Gregory Y H Lip

Aalborg University, Ålborg, North Denmark, Denmark

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Publications (942)5673.93 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Atrial fibrillation (AF) is associated with cognitive decline and may contribute to an increased risk of dementia. The goal of the present study was to investigate whether statin use prevented non-vascular dementia in subjects with AF. Data from the National Health Insurance Research Database of Taiwan were used in this study. The study group comprised 51,253 AF subjects aged ≥60years who had received statin treatment. For each study patient, four age- and sex-matched AF subjects without statin exposure were selected as the control group (n=205,012). The risk of non-vascular dementia was compared between the statin and control groups. During the follow-up period, 17,201 patients experienced non-vascular dementia. The annual incidence of non-vascular dementia was lower in the statin group than in the control group (1.89% vs. 2.20%; p<0.001). Statin use exhibited a protective effect on the occurrence of non-vascular dementia, with an adjusted hazard ratio (HR) of 0.832 (95% confidence interval=0.801-0.864). Among statin types, the use of rosuvastatin was associated with the largest risk reduction (adjusted HR=0.661). Statin exposure duration was related inversely to the risk of non-vascular dementia. In this large-scale nationwide cohort study, statin use was associated with a lower risk of non-vascular dementia in AF. Use of more potent statin and longer exposure time may be associated with greater benefits. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    International journal of cardiology 10/2015; 196. DOI:10.1016/j.ijcard.2015.05.159 · 6.18 Impact Factor
  • Qinmei Xiong · Sisi Chen · Keitaro Senoo · Marco Proietti · Kui Hong · Gregory Y.H. Lip
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    ABSTRACT: Both the CHADS2 and CHA2DS2-VASc scores are well-validated in Western populations for predicting risk of stroke among patients with atrial fibrillation (AF). There is some uncertainty as to which risk score is best to guide optimal anticoagulant therapy among Asian populations with AF. A systemic literature search of Cochrane library, Scopus, and PubMed databases was conducted using search terms: atrial fibrillation, CHADS2 and CHA2DS2-VASc. Stroke/thromboembolism (TE) outcome events at low, moderate, and high risk groups were compared in relation to both scores. Statistical analyses were performed using Revman 5.3 software. 493 records were retrieved, of which 6 cohort studies focusing on patients from Asian regions were finally appraised and included. Absolute event rates were usually lower when patients were categorized as CHA2DS2-VASc of 0-1, rather than CHADS2 of 0-1, respectively. Meta-analysis revealed that when compared with the CHA2DS2-VASc score, there was a 1.71-fold elevated risk of stroke when patients were stratified as 'low risk' using a CHADS2 score=0, or a 1.40-fold increase with a CHADS2 score=1. A 1.19-fold elevated event rate was observed among CHADS2 score ≥2 compared to CHA2DS2-VASc, but the total stroke/TE events were numerically higher in patients categorized as CHA2DS2-VASc ≥2. The CHA2DS2-VASc score is superior to the CHADS2 score in identifying 'low risk' East Asian AF patients. Rather than a categorical approach, Asian guidelines should adopt a 2 step approach, by initially identifying the truly low risk patients, following which effective stroke prevention can be offered to those with ≥1 additional stroke risk factors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    International journal of cardiology 09/2015; 195. DOI:10.1016/j.ijcard.2015.05.115 · 6.18 Impact Factor
  • Eduard Shantsila · Gregory Yh Lip
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    ABSTRACT: Despite major advances in stroke prevention in atrial fibrillation (AF), such complications are still not uncommon.(1) The study by Saliba et al. published in this issue of Journal of Thrombosis and Hemostasis shows a 3.17% overall annual rate of stroke despite oral anticoagulation use based on modern guideline recommendations and it suggests independent ling between high neutrophil-lymphocyte ratio (NLR) and the risk of stroke in AF.(2) Whilst potent oral anticoagulants could ameliorate the prothrombotic shift associated with AF, anticoagulation cannot modify all components of Virchow triad of thrombogenesis (thrombus formation). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 08/2015; DOI:10.1111/jth.13121 · 5.55 Impact Factor
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    ABSTRACT: Atrial fibrillation (AF) is associated with structural, electrical, and contractile remodeling of the atria. Development and progression of atrial fibrosis is the hallmark of structural remodeling in AF and is considered the substrate for AF perpetuation. In contrast, experimental and clinical data on the effect of ventricular fibrotic processes in the pathogenesis of AF and its complications are controversial. Ventricular fibrosis seems to contribute to abnormalities in cardiac relaxation and contractility and to the development of heart failure, a common finding in AF. Given that AF and heart failure frequently coexist and that both conditions affect patient prognosis, a better understanding of the mutual effect of fibrosis in AF and heart failure is of particular interest. In this review paper, we provide an overview of the general mechanisms of cardiac fibrosis in AF, differences between fibrotic processes in atria and ventricles, and the clinical and prognostic significance of cardiac fibrosis in AF. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Cardiology 08/2015; 66(8):943-59. DOI:10.1016/j.jacc.2015.06.1313 · 15.34 Impact Factor
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    European Journal of Heart Failure 08/2015; DOI:10.1002/ejhf.338 · 6.58 Impact Factor
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    ABSTRACT: Limited data exists on the impact of sex on clinical characteristics and outcomes among nonvalvular AF patients from China. We investigated the impact of gender on risk factors and inpatient mortality in a hospitalized nonvalvular AF cohort in Nanchang, China. We studied consecutive patients hospitalized with nonvalvular AF between May 2011 and December 2013. Predictors of inpatient mortality were evaluated using multivariate regression analyses. We studied 2442 patients (43.7% female; mean age 71.8), with a median hospital stay of 10days (IQR: 7-14). Inpatient mortality was 2.2%. Mean age, CHADS2 and CHA2DS2-VASc scores were higher in females vs. males (all p<0.0001). Oral anticoagulation use during hospitalization was 33.3% without sex differences, and length of stay and inpatient outcomes were comparable between sexes. On multivariate analyses, the significant risk factors of inpatient death in females were previous ischemic stroke/transient ischemic attack (TIA)/thromboembolism (TE) (Odds Ratio (OR): 2.27; 95% Confidence Intervals (CI): 1.43-3.61), peripheral artery disease (OR: 5.75, 95% CI: 1.49-22.16) and chronic renal disease (OR: 5.68, 95% CI: 1.46-22.13). Among males, only age (OR: 1.06, 95% CI: 1.02-1.11) and previous ischemic stroke/TIA/TE (OR: 1.81, 95% CI: 1.25-2.63) were independent predictors of inpatient mortality. Sex related differences in clinical characteristics and stroke risk profile were evident in Chinese nonvalvular AF patients, but no sex disparity was evident in the low antithrombotic therapy use or inpatient mortality. Previous ischemic stroke/TIA/TE was an important predictor of inpatient mortality in both female and male patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    International journal of cardiology 08/2015; 201:195-199. DOI:10.1016/j.ijcard.2015.08.076 · 6.18 Impact Factor
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    ABSTRACT: A substantial part of ischemic strokes is attributed to atrial fibrillation (AF). We hypothesized that patients with ischemic stroke without prior diagnosed AF were at higher risk of having a subsequent diagnosis of AF, and this was associated with multiple risk factors. This French longitudinal cohort study was based on the national database covering hospital care from 2008 to 2012 for the entire population. Of 65 807 patients with ischemic stroke in 2009, 48 992 did not have AF at baseline. A total of 4828 of these patients were diagnosed as having AF during a follow-up of 15±15 months (incidence rate 7.9 per 100 person-years). By comparison, the yearly rate of new-onset AF for the 826 416 patients with a cardiac hospitalization was 5.9%. CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack) and CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack [doubled], vascular disease, age 65-75 years, and sex category [female]) scores were both associated with the risk of new-onset AF during follow-up (CHADS2: hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.66-1.75; CHA2DS2-VASc: HR 1.45, 95% CI 1.42-1.48). The c statistics were 0.700 (95% CI 0.696-0.706) for CHADS2 and 0.706 (95% CI 0.702-0.710) with CHA2DS2-VASc (P=0.003 for comparison of the 2 scores). Independent predictors of subsequent diagnosis of AF were age 65 to 74 years (HR 2.29, 95% CI 2.06-2.54), age ≥75 years (HR 3.31, 95% CI 3.02-3.64), hypertension (HR 1.22, 95% CI 1.13-1.32), heart failure (HR 2.56, 95% CI 2.41-2.72), and vascular disease (HR 1.10, 95% CI 1.04-1.17). Ischemic stroke was associated with a substantially increased risk of incident AF, particularly among individuals with higher CHADS2 or CHA2DS2-VASc scores. These risk scores seem to be simple tools for identifying patients at higher risk of incident AF after ischemic stroke. © 2015 American Heart Association, Inc.
    Stroke 08/2015; DOI:10.1161/STROKEAHA.115.010270 · 6.02 Impact Factor
  • Qinmei Xiong · Yee C Lau · Gregory Yh Lip
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    ABSTRACT: Oral anticoagulation therapy is the mainstay of stroke prevention in nonvalvular atrial fibrillation patients. Vitamin K antagonists (such as warfarin) have been effective conventional oral anticoagulants for several decades. However, due to their limitations in clinical use, several nonvitamin K antagonist oral anticoagulants (NOACs, including dabigatran, rivaroxaban, apixaban and edoxaban) have been developed. Nonetheless, no head to head trials have been performed to directly compare these NOACs in patient cohorts. In this review article, two direct factor Xa inhibitors, apixaban and edoxaban, are briefly described with focus on their pharmacokinetic and pharmacodynamic profiles, plus drug interactions. Moreover, both efficacy and safety will be discussed based on the available data from the large Phase III clinical trials and indirect comparison studies.
    08/2015; 4(4):367-76. DOI:10.2217/cer.15.15
  • Journal of the American College of Cardiology 07/2015; 66(4):488-90. DOI:10.1016/j.jacc.2015.05.044 · 15.34 Impact Factor
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    ABSTRACT: The CHA2DS2-VASc and HAS-BLED are well-validated stroke risk prediction scores for atrial fibrillation (AF), but their role in risk stratification of major adverse cardiac events (MACEs) and major bleeding for non-AF patients undergoing percutaneous coronary intervention (PCI) is unknown. Consecutive patients without AF undergoing PCI at two Italian centers were analyzed with different measures of discrimination, net reclassification improvement and net prognostic benefit. MACE included all-cause death, myocardial infarction, destabilizing symptoms leading to hospitalization, and nonfatal stroke. Major bleeding was defined according to the TIMI classification. Of 1437 subjects undergoing PCI, 1330 (mean age 63.6±10.9years, 75.7% male) fulfilled the inclusion criteria. During 2.7±1.2years of follow-up representing 3539 patient-years at risk, 187 patients had a MACE (5.3%/year) and 48 had a major bleeding (1.4%/year). The cumulative incidences of MACE were significantly stratified by both high CHA2DS2-VASc (P=0.020) or HAS-BLED (P<0.001) scores, whereas major bleeding episodes were not. The CHA2DS2-VASc and the HAS-BLED scores had similar C-statistics for MACE (0.56 vs 0.60; P=0.52) and major bleeding (0.63 vs 0.60; P=0.63). Compared with CHA2DS2-VASc, the HAS-BLED score more accurately reclassified events and no events both for MACE (NRI 8.21%) and major bleeding (NRI 6.85%). In patients without AF undergoing PCI and discharged on dual antiplatelet therapy, the HAS-BLED score performed better than the CHA2DS2-VASc for the prediction of MACE. Although both scores predict MACE, their discrimination was modest. Conversely, both scores did not significantly predict major bleeding in non-AF patients undergoing PCI. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    International journal of cardiology 07/2015; 199:319-325. DOI:10.1016/j.ijcard.2015.07.064 · 6.18 Impact Factor
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    ABSTRACT: Atrial fibrillation (AF) and heart failure frequently coexist and are associated with increased morbidity and mortality. We investigated the prognosis of anticoagulated patients with permanent AF and nonpermanent AF according to pre-existing heart failure in the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial. The primary outcome was a composite of cardiovascular death and stroke or systemic embolism, analyzed using a Cox proportional hazards model, adjusted for baseline age, sex, diabetes mellitus, hypertension, creatinine, and previous cardiovascular diseases. The median follow-up was 11.6 months (interquartile range, 6.2-15.2). Nonpermanent AF was present in 2072 patients (46% of cohort), of which 339 (16%) had pre-existing heart failure. A total of 2484 patients had permanent AF (54% of cohort), with a higher burden of heart failure including 730 patients (29%; P<0.001). Overall, death because of cardiovascular causes occurred in 57 patients and 45 had stroke or systemic embolism (1.4/100 person-years for each). Overall, the adjusted incidence of the composite outcome was higher in patients with permanent AF than in patients with nonpermanent AF. In multivariate analysis, permanency of AF, creatinine, prior cerebrovascular events, and previous coronary disease were independently associated with the primary outcome. The hazard ratio for permanent versus nonpermanent AF was 1.68 (95% confidence interval, 1.08-2.55; P=0.02). The presence of heart failure increased the risk of adverse outcomes in a similar way in both permanent and nonpermanent AF (interaction P value=0.76). The risk of cardiovascular death, stroke, or systemic embolism is higher in anticoagulated patients with permanent AF than in those with nonpermanent AF, regardless of pre-existing heart failure. © 2015 American Heart Association, Inc.
    Stroke 07/2015; DOI:10.1161/STROKEAHA.115.009487 · 6.02 Impact Factor
  • Gregory Yh Lip
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    ABSTRACT: Although nonsteroidal anti-inflammatory drugs (NSAIDs) have generally conferred increased gastrointestinal bleeding risk, the data for bleeding risks with these drugs in anticoagulated atrial fibrillation (AF) patients per se were much more limited. Recent evidence shows that concomitant use of NSAIDs in anticoagulated AF patients carries a real risk of serious bleeding, as well as thromboembolism. Thus, physicians should clearly exercise extra caution with NSAIDs in patients with AF, especially if they are anticoagulated. Also, AF patients with NSAIDs should also undergo regular clinical review, and clinicians should regularly reassess the need for NSAID use. Finally, as a part of regular clinical assessment, bleeding risk should be routinely assessed, and the HAS-BLED score is now recommended in many guidelines for this purpose.
    Expert Review of Cardiovascular Therapy 07/2015; DOI:10.1586/14779072.2015.1071665
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    ABSTRACT: Statin therapy may lower plasma coenzyme Q10 (CoQ10) concentrations, but the evidence as to the significance of this effect is unclear. We assessed the impact of statin therapy on plasma CoQ10 concentrations through the meta-analysis of available RCTs. The literature search included selected databases up to April 30, 2015. The meta-analysis was performed using either a fixed-effects or random-effect model according to I2 statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). The data from 8 placebo-controlled treatment arms suggested a significant reduction in plasma CoQ10 concentrations following treatment with statins (WMD: −0.44 μmol/L, 95%CI: −0.52, −0.37, p < 0.001). The pooled effect size was robust and remained significant in the leave-one-out sensitivity analysis. Subgroup analysis suggested that the impact of statins on plasma CoQ10 concentrations is significant for all 4 types of statins studied i.e. atorvastatin (WMD: −0.41 μmol/L, 95%CI: −0.53, −0.29, p < 0.001), simvastatin (WMD: −0.47 μmol/L, 95% CI: −0.61, −0.33, p < 0.001), rosuvastatin (WMD: −0.49 μmol/L, 95%CI: −0.67, −0.31, p < 0.001) and pravastatin (WMD: −0.43 μmol/L, 95%CI: −0.69, −0.16, p = 0.001). Likewise, there was no differential effect of lipophilic (WMD: −0.43 μmol/L, 95%CI: −0.53, −0.34, p < 0.001) and hydrophilic statins (WMD: −0.47 μmol/L, 95%CI: −0.62, −0.32, p < 0.001). With respect to treatment duration, a significant effect was observed in both subsets of trials lasting <12 weeks (WMD: −0.51 μmol/L, 95%CI: −0.64, −0.39, p < 0.001) and ≥12 weeks (WMD: −0.40 μmol/L, 95%CI: −0.50, −0.30, p < 0.001). The meta-analysis showed a significant reduction in plasma CoQ10 concentrations following treatment with statins. Further well-designed trials are required to confirm our findings and elucidate their clinical relevance.
    Pharmacological Research 07/2015; DOI:10.1016/j.phrs.2015.07.008 · 3.98 Impact Factor
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    ABSTRACT: Atrial fibrillation (AF) is increasingly prevalent with age, and increasing age is an independent risk factor for ischemic stroke. Oral anticoagulant (OAC) therapy use in the extreme elderly (age ≥85 years) is challenging. The Fushimi AF Registry is a community-based prospective study of Japanese AF patients (79 participating medical institutions in Fushimi-ku, Kyoto). The enrollment of patients was started in March 2011, and follow-up data were available for 3,304 patients as of July 2014. We compared clinical characteristics and outcomes between the extreme elderly group (n=479, 14.5%) and others. The extreme elderly had a higher prevalence of major co-morbidities and risk scores for stroke, but received less OAC. After a mean follow-up of 2.0 years, endpoints in the extreme elderly group were as follows: all-cause death 17.6, stroke or systemic embolism (SE) 5.1, and major bleeding 2.0 per 100 person-years, respectively. The extreme elderly group was associated with a higher incidence of combined stroke/SE and all-cause death (hazard ratio (HR) 3.20, 95% confidence interval (CI) 2.66-3.84, p<0.01), higher incidences of stroke/SE (HR 2.57, 95% CI 1.77-3.65, p<0.01) and mortality (HR 3.48, 95% CI 2.84-4.25, p<0.01), compared with others (aged ≤84). The incidence of major bleeding was not significantly different (HR 1.40, 95% CI 0.78-2.36, p=0.25). In our community-based prospective cohort, Japanese extreme elderly AF patients had a higher incidence of stroke but similar major bleeding risks compared with the younger AF population. UMIN Clinical Trials Registry; No.: UMIN000005834; URL:
    Chest 07/2015; DOI:10.1378/chest.15-1095 · 7.13 Impact Factor
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    ABSTRACT: BackgroundAZD0837 is a novel oral anticoagulant investigated in clinical studies for stroke prevention in patients with atrial fibrillation (AF). It is bioconverted to its active form, AR-H067637, a potent, specific and reversible thrombin inhibitor.ObjectivesA population pharmacokinetic (PK) analysis was performed and the effect of AZD0837 therapy on fibrin D-dimer levels was correlated to the PK exposure of AR-H067637, as well as the effect on thrombin generation measured ex vivo, to guide selection of the effective dose regimen for a confirmatory efficacy study in AF patients.Patients and Methods Blood samples were obtained from 601 AF patients randomized to receive 1 of 4 doses of AZD0837 (blinded treatment) or dose-adjusted vitamin K antagonists (VKA, open treatment) for 3-9 months. A pharmacodynamic model was developed to describe time course of the AR-H067637 exposure dependent effects and the effect of VKA on fibrin D-dimer. The concentration-effect relationship for thrombin generation measured ex vivo in venous plasma was also investigated.ResultsAZD0837 was rapidly bioconverted to AR-H067637, showing stable exposure with an estimated interindividual variability of 33% with no or only minor influence of patient demographics or comedications. For all dose groups of AZD0837, D-dimer levels decreased with more rapid onset of effect compared to VKA. The decrease in D-dimer levels correlated to the steady state plasma concentrations (Css) of AR-H067637, with a maximum decrease of baseline D-dimer levels estimated to approximately 60% for both AZD0837 and VKA therapy. Anticoagulant effect measured ex vivo as decreased thrombin generation correlated closely with the plasma concentration of AR-H067637.Conclusions Following oral therapy with AZD0837, inhibitory effects on thrombin generation and fibrin D-dimer levels were correlated to the plasma concentration of its active form and provides comparable effects as well-controlled VKA therapy at an exposure at least corresponding to the 300 mg qd dose AZD0837.
    British Journal of Clinical Pharmacology 07/2015; DOI:10.1111/bcp.12719 · 3.69 Impact Factor
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    ABSTRACT: Following the publication of the Task Force document on heart rate variability (HRV) in 1996, a number of articles have been published to describe new HRV methodologies and their application in different physiological and clinical studies. This document presents a critical review of the new methods. A particular attention has been paid to methodologies that have not been reported in the 1996 standardization document but have been more recently tested in sufficiently sized populations. The following methods were considered: Long-range correlation and fractal analysis; Short-term complexity; Entropy and regularity; and Nonlinear dynamical systems and chaotic behaviour. For each of these methods, technical aspects, clinical achievements, and suggestions for clinical application were reviewed. While the novel approaches have contributed in the technical understanding of the signal character of HRV, their success in developing new clinical tools, such as those for the identification of high-risk patients, has been rather limited. Available results obtained in selected populations of patients by specialized laboratories are nevertheless of interest but new prospective studies are needed. The investigation of new parameters, descriptive of the complex regulation mechanisms of heart rate, has to be encouraged because not all information in the HRV signal is captured by traditional methods. The new technologies thus could provide after proper validation, additional physiological, and clinical meaning. Multidisciplinary dialogue and specialized courses in the combination of clinical cardiology and complex signal processing methods seem warranted for further advances in studies of cardiac oscillations and in the understanding normal and abnormal cardiac control processes. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email:
    Europace 07/2015; DOI:10.1093/europace/euv015 · 3.05 Impact Factor
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    ABSTRACT: To investigate lipid metabolism and the relationship with monocyte expression of the fatty acid translocase CD36 in South Asians. An observational study of South Asians whom as an ethnic group have - a higher risk of developing diabetes. The susceptibility to diabetes is coupled with an earlier and more rapid progression of micro-, and macro-vascular complications. Twenty-nine healthy South Asian participants [mean age 34.6 (8.9) years, 76.2% male, mean body-mass index 25.0 (5.2) kg/m(2)] were recruited from an urban residential area of central Birmingham (United Kingdom). The main outcomes measured were post prandial (30 min) and post absorptive (120 min) changes from fasting (0 min) in circulating lipoproteins, lipds and hormones, and monocyte expression of CD36 post injection of a 75 g oral glucose challenge. The inducements of variations of monocyte CD36 expression were analysed. Our results showed evident changes in monocyte CD36 expression following the glucose challenge (P < 0.001). Non-esterified fatty acids (NEFA) levels decreased progressively during the challenge (P < 0.001), in contrast to increased cholesterol (but not triglyceride) concentrations within very low density lipoprotein (VLDL) and low density lipoprotein subfractions (P < 0.01). Levels of, glucose, serum triglycerides and high density lipoprotein cholesterol remained largely unchanged. Variations of monocyte CD36 were negatively (r = -0.47, P = 0.04) associated to fat from the diet and positively to carbohydrate from the diet (r = 0.65, P < 0.001). These data suggest that the initiation of VLDL genesis follows the consumption of glucose within this population, inferring that the sequestration of NEFA from these particles happens due to the increased availability of CD36 receptors. While these are preliminary results, it would appear that lifestyle exposures have a role in moderating the expression of CD36.
    07/2015; 6(7):983-989. DOI:10.4239/wjd.v6.i7.983
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    ABSTRACT: Healthy ageing and alterations in respiratory-sympathetic coupling have been independently linked with heightened sympathetic neural vasoconstrictor activity. We investigated how age influences the respiratory related modulation of muscle sympathetic nerve activity (MSNA), and the association between the rhythmic fluctuations in MSNA and blood pressure that occur with respiration (Traube-Hering Waves; THW). Ten young (22 ± 2 years, mean±SD) and ten older (58 ± 6 years) healthy men were studied while resting supine and breathing spontaneously. MSNA, blood pressure and respiration were simultaneously recorded. Resting values were ascertained and respiratory cycle triggered averaging of MSNA and blood pressure measurements performed. MSNA burst incidence was higher in older individuals (22.7 ± 9.2 vs. 42.2 ± 13.7 bursts·100 heartbeats(-1) P<0.05), and was similarly reduced in the inspiratory to post-inspiratory period in young and older subjects (by ∼25% compared to mid-to-late expiration). A similar attenuation of MSNA burst frequency (bursts per minute), amplitude and total activity (burst frequency × mean burst amplitude) was also observed in the inspiratory to post-inspiratory period in both groups. A significant positive correlation between respiratory related MSNA and THW magnitude was observed in all young (100%) and most older (80%) subjects. These data suggest that the strength of the cyclical inhibition of MSNA during respiration is similar between young and older individuals and thus alterations in respiratory-sympathetic coupling appear not to contribute to the age-related elevation in MSNA. Furthermore, central respiratory-sympathetic coupling plays a role in the generation of THW in both healthy young and older humans. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Experimental physiology 07/2015; DOI:10.1113/EP085071 · 2.87 Impact Factor
  • Tatjana S Potpara · Gregory Y.H. Lip
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    ABSTRACT: Atrial fibrillation (AF) is associated with a 5-fold greater risk of ischemic stroke or systemic embolism compared with normal sinus rhythm. Cardioembolic AF-related strokes are often more severe, fatal or associated with greater permanent disability and higher recurrence rates than strokes of other aetiologies. These strokes may be effectively prevented with oral anticoagulant (OAC) therapy, using either vitamin K antagonists (VKAs) or non-vitamin K antagonist oral OACs (NOACs) such as the direct thrombin inhibitor dabigatran or direct factor Xa inhibitors rivaroxaban, apixaban or edoxaban. Most AF patients have a positive net clinical benefit from OAC, excluding those with AF and no conventional stroke risk factors. Balancing the risks of stroke and bleeding is necessary for optimal use of OAC in clinical practice, and modifiable bleeding risk factors must be addressed. Concerns remain over 'non-changeable' bleeding risk factors such as older age, significant renal or hepatic impairment, prior stroke(s) or prior bleeding event(s) and active malignancies. Such AF patients are often termed 'special' AF populations, due to their 'special' risk profile that includes increased risks of both thromboembolic and bleeding events, and due to fear of bleeding complications these AF patients are often denied OAC. Evidence shows, however, that the absolute benefits of OAC are the greatest in patients at the highest risk, and NOACs may offer even a greater net clinical benefit compared to warfarin particularly in these high risk patients. In this review article, we summarize available data on stroke prevention in AF patients at increased risk of both stroke and bleeding and discuss the use of NOACs for thromboprophylaxis in these 'special' AF populations. Copyright © 2015. Published by Elsevier Inc.
    07/2015; DOI:10.1016/j.pcad.2015.07.003

Publication Stats

25k Citations
5,673.93 Total Impact Points


  • 2012–2015
    • Aalborg University
      Ålborg, North Denmark, Denmark
    • University of Oxford
      • Department of Primary Care Health Sciences
      Oxford, ENG, United Kingdom
    • University of Iowa
      Iowa City, Iowa, United States
  • 2005–2015
    • Sandwell and West Birmingham Hospitals NHS Trust
      Birmingham, England, United Kingdom
    • University of Oslo
      Kristiania (historical), Oslo, Norway
    • Hamilton Health Sciences
      Hamilton, Ontario, Canada
  • 1996–2015
    • Birmingham City University
      Birmingham, England, United Kingdom
    • University of Birmingham
      • • Centre for Cardiovascular Sciences
      • • School of Sport and Exercise Sciences
      Birmingham, England, United Kingdom
  • 2013
    • Sapienza University of Rome
      Roma, Latium, Italy
    • Hospital Universitario Virgen de la Arrixaca
      • Departamento de Cardiología
      Murcia, Murcia, Spain
    • Queen Mary, University of London
      • Centre for Primary Care and Public Health
      London, ENG, United Kingdom
  • 2012–2013
    • Chinese PLA General Hospital (301 Hospital)
      Peping, Beijing, China
  • 2010–2013
    • Aston University
      • School of Life and Health Sciences
      Birmingham, England, United Kingdom
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Academic Medical Center
      Amsterdamo, North Holland, Netherlands
  • 2002–2012
    • McMaster University
      • Department of Medicine
      Hamilton, Ontario, Canada
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1996–2012
    • University Hospitals Birmingham NHS Foundation Trust
      • Department of Medicine
      Birmingham, England, United Kingdom
  • 2009
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 2008
    • University of Murcia
      • Faculty of Medicine
      Murcia, Murcia, Spain
  • 2007–2008
    • University Hospital of Heraklion
      Irákleio, Attica, Greece
  • 2006
    • Saint Luke's Hospital (NY, USA)
      New York, New York, United States
  • 1998–2006
    • WWF United Kingdom
      Londinium, England, United Kingdom
  • 2002–2005
    • Hospital General Universitario de Alicante
      Alicante, Valencia, Spain
  • 2003
    • Medical University of Vienna
      • Universitätsklinik für Klinische Pharmakologie
      Vienna, Vienna, Austria
    • The University of Edinburgh
      • Division of Clinical Neurosciences
      Edinburgh, SCT, United Kingdom
  • 2001
    • Beaumont Hospital
      Dublin, Leinster, Ireland
  • 1999
    • Birmingham Children's Hospital NHS Foundation Trust
      Birmingham, England, United Kingdom
  • 1997
    • University Hospital Of South Manchester NHS Foundation Trust
      Manchester, England, United Kingdom
  • 1995
    • University of Glasgow
      • School of Medicine
      Glasgow, Scotland, United Kingdom