnosis of intracranial bleeding, gastrointestinal bleeding, or major or clinically relevant bleeding in other anatomic sites. Treatment effect estimates were based on an intention-to-treat and per-protocol approach. A total of 3726 patients with AF and aortic stenosis claimed a prescription for either a NOAC (2357 patients) or warfarin (1369 patients) and met the eligibility criteria for the trial. During 3 years of follow-up, the adjusted hazard ratios for thromboembolism and major bleeding were 1.62 (95% CI, 1.08-2.45) and 0.73 (0.59-0.91) for NOAC compared with warfarin in the intention-to-treat analyses. Similar results were observed in the per-protocol analyses. Conclusions In this observational study, we observed a higher risk of thromboembolism but a lower risk of major bleeding for treatment with NOACs compared with warfarin in patients with AF and aortic stenosis. This observation needs confirmation in large randomized trials in these commonly encountered patients.

Thromboembolism and bleeding complications in anticoagulated patients with atrial fibrillation and native aortic or mitral valvular heart disease: a descriptive nationwide cohort study.

AIMS: To describe the risks of thromboembolism and major bleeding complications in anticoagulated patients with atrial fibrillation (AF) and native aortic or mitral valvular heart disease using data reflecting clinical practice. METHODS AND RESULTS: Descriptive cohort study of anticoagulated patients with incident AF and native aortic or mitral valvular heart disease, identified in nationwide Danish registries from 2000 to 2018. A total of 10 043 patients were included, of which 5190 (51.7%) patients had aortic stenosis, 1788 (17.8%) patients had aortic regurgitation, 327 (3.3%) patients had mitral stenosis, and 2738 (27.3%) patients had mitral regurgitation. At 1 year after AF diagnosis, the risk of thromboembolism was 4.6% in patients with mitral stenosis taking a vitamin K antagonist (VKA), and 2.6% in patients with aortic stenosis taking a VKA or non-vitamin K antagonist oral anticoagulant (NOAC). For patients with aortic or mitral regurgitation, the risks of thromboembolism ranged between 1.5%-1.8% in both treatment groups. For the endpoint of major bleeding, the risk was ∼5.5% in patients with aortic stenosis or mitral stenosis treated with a VKA, and 3.3-4.0% in patients with aortic or mitral regurgitation. For patients treated with a NOAC, the risk of major bleeding was 3.7% in patients with aortic stenosis and ∼2.5% in patients with aortic or mitral regurgitation. CONCLUSION: When using data reflecting contemporary clinical practice, our observations suggested that 1 year after a diagnosis of AF, anticoagulated patients with aortic or mitral valvular heart disease had dissimilar risk of thromboembolism and major bleeding complications. Specifically, patients with aortic stenosis or mitral stenosis were high-risk subgroups. This observation may guide clinicians regarding intensity of clinical follow-up.

Thromboembolic Risk in Nonanticoagulated Patients With Atrial Fibrillation and Valvular Heart Disease.

OBJECTIVES: This study sought to describe the risk of thromboembolism in nonanticoagulated atrial fibrillation patients with Evaluated Heartvalves, Rheumatic or Artificial (EHRA) Type 2 valvular heart disease (VHD) <65 or 65 to 74 years of age and with 0 or 1 non-sex comorbidity of the CHA2DS2-VASc score. BACKGROUND: A minor, but important, proportion of patients with atrial fibrillation and VHD beyond moderate-to-severe mitral stenosis and/or a mechanical prosthetic valve, so-called EHRA Type 2 VHD, have 0 or 1 coexisting non-sex comorbidities of the CHA2DS2-VASc score, and are therefore not strongly recommended oral anticoagulant therapy according to guidelines. Whether these patients are truly low risk of thromboembolism has not been investigated. METHODS: This was a cohort study of 55,613 patients identified in nationwide Danish registries from 2000 to 2018, of which 1,907 patients had EHRA Type 2 VHD. Risk of thromboembolism after 1 and 5 years of follow-up were calculated. RESULTS: At 1 year after atrial fibrillation diagnosis, patients with EHRA Type 2 VHD had a risk of thromboembolism between 1.2% and 1.5%, according to age group (<65 or 65 to 74 years of age), and number of non-sex comorbidities of the CHA2DS2-VASc score (0 or 1). Interestingly, in patients with EHRA Type 2 VHD <65 years of age with 0 or 1 comorbidity, the risk was 1.5% (95% confidence interval: 0.7% to 2.8%) and 1.5% (95% confidence interval: 0.6% to 3.4%) at 1 year after the atrial fibrillation diagnosis. CONCLUSIONS: These observations suggest that in atrial fibrillation patients with EHRA Type 2 VHD, who are not currently recommended oral anticoagulant therapy according to guidelines, the risk of thromboembolism may exceed the level above which oral anticoagulation is considered beneficial.

Thromboembolic and bleeding outcomes in patients with atrial fibrillation and valvular heart disease: A descriptive nationwide cohort study.

AIMS: The risks of thromboembolism and bleeding in patients with atrial fibrillation (AF) and valvular heart disease (VHD) are sparsely described. We described the risk of events in non-anticoagulated and anticoagulated patients with AF and VHD according to the evaluated heart valves, rheumatic or artificial valve classification (EHRA classification), EHRA Type 1 and Type 2 VHD, and within subgroups of EHRA Type 1 and Type 2 VHD. METHODS AND RESULTS: Cohort study of AF patients with coexisting VHD, identified in nationwide Danish registries from 2000 to 2018. Risk of thromboembolism and bleeding after 1 year of follow-up were calculated in each group. We identified 28 770 incident AF patients with VHD. Not surprisingly, we observed the highest risks of thromboembolism in the non-anticoagulated AF patients with EHRA Type 1 and Type 2 VHD (4.9% vs 2.6% and 3.2% vs 1.9%) and the highest risks of bleeding in the anticoagulated AF patients with EHRA Type 1 and Type 2 VHD (6.6% vs 4.3% and 6.1% vs 4.9%). However, within the subgroups of AF patients with EHRA Type 1 and Type 2 VHD, we observed a large proportion of non-anticoagulated patients (32.9%-49.2%), despite a CHA2 DS2 -VASc score of 2≤ in the majority of these patients (81.9%-95.6%). CONCLUSIONS: When using data reflecting contemporary clinical practice, we observed markedly different risks of thromboembolism and bleeding in EHRA Type 1 and Type 2 VHD. Additionally, we observed a potential underuse of oral anticoagulation within the subgroups of AF patients with EHRA Type 1 and Type 2 VHD, underlining need for further attention on this patient group.

Psychotropic drug use following venous thromboembolism versus diabetes mellitus in adolescence or young adulthood: a Danish nationwide cohort study.

OBJECTIVES: Critical and chronic illness in youth such as diabetes can lead to impaired mental health. Despite the potentially traumatic and life-threatening nature of venous thromboembolism (VTE), the long-term mental health of adolescents and young adults with VTE is unclear. We compared the long-term mental health of adolescents and young adults with VTE versus adolescents and young adults with insulin-dependent diabetes mellitus (IDDM) using psychotropic drug purchase as proxy for mental health. DESIGN: Nationwide registry-based cohort study. SETTING: Denmark 1997-2015. PARTICIPANTS: All patients aged 13-33 years with an incident diagnosis of VTE (n=5065) or IDDM (n=6609). EXPOSURE: First time primary hospital diagnosis of VTE or IDDM. PRIMARY AND SECONDARY OUTCOME MEASURES: Adjusted absolute risk and risk difference at 1 and 5 years follow-up for first psychotropic drug purchase comparing patients with VTE and patients with IDDM. RESULTS: The absolute 1 year risk of psychotropic drug use was 6.2% among VTE patients versus 3.6% among patients with IDDM, at 5 years this was 19.3%-14.7%, respectively. After adjusting for the effect of sex, age and risk factors for VTE this corresponded to a 1 year risk differences of 1.9% (95 % CI 0.1% to 3.3%). At 5 years follow-up the risk difference was 1.9% (95% CI 0.5% to 3.3%). CONCLUSION: One-fifth of adolescents and young adults with incident VTE had claimed a prescription for a psychotropic drug within 5 years, a risk comparable to that of young patients with IDDM.

Stroke and bleeding risk scores in patients with atrial fibrillation and valvular heart disease: evaluating 'valvular heart disease' in a nationwide cohort study.

AIMS: Substantial interest has been directed towards stroke risk stratification in patients with atrial fibrillation (AF) but prior studies have focused on AF without significant valvular heart disease (VHD), so-called 'non-valvular AF'. A formal validation exercise addressing stroke risks in relation to the CHA2DS2-VASc risk factor(s) in AF patients with VHD is lacking. Also, the use of the HAS-BLED score in anticoagulated patients with VHD has not been previously studied. The aim of this study was to investigate stroke and bleeding rates in AF patients with VHD in relation to the CHA2DS2-VASc and HAS-BLED scores. METHODS AND RESULTS: We conducted a nationwide cohort study. VHD were categorized based on the 2017 joint European consensus document definition, i.e. Evaluated Heartvalves, Rheumatic or Artificial (EHRA) categorization, as follows: (i) EHRA Type 1 VHD, which refers to AF patients with 'VHD needing therapy with a Vitamin K antagonist (VKA)', thus including severe native mitral stenosis and prosthetic mechanical heart valves and (ii) EHRA Type 2 VHD, which refers to AF patients with 'VHD needing therapy with a VKA or a non-VKA oral anticoagulant (NOAC)', thus including all other forms of VHD. We identified 25 818 AF patients with VHD with EHRA Type 2 in 90% (n = 23 253). Thromboembolism and bleeding events increased with increasing CHA2DS2-VASc and HAS-BLED scores, whether with 1 or 2.5 years follow-up. EHRA Type 1 outcomes: The predictive value of CHA2DS2-VASc score for thromboembolism was modest, c-indexes 0.62 (0.55-0.70) at 1 year. The predictive value of the HAS-BLED score for bleeding was also modest being 0.59 (0.53-0.65) at 1 year. EHRA Type 2 outcomes: The predictive value of CHA2DS2-VASc score for thromboembolism was modest, c-indexes 0.63 (0.60-0.65) at 1 year. The predictive value of the HAS-BLED score for bleeding was also modest being 0.59 (0.53-0.65) at 1 year. CONCLUSION: This is the first validation of CHA2DS2-VASc and HAS-BLED scores in AF patients with VHD (so-called 'valvular AF') using the new EHRA classification. Both scores are modestly predictive of thromboembolism and bleeding events in VHD, respectively. Event rates increased with increasing risk factors as evident by increasing CHA2DS2-VASc and HAS-BLED score points, consistent with performance of these clinical scores in 'non-valvular AF' patients.

Sex differences in risk of incident venous thromboembolism in heart failure patients.

BACKGROUND: In patients with incident heart failure, the risk of venous thromboembolism (VTE), defined as pulmonary embolism (PE) and/or deep venous thrombosis (DVT), is sparsely described, especially potential sex differences. We conducted an observational study to evaluate risk of VTE among male and female heart failure patients. METHODS: Population-based cohort study of patients diagnosed with incident heart failure during 2000-2015, identified by record linkage between nationwide registries in Denmark. Using a pseudo-value approach, we calculated relative risks [RR] of VTE at 1 and 3 years of follow-up. Crude VTE risk for males and females are reported and contrasted after adjustment for established clinical risk factors for VTE. RESULTS: A total of 32,330 heart failure patients were included, of which 15,238 (47%) were females. For the combined endpoint of VTE, female sex was associated with a higher risk (1-year adjusted RR: 1.30, 95% confidence interval [CI]: 0.97-1.73; 3-year adjusted RR: 1.34, 95% CI: 1.07-1.67) compared to male patients. For the individual endpoints of PE and DVT after 1-year of follow-up, female sex was only associated with a higher risk of PE and not DVT, compared to male patients. However, female sex was associated with a higher risk of both PE and DVT after 3 years of follow-up. CONCLUSIONS: Among incident heart failure patients, female sex is associated with a higher risk of VTE, mainly driven by an excess risk of PE. This finding may help improve clinical decision-making regarding VTE prophylaxis in patients with heart failure.

Risk of stroke and bleeding in patients with heart failure and chronic kidney disease: a nationwide cohort study.

AIMS: The aim of this study was to assess the prognostic value of chronic kidney disease (CKD) in relation to ischaemic stroke, intracranial haemorrhage, major bleeding, and all-cause death in heart failure patients without atrial fibrillation. METHODS AND RESULTS: In this observational cohort study, heart failure patients without atrial fibrillation were identified using Danish nationwide registries. Risk of stroke, major haemorrhage, and death were calculated after 1 and 5 years to compare patients with and without CKD, ±dialysis [dialysis: CKD with renal replacement therapy (CKD-RRT); no dialysis: CKD-no RRT]. A total of 43 199 heart failure patients were included, among which 0.8% had CKD-RRT and 5.9% had CKD-no RRT. When compared with heart failure patients without CKD, both CKD-RRT and CKD-no RRT were associated with a higher 5 year rate of major bleeding (CKD-RRT: adjusted hazard ratio (aHR): 2.91, 95% confidence interval (CI): 2.29 to 3.70; CKD-no RRT: aHR: 1.28, 95% CI: 1.13 to 1.45) and all-cause death (CKD-RRT: aHR: 2.40, 95% CI: 2.07 to 2.77; CKD-no RRT: aHR: 1.63, 95% CI: 1.55 to 1.73). For the endpoints of ischaemic stroke and intracranial bleeding, only CKD-no RRT was associated with significantly higher 5 year rates (ischaemic stroke: aHR: 1.31, 95% CI: 1.13 to 1.52; intracranial haemorrhage: aHR: 1.66, 95% CI: 1.04 to 2.65). CONCLUSIONS: Compared with patients without CKD, among incident heart failure patients without atrial fibrillation, CKD both with and without dialysis was associated with a higher rate of major bleeding and all-cause death. Only CKD-no RRT was associated with a higher rate of ischaemic stroke and intracranial bleeding.

Vascular Disease and Risk Stratification for Ischemic Stroke and All-Cause Death in Heart Failure Patients without Diagnosed Atrial Fibrillation: A Nationwide Cohort Study.

BACKGROUND: Stroke and mortality risk among heart failure patients previously diagnosed with different manifestations of vascular disease is poorly described. We conducted an observational study to evaluate the stroke and mortality risk among heart failure patients without diagnosed atrial fibrillation and with peripheral artery disease (PAD) or prior myocardial infarction (MI). METHODS: Population-based cohort study of patients diagnosed with incident heart failure during 2000-2012 and without atrial fibrillation, identified by record linkage between nationwide registries in Denmark. Hazard rate ratios of ischemic stroke and all-cause death after 1 year of follow-up were used to compare patients with either: a PAD diagnosis; a prior MI diagnosis; or no vascular disease. RESULTS: 39,357 heart failure patients were included. When compared to heart failure patients with no vascular disease, PAD was associated with a higher 1-year rate of ischemic stroke (adjusted hazard rate ratio [HR]: 1.34, 95% confidence interval [CI]: 1.08-1.65) and all-cause death (adjusted HR: 1.47, 95% CI: 1.35-1.59), whereas prior MI was not (adjusted HR: 1.00, 95% CI: 0.86-1.15 and 0.94, 95% CI: 0.89-1.00, for ischemic stroke and all-cause death, respectively). When comparing patients with PAD to patients with prior MI, PAD was associated with a higher rate of both outcomes. CONCLUSIONS: Among incident heart failure patients without diagnosed atrial fibrillation, a previous diagnosis of PAD was associated with a significantly higher rate of the ischemic stroke and all-cause death compared to patients with no vascular disease or prior MI. Prevention strategies may be particularly relevant among HF patients with PAD.

Diabetes mellitus and risk of ischemic stroke in patients with heart failure and no atrial fibrillation.

OBJECTIVE: The risk of ischemic stroke, systemic thromboembolism, and all-cause death among heart failure patients previously diagnosed with diabetes mellitus is poorly described. We evaluated the risk of these endpoints among heart failure patients without diagnosed atrial fibrillation according to the presence of diabetes mellitus. METHODS: Population-based nationwide cohort study of non-anticoagulated patients diagnosed with incident heart failure during 2000-2012, identified by record linkage between nationwide registries in Denmark. We calculated relative risks after 1year to evaluate the association between diabetes and risk of events in 39,357 heart failure patients, among whom 18.1% had diabetes. Analysis took into account competing risks of death. RESULTS: Absolute risks of all endpoints were higher in patients with diabetes compared to patients without diabetes after 1-year follow-up (ischemic stroke: 4.1% vs. 2.8%; systemic thromboembolism: 11.9% vs. 8.6%; all-cause death: 22.1% vs. 21.4%). Diabetes was significantly associated with an increased risk of ischemic stroke (adjusted relative risk [RR]: 1.27, 95% confidence interval [CI]: 1.07-1.51); systemic thromboembolism (RR: 1.20, 95% CI: 1.11-1.30); and all-cause death (RR: 1.17, 95% CI: 1.11-1.23). Additionally, time since diabetes diagnosis was associated with higher adjusted cumulative incidences of ischemic stroke, systemic thromboembolism, and all-cause death (p for trend, p<0.001). CONCLUSIONS: Among heart failure patients without atrial fibrillation, diabetes was associated with a significantly increased risk of ischemic stroke, systemic thromboembolism, and all-cause death compared to those without diabetes, even after adjustment for concomitant cardiovascular risk factors. Increased focus on secondary prevention in heart failure patients with diabetes may be warranted.

Assessment of the CHA2DS2-VASc Score in Predicting Ischemic Stroke, Thromboembolism, and Death in Patients With Heart Failure With and Without Atrial Fibrillation.

IMPORTANCE: The CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]) is used clinically for stroke risk stratification in atrial fibrillation (AF). Its usefulness in a population of patients with heart failure (HF) is unclear. OBJECTIVE: To investigate whether CHA2DS2-VASc predicts ischemic stroke, thromboembolism, and death in a cohort of patients with HF with and without AF. DESIGN, SETTING, AND POPULATION: Nationwide prospective cohort study using Danish registries, including 42 987 patients (21.9% with concomitant AF) not receiving anticoagulation who were diagnosed as having incident HF during 2000-2012. End of follow-up was December 31, 2012. EXPOSURES: Levels of the CHA2DS2-VASc score (based on 10 possible points, with higher scores indicating higher risk), stratified by concomitant AF at baseline. Analyses took into account the competing risk of death. MAIN OUTCOMES AND MEASURES: Ischemic stroke, thromboembolism, and death within 1 year after HF diagnosis. RESULTS: In patients without AF, the risks of ischemic stroke, thromboembolism, and death were 3.1% (n = 977), 9.9% (n = 3187), and 21.8% (n = 6956), respectively; risks were greater with increasing CHA2DS2-VASc scores as follows, for scores of 1 through 6, respectively: (1) ischemic stroke with concomitant AF: 4.5%, 3.7%, 3.2%, 4.3%, 5.6%, and 8.4%; without concomitant AF: 1.5%, 1.5%, 2.0%, 3.0%, 3.7%, and 7% and (2) all-cause death with concomitant AF: 19.8%, 19.5%, 26.1%, 35.1%, 37.7%, and 45.5%; without concomitant AF: 7.6%, 8.3%, 17.8%, 25.6%, 27.9%, and 35.0%. At high CHA2DS2-VASc scores (≥4), the absolute risk of thromboembolism was high regardless of presence of AF (for a score of 4, 9.7% vs 8.2% for patients without and with concomitant AF, respectively; overall P<.001 for interaction). C statistics and negative predictive values indicate that the CHA2DS2-VASc score performed modestly in this HF population with and without AF (for ischemic stroke, 1-year C statistics, 0.67 [95% CI, 0.65-0.68] and 0.64 [95% CI, 0.61-0.67], respectively; 1-year negative predictive values, 92% [95% CI, 91%-93%] and 91% [95% CI, 88%-95%], respectively). CONCLUSIONS AND RELEVANCE: Among patients with incident HF with or without AF, the CHA2DS2-VASc score was associated with risk of ischemic stroke, thromboembolism, and death. The absolute risk of thromboembolic complications was higher among patients without AF compared with patients with concomitant AF at high CHA2DS2-VASc scores. However, predictive accuracy was modest, and the clinical utility of the CHA2DS2-VASc score in patients with HF remains to be determined.

Female sex is associated with a lower risk of stroke in patients with heart failure.

BACKGROUND: Stroke in patients with heart failure is associated with poor outcomes. Risk stratification schemes may improve clinical decision making in this patient population. This study investigated whether female sex is a risk factor for stroke in patients with heart failure in sinus rhythm. METHODS: This is a population-based cohort study of patients diagnosed with heart failure during 2000 to 2012, identified by record linkage between nationwide Danish registries. Our primary outcome was stroke, and secondary outcome was thromboembolic event. We used relative risks (RRs) after 1 and 5 years to compare males with females within each of the following age groups: 50 to 59 years, 60 to 69 years, 70 to 79 years, 80 to 89 years, and 90+ years. Analyses took into account the competing risks of death. RESULTS: During the study period, 84,142 patients were diagnosed with heart failure, of which 39,946 (47.5%) were females. At 5-year follow-up, female sex was associated with a lower risk of stroke compared with males (adjusted overall hazard ratio 0.91, 95% CI 0.85-0.96). The observed lower risks of stroke in females were not present in the older age groups, where the competing risk of death was substantial among males in particular. When considering a more broadly defined thromboembolic end point, a decreased risk among females persisted across nearly all age groups after 5-year follow-up (adjusted overall hazard ratio 0.93, 95% CI 0.91-0.96). CONCLUSIONS: We found an association between female sex and decreased stroke risk in patients with heart failure, which persisted after adjustment for concomitant cardiovascular risk factors. The association was attenuated with increasing age, possibly because of competing risks of death.

Microdialysis of inflammatory mediators in the skin: a review.

Skin microdialysis is an established method for in vivo sample collection from the extracellular fluid space. This method has been extensively used in studies of inflammatory reactions in the skin of animals and humans. Skin microdialysis consists of the implantation of semi-permeable probes into the upper dermis, perfusion with a physiological buffer, and the recovery of the substances that diffused from the skin into the perfusion fluid. Microdialysis allows the simultaneous assessment of the temporal variations of inflammatory mediator release in the skin as well as the monitoring of vascular and sensory functions. By the aid of this technique, potential associations can be found between functional changes and a variety of substances and mediators released at the site of interest. This allows further insights into the possible mechanisms underlying physiological and pathophysiological events in the skin, including cutaneous inflammation. This review provides a comprehensive but not exhaustive review of the use of microdialysis in studies of experimental and clinical inflammatory reactions in the skin in animals and humans.

Age dependence of risk factors for stroke and death in young patients with atrial fibrillation: a nationwide study.

BACKGROUND AND PURPOSE: The risk of stroke and death in patients with atrial fibrillation is strongly associated with age and concomitant comorbidities. The aim of this study was to examine the age dependence of risk factors for stroke and mortality in young patients with atrial fibrillation. METHODS: This study is a population-based cohort study of 30- to 65-year-old patients with atrial fibrillation and diagnosed during 2000 to 2011, identified by record linkage between nationwide Danish registries. Cox regression models were used to estimate the risk of stroke and mortality according to risk factors within age groups: 30 to 50, 50 to 65, and 65 to 75 years. RESULTS: We identified 73,799 nonvalvular atrial fibrillation patients, of which 37,782 (51.2%) were <65 years old (mean age 62.8). A higher modified cardiac failure or dysfunction, hypertension, age 75 (doubled), diabetes, stroke (doubled), vascular disease, age 65-74 and sex category (female) score (CHA2DS2-VASc score) was associated with decreased survival probability in all age groups. The overall incidence of stroke per year for 1 year (5 years) follow-up was 1.2% (0.6%), 3.5% (1.6%), and 5.6% (2.8%), respectively, for the age groups of 30 to 50, 50 to 65, and 65 to 75. Overall, risk factors such as previous stroke, heart failure, vascular disease, diabetes mellitus, and hypertension remained independent predictors of stroke and death in patients<65 years old with nonvalvular atrial fibrillation. CONCLUSIONS: The CHA2DS2-VASc score is an applicable tool for all age groups and in nonvalvular atrial fibrillation patients<65 years old, the same risk factors apply.