Gregory Y H Lip

Aalborg University, Ålborg, North Denmark, Denmark

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Publications (826)4255.16 Total impact

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    ABSTRACT: Recent findings suggest that patients with atrial fibrillation (AF), in addition to thromboembolic risk, are also at risk for myocardial infarction (MI). Our aim was to investigate predictors of MI and cardiovascular death in a cohort of anticoagulated AF patients. We prospectively followed-up 1019 AF patients for a median of 33.7 months (3223 person/years). All patients were treated with oral vitamin K antagonists. Primary outcome was a composite endpoint of cardiovascular events (CVEs) including fatal/non-fatal MI, cardiac revascularization and cardiovascular death. Mean age was 73.2 years, 43.8% were female. At follow-up, 111 CVEs (3,43%/year) occurred: 47 fatal-nonfatal MI/revascularization and 64 cardiovascular deaths. In addition, 31 stroke/TIA (0.96%/year) were recorded. Patients experiencing CVEs were older (p<0.001), with a higher prevalence of metabolic syndrome (MetS, p=0.005), heart failure (HF, p=0.001), prior cardiac (p<0.001) and cerebrovascular events (p<0.001). On a Cox proportional hazard analysis, age (hazard ratio [HR] 1.083, 95% confidence interval [CI], 1.053-1.113, p<0.001), smoking (HR 2.158, 95% CI, 1.193-3.901, p=0.011), history of cerebrovascular (HR 1.704, 95% CI, 1.119-2.597, p=0.013), and cardiac events (HR 1.658, 95% CI, 1.105-2.489, p=0.015), MetS (HR 1.663, 95% CI, 1.107-2.499, p=0.014), HF (HR 1.584, 95% CI, 1.021-2.456, p=0.040), male sex (HR 1.499, 95% CI, 1.010-2.223, p=0.044) predicted CVEs. AF patients still experience a high rate of CVEs despite being on anticoagulant treatment. MetS is a common clinical feature in AF patients, which increases the risk of CVEs. A holistic approach is needed to reduce the risk of cardiovascular risk in patients with AF. ClinicalTrials.gov NCT01882114.
    Chest 11/2014; · 7.13 Impact Factor
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    ABSTRACT: Atrial fibrillation (AF) is increasingly prevalent in the elderly, but such patients tend to be under-represented in clinical trials. Increasing age confers a higher risk of stroke and bleeding when antithrombotic therapy is used. We examined risk factors for stroke and bleeding among elderly (age, >75 years) patients within a real world hospitalized cohort from the Loire Valley AF project. We identified elderly (age, >75 years) patients with AF, assessed their risk factors, and followed up for stroke, thromboembolism, death, or major bleeding. The effect of vitamin K antagonist (VKA) use on these end points was assessed. We studied 8962 patients with AF, and we identified 4130 elderly (age, ≥75 years) patients. Using Kaplan-Meier analyses, event rates of death, stroke/thromboembolism, the composite of stroke/thromboembolism/death, and major bleeding increased with increasing age. For mortality, VKA-treated patients did better than non-VKA-treated patients. The risk of death and stroke/thromboembolism/death increased with increasing age. The risk of major bleeding did not increase with increasing age strata. VKA treatment was associated with lower mortality in those aged <75 years (adjusted hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.45-0.72), and the effect size was maintained with increasing age strata (Pint=0.67). For stroke/thromboembolism/death, VKA also has a significant benefit in those aged <75 years (adjusted HR, 0.69; [0.57-0.83]), and the effect size was maintained with increasing age strata (Pint=0.58). For major bleeding, there was no statistically significant difference between age strata (Pint=0.67). In elderly patients, age and previous stroke emerged as the main predictors of stroke and thromboembolism. Renal impairment and VKA use were predictors of major bleeding. Elderly patients with AF have a higher risk of stroke and bleeding, but the benefits of VKA therapy for stroke/thromboembolism or mortality were present regardless of increasing age. © 2014 American Heart Association, Inc.
    11/2014;
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    ABSTRACT: To investigate the relative effect of warfarin versus non-vitamin K oral anticoagulants (NOACs) in thrombotic and bleeding outcomes in subgroups of atrial fibrillation (AF) patients with varying degrees of renal dysfunction. Systemic review and meta-regression analyses on NOACs versus warfarin, supplemented with indirect comparisons were conducted. The eligibility criteria for inclusion were randomised controlled trials comparing NOACs against warfarin for stroke prevention in AF patients. Outcomes of interest were stroke or systemic embolism (SE) and major bleeding. Five studies comprising 72,845 AF patients randomised to either a NOAC or warfarin were included in the meta-regression analysis. A shift in strata from no renal impairment to renal impairment resulted in a non-significant impact on bleeding and stroke/SE, indicating similar safety and efficacy, despite renal function status. Apixaban was associated with less major bleeding compared to dabigatran and rivaroxaban but not edoxaban in patients with moderate renal impairment. For efficacy outcomes, only dabigatran 150 mg was statistically significantly favoured compared to edoxaban 30 mg. For efficacy outcomes in mild renal impairment, both dabigatran 150 mg and rivaroxaban 10 mg (J-ROCKET) were statistically significantly favoured against edoxaban 30 mg. Non-vitamin K oral anticoagulants had similar efficacy and safety compared to warfarin across different levels of renal function. Indirect comparisons suggest that apixaban and edoxaban were associated with a better safety profile in patients with moderate renal impairment. However, caution is warranted when interpreting indirect comparisons of drugs investigated in different trials. Prescribers should fit the most appropriate NOAC to the AF patient characteristics (and vice versa) to individualise effective stroke prevention.
    Clinical research in cardiology : official journal of the German Cardiac Society. 11/2014;
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    ABSTRACT: Background Diabetes mellitus is recognized as a stroke risk factor in atrial fibrillation (AF). Diabetics with retinopathy have an increased risk of systemic cardiovascular complications, and also, severe diabetic retinopathy predisposes to ocular bleeds.We hypothesised that diabetic AF patients with retinopathy have increased stroke/thromboembolism and severe bleeding risks in AF, when compared to diabetic AF patients without retinopathy, or to non-diabetics with AF. Methods and ResultsWe tested our hypothesis in a large "real- world" cohort of individuals with AF from the Loire Valley Atrial Fibrillation project.Of 8962 patients with AF on our dataset, 1409 (16%) had documented diabetes mellitus, of which, 163 (1.8% of the whole cohort) were patients with diabetic retinopathy.After a followup of 31±36 months, when compared to non-diabetics, the risk of stroke/TE in diabetics with no retinopathy increased 1.3 fold (RR 1.30; 95%CI 1.07-1.59, p=0.01), and in diabetics with retinopathy, the risk of stroke/TE was increased 1.58 fold (RR 1.58; 95%CI 1.07-2.32, p=0.02). There was no significant difference when diabetics with no retinopathy were compared to diabetics with retinopathy (RR 1.21, 95%CI 0.80-1.84, p=0.37). A similar pattern was seen for mortality and severe bleeding. On multivariate analysis, the presence of diabetic retinopathy did not emerge as an independent predictor for stroke/TE or severe bleeding. Conclusion Crude rates of stroke/TE increased in a stepwise fashion when non-diabetic AF patients were compared to diabetics with no retinopathy and diabetics with retinopathy. However, we have shown for the first time that the presence of diabetic retinopathy did not emerge as an independent predictor for stroke/TE or severe bleeding on multivariate analysis. Diabetes mellitus is recognized as a stroke risk factor in atrial fibrillation (AF). Diabetics with retinopathy have an increased risk of systemic cardiovascular complications, and also, severe diabetic retinopathy predisposes to ocular bleeds. We hypothesised that diabetic AF patients with retinopathy have increased stroke/thromboembolism and severe bleeding risks in AF, when compared to diabetic AF patients without retinopathy, or to non-diabetics with AF. We tested our hypothesis in a large "real- world" cohort of individuals with AF from the Loire Valley Atrial Fibrillation project. Of 8962 patients with AF on our dataset, 1409 (16%) had documented diabetes mellitus, of which, 163 (1.8% of the whole cohort) were patients with diabetic retinopathy. After a followup of 31±36 months, when compared to non-diabetics, the risk of stroke/TE in diabetics with no retinopathy increased 1.3 fold (RR 1.30; 95%CI 1.07-1.59, p=0.01), and in diabetics with retinopathy, the risk of stroke/TE was increased 1.58 fold (RR 1.58; 95%CI 1.07-2.32, p=0.02). There was no significant difference when diabetics with no retinopathy were compared to diabetics with retinopathy (RR 1.21, 95%CI 0.80-1.84, p=0.37). A similar pattern was seen for mortality and severe bleeding. On multivariate analysis, the presence of diabetic retinopathy did not emerge as an independent predictor for stroke/TE or severe bleeding. Crude rates of stroke/TE increased in a stepwise fashion when non-diabetic AF patients were compared to diabetics with no retinopathy and diabetics with retinopathy. However, we have shown for the first time that the presence of diabetic retinopathy did not emerge as an independent predictor for stroke/TE or severe bleeding on multivariate analysis.
    Chest 11/2014; · 7.13 Impact Factor
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    ABSTRACT: Background:The risk of ischemic stroke/thromboembolic events after an intracranial haemorrhage (ICH) in atrial fibrillation (AF) patients on warfarin treatment is poorly characterised. The aim of this study was to assess the association between the risk of ischaemic stroke/thromboembolic events and ICH. Methods:Linkage of three Danish nationwide administrative registries in the period between 1999-2012 identified AF patients on warfarin treatment. Event rate ratios of stroke/thromboembolic events, major bleeding and all-cause mortality stratified by ICH were calculated, and Cox proportional hazard models were used to compare event rates among ICH survivors. A matched odds ratio (OR) was calculated for ICH occurrences within 0-3 months relative to 3-6 months prior to a stroke/thromboembolic event. A rate ratio of claimed warfarin prescriptions in a 3-month period pre- and post-ICH was also calculated. Results:We studied 58,815 AF patients (median age 72.6 years; 60% male). When compared to the non-ICH group, the ICH group was at increased risk for stroke/SE/TIA [Rate Ratio 3.67 (95% confidence interval [CI], 3.12 to 4.31] and mortality [5.55 (95% CI, 5.20 to 5.92)], but not for major bleeding [1.06 (95% CI, 0.81 to 1.39)]. The matched OR of ICH occurrences prior to a stroke/SE/TIA was 4.33 (95% CI, 2.44 to 8.15). The rate ratio of claimed warfarin prescriptions post and pre-ICH event was 0.28 (95% CI, 0.24 to 0.33). Conclusion:In this large-scale study of AF patients treated with warfarin, first-time ICH was associated with an increased rate of ischaemic stroke/SE/TIA and mortality compared to the non-ICH group. There was a decrease in the warfarin prescription purchase rate post-ICH period compared to pre-ICH, which may partly explain the excess risk. The risk of ischemic stroke/thromboembolic events after an intracranial haemorrhage (ICH) in atrial fibrillation (AF) patients on warfarin treatment is poorly characterised. The aim of this study was to assess the association between the risk of ischaemic stroke/thromboembolic events and ICH. Linkage of three Danish nationwide administrative registries in the period between 1999-2012 identified AF patients on warfarin treatment. Event rate ratios of stroke/thromboembolic events, major bleeding and all-cause mortality stratified by ICH were calculated, and Cox proportional hazard models were used to compare event rates among ICH survivors. A matched odds ratio (OR) was calculated for ICH occurrences within 0-3 months relative to 3-6 months prior to a stroke/thromboembolic event. A rate ratio of claimed warfarin prescriptions in a 3-month period pre- and post-ICH was also calculated. We studied 58,815 AF patients (median age 72.6 years; 60% male). When compared to the non-ICH group, the ICH group was at increased risk for stroke/SE/TIA [Rate Ratio 3.67 (95% confidence interval [CI], 3.12 to 4.31] and mortality [5.55 (95% CI, 5.20 to 5.92)], but not for major bleeding [1.06 (95% CI, 0.81 to 1.39)]. The matched OR of ICH occurrences prior to a stroke/SE/TIA was 4.33 (95% CI, 2.44 to 8.15). The rate ratio of claimed warfarin prescriptions post and pre-ICH event was 0.28 (95% CI, 0.24 to 0.33). In this large-scale study of AF patients treated with warfarin, first-time ICH was associated with an increased rate of ischaemic stroke/SE/TIA and mortality compared to the non-ICH group. There was a decrease in the warfarin prescription purchase rate post-ICH period compared to pre-ICH, which may partly explain the excess risk.
    Chest 11/2014; · 7.13 Impact Factor
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    ABSTRACT: Nonsteroidal anti-inflammatory drugs (NSAIDs) are assumed to increase bleeding risk, but their actual relation to serious bleeding in patients with atrial fibrillation (AF) who are receiving antithrombotic medication is unknown.
    Annals of internal medicine 11/2014; 161(10):690-8. · 13.98 Impact Factor
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    ABSTRACT: New oral anticoagulants require dosing adjustment according to renal function. We aimed to determine discordance in hypothetical recommended dosing of these drugs using different estimated glomerular filtration rate equations in patients with atrial fibrillation.Methods Cross-sectional analysis of 910 patients with atrial fibrillation and an indication for oral anticoagulation. The glomerular filtration rate was estimated using the Cockcroft-Gault, Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations. For dabigatran, rivaroxaban, and apixaban we identified dose discordance when there was disagreement in the recommended dose based on different equations.ResultsAmong the overall population, relative to Cockcroft-Gault, discordance in dabigatran dosage was 11.4% for Modification of Diet in Renal Disease and 10% for Chronic Kidney Disease Epidemiology Collaboration, discordance in rivaroxaban dosage was 10% for Modification of Diet in Renal Disease and 8.5% for the Chronic Kidney Disease Epidemiology Collaboration. The lowest discordance was observed for apixaban: 1.4% for Modification of Diet in Renal Disease and 1.5% for the Chronic Kidney Disease Epidemiology Collaboration. In patients with Cockcroft-Gault < 60 mL/min or elderly patients, discordances in dabigatran and rivaroxaban dosages were higher, ranging from 13.2% to 30.4%. Discordance in apixaban dosage remained < 5% in these patients.Conclusions Discordance in new oral anticoagulation dosages using different equations is frequent, especially among elderly patients with renal impairment. This discordance was higher in dabigatran and rivaroxaban dosages than in apixaban dosages. Further studies are needed to clarify the clinical importance of these discordances and the optimal anticoagulant dosages depending on the use of different equations to estimate renal function.Full English text available from: www.revespcardiol.org/en
    Revista Española de Cardiología. 11/2014;
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    ABSTRACT: Objective To evaluate the efficacy of coenzyme Q10 (CoQ10) supplementation on statin-induced myopathy. Participants and Methods We searched the MEDLINE, Cochrane Library, Scopus, and EMBASE databases (November 1, 1987, to May 1, 2014) to identify randomized controlled trials investigating the impact of CoQ10 on muscle pain and plasma creatine kinase (CK) activity as 2 measures of statin-induced myalgia. Two independent reviewers extracted data on study characteristics, methods, and outcomes. Results We included 6 studies with 302 patients receiving statin therapy: 5 studies with 226 participants evaluated the effect of CoQ10 supplementation on plasma CK activity, and 5 studies (4 used in the CK analysis and 1 other study) with 253 participants were included to assess the effect of CoQ10 supplementation on muscle pain. Compared with the control group, plasma CK activity was increased after CoQ10 supplementation, but this change was not significant (mean difference, 11.69 U/L [to convert to μkat/L, multiply by 0.0167]; 95% CI, –14.25 to 37.63 U/L; P=.38). Likewise, CoQ10 supplementation had no significant effect on muscle pain despite a trend toward a decrease (standardized mean difference, –0.53; 95% CI, –1.33 to 0.28; P=.20). No dose-effect association between changes in plasma CK activity (slope, –0.001; 95% CI, –0.004 to 0.001; P=.33) or in the indices of muscle pain (slope, 0.002; 95% CI, –0.005 to 0.010; P=.67) and administered doses of CoQ10 were observed. Conclusion The results of this meta-analysis of available randomized controlled trials do not suggest any significant benefit of CoQ10 supplementation in improving statin-induced myopathy. Larger, well-designed trials are necessary to confirm the findings from this meta-analysis.
    Mayo Clinic Proceedings 11/2014; · 5.79 Impact Factor
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  • Mikhail S. Dzeshka, Gregory Y.H. Lip
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    ABSTRACT: Atrial fibrillation (AF) confers increased risk of stroke and other thromboembolic events, and oral anticoagulation therefore is the essential part of AF management to reduce the risk of this complication. Until recently, the vitamin K antagonists (VKAs, e.g. warfarin) were the only oral anticoagulants available, acting by decreased synthesis of vitamin K-dependent coagulation factors (II, VI, IX, and X). The VKAs had many limitations: delayed onset and prolonged offset of action, variability of anticoagulant effect among patients, multiple food and drug interactions affecting pharmacological properties of warfarin, narrow therapeutic window, obligatory regular laboratory control, which all made warfarin ‘inconvenient’ both for patients and clinicians. The limitations of VKAs led to development of new class of drugs collectively defined as non-VKA oral anticoagulants (NOACs), which included direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban, edoxaban). The NOACs avoid many of the VKA drawbacks. In this review, we will focus on the current evidence justifying use of NOACs in non-valvular AF.
    Trends in Cardiovascular Medicine. 10/2014;
  • Mikhail S Dzeshka, Gregory YH Lip
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    ABSTRACT: Introduction: Oral anticoagulation is the mainstay for stroke and thromboembolic event prevention in patients with atrial fibrillation (AF). Given limitations of warfarin therapy, non-vitamin K oral anticoagulants have been developed including direct thrombin inhibitors (i.e., dabigatran etexilate). Dabigatran etexilate has been tested thoroughly in terms of efficacy and safety in clinical trials and studies, involving ‘real-world’ cohorts. In this review, currently available evidence in patients with non-valvular AF is discussed.Areas covered: The pharmacology, efficacy and safety, and current aspects of use of dabigatran etexilate in patients with non-valvular AF are reviewed in a comparative manner to warfarin both for chronic anticoagulation and in different clinical settings.Expert opinion: Dabigatran etexilate appeared to have several pharmacokinetic and pharmacodynamic advantages over warfarin, as well as a favorable efficacy and safety profile being at least noninferior and often superior to warfarin in patients with non-valvular AF. The latter was shown in the clinical trials, meta-analyses and studies with ‘real-world’ data. Currently ongoing trials will expand the body of evidence on warfarin and will aid decision making in currently controversial areas. Important limitations of dabigatran etexilate include contraindications for its use in patients with prosthetic heart valves and end-stage chronic kidney disease.
    Expert Opinion on Drug Safety 10/2014; · 2.74 Impact Factor
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    ABSTRACT: Introduction Vitamin D (vit D) deficiency may be associated with an increased risk of statin-related symptomatic myalgia in statin-treated patients. The aim of this meta-analysis was to substantiate the role of serum vitamin D levels in statin-associated myalgia. Methods The search included PUBMED, Cochrane Library, Scopus, and EMBASE from January 1, 1987 to April 1, 2014 to identify studies that investigated the impact of vit D levels in statin-treated subjects with and without myalgia. Two independent reviewers extracted data on study characteristics, methods and outcomes. Quantitative data synthesis was performed using a fixed-effect model. Results The electronic search yielded 437 articles; of those 20 were scrutinized as full texts and 13 studies were considered unsuitable. The final analysis included 7 studies with 2420 statin-treated patients divided into subgroups of patients with (n =666 [27.5%]) or without (n =1754) myalgia. Plasma vit D concentrations in the symptomatic and asymptomatic subgroups were 28.4 ± 13.80 ng/mL and 34.86 ± 11.63 ng/mL, respectively. The combination of data from individual observational studies showed that vit D plasma concentrations were significantly lower in patients with statin-associated myalgia compared with patients not manifesting this side effect (weighted mean difference −9.41 ng/mL; 95% confidence interval: −10.17 to −8.64; p <0.00001). Conclusions This meta-analysis provides evidence that low vit D levels are associated with myalgia in patients on statin therapy. Randomized controlled trials are necessary to establish whether vitamin D supplementation reduces the risk for statin-associated myalgia.
    International Journal of Cardiology 10/2014; · 6.18 Impact Factor
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    ABSTRACT: Increased combined free light chains (cFLC) are strongly prognostic of death in general populations and in patients with chronic kidney disease, but scarce data are available on cFLC in heart failure (HF). We aimed to assess the dynamics and prognostic significance of cFLC levels in patients following admission with acute heart failure (AHF). cFLC measurements were compared in 49 patients with AHF, 37 patients with stable HF, 43 patients with stable coronary artery disease and without HF (‘disease controls’), and 37 healthy controls. The association of cFLC with death and/or rehospitalisation was assessed. Patients with AHF had significantly elevated cFLC levels, compared to other groups (p<0.001). Patients with stable HF showed higher levels of cFLC than healthy controls. In AHF, cFLC levels correlated with cystatin C (Spearman r=0.63, p<0.001), and creatinine (Spearman r=0.47, p=0.002). During 3 months follow up brain natriuretic peptide (BNP) reduced significantly (p=0.017), but cFLC did not change significantly. In a multivariate Cox regression analysis, the higher quartiles of cFLC were significantly associated with death/readmission (hazard ratio (HR) 8.34 [95% CI 2.38-29.22] p=0.0009) after adjustment for age, gender, BNP and cystatin C levels. Higher quartiles of cFLC were prognostic for death alone (HR 14.0 [95% CI 1.72-113.8], p=0.014). In conclusion, raised serum cFLC concentrations in patients with AHF were independently associated with prognosis. In AHF, elevated cFLC levels persist long after clinical stabilisation, which may reflect immune disturbances and/or the reduced capacity of (perhaps functionally impaired) kidneys and the endothelium to eliminate them.
    The American Journal of Cardiology 10/2014; · 3.21 Impact Factor
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    ABSTRACT: Introduction: Choosing between different nonvitamin K antagonist oral anticoagulants (NOACs) in nonvalvular atrial fibrillation (NVAF) is difficult due to the absence of head to head comparative studies. We performed a Bayesian meta-analysis to explore similarities and differences between different NOACs and to rank treatments overall for safety and efficacy outcomes.Areas covered: Through a systematic literature search we identified randomized controlled Phase III trials of dabigatran, rivaroxaban, apixaban, and edoxaban versus adjusted-dose warfarin in patients with NVAF.Expert opinion: Warfarin ranked worst for all-cause mortality and intracranial bleedings and had a nil probability of ranking first for any outcome. The risk of major bleeding versus warfarin was lower with apixaban, dabigatran 110 mg, and both doses of edoxaban. All agents reduced the risk of intracranial bleeding versus warfarin. Edoxaban 30 mg was the best among the treatments being compared for major and gastrointestinal bleeding. Dabigatran 150 mg was the best for stroke and systemic embolism. This study suggests that NOACs are generally preferable to warfarin in patients with NVAF. However, safety and efficacy differences do exist among NOACs, which might drive their use in specific subsets of AF patients, allowing prescribers to tailor treatment to distinct patient profiles.
    Expert Opinion on Drug Safety 10/2014; · 2.74 Impact Factor
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    ABSTRACT: Background: There is growing evidence that chemokines are potentially important mediators of the pathogenesis of atherosclerotic disease. Major atherothrombotic complications, such as stroke and myocardial infarction, are common among atrial fibrillation (AF) patients. This increase in risk of adverse events may be predicted by a score based on the presence of certain clinical features of chronic heart failure, hypertension, age 75 years or greater, diabetes and stroke (the CHADS2 score). Our objective was to assess the prognostic value of plasma chemokines CCL2, CXCL4 and CX3CL1, and their relationship with the CHADS2 score, in AF patients. Methods: Plasma CCL2, CXCL4 and CX3CL1 were measured in 441 patients (59% male, mean age 75 years, 12% paroxysmal, 99% on warfarin) with AF. Baseline clinical and demographic factors were used to define each subject's CHADS2 score. Patients were followed up for a mean 2.1 years, and major adverse cardiovascular and cerebrovascular events (MACCE) were sought, being the combination of cardiovascular death, acute coronary events, stroke and systemic embolism. Results: Fifty-five of the AF patients suffered a MACCE (6% per year). Those in the lowest CX3CL1 quartile (≤0.24 ng/ml) had fewest MACCE (p = 0.02). In the Cox regression analysis, CX3CL1 levels >0.24 ng/ml (Hazard ratio 2.8, 95% CI 1.02-8.2, p = 0.045) and age (p = 0.042) were independently linked with adverse outcomes. The CX3CL1 levels rose directly with the CHADS2 risk score (p = 0.009). The addition of CX3CL1 did not significantly increased the discriminatory ability of the CHADS2 clinical factor-based risk stratification (c-index 0.60 for CHADS2 alone versus 0.67 for CHADS2 plus CX3CL1 >0.24 ng/ml, p = 0.1). Aspirin use was associated with lower levels of CX3CL1 (p = 0.0002) and diabetes with higher levels (p = 0.031). There was no association between CXCL4 and CCL2 plasma levels and outcomes. Conclusion: There is an independent association between low plasma CX3CL1 levels and low risk of major cardiovascular events in AF patients, as well as a linear association between CX3CL1 plasma levels and CHADS2-defined cardiovascular risk. The potential for CX3CL1 in refining risk stratification in AF patients merits consideration. © 2014 S. Karger AG, Basel.
    Cerebrovascular diseases (Basel, Switzerland). 10/2014; 38(3):204-211.
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    ABSTRACT: Background:We explored 12-month clinical outcomes of 929 patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) with bare-metal stents (BMS) vs. drug-eluting stents (DES) from the prospective multicenter AFCAS (Atrial Fibrillation undergoing Coronary Artery Stenting) registry.Methods and Results:Endpoints included the first occurrence of major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of all-cause death, myocardial infarction (MI), target vessel revascularization, definite/probable stent thrombosis (ST), transient ischemic attack or stroke. Bleeding events were defined according to the Bleeding Academic Research Consortium criteria. Altogether, 673 (72.4%) patients received BMS and 220 (23.7%) at least one DES. Patients treated with DES more often had diabetes and prior ischemic events, and a longer stent length (P<0.05 for all), whereas patients treated with BMS more often had heart failure and were more likely to present with acute ST-elevation MI (P<0.05 for both). At 12-month follow-up, rates and risks of MACCE and total bleeding events were comparable between the groups (22.0% with BMS vs. 19.5% with DES, P=0.51, hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.63-1.25 for DES) and (19.5% vs. 15.0%, respectively, P=0.16, HR 0.75, 95% CI 0.51-1.09 for DES). Definite/probable ST was more frequent in the BMS group (1.9% vs. 0%, respectively, P=0.046).Conclusions:In real-world patients with AF undergoing PCI, DES use was associated with outcomes comparable to those with BMS without excess bleeding complications. More ST was seen in BMS-treated patients.
    Circulation journal : official journal of the Japanese Circulation Society. 10/2014;
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    ABSTRACT: Background and Purpose: WARCEF randomized 2,305 patients in sinus rhythm with ejection fraction (EF) ≤35% to warfarin (INR 2.0-3.5) or aspirin 325 mg. Warfarin reduced the incident ischemic stroke (IIS) hazard rate by 48% over aspirin in a secondary analysis. The IIS rate in heart failure (HF) is too low to warrant routine anticoagulation but epidemiologic studies show that prior stroke increases the stroke risk in HF. In this study, we explore IIS rates in WARCEF patients with and without baseline stroke to look for risk factors for IIS and determine if a subgroup with an IIS rate high enough to give a clinically relevant stroke risk reduction can be identified. Methods: We compared potential stroke risk factors between patients with baseline stroke and those without using the exact conditional score test for Poisson variables. We looked for risk factors for IIS, by comparing IIS rates between different risk factors. For EF we tried cut-off points of 10, 15 and 20%. The cut-off point 15% was used as it was the highest EF that was associated with a significant increase in IIS rate. IIS and EF strata were balanced as to warfarin/aspirin assignment by the stratified randomized design. A multiple Poisson regression examined the simultaneous effects of all risk factors on IIS rate. IIS rates per hundred patient years (/100PY) were calculated in patient groups with significant risk factors. Missing values were assigned the modal value. Results: Twenty of 248 (8.1%) patients with baseline stroke and 64 of 2,048 (3.1%) without had IIS. IIS rate in patients with baseline stroke (2.37/100PY) was greater than patients without (0.89/100PY) (rate ratio 2.68, p < 0.001). Fourteen of 219 (6.4%) patients with ejection fraction (EF) <15% and 70 of 2,079 (3.4%) with EF ≥15% had IIS. In the multiple regression analysis stroke at baseline (p < 0.001) and EF <15% vs. ≥15% (p = 0.005) remained significant predictors of IIS. IIS rate was 2.04/100PY in patients with EF <15% and 0.95/100PY in patients with EF ≥15% (p = 0.009). IIS rate in patients with baseline stroke and reduced EF was 5.88/100PY with EF <15% decreasing to 2.62/100PY with EF <30%. Conclusions: In a WARCEF exploratory analysis, prior stroke and EF <15% were risk factors for IIS. Further research is needed to determine if a clinically relevant stroke risk reduction is obtainable with warfarin in HF patients with prior stroke and reduced EF. © 2014 S. Karger AG, Basel.
    Cerebrovascular diseases (Basel, Switzerland). 10/2014; 38(3):176-181.
  • Helen R Griffiths, Gregory Y H Lip
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    ABSTRACT: Advances in our understanding of pathological mechanisms can inform the identification of various biomarkers for risk stratification, monitoring drug efficacy and toxicity; and enabling careful monitoring of polypharmacy. Biomarkers in the broadest sense refer to 'biological markers' and this can be blood-based (eg. fibrin D-dimer, von Willebrand factor, etc) urine-based (eg. thromboxane), or even related to cardiac or cerebral imaging(1). Most biomarkers offer improvements over clinical risk scores in predicting high risk patients - at least statistically - but usually at the loss of simplicity and practicality for easy application in everyday clinical practice. Given the various biomarkers can be informed by different aspects of pathophysiology (e.g. inflammation, clotting, collagen turnover) they can nevertheless contribute to a better understanding of underlying disease processes(2). Indeed, many age-related diseases share common modifiable underpinning mechanisms e.g. inflammation, oxidative stress and visceral adiposity.
    Circulation 10/2014; · 15.20 Impact Factor
  • Tatjana S Potpara, Gregory Y H Lip
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    ABSTRACT: Ever since the original description of a 'peculiar pulse irregularity', atrial fibrillation (AF) has been studied extensively and has come a long journey from the recognition of its cardiac origins, to the modern concept of AF as a serious public health challenge with profound social and economic implications. This arrhythmia affects around 2% of adult population, and the most common underlying heart diseases accompanying AF in the modern era are hypertension, heart failure and coronary artery disease, as well as valvular heart diseases and numerous other cardiac as well as non-cardiac disorders which have been shown to predispose to AF. On occasions, AF occurs in young otherwise apparently healthy individuals (so called 'lone AF'). For a long time, 'lone' AF has been believed to bear a favourable prognosis as compared to AF with underlying structural heart disease, but increasing evidence suggests that 'lone' AF patients represent a rather heterogeneous cohort, with highly variable individual risk profiles due to the presence of various subclinical cardiovascular risk factors or genetically determined subtle alterations at the cellular or molecular level. For these reasons, the existence of truly 'lone' AF has recently been questioned. In this review article, we present a brief history of the recognition of the public health burden of AF. We discuss some of the misconceptions and breakthroughs on modern knowledge on AF, including the rise (and fall) of the 'lone' AF concept.
    Current pharmaceutical design. 09/2014;
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    ABSTRACT: Guidelines for anticoagulant therapy in patients with atrial fibrillation are based on stroke risk as calculated by either the CHADS2 or the CHA2DS2VASc scores and do not integrate bleeding risk in an explicit, quantitative manner. Our objective was to quantify the net clinical benefit resulting from improved decision making about antithrombotic therapy.
    Circulation Cardiovascular Quality and Outcomes 09/2014; · 5.66 Impact Factor

Publication Stats

14k Citations
4,255.16 Total Impact Points

Institutions

  • 2013–2014
    • Aalborg University
      • Faculty of Medicine
      Ålborg, North Denmark, Denmark
    • Aalborg University Hospital
      • Department of Cardiology
      Aalborg, Region North Jutland, Denmark
    • Attikon University Hospital
      Athínai, Attica, Greece
    • Azienda Ospedaliera Santa Maria della Misericordia
      Udine, Friuli Venezia Giulia, Italy
    • University of Leipzig
      • Department of Cardiac Surgery
      Leipzig, Saxony, Germany
    • Aston University
      • School of Life and Health Sciences
      Birmingham, ENG, United Kingdom
    • Queen Mary, University of London
      • Centre for Primary Care and Public Health
      London, ENG, United Kingdom
  • 2002–2014
    • University of Birmingham
      • • Centre for Cardiovascular Sciences
      • • School of Sport and Exercise Sciences
      Birmingham, England, United Kingdom
    • McMaster University
      • Department of Medicine
      Hamilton, Ontario, Canada
  • 2012–2013
    • Chinese PLA General Hospital (301 Hospital)
      Peping, Beijing, China
    • Hospital General Universitario Morales Meseguer
      Murcia, Murcia, Spain
    • Boehringer Ingelheim
      Ingelheim, Rheinland-Pfalz, Germany
    • Università di Pisa
      Pisa, Tuscany, Italy
    • University of Belgrade
      • Chair of Pharmacology, Clinical Pharmacology and Toxicology
      Beograd, Central Serbia, Serbia
    • University of Iowa
      Iowa City, Iowa, United States
    • University of Oxford
      • Department of Primary Care Health Sciences
      Oxford, ENG, United Kingdom
    • Copenhagen University Hospital Gentofte
      • Department of Dermato-Allergology
      Hellebæk, Capital Region, Denmark
    • Vilnius University Hospital Santariškių Klinikos
      Vil'nyus, Vilniaus Apskritis, Lithuania
    • University of Lodz
      • Department of Cytobiochemistry
      Łódź, Łódź Voivodeship, Poland
  • 2011–2013
    • University of Murcia
      Murcia, Murcia, Spain
    • Klinički centar Srbije
      • Institute for Cardiovascular Diseases
      Beograd, Central Serbia, Serbia
    • Sapienza University of Rome
      • Department of Experimental Medicine
      Roma, Latium, Italy
    • University of Bologna
      • Institute of Cardiology
      Bologna, Emilia-Romagna, Italy
    • Centre Hospitalier Universitaire de Tours
      Tours, Centre, France
    • Universitätsklinikum Münster
      Muenster, North Rhine-Westphalia, Germany
    • Oulu University Hospital
      • Department of Surgery
      Oulu, Oulu, Finland
    • East Coast Community Healthcare CIC
      Beccles, England, United Kingdom
    • Maastricht Universitair Medisch Centrum
      Maestricht, Limburg, Netherlands
    • Turku University Hospital
      • Turku PET Centre
      Turku, Province of Western Finland, Finland
    • Azienda Ospedaliero Universitaria Careggi
      • Department of Heart and Vessels
      Firenzuola, Tuscany, Italy
    • Uppsala University
      • Department of Medical Sciences
      Uppsala, Uppsala, Sweden
  • 2008–2013
    • Hospital Universitario Virgen de la Arrixaca
      • Departamento de Cardiología
      Murcia, Murcia, Spain
    • Ilustre Colegio Oficial de Médicos de Alicante
      Alicante, Valencia, Spain
    • Royal College of Physicians
      Londinium, England, United Kingdom
    • University Hospital of Heraklion
      Irákleio, Attica, Greece
  • 2006–2013
    • Hospital General Universitario de Alicante
      • Departamento de Cardiología
      Alicante, Valencia, Spain
  • 2001–2013
    • University Hospitals Birmingham NHS Foundation Trust
      • Department of Medicine
      Birmingham, England, United Kingdom
  • 2007–2011
    • Maastricht University
      • Cardiologie
      Maastricht, Provincie Limburg, Netherlands
  • 2010
    • Baker IDI Heart and Diabetes Institute
      Melbourne, Victoria, Australia
  • 2009
    • Medical University of Gdansk
      • Department of Cardiology and Heart Electrotherapy
      Danzig, Pomeranian Voivodeship, Poland
  • 2008–2009
    • Justus-Liebig-Universität Gießen
      Gieben, Hesse, Germany
  • 2005–2009
    • Sandwell and West Birmingham Hospitals NHS Trust
      Birmingham, England, United Kingdom
    • Hospital Universitario San Juan De Alicante
      Alicante, Valencia, Spain
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 1996–2009
    • Birmingham City University
      Birmingham, England, United Kingdom
  • 2003
    • Medical University of Vienna
      • Universitätsklinik für Klinische Pharmakologie
      Vienna, Vienna, Austria
    • The University of Edinburgh
      • Division of Clinical Neurosciences
      Edinburgh, SCT, United Kingdom