Time filter

Source Type

News Article | October 11, 2016
Site: www.biosciencetechnology.com

If you're angry or upset, you might want to simmer down before heading out for an intense run or gym workout. A large, international study ties heavy exertion while stressed or mad to a tripled risk of having a heart attack within an hour. Regular exercise is a healthy antidote to stress and can help prevent heart disease - the biggest problem is that too many people get too little of it. But the new research suggests there may be better or worse times to exercise, and that extremes can trigger harm. "This study is further evidence of the connection between mind and body. When you're angry, that's not the time to go out and chop a stack of wood," said Barry Jacobs, a psychologist at the Crozer-Keystone Health System in suburban Philadelphia and an American Heart Association volunteer. He had no role in the study , led by the Population Health Research Institute at McMaster University in Hamilton, Ontario. Results were published Monday in the Heart Association journal Circulation. Earlier studies have looked at anger and exertion as heart attack triggers but most were small or in one country, or included few women or minorities. The new study involved 12,461 people suffering a first heart attack in 52 countries. Their average age was 58 and three-fourths were men. They answered a survey about whether they were angry or upset, or had heavy exertion, in the hour before their heart attack or during the same time period the previous day. That way researchers could compare risk at different times in the same people and the effect of these potential heart attack triggers. Being angry or upset doubled the risk of suffering heart attack symptoms within an hour; heavy physical exertion did the same. Having both at the same time more than tripled the risk for a heart attack. The risk was greatest between 6 p.m. and midnight, and was independent of other factors such as smoking, high blood pressure or obesity. Big caveats: Patients reported their own stress or anger, and people who just had a heart attack may be more prone to recall or think they suffered one of these triggers than they otherwise might have been. Also, strenuous exertion is whatever the patient perceives it to be - for some people that could be climbing stairs and for others, running a marathon. The study also is observational, so it cannot prove cause and effect. But it's likely to be the best kind of information available - it's not possible to randomly assign people to be angry and exercise, then see how many have heart attacks. "This is a large enough sample size that we can put stock in the findings," Jacobs said. "We all need to find ways of modifying our emotional reactions and to avoid extreme anger," such as distracting ourselves, walking away from the stressful situation, trying to see it from a different perspective, talking it out and getting support from other people, he said. The study's findings also are biologically plausible. Emotional stress and exertion can raise blood pressure and heart rate, change the flow of blood in the vessels and reduce the heart's blood supply, said the study leader, Dr. Andrew Smyth of McMaster University. In an artery already clogged with plaque, a trigger could block blood flow and lead to a heart attack. "From a practical perspective, there will be times when exposure to such extremes is unavoidable," Smyth said. "We continue to advise regular physical activity for all, including those who use exercise to relieve stress," but people should not go beyond their usual routine at such times, he said. The study was funded by the Canadian Institutes of Health Research, other governmental bodies from various countries that participated, and grants from several drug companies.


News Article | October 10, 2016
Site: www.rdmag.com

If you're angry or upset, you might want to simmer down before heading out for an intense run or gym workout. A large, international study ties heavy exertion while stressed or mad to a tripled risk of having a heart attack within an hour. Regular exercise is a healthy antidote to stress and can help prevent heart disease — the biggest problem is that too many people get too little of it. But the new research suggests there may be better or worse times to exercise, and that extremes can trigger harm. "This study is further evidence of the connection between mind and body. When you're angry, that's not the time to go out and chop a stack of wood," said Barry Jacobs, a psychologist at the Crozer-Keystone Health System in suburban Philadelphia and an American Heart Association volunteer. He had no role in the study , led by the Population Health Research Institute at McMaster University in Hamilton, Ontario. Results were published Monday in the Heart Association journal Circulation. Earlier studies have looked at anger and exertion as heart attack triggers but most were small or in one country, or included few women or minorities. The new study involved 12,461 people suffering a first heart attack in 52 countries. Their average age was 58 and three-fourths were men. They answered a survey about whether they were angry or upset, or had heavy exertion, in the hour before their heart attack or during the same time period the previous day. That way researchers could compare risk at different times in the same people and the effect of these potential heart attack triggers. Being angry or upset doubled the risk of suffering heart attack symptoms within an hour; heavy physical exertion did the same. Having both at the same time more than tripled the risk for a heart attack. The risk was greatest between 6 p.m. and midnight, and was independent of other factors such as smoking, high blood pressure or obesity. Big caveats: Patients reported their own stress or anger, and people who just had a heart attack may be more prone to recall or think they suffered one of these triggers than they otherwise might have been. Also, strenuous exertion is whatever the patient perceives it to be — for some people that could be climbing stairs and for others, running a marathon. The study also is observational, so it cannot prove cause and effect. But it's likely to be the best kind of information available — it's not possible to randomly assign people to be angry and exercise, then see how many have heart attacks. "This is a large enough sample size that we can put stock in the findings," Jacobs said. "We all need to find ways of modifying our emotional reactions and to avoid extreme anger," such as distracting ourselves, walking away from the stressful situation, trying to see it from a different perspective, talking it out and getting support from other people, he said. The study's findings also are biologically plausible. Emotional stress and exertion can raise blood pressure and heart rate, change the flow of blood in the vessels and reduce the heart's blood supply, said the study leader, Dr. Andrew Smyth of McMaster University. In an artery already clogged with plaque, a trigger could block blood flow and lead to a heart attack. "From a practical perspective, there will be times when exposure to such extremes is unavoidable," Smyth said. "We continue to advise regular physical activity for all, including those who use exercise to relieve stress," but people should not go beyond their usual routine at such times, he said. The study was funded by the Canadian Institutes of Health Research, other governmental bodies from various countries that participated, and grants from several drug companies.


Birnie D.H.,University of Ottawa | Healey J.S.,Population Health Research Institute | Wells G.A.,University of Ottawa | Verma A.,Southlake Regional Health Center | And 8 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: Many patients requiring pacemaker or implantable cardioverter-defibrillator (ICD) surgery are taking warfarin. For patients at high risk for thromboembolic events, guidelines recommend bridging therapy with heparin; however, case series suggest that it may be safe to perform surgery without interrupting warfarin treatment. There have been few results from clinical trials to support the safety and efficacy of this approach. METHODS: We randomly assigned patients with an annual risk of thromboembolic events of 5% or more to continued warfarin treatment or to bridging therapy with heparin. The primary outcome was clinically significant device-pocket hematoma, which was defined as device-pocket hematoma that necessitated prolonged hospitalization, interruption of anticoagulation therapy, or further surgery (e.g., hematoma evacuation). RESULTS: The data and safety monitoring board recommended termination of the trial after the second prespecified interim analysis. Clinically significant device-pocket hematoma occurred in 12 of 343 patients (3.5%) in the continued-warfarin group, as compared with 54 of 338 (16.0%) in the heparin-bridging group (relative risk, 0.19; 95% confidence interval, 0.10 to 0.36; P<0.001). Major surgical and thromboembolic complications were rare and did not differ significantly between the study groups. They included one episode of cardiac tamponade and one myocardial infarction in the heparin-bridging group and one stroke and one transient ischemic attack in the continued-warfarin group. CONCLUSIONS: As compared with bridging therapy with heparin, a strategy of continued warfarin treatment at the time of pacemaker or ICD surgery markedly reduced the incidence of clinically significant device-pocket hematoma. (Funded by the Canadian Institutes of Health Research and the Ministry of Health and Long-Term Care of Ontario; BRUISE CONTROL ClinicalTrials.gov number, NCT00800137.) Copyright © 2013 Massachusetts Medical Society.


Siegal D.M.,McMaster University | Curnutte J.T.,Portola Pharmaceuticals, Inc. | Connolly S.J.,McMaster University | Connolly S.J.,Population Health Research Institute | And 10 more authors.
New England Journal of Medicine | Year: 2015

BACKGROUND Bleeding is a complication of treatment with factor Xa inhibitors, but there are no specific agents for the reversal of the effects of these drugs. Andexanet is designed to reverse the anticoagulant effects of factor Xa inhibitors. METHODS Healthy older volunteers were given 5 mg of apixaban twice daily or 20 mg of rivaroxaban daily. For each factor Xa inhibitor, a two-part randomized placebocontrolled study was conducted to evaluate andexanet administered as a bolus or as a bolus plus a 2-hour infusion. The primary outcome was the mean percent change in anti-factor Xa activity, which is a measure of factor Xa inhibition by the anticoagulant. RESULTS Among the apixaban-treated participants, anti-factor Xa activity was reduced by 94% among those who received an andexanet bolus (24 participants), as compared with 21% among those who received placebo (9 participants) (P<0.001), and unbound apixaban concentration was reduced by 9.3 ng per milliliter versus 1.9 ng per milliliter (P<0.001); thrombin generation was fully restored in 100% versus 11% of the participants (P<0.001) within 2 to 5 minutes. Among the rivaroxabantreated participants, anti-factor Xa activity was reduced by 92% among those who received an andexanet bolus (27 participants), as compared with 18% among those who received placebo (14 participants) (P<0.001), and unbound rivaroxaban concentration was reduced by 23.4 ng per milliliter versus 4.2 ng per milliliter (P<0.001); thrombin generation was fully restored in 96% versus 7% of the participants (P<0.001). These effects were sustained when andexanet was administered as a bolus plus an infusion. In a subgroup of participants, transient increases in levels of d-dimer and prothrombin fragments 1 and 2 were observed, which resolved within 24 to 72 hours. No serious adverse or thrombotic events were reported. CONCLUSIONS Andexanet reversed the anticoagulant activity of apixaban and rivaroxaban in older healthy participants within minutes after administration and for the duration of infusion, without evidence of clinical toxic effects. Copyright © 2015 Massachusetts Medical Society. All rights reserved.


Benavente O.R.,University of British Columbia | Hart R.G.,Population Health Research Institute | McClure L.A.,University of Alabama at Birmingham | Szychowski J.M.,University of Alabama at Birmingham | Coffey C.S.,University of Iowa
New England Journal of Medicine | Year: 2012

BACKGROUND: Lacunar infarcts are a frequent type of stroke caused mainly by cerebral small-vessel disease. The effectiveness of antiplatelet therapy for secondary prevention has not been defined. METHODS: We conducted a double-blind, multicenter trial involving 3020 patients with recent symptomatic lacunar infarcts identified by magnetic resonance imaging. Patients were randomly assigned to receive 75 mg of clopidogrel or placebo daily; patients in both groups received 325 mg of aspirin daily. The primary outcome was any recurrent stroke, including ischemic stroke and intracranial hemorrhage. RESULTS: The participants had a mean age of 63 years, and 63% were men. After a mean follow-up of 3.4 years, the risk of recurrent stroke was not significantly reduced with aspirin and clopidogrel (dual antiplatelet therapy) (125 strokes; rate, 2.5% per year) as compared with aspirin alone (138 strokes, 2.7% per year) (hazard ratio, 0.92; 95% confidence interval [CI], 0.72 to 1.16), nor was the risk of recurrent ischemic stroke (hazard ratio, 0.82; 95% CI, 0.63 to 1.09) or disabling or fatal stroke (hazard ratio, 1.06; 95% CI, 0.69 to 1.64). The risk of major hemorrhage was almost doubled with dual antiplatelet therapy (105 hemorrhages, 2.1% per year) as compared with aspirin alone (56, 1.1% per year) (hazard ratio, 1.97; 95% CI, 1.41 to 2.71; P<0.001). Among classifiable recurrent ischemic strokes, 71% (133 of 187) were lacunar strokes. All-cause mortality was increased among patients assigned to receive dual antiplatelet therapy (77 deaths in the group receiving aspirin alone vs. 113 in the group receiving dual antiplatelet therapy) (hazard ratio, 1.52; 95% CI, 1.14 to 2.04; P = 0.004); this difference was not accounted for by fatal hemorrhages (9 in the group receiving dual antiplatelet therapy vs. 4 in the group receiving aspirin alone). CONCLUSIONS: Among patients with recent lacunar strokes, the addition of clopidogrel to aspirin did not significantly reduce the risk of recurrent stroke and did significantly increase the risk of bleeding and death. (Funded by the National Institute of Neurological Disorders and Stroke and others; SPS3 ClinicalTrials.gov number, NCT00059306.) Copyright © 2012 Massachusetts Medical Society. All rights reserved.


Maimaris W.,London School of Hygiene and Tropical Medicine | Paty J.,Population Health Research Institute | Perel P.,London School of Hygiene and Tropical Medicine | Legido-Quigley H.,London School of Hygiene and Tropical Medicine | And 4 more authors.
PLoS Medicine | Year: 2013

Background:Hypertension (HT) affects an estimated one billion people worldwide, nearly three-quarters of whom live in low- or middle-income countries (LMICs). In both developed and developing countries, only a minority of individuals with HT are adequately treated. The reasons are many but, as with other chronic diseases, they include weaknesses in health systems. We conducted a systematic review of the influence of national or regional health systems on HT awareness, treatment, and control.Methods and Findings:Eligible studies were those that analyzed the impact of health systems arrangements at the regional or national level on HT awareness, treatment, control, or antihypertensive medication adherence. The following databases were searched on 13th May 2013: Medline, Embase, Global Health, LILACS, Africa-Wide Information, IMSEAR, IMEMR, and WPRIM. There were no date or language restrictions. Two authors independently assessed papers for inclusion, extracted data, and assessed risk of bias. A narrative synthesis of the findings was conducted. Meta-analysis was not conducted due to substantial methodological heterogeneity in included studies. 53 studies were included, 11 of which were carried out in LMICs. Most studies evaluated health system financing and only four evaluated the effect of either human, physical, social, or intellectual resources on HT outcomes. Reduced medication co-payments were associated with improved HT control and treatment adherence, mainly evaluated in US settings. On balance, health insurance coverage was associated with improved outcomes of HT care in US settings. Having a routine place of care or physician was associated with improved HT care.Conclusions:This review supports the minimization of medication co-payments in health insurance plans, and although studies were largely conducted in the US, the principle is likely to apply more generally. Studies that identify and analyze complexities and links between health systems arrangements and their effects on HT management are required, particularly in LMICs.Please see later in the article for the Editors' Summary. © 2013 Maimaris et al.


Hijazi Z.,Uppsala University | Oldgren J.,Uppsala University | Andersson U.,Uppsala University | Connolly S.J.,Population Health Research Institute | And 7 more authors.
Circulation | Year: 2012

Background: Cardiac biomarkers are strong predictors of adverse outcomes in several patient populations. We evaluated the prevalence of elevated troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and their association to cardiovascular events in atrial fibrillation (AF) patients in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Methods and Results-Biomarkers at randomization were analyzed in 6189 patients. Outcomes were evaluated by Cox proportional hazards models adjusting for established cardiovascular risk factors and the CHADS 2 and CHA 2DS 2-VASc risk scores. Patients were stratified based on troponin I concentrations: <0.010 μg/L, n=2663; 0.010 to 0.019 μg/L, n=2006; 0.020 to 0.039 μg/L, n=1023; ≥0.040 μg/L, n=497; and on NT-proBNP concentration quartiles: <387; 387 to 800; 801 to 1402; >1402 ng/L. Rates of stroke were independently related to levels of troponin I with 2.09%/year in the highest and 0.84%/year in the lowest troponin I group (hazard ratio [HR], 1.99 [95% CI, 1.17-3.39]; P=0.0040), and to NT-proBNP with 2.30%/year versus 0.92% in the highest versus lowest NT-proBNP quartile groups, (HR, 2.40 [95% CI, 1.41- 4.07]; P=0.0014). Vascular mortality was also independently related to biomarker levels with 6.56%/year in the highest and 1.04%/year the lowest troponin I group (HR, 4.38 [95% CI, 3.05- 6.29]; P=0.0001), and 5.00%/year in the highest and 0.61%/year in the lowest NT-proBNP quartile groups (HR, 6.73 [3.95-11.49]; P=0.0001). Biomarkers increased the C-statistic from 0.68 to 0.72, P=0.0001, for a composite of thromboembolic events. Conclusions-Elevations of troponin I and NT-proBNP are common in patients with AF and independently related to increased risks of stroke and mortality. Cardiac biomarkers seem useful for improving risk prediction in AF beyond currently used clinical variables. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600. (Circulation. 2012;125:1605-1616.) © 2012 American Heart Association, Inc.


Hijazi Z.,Uppsala University | Hohnloser S.H.,Goethe University Frankfurt | Oldgren J.,Uppsala University | Andersson U.,Uppsala University | And 7 more authors.
Circulation | Year: 2014

BACKGROUND-: Renal impairment increases the risk of stroke and bleeding in patients with atrial fibrillation. In the Randomized Evaluation of Long-Term Anticoagulant Therapy (RELY) trial, dabigatran, with ≈80% renal elimination, displayed superiority over warfarin for prevention of stroke and systemic embolism in the 150-mg dose and significantly less major bleeding in the 110-mg dose in 18 113 patients with nonvalvular atrial fibrillation. This prespecified study investigated these outcomes in relation to renal function. METHODS AND RESULTS-: Glomerular filtration rate was estimated with the Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Modification of Diet in Renal Disease (MDRD) equations in all randomized patients with available creatinine at baseline (n=17 951), and cystatin C-based glomerular filtration rate was estimated in a subpopulation with measurements available (n=6190). A glomerular filtration rate ≥80, 50 to <80, and <50 mL/min was estimated in 32.6%, 47.6%, and 19.8% and in 21.6%, 59.6%, and 18.8% of patients based on Cockcroft-Gault and CKD-EPI, respectively. Rates of stroke or systemic embolism, major bleeding, and all-cause mortality increased as renal function decreased. The rates of stroke or systemic embolism were lower with dabigatran 150 mg and similar with 110 mg twice daily compared with warfarin, without significant heterogeneity in subgroups defined by renal function (interaction P>0.1 for all). For the outcome of major bleeding, there were significant interactions between treatment and renal function according to CKD-EPI and MDRD equations, respectively (P<0.05). The relative reduction in major bleeding with either dabigatran dose compared with warfarin was greater in patients with glomerular filtration rate ≥80 mL/min. CONCLUSIONS-: The efficacy of both dosages of dabigatran was consistent with the overall trial irrespective of renal function. However, with the CKD-EPI and MDRD equations, both dabigatran dosages displayed significantly lower rates of major bleeding in patients with glomerular filtration rate ≥80 mL/min. CLINICAL TRIAL REGISTRATION-: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600. © 2014 American Heart Association, Inc.


Deng W.Q.,McMaster University | Pare G.,McMaster University | Pare G.,Population Health Research Institute
Genetic Epidemiology | Year: 2011

Detection of gene-environment interactions using an exhaustive search necessarily raises the multiple hypothesis problem. While frequently used to control for experiment-wise type I error, Bonferroni correction is overly conservative and results in reduced statistical power. We have previously shown that prioritizing SNPs on the basis of heterogeneity in quantitative trait variance per genotype leads to increased power to detect genetic interactions. Our proposed method, variance prioritization (VP), selects SNPs having significant heterogeneity in variance per genotype using a pre-determined P-value threshold. We now suggest prioritizing SNPs individually such that the optimal heterogeneity of variance P-value is determined for each SNP. The large number of SNPs in genome-wide studies calls for a fast algorithm to output the optimal prioritization threshold for each SNP. In this report, we present such an algorithm, the Gene Environment Wide Interaction Search Threshold (GEWIST), and show that the use of GEWIST will increase power under a variety of interaction scenarios. Furthermore, by integrating over possible interaction effect sizes, we provide a framework to optimize prioritization in situations where interactions are a priori unknown. © 2011 Wiley Periodicals, Inc.


Sohani Z.N.,Population Health Research Institute | Samaan Z.,McMaster University
Cardiology Research and Practice | Year: 2012

Prevalence studies have noted the cooccurrence of cognitive decline and depression in persons with heart failure. Cognitive impairment is associated with significant mortality and deteriorated quality of life, likely due to impairments in memory and executive function, which impact a patient's ability to understand and comply with prescribed treatment plans. This is especially true in complex diseases such as heart failure. Evidence from literature supports the possibility of a pathophysiological relationship between cognitive impairment, depression, and heart failure. Yet, very few studies have sought to investigate this relationship. This paper reviews current literature on the association between depression and cognitive impairment in persons with heart failure and explores possible mechanisms explaining this complex triad. © 2012 Z. N. Sohani and Z. Samaan.

Loading Population Health Research Institute collaborators
Loading Population Health Research Institute collaborators