Publications by authors named "Salim Yusuf"

938 Publications

LVS-HARMED Risk Score for Incident Heart Failure in Patients With Atrial Fibrillation Who Present to the Emergency Department: Data from a World-Wide Registry.

J Am Heart Assoc 2021 Sep 13;10(18):e017735. Epub 2021 Sep 13.

Population Health Research Institute McMaster University Hamilton Onatrio Canada.

Background Heart failure (HF) is a common complication to atrial fibrillation (AF), leading to rehospitalization and death. Early identification of patients with AF at risk for HF might improve outcomes. We aimed to derive a score to predict 1-year risk of new-onset HF after an emergency department (ED) visit with AF. Methods and Results The RE-LY AF (Randomized Evaluation of Long-Term Anticoagulant Therapy) registry enrolled patients with AF presenting to an ED in 47 countries, and followed them for a year. The end point was HF hospitalization and/or HF death. Among 15 400 ED patients, 9765 had no prior HF (mean age, 64.9±14.9 years). Within 1 year, new-onset HF developed in 6.8% of patients, of whom 21% died of HF. Independent predictors of HF included left ventricular hypertrophy (odds ratio [OR], 1.47; 95% CI, 1.19-1.82), valvular heart disease (OR, 1.55; 95% CI, 1.18-2.04), smoking (OR, 1.42; 95% CI, 1.12-1.78), height (OR, 0.93; 95% CI, 0.90-0.95 per 3 cm), age (OR, 1.11; 95% CI, 1.07-1.15 per 5 years), rheumatic heart disease (OR, 1.77, 95% CI, 1.24-2.51), prior myocardial infarction (OR, 1.85; 95% CI, 1.45-2.36), remaining in AF at ED discharge (OR, 1.86; 95% CI, 1.46-2.36), and diabetes (OR, 1.33; 95% CI, 1.09-1.64). A continuous risk prediction score (LVS-HARMED [left ventricular, valvular heart disease, smoking or other tobacco use, height, age, rheumatic heart disease, myocardial infarction, emergency department discharge rhythm, and diabetes]) had good discrimination (C statistic, 0.735; 95% CI, 0.716-0.755). Validation was conducted internally using bootstrapping (optimism-corrected C statistic, 0.705) and externally (C statistic, 0.699). The 1-year incidence of HF hospitalization and/or HF death across quartile groups of the score was 1.1%, 4.5%, 6.9%, and 14.4%, respectively. LVS-HARMED also predicted incident stroke (C statistic, 0.753; 95% CI, 0.728-0.778). Conclusions The LVS-HARMED score predicts new-onset HF after an ED visit for AF. Preventative strategies should be considered in patients with high LVS-HARMED HF risk.
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http://dx.doi.org/10.1161/JAHA.120.017735DOI Listing
September 2021

Effect of Cognitive Reserve on the Association of Vascular Brain Injury With Cognition: Analysis of the PURE and CAHHM Studies.

Neurology 2021 Sep 9. Epub 2021 Sep 9.

Department of Social Medicine, Wroclaw Medical University.

Objective: To determine whether cognitive reserve attenuates the association of vascular brain injury with cognition.

Methods: Cross-sectional data were analyzed from two harmonized studies: the Canadian Alliance for Healthy Hearts and Healthy Minds (CAHHM) and the Prospective Urban and Rural Epidemiology (PURE) study. Markers of cognitive reserve were education, involvement in social activities, marital status, height, and leisure physical activity, which were combined into a composite score. Vascular brain injury was defined asnon-lacunar brain infarcts or high white matter hyperintensity (WMH) burden on MRI. Cognition was assessed using the Montreal Cognitive Assessment Tool (MoCA) and the Digit Symbol Substitution Test (DSST).

Results: There were 10,450 participants age 35-81. Mean age was 58.8 years (range 35 to 81) and 55.8% were female. Education, moderate leisure physical activity, being in a marital partnership, being taller, and participating in social groups were each independently associated with higher cognition, as was the composite cognitive reserve score. Vascular brain injury was associated with lower cognition (beta-0.35 [95% CI -0.53 to -0.17] for MoCA and beta -2.19 [95% CI-3.22 to -1.15] for DSST)-but the association was not modified by the composite cognitive reserve variable (interaction p=0.59 for MoCA and p=0.72 for DSST).

Conclusions: Both vascular brain injury and markers of cognitive reserve are associated with cognition. However, the effects were independent such that the adverse effects of covert vascular brain injury were not attenuated by higher cognitive reserve. To improve cognitive brain health, interventions to both prevent cerebrovascular disease and promote positive lifestyles are needed.
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http://dx.doi.org/10.1212/WNL.0000000000012765DOI Listing
September 2021

Fixed-dose combination therapies with and without aspirin for primary prevention of cardiovascular disease: an individual participant data meta-analysis.

Lancet 2021 Aug 27. Epub 2021 Aug 27.

Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada. Electronic address:

Background: In randomised controlled trials, fixed-dose combination treatments (or polypills) have been shown to reduce a composite of cardiovascular disease outcomes in primary prevention. However, whether or not aspirin should be included, effects on specific outcomes, and effects in key subgroups are unknown.

Methods: We did an individual participant data meta-analysis of large randomised controlled trials (each with ≥1000 participants and ≥2 years of follow-up) of a fixed-dose combination treatment strategy versus control in a primary cardiovascular disease prevention population. We included trials that evaluated a fixed-dose combination strategy of at least two blood pressure lowering agents plus a statin (with or without aspirin), compared with a control strategy (either placebo or usual care). The primary outcome was time to first occurrence of a composite of cardiovascular death, myocardial infarction, stroke, or arterial revascularisation. Additional outcomes included individual cardiovascular outcomes and death from any cause. Outcomes were also evaluated in groups stratified by the inclusion of aspirin in the fixed-dose treatment strategy, and effect sizes were estimated in prespecified subgroups based on risk factors. Kaplan-Meier survival curves and Cox proportional hazard regression models were used to compare strategies.

Findings: Three large randomised trials were included in the analysis (TIPS-3, HOPE-3, and PolyIran), with a total of 18 162 participants. Mean age was 63·0 years (SD 7·1), and 9038 (49·8%) participants were female. Estimated 10-year cardiovascular disease risk for the population was 17·7% (8·7). During a median follow-up of 5 years, the primary outcome occurred in 276 (3·0%) participants in the fixed-dose combination strategy group compared with 445 (4·9%) in the control group (hazard ratio 0·62, 95% CI 0·53-0·73, p<0·0001). Reductions were also observed for the separate components of the primary outcome: myocardial infarction (0·52, 0·38-0·70), revascularisation (0·54, 0·36-0·80), stroke (0·59, 0·45-0·78), and cardiovascular death (0·65, 0·52-0·81). Significant reductions in the primary outcome and its components were observed in the analyses of fixed-dose combination strategies with and without aspirin, with greater reductions for strategies including aspirin. Treatment effects were similar at different lipid and blood pressure levels, and in the presence or absence of diabetes, smoking, or obesity. Gastrointestinal bleeding was uncommon but slightly more frequent in the fixed-dose combination strategy with aspirin group versus control (19 [0·4%] vs 11 [0·2%], p=0·15). The frequencies of haemorrhagic stroke (10 [0·2%] vs 15 [0·3%]), fatal bleeding (two [<0·1%] vs four [0·1%]), and peptic ulcer disease (32 [0·7%] vs 34 [0·8%]) were low and did not differ significantly between groups. Dizziness was more common with fixed-dose combination treatment (1060 [11·7%] vs 834 [9·2%], p<0·0001).

Interpretation: Fixed-dose combination treatment strategies substantially reduce cardiovascular disease, myocardial infarction, stroke, revascularisation, and cardiovascular death in primary cardiovascular disease prevention. These benefits are consistent irrespective of cardiometabolic risk factors.

Funding: Population Health Research Institute.
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http://dx.doi.org/10.1016/S0140-6736(21)01827-4DOI Listing
August 2021

Low-dose rivaroxaban and aspirin among patients with peripheral artery disease: a meta-analysis of the COMPASS and VOYAGER trials.

Eur J Prev Cardiol 2021 Aug 31. Epub 2021 Aug 31.

Department of Cardiology, University of Colorado School of Medicine, 13001 E 17th Pl, Boulder, Colorado 80045, USA.

Aims: Peripheral artery disease (PAD) patients suffer a high risk of major cardiovascular (CV) events, with athero-thrombo-embolism as the underlying pathophysiologic mechanism. Recently, two large randomized clinical trials evaluated the efficacy and safety of low-dose rivaroxaban twice daily plus aspirin in stable PAD outpatients and those immediately after peripheral revascularization. We sought to determine if the effects of low-dose rivaroxaban and aspirin compared to aspirin alone are consistent across this broad spectrum of PAD patients.

Methods And Results: We conducted a random-effects meta-analysis of the COMPASS and VOYAGER randomized trials among 11 560 PAD patients (4996 from COMPASS and 6564 from VOYAGER) in the primary analysis and 9332 (2768 from COMPASS and 6564 from VOYAGER) with lower extremity (LE)-PAD in the secondary analysis. The hazard ratio (HR) for the composite of CV death, myocardial infarction, ischaemic stroke, acute limb ischaemia, or major vascular amputation was 0.79 (95% confidence interval, CI: 0.65-0.95) comparing low-dose rivaroxaban plus aspirin to aspirin alone. While the risk of major bleeding was increased with low-dose rivaroxaban plus aspirin compared to aspirin alone [HR: 1.51 (95% CI: 1.22-1.87)], there was no significant increase in severe bleeding [HR: 1.18 (95% CI: 0.79-1.76)]. Similar effects were observed in the subset with symptomatic LE-PAD.

Conclusions: Among PAD patients, low-dose rivaroxaban plus aspirin is superior to aspirin alone in reducing CV and limb outcomes including acute limb ischaemia and major vascular amputation. This reduction is offset by a relative increase in major bleeding, but not by an excess of fatal or critical organ bleeding. The consistency of findings of these trials supports the use of combination low-dose rivaroxaban plus aspirin in PAD patients across a broad spectrum of disease.
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http://dx.doi.org/10.1093/eurjpc/zwab128DOI Listing
August 2021

Measuring sodium intake: research and clinical applications.

J Hypertens 2021 Aug 20. Epub 2021 Aug 20.

HRB-Clinical Research Facility, NUI Galway, Galway, Ireland Population Health Research Institute, Hamilton Health Sciences and McMaster University, Ontario, Canada.

Although most current guidelines recommend a daily sodium intake of less than 2.3 g/day, most people do not have a reliable estimate of their usual sodium intake. In this review, we describe the different methods used to estimate sodium intake and discuss each method in the context of specific clinical or research questions. We suggest the following classification for sodium measurement methods: preingestion measurement (controlled intake), peri-ingestion measurement (concurrent), and postingestion measurement. On the basis of the characteristics of the available tools, we suggest that: validated 24-h recall methods are a reasonable approach to estimate sodium intake in large epidemiologic studies and individual clinical counselling sessions, methods (such as single 24-h urine collection, single-time urine collection, or 24-h recall methods), are of value in population-level estimation of mean sodium intake, but are less suited for individual level estimation and a feeding-trial design using a controlled diet is the most valid and reliable method for establishing the effect of reducing sodium to a specific intake target in early phase clinical trials. By considering the various approaches to sodium measurement, investigators and public health practitioners may be better informed in assessing the health implications of sodium consumption at the individual and population level.
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http://dx.doi.org/10.1097/HJH.0000000000002951DOI Listing
August 2021

Multiplex protein screening of biomarkers associated with major bleeding in patients with atrial fibrillation treated with oral anticoagulation.

J Thromb Haemost 2021 Aug 14. Epub 2021 Aug 14.

Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.

Background: Oral anticoagulants (OAC) in patients with atrial fibrillation (AF) prevent thromboembolic events, but are associated with significant risk of bleeding.

Objectives: To explore associations between a wide range of biomarkers and bleeding risk in patients with AF on OAC.

Method: Biomarkers were analyzed in a random sample of 4200 patients, 204 cases with major bleedings, from ARISTOTLE. The replication cohort included 344 cases with major bleeding and 1024 random controls from RE-LY. Plasma samples obtained at randomization were analyzed by the Olink Proximity Extension Assay cardiovascular and inflammation panels and conventional immunoassays. The associations between biomarker levels and major bleeding over 1 to 3 years of follow-up were evaluated by random survival forest/Boruta analyses and Cox regression analyses to assess linear associations and hazard ratios for identified biomarkers.

Results: Out of 268 proteins, nine biomarkers were independently associated with bleeding in both cohorts. In the replication cohort the linear hazard ratios (95% confidence intervals) per interquartile range were for these biomarkers: TNF-R1 1.748 (1.456, 2.098), GDF-15 1.653 (1.377, 1.985), EphB4 1.575 (1.320, 1.880), suPAR 1.548 (1.294, 1.851), OPN 1.476 (1.240, 1.757), OPG 1.397 (1.156, 1.688), TNF-R2 1.360 (1.144,1.616), cTnT-hs 1.232 (1.067, 1.423), and TRAIL-R2 1.202 (1.069, 1.351).

Conclusions: In patients with AF on OAC, GDF-15, cTnT-hs, and seven novel biomarkers were independently associated with major bleedings and reflect pathophysiologic processes of inflammation, apoptosis, oxidative stress, vascular calcification, coagulation, and fibrinolysis. Investigations of the utility of these markers to refine risk stratification and guide the management of patients at high risk of bleeding are warranted.
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http://dx.doi.org/10.1111/jth.15498DOI Listing
August 2021

Clinical Profiles and Outcomes of Heart Failure in Five African Countries: Results from INTER-CHF Study.

Glob Heart 2021 30;16(1):50. Epub 2021 Jul 30.

Population Health Research Institute, McMaster University, Hamilton, CA.

Background: A wide knowledge gap exists on the clinical profiles and outcomes of heart failure (HF) in sub-Saharan Africa.

Objectives: To determine the clinical profiles and outcomes of HF patients from five African countries.

Methods: The INTERnational Congestive Heart Failure Study (INTER-CHF) is a prospective, multicenter cohort study. A total of 1,294 HF patients were consecutively recruited from Nigeria (383 patients), South Africa (169 patients), Sudan (501 patients), Uganda (151patients), and Mozambique (90 patients). HF was defined according to the Boston criteria for diagnosis. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) score.

Results: Of the 1294 patients, 51.4% were recruited as out-patients, 53.7% had HF with reduced ejection fraction (EF), 30.1% had HF with mid-range EF and 16.2% had HF with preserved EF (16.2%). The commonest etiologies of HF were hypertensive heart disease (35%) and ischemic heart disease (20%). The mean MoCA score was highest in Uganda (24.3 ± 1.1) and lowest in Sudan (13.6 ± 0.3). Prescriptions for guideline-recommended HF therapies were poor; only 1.2% of South African patients received an Implantable Cardioverter Defibrillator, and none of the patients received Cardiac Resynchronised Therapy. The composite outcome of death or HF hospitalization at one year among the patients was highest in Sudan (59.7%) and lowest in Mozambique (21.1%). Six variables were associated with higher mortality risk, while digoxin use (adjusted hazard ratio [aHR]: 0.69; 95% confidence interval [CI]: 0.49-0.97; p = 0.034) and 10mmHg unit increase in systolic blood pressure (aHR 0.86; 95%CI 0.81-0.93; p < 0.001) were associated with lower risk for mortality.

Conclusions: This is the largest HF study in Africa that included in- and out-patients from the West, East, North, Central and South African sub-regions. Clinically relevant differences, including cognitive functional impairment, were found between the involved countries.
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http://dx.doi.org/10.5334/gh.940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323533PMC
July 2021

Using multimarker screening to identify biomarkers associated with cardiovascular death in patients with atrial fibrillation.

Cardiovasc Res 2021 Aug 6. Epub 2021 Aug 6.

Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.

Aims: Atrial fibrillation (AF) is associated with higher mortality. Biomarkers may improve the understanding of key pathophysiologic processes in AF that lead to death. Using a new multiplex analytic technique, we explored the association between 268 biomarkers and cardiovascular (CV) death in anticoagulated patients with AF.

Methods And Results: A case-cohort design with 1.8 -1.9 years follow-up. The identification cohort included 517 cases and 4057 randomly selected patients from ARISTOTLE. The validation cohort included 277 cases and 1042 randomly selected controls from RE-LY. Plasma collected at randomization was analyzed with conventional immunoassays and the OLINK proximity extension assay-panels; CVDII, CVDIII, and Inflammation. Association between biomarkers and CV-death was evaluated using Random Survival Forest, Boruta and adjusted Cox-regression analyses.The biomarkers most strongly and consistently associated with CV-death were (hazard ratio for inter-quartile comparison [95% CI]): N-terminal pro-B-type natriuretic peptide (NT-proBNP; 1.63 [1.37-1.93]), cardiac troponin T (cTnT-hs; 1.60[1.35-1.88]), interleukin-6 (IL-6; 1.29[1.13-1.47]), growth differentiation factor-15 (GDF-15; 1.30[1.10-1.53]) fibroblast growth factor 23 (FGF-23; 1.21[1.10-1.33]), urokinase receptor (uPAR; 1.38[1.16-1.64]), trefoil factor 3 (TFF3; 1.27[1.10-1.46]), tumor necrosis factor receptor 1 (TNFR1; 1.21[1.01-1.45]), TNF-related apoptosis-inducing ligand receptor 2 (TRAILR2; 1.18[1.04-1.34]) and cathepsin L1 (CTSL1; 1.22[1.07-1.39]).

Conclusion: In this comprehensive screening of 268 biomarkers in anticoagulated patients with AF the underlying mechanisms most strongly associated with CV-death were cardiorenal dysfunction (NT-proBNP, cTnT-hs, CTSL1, TFF3), oxidative stress (GDF-15), inflammation (IL-6, GDF-15), calcium balance, vascular and renal dysfunction (FGF-23), fibrinolysis (suPAR) and apoptosis (TNFR1, TRAILR2). These findings provide novel insights into pathophysiologic aspects associated with CV-death in AF.

Translational Perspective: In patients with AF there is an unmet need for better understanding of the pathophysiological processes involved with CV-death. Using a targeted proteomic approach, 10 biomarkers were identified as having a strong association with CV-death. The identified biomarkers reflect several biological pathways involved with CV-death in AF. The present study provides valuable insights into important processes involved with CV-death in patients with AF and may facilitate the identification of important risk factors for death, thus allowing for earlier intervention and possibly even for targeted therapy to reduce AF-related mortality.

Clinicaltrials.gov Identifier: NCT00412984 and NCT00262600.
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http://dx.doi.org/10.1093/cvr/cvab262DOI Listing
August 2021

Prevalence of metabolic syndrome and diabetes mellitus type-2 and their association with intake of dairy and legume in Andean communities of Ecuador.

PLoS One 2021 23;16(7):e0254812. Epub 2021 Jul 23.

Masira Research Institute, Medical School, Santander University (UDES), Santander, Colombia.

Metabolic syndrome (MetS) and type 2 diabetes (T2D) are metabolic alterations associated with high morbidity and mortality, particularly in low and middle-income countries. Diet has a significant impact on the risk to develop MetS and T2D; in this regard, consumption of fruits, vegetables, and protein rich foods (from plant and animals) are important to prevent and manage these pathologies. There are limited studies regarding the potential association between Andean foods rich in proteins and the presence of cardio-metabolic conditions in Ecuador. It is necessary to develop new low-cost, local-culturally acceptable strategies to reduce the burden of cardio-metabolic diseases. We describe the prevalence (baseline data) of MetS and T2D in the Ecuadorian cohort of the Prospective Urban and Rural Epidemiology (PURE) study and their potential association with the consumption of protein rich foods, including beef, white meat, dairy and legumes. In this cross-sectional study, we assessed 1,997 individuals aged 35-70 years (mean age 51 years, 72% women), included in the Ecuadorian cohort of the PURE study, from February to December 2018. The prevalence of MetS was 42% for male and 44% for female participants; the prevalence of T2D was 9% for male and 10% for female. Metabolic syndrome and T2D were more common in women older than 50 years of age with primary education or less, low economic income, and with obesity; MetS was more frequent in the rural area while T2D was more frequent in the urban area. Using logistic regression analysis, we observed a significant protective effect of higher consumption of dairy and legumes in the prevalence of MetS and T2D compared with low consumption. It will be important to develop policies for ample production and consumption of protein rich foods such as legumes and dairy, part of traditional diets, to reduce the burden of cardio-metabolic diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254812PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301611PMC
July 2021

Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality. Reply.

N Engl J Med 2021 07;385(4):379-380

Population Health Research Institute, Hamilton, ON, Canada.

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http://dx.doi.org/10.1056/NEJMc2107926DOI Listing
July 2021

Association of ultra-processed food intake with risk of inflammatory bowel disease: prospective cohort study.

BMJ 2021 07 14;374:n1554. Epub 2021 Jul 14.

Hatta Hospital, Dubai Medical University, Dubai Health Authority, Dubai, United Arab Emirates.

Objective: To evaluate the relation between intake of ultra-processed food and risk of inflammatory bowel disease (IBD).

Design: Prospective cohort study.

Setting: 21 low, middle, and high income countries across seven geographical regions (Europe and North America, South America, Africa, Middle East, south Asia, South East Asia, and China).

Participants: 116 087 adults aged 35-70 years with at least one cycle of follow-up and complete baseline food frequency questionnaire (FFQ) data (country specific validated FFQs were used to document baseline dietary intake). Participants were followed prospectively at least every three years.

Main Outcome Measures: The main outcome was development of IBD, including Crohn's disease or ulcerative colitis. Associations between ultra-processed food intake and risk of IBD were assessed using Cox proportional hazard multivariable models. Results are presented as hazard ratios with 95% confidence intervals.

Results: Participants were enrolled in the study between 2003 and 2016. During the median follow-up of 9.7 years (interquartile range 8.9-11.2 years), 467 participants developed incident IBD (90 with Crohn's disease and 377 with ulcerative colitis). After adjustment for potential confounding factors, higher intake of ultra-processed food was associated with a higher risk of incident IBD (hazard ratio 1.82, 95% confidence interval 1.22 to 2.72 for ≥5 servings/day and 1.67, 1.18 to 2.37 for 1-4 servings/day compared with <1 serving/day, P=0.006 for trend). Different subgroups of ultra-processed food, including soft drinks, refined sweetened foods, salty snacks, and processed meat, each were associated with higher hazard ratios for IBD. Results were consistent for Crohn's disease and ulcerative colitis with low heterogeneity. Intakes of white meat, red meat, dairy, starch, and fruit, vegetables, and legumes were not associated with incident IBD.

Conclusions: Higher intake of ultra-processed food was positively associated with risk of IBD. Further studies are needed to identify the contributory factors within ultra-processed foods.

Study Registration: ClinicalTrials.gov NCT03225586.
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http://dx.doi.org/10.1136/bmj.n1554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279036PMC
July 2021

Mortality Benefit of Rivaroxaban Plus Aspirin in Patients With Chronic Coronary or Peripheral Artery Disease.

J Am Coll Cardiol 2021 07;78(1):14-23

Population Health Research Institute, Hamilton Ontario, Canada; Hamilton Health Sciences, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Background: The combination of 2.5 mg rivaroxaban twice daily and 100 mg aspirin once daily compared with 100 mg aspirin once daily reduces major adverse cardiovascular (CV) events in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD).

Objectives: The aim of this work was to report the effects of the combination on overall and cause-specific mortality.

Methods: The COMPASS trial enrolled 27,395 patients of whom 18,278 were randomized to the combination (n = 9,152) or aspirin alone (n = 9,126). Deaths were adjudicated by a committee blinded to treatment allocation. Previously identified high-risk baseline features were polyvascular disease, chronic kidney disease, mild or moderate heart failure, and diabetes.

Results: During a median of 23 months of follow-up (maximum 47 months), 313 patients (3.4%) allocated to the combination and 378 patients (4.1%) allocated to aspirin alone died (hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.71-0.96; P = 0.01). Compared with aspirin, the combination reduced CV death (160 [1.7%] vs 203 [2.2%]; HR: 0.78; 95% CI: 0.64-0.96; P = 0.02) but not non-CV death. There were fewer deaths following MI, stroke, and CV procedures, as well as fewer sudden cardiac, other, and unknown causes of CV deaths and coronary heart disease deaths. Patients with 0, 1, 2, and 3 or 4 high-risk features at baseline had 4.2, 4.8, 25.0, and 53.9 fewer deaths, respectively, per 1000 patients treated for 30 months.

Conclusions: The combination of rivaroxaban and aspirin compared with aspirin reduced overall and CV mortality with consistent reductions in cause specific CV mortality in patients with chronic CAD or PAD. The absolute mortality benefits are greater with increasing baseline risk. (Cardiovascular Outcomes for People Using Anticoagulant Strategies [COMPASS]; NCT01776424).
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http://dx.doi.org/10.1016/j.jacc.2021.04.083DOI Listing
July 2021

Low-dose rivaroxaban plus aspirin in patients with polypharmacy and multimorbidity: an analysis from the COMPASS trial.

Eur Heart J Cardiovasc Pharmacother 2021 Jun 30. Epub 2021 Jun 30.

Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada.

Background: In patients with coronary or peripheral arterial disease, adding low dose rivaroxaban to aspirin reduces cardiovascular events and mortality. Polypharmacy and multimorbidity are frequent in such patients.

Aims: To analyze whether the benefits and risks of rivaroxaban plus aspirin varies in patients with comorbidities and receiving multiple drugs.

Methods And Results: We describe ischemic events (cardiovascular death, stroke, or myocardial infarction) and major bleeding in participants from the randomised, double-blind COMPASS study by number of cardiovascular medications and concomitant medical conditions. We compared event rates and hazard ratios (HR) for rivaroxaban plus aspirin versus aspirin alone by the number of medications and concomitant conditions, and tested for interaction between polypharmacy or multimorbidity and the antithrombotic regimen.The risk of ischemic events was higher in patients with more concomitant drugs (HR 1.7, 95%CI 1.5-2.1 for >4 vs 0-2) and with more comorbidities (HR 2.3, 1.8-2.1 for >3 vs 0-1). Multimorbidity, but not polypharmacy, was associated with a higher risk of major bleeding. The relative efficacy, safety, and net clinical benefit of rivaroxaban were not affected by the number of drugs or comorbidities. Patients taking more concomitant medications derived the largest absolute reduction in the net clinical outcome with added rivaroxaban (1.1% vs 0.4% reduction with >4 vs 0-2 cardiovascular drugs, NNT 91 vs 250).

Conclusion: Adding low-dose rivaroxaban to aspirin resulted in benefits irrespective of the number of concomitant drugs or comorbidities. Multiple comorbidities and/or polypharmacy should not dissuade the addition of rivaroxaban to aspirin in otherwise eligible patients.
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http://dx.doi.org/10.1093/ehjcvp/pvab050DOI Listing
June 2021

Timing and Length of Nocturnal Sleep and Daytime Napping and Associations With Obesity Types in High-, Middle-, and Low-Income Countries.

JAMA Netw Open 2021 Jun 1;4(6):e2113775. Epub 2021 Jun 1.

Population Health Research Institute, McMaster University, Hamilton, Canada.

Importance: Obesity is a growing public health threat leading to serious health consequences. Late bedtime and sleep loss are common in modern society, but their associations with specific obesity types are not well characterized.

Objective: To assess whether sleep timing and napping behavior are associated with increased obesity, independent of nocturnal sleep length.

Design, Setting, And Participants: This large, multinational, population-based cross-sectional study used data of participants from 60 study centers in 26 countries with varying income levels as part of the Prospective Urban Rural Epidemiology study. Participants were aged 35 to 70 years and were mainly recruited during 2005 and 2009. Data analysis occurred from October 2020 through March 2021.

Exposures: Sleep timing (ie, bedtime and wake-up time), nocturnal sleep duration, daytime napping.

Main Outcomes And Measures: The primary outcomes were prevalence of obesity, specified as general obesity, defined as body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or greater, and abdominal obesity, defined as waist circumference greater than 102 cm for men or greater than 88 cm for women. Multilevel logistic regression models with random effects for study centers were performed to calculate adjusted odds ratios (AORs) and 95% CIs.

Results: Overall, 136 652 participants (81 652 [59.8%] women; mean [SD] age, 51.0 [9.8] years) were included in analysis. A total of 27 195 participants (19.9%) had general obesity, and 37 024 participants (27.1%) had abdominal obesity. The mean (SD) nocturnal sleep duration was 7.8 (1.4) hours, and the median (interquartile range) midsleep time was 2:15 am (1:30 am-3:00 am). A total of 19 660 participants (14.4%) had late bedtime behavior (ie, midnight or later). Compared with bedtime between 8 pm and 10 pm, late bedtime was associated with general obesity (AOR, 1.20; 95% CI, 1.12-1.29) and abdominal obesity (AOR, 1.20; 95% CI, 1.12-1.28), particularly among participants who went to bed between 2 am and 6 am (general obesity: AOR, 1.35; 95% CI, 1.18-1.54; abdominal obesity: AOR, 1.38; 95% CI, 1.21-1.58). Short nocturnal sleep of less than 6 hours was associated with general obesity (eg, <5 hours: AOR, 1.27; 95% CI, 1.13-1.43), but longer napping was associated with higher abdominal obesity prevalence (eg, ≥1 hours: AOR, 1.39; 95% CI, 1.31-1.47). Neither going to bed during the day (ie, before 8pm) nor wake-up time was associated with obesity.

Conclusions And Relevance: This cross-sectional study found that late nocturnal bedtime and short nocturnal sleep were associated with increased risk of obesity prevalence, while longer daytime napping did not reduce the risk but was associated with higher risk of abdominal obesity. Strategic weight control programs should also encourage earlier bedtime and avoid short nocturnal sleep to mitigate obesity epidemic.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.13775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246307PMC
June 2021

Cardiovascular outcomes in patients at high cardiovascular risk with previous myocardial infarction or stroke.

J Hypertens 2021 Aug;39(8):1602-1610

Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Saarland University, Homburg.

Background: Guidelines recommend to start blood pressure (BP)-lowering drugs also according to cardiovascular risk including history of cardiovascular events. We hypothesized that in patients with a history of myocardial infarction (MI), stroke, both or none of those, the index events predict the next event and have different SBP risk associations to different cardiovascular outcomes.

Design And Measurements: In this pooled posthoc, nonprespecified analysis, we assessed outcome data from high-risk patients aged 55 years or older with a history of cardiovascular events or proven cardiovascular disease, randomized to the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial and to Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease Trial investigating telmisartan, ramipril and their combination with a median follow-up of 56 months. Standardized office BP was measured every 6 months. Associations of mean achieved BP on treatment were investigated on MI, stroke and cardiovascular death. We identified patients with previous MI (N = 13 487), stroke (N = 4985), both (N = 1509) or none (N = 10 956) of these index events. Analyses were done by Cox regression, analysis of variance and Chi2-test. 30 937 patients with complete data were enrolled between 1 December 2001 and 31 July 2003, and followed until 31 July 2008. Data of both trials were pooled as the outcomes were similar.

Results: Patients with MI as index event had a higher risk to experience a second MI [hazard ratio 1.42 (confidence interval (CI) 1.20-1.69), P < 0.0001] compared with patients with no events but no increased risk for a stroke as a next event [hazard ratio 0.95 (CI 0.73-1.23), n.s.]. The risk was roughly doubled when they had both, MI and stroke before [hazard ratio 2.07 (CI 1.58-2.71), P < 0.0001]. Patients with a stroke history had a roughly three-fold higher likelihood to experience a second stroke [hazard ratio 2.89 (CI 2.37-3.53) P < 0.0001] but not MI [hazard ratio 1.07 (CI 0.88-1.32), n.s.]. Both types of index events increased roughly three-fold the risk of a second stroke compared with no previous events. The SBP-risk relationship was not meaningfully altered by the event history. After MI and stroke the risk for subsequent events and cardiovascular death was increased over the whole SBP spectrum. A J-shape relationship between BP and outcome was only observed for cardiovascular death.

Conclusion: Previous MI and previous stroke are associated with increased risk for the same event in the future, independent of achieved SBP. Thus, secondary prevention may also be chosen according to the event history of patients.

Clinical Trial Registration: http://clinicaltrials.gov. Unique identifier: NCT00153101.
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http://dx.doi.org/10.1097/HJH.0000000000002822DOI Listing
August 2021

Fishing for an Association With Sudden Cardiac Death-Reply.

JAMA Intern Med 2021 Aug;181(8):1140-1141

Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada.

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http://dx.doi.org/10.1001/jamainternmed.2021.3036DOI Listing
August 2021

Skeletonized vs Pedicled Internal Mammary Artery Graft Harvesting in Coronary Artery Bypass Surgery: A Post Hoc Analysis From the COMPASS Trial.

JAMA Cardiol 2021 Jun 16. Epub 2021 Jun 16.

Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada.

Importance: The relative safety and patency of skeletonized vs pedicled internal mammary artery grafts in patients undergoing coronary artery bypass graft (CABG) surgery are unknown.

Objective: To investigate the association of skeletonized vs pedicled harvesting with internal mammary artery graft patency and clinical outcomes 1 year after CABG surgery.

Design, Setting, And Participants: This study was a post hoc analysis of the multicenter, randomized, double-blind, placebo-controlled Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) clinical trial, which enrolled 27 395 patients from 602 centers in 33 countries from March 2013 through May 2016. Eligibility criteria for the trial included CABG surgery for coronary artery disease with at least 2 grafts implanted and an estimated glomerular filtration rate of at least 30 mL/min. A total of 1002 of 1448 patients were randomized to the CABG arm of the COMPASS trial and underwent skeletonized (282 [28.1%]) or pedicled (720 [71.9%]) internal mammary artery harvesting. The patients had evaluable angiography results 1 year after surgery. Data were analyzed from October 11, 2019, to May 14, 2020.

Interventions: Patients underwent graft harvesting with either the pedicled technique or skeletonized technique.

Main Outcomes And Measures: The primary outcome was graft occlusion 1 year after CABG surgery, as assessed by computed tomography angiography.

Results: A total of 1002 patients underwent skeletonized (282 [28.1%]; mean [SD] age, 65.9 [8.1] years; 229 men [81.2%]; 194 White patients [68.8%]) or pedicled (720 [71.9%]; mean [SD] age, 64.8 [7.6] years; 603 men [83.8%]; 455 White patients [63.2%]) internal mammary artery harvesting. Rates of internal mammary artery graft occlusion 1 year after CABG surgery were higher in the skeletonized group than in the pedicled group (33 of 344 [9.6%] vs 30 of 764 [3.9%]; graft-level adjusted odds ratio, 2.41; 95% CI, 1.39-4.20; P = .002), including the left internal mammary artery to left anterior descending artery (21 of 289 [7.3%] vs 25 of 725 [3.4%]; graft-level adjusted odds ratio, 2.10; 95% CI, 1.14-3.88, P = .02). After a mean follow-up of 23 months, skeletonized graft harvesting was also associated with a higher rate of major adverse cardiovascular events (20 [7.1%] vs 15 [2.1%]; adjusted hazard ratio, 3.19; 95% CI, 1.53-6.67; P = .002) and repeated revascularization (14 [5.0%] vs 10 [1.4%]; adjusted hazard ratio, 2.75; 95% CI, 1.10-6.88; P = .03).

Conclusions And Relevance: This post hoc analysis of the COMPASS randomized clinical trial found that harvesting of the internal mammary artery during CABG surgery using a skeletonized technique was associated with a higher rate of graft occlusion and worse clinical outcomes than the traditional pedicled technique. Future randomized clinical trials are needed to establish the safety and patency of the skeletonized technique.

Trial Registration: ClinicalTrials.gov Identifier: NCT01776424.
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http://dx.doi.org/10.1001/jamacardio.2021.1686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209583PMC
June 2021

Does a High-inflammatory Diet Increase the Risk of Inflammatory Bowel Disease? Results From the Prospective Urban Rural Epidemiology (PURE) Study: A Prospective Cohort Study.

Gastroenterology 2021 Jun 10. Epub 2021 Jun 10.

Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.

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http://dx.doi.org/10.1053/j.gastro.2021.06.007DOI Listing
June 2021

Reply.

J Hypertens 2021 Jul;39(7):1467-1469

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing.

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http://dx.doi.org/10.1097/HJH.0000000000002874DOI Listing
July 2021

New-Onset Perioperative Atrial Fibrillation After Coronary Artery Bypass Grafting and Long-Term Risk of Adverse Events: An Analysis From the CORONARY Trial.

J Am Heart Assoc 2021 Jun 29;10(12):e020426. Epub 2021 May 29.

Population Health Research Institute McMaster University Hamilton Canada.

Background Perioperative atrial fibrillation (POAF) is common in patients undergoing cardiac surgery. Conflicting evidence exists whether patients with POAF after cardiac surgery have an increased long-term risk of stroke and other adverse events. Methods and Results We prospectively followed for up to 5 years 4624 patients without prior atrial fibrillation who underwent coronary artery bypass grafting in an international study. POAF was defined as atrial fibrillation that occurred during the initial hospitalization for surgery, lasted for ≥5 minutes, and required treatment. Outcomes assessed were a composite of death, nonfatal myocardial infarction or nonfatal stroke, and its individual components. Median age was 67 years, and 778 (16.8%) had an episode of POAF. The incidence of the composite outcome was 6.84 and 4.10 per 100 patient-years in patients with and without POAF, and the incidence of stroke was 0.75 versus 0.45, respectively. The adjusted hazard ratios (aHRs) were 1.36 (95% CI, 1.16-1.59) for the composite outcome; 1.33 (95% CI, 1.10-1.61) for death; 1.58 (95% CI, 1.23-2.02) for myocardial infarction, and 1.27 (95% CI, 0.81-2.00) for stroke. In a landmark analysis excluding events of the initial hospital admission, the aHRs were 1.26 (95% CI, 1.03-1.54) for the composite outcome, 1.28 (95% CI, 1.03-1.59) for death, 1.70 (95% CI, 0.86-3.36) for myocardial infarction, and 1.07 (95% CI, 0.59-1.93) for stroke. At hospital discharge, 10.7% and 1.4% of patients with and without POAF received oral anticoagulation, respectively. Conclusions Patients with POAF after cardiac surgery had an increased long-term risk of adverse outcomes, mainly death and myocardial infarction. The risk of stroke was low and not increased in patients with POAF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00463294.
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http://dx.doi.org/10.1161/JAHA.120.020426DOI Listing
June 2021

Cardiovascular consequences of discontinuing low-dose rivaroxaban in people with chronic coronary or peripheral artery disease.

Heart 2021 Jul 21;107(14):1130-1137. Epub 2021 May 21.

Population Health Research Institute, Hamilton Health Sciences/McMaster University, Hamilton, Ontario, Canada.

Objective: In patients with chronic coronary or peripheral artery disease enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies trial, randomised antithrombotic treatments were stopped after a median follow-up of 23 months because of benefits of the combination of rivaroxaban 2.5 mg two times per day and aspirin 100 mg once daily compared with aspirin 100 mg once daily. We assessed the effect of switching to non-study aspirin at the time of early stopping.

Methods: Incident composite of myocardial infarction, stroke or cardiovascular death was estimated per 100 person-years (py) during randomised treatment (n=18 278) and after study treatment discontinuation to non-study aspirin (n=14 068).

Results: During randomised treatment, the combination compared with aspirin reduced the composite (2.2 vs 2.9/100 py, HR: 0.76, 95% CI 0.66 to 0.86), stroke (0.5 vs 0.8/100 py, HR: 0.58, 95% CI 0.44 to 0.76) and cardiovascular death (0.9 vs 1.2/100 py, HR: 0.78, 95% CI 0.64 to 0.96). During 1.02 years after early stopping, participants originally randomised to the combination compared with those randomised to aspirin had similar rates of the composite (2.1 vs 2.0/100 py, HR: 1.08, 95% CI 0.84 to 1.39) and cardiovascular death (1.0 vs 0.8/100 py, HR: 1.26, 95% CI 0.85 to 1.86) but higher stroke rate (0.7 vs 0.4/100 py, HR: 1.74, 95% CI 1.05 to 2.87) including a significant increase in ischaemic stroke during the first 6 months after switching to non-study aspirin.

Conclusion: Discontinuing study rivaroxaban and aspirin to non-study aspirin was associated with the loss of cardiovascular benefits and a stroke excess.

Trial Registration Number: NCT01776424.
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http://dx.doi.org/10.1136/heartjnl-2020-318758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257559PMC
July 2021

Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke.

N Engl J Med 2021 06 15;384(22):2081-2091. Epub 2021 May 15.

From McMaster University (R.P.W., E.P.B.-C., J.S.H., M.S., P.J.D., J.N., K. Balasubramanian, A.L., S.Y., S.J.C.), Hamilton Health Sciences (R.P.W., E.P.B.-C., J.S.H., K. Brady, M.S., P.J.D., J.V., A.L., S.Y., S.J.C.), and the Population Health Research Institute (R.P.W., E.P.B.-C., J.S.H., K. Brady, M.S., P.J.D., J.N., K. Balasubramanian, J.V., A.L., S.Y., S.J.C.), Hamilton, ON, Southlake Regional Health Centre, Newmarket, ON (K.H.T.T.), the University of Toronto and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto (C.D.M.), and Quebec Heart and Lung Institute, Quebec, QC (P.V.) - all in Canada; University of Foggia, Foggia (D.P.), Santa Maria Hospital, Gruppo Villa Maria Care and Research, Bari (D.P.), and the University of Pisa, Pisa (A.C.) - all in Italy; Rhön-Klinikum Campus Bad Neustadt, Bad Neustadt (W.R.), and University Hospital Giessen, Giessen (A.B.) - both in Germany; the Institute for Clinical and Experimental Medicine, Prague (P.B.), and the Center of Cardiovascular Surgery and Transplantation, Brno (P.F.) - both in the Czech Republic; "G. Papanikolaou" Hospital (A.J.B.) and Aristotle University of Thessaloniki (G.I.T.) - both in Thessaloniki, Greece; E. Meshalkin National Medical Research Center, Novosibirsk, Russia (A.B.-P.); the University of Louisville, Louisville, KY (M.S.S.); the University of Melbourne and Royal Melbourne Hospital, Melbourne, VIC, Australia (A.G.R.); Auckland City Hospital, Auckland, New Zealand (S.M.); Amphia Ziekenhuis, Breda (M.A.), and Medical Center Leeuwarden, Leeuwarden (R.J.F.) - both in the Netherlands; the National Heart and Lung Institute, Imperial College London, London (P.P.P.); and the International Research Center, Hospital Alemão Oswaldo Cruz, São Paulo (Á.A.).

Background: Surgical occlusion of the left atrial appendage has been hypothesized to prevent ischemic stroke in patients with atrial fibrillation, but this has not been proved. The procedure can be performed during cardiac surgery undertaken for other reasons.

Methods: We conducted a multicenter, randomized trial involving participants with atrial fibrillation and a CHADS-VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating greater risk of stroke) who were scheduled to undergo cardiac surgery for another indication. The participants were randomly assigned to undergo or not undergo occlusion of the left atrial appendage during surgery; all the participants were expected to receive usual care, including oral anticoagulation, during follow-up. The primary outcome was the occurrence of ischemic stroke (including transient ischemic attack with positive neuroimaging) or systemic embolism. The participants, research personnel, and primary care physicians (other than the surgeons) were unaware of the trial-group assignments.

Results: The primary analysis population included 2379 participants in the occlusion group and 2391 in the no-occlusion group, with a mean age of 71 years and a mean CHADS-VASc score of 4.2. The participants were followed for a mean of 3.8 years. A total of 92.1% of the participants received the assigned procedure, and at 3 years, 76.8% of the participants continued to receive oral anticoagulation. Stroke or systemic embolism occurred in 114 participants (4.8%) in the occlusion group and in 168 (7.0%) in the no-occlusion group (hazard ratio, 0.67; 95% confidence interval, 0.53 to 0.85; P = 0.001). The incidence of perioperative bleeding, heart failure, or death did not differ significantly between the trial groups.

Conclusions: Among participants with atrial fibrillation who had undergone cardiac surgery, most of whom continued to receive ongoing antithrombotic therapy, the risk of ischemic stroke or systemic embolism was lower with concomitant left atrial appendage occlusion performed during the surgery than without it. (Funded by the Canadian Institutes of Health Research and others; LAAOS III ClinicalTrials.gov number, NCT01561651.).
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http://dx.doi.org/10.1056/NEJMoa2101897DOI Listing
June 2021

Lowering cholesterol, blood pressure, or both to prevent cardiovascular events: results of 8.7 years of follow-up of Heart Outcomes Evaluation Prevention (HOPE)-3 study participants.

Eur Heart J 2021 08;42(31):2995-3007

The Population Health Research Institute, Hamilton Health Sciences, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.

Aims: Rosuvastatin (10 mg per day) compared with placebo reduced major adverse cardiovascular (CV) events by 24% in 12 705 participants at intermediate CV risk after 5.6 years. There was no benefit of blood pressure (BP) lowering treatment in the overall group, but a reduction in events in the third of participants with elevated systolic BP. After cessation of all the trial medications, we examined whether the benefits observed during the active treatment phase were sustained, enhanced, or attenuated.

Methods And Results: After the randomized treatment period (5.6 years), participants were invited to participate in 3.1 further years of observation (total 8.7 years). The first co-primary outcome for the entire length of follow-up was the composite of myocardial infarction, stroke, or CV death [major adverse cardiovascular event (MACE)-1], and the second was MACE-1 plus resuscitated cardiac arrest, heart failure, or coronary revascularization (MACE-2). In total, 9326 (78%) of 11 994 surviving Heart Outcomes Prevention Evaluation (HOPE)-3 subjects consented to participate in extended follow-up. During 3.1 years of post-trial observation (total follow-up of 8.7 years), participants originally randomized to rosuvastatin compared with placebo had a 20% additional reduction in MACE-1 [95% confidence interval (CI), 0.64-0.99] and a 17% additional reduction in MACE-2 (95% CI 0.68-1.01). Therefore, over the 8.7 years of follow-up, there was a 21% reduction in MACE-1 (95% CI 0.69-0.90, P = 0.005) and 21% reduction in MACE-2 (95% CI 0.69-0.89, P = 0.002). There was no benefit of BP lowering in the overall study either during the active or post-trial observation period, however, a 24% reduction in MACE-1 was observed over 8.7 years.

Conclusion: The CV benefits of rosuvastatin, and BP lowering in those with elevated systolic BP, compared with placebo continue to accrue for at least 3 years after cessation of randomized treatment in individuals without cardiovascular disease indicating a legacy effect.

Trial Registration Number: NCT00468923.
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http://dx.doi.org/10.1093/eurheartj/ehab225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370761PMC
August 2021

Risk stratification of cardiovascular complications using CHADS-VASc and CHADS scores in chronic atherosclerotic cardiovascular disease.

Int J Cardiol 2021 Aug 3;337:9-15. Epub 2021 May 3.

Cardiology Research Unit, University Hospital Geelong, Barwon Health, Geelong, Australia.

Background The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial showed that rivaroxaban plus aspirin reduced major adverse cardiovascular events (MACE) in patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD). We explored whether CHADS-VASc or CHADS scores, well-validated tools for assessing risk of thromboembolic events in atrial fibrillation, can identify vascular patients at highest risk of recurrent events who may derive greatest benefits of treatment. Methods Predictive accuracies of the CHADS-VASc and CHADS scores for MACE, were assessed in this analysis of the COMPASS trial. Kaplan-Meier estimates of cumulative risk were used to compare the effects of rivaroxaban plus aspirin (n = 9152) with aspirin alone (n = 9126) according to risk scores. Results High CHADS-VASc (6-9) or CHADS (3-6) scores were associated with over three times greater absolute risk of MACE compared with CHADS-VASc score of 1-2 or CHADS score of 0. The effects of rivaroxaban plus aspirin compared with aspirin alone were consistent across CHADS-VASc and CHADS score categories for MACE, bleeding and net clinical benefit, with greatest reduction in MACE observed in patients treated for 30 months with highest CHADS score (3-6) (hazard ratio = 0.67, 95% CI: 0.53-0.86, p = 0.0012, 25 events per 1000 patients prevented). Conclusion The CHADS-VASc and CHADS scores can be used in patients with chronic CAD and/or PAD to identify patients who are at highest risk of MACE. Those identified at highest risk by CHADS scores had greatest benefit from dual pathway inhibition with rivaroxaban plus aspirin. Clinical Trial Registration: NCT01776424.
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http://dx.doi.org/10.1016/j.ijcard.2021.04.067DOI Listing
August 2021

Renal Impairment and Risk of Acute Stroke: The INTERSTROKE Study.

Neuroepidemiology 2021 5;55(3):206-215. Epub 2021 May 5.

Estudios Clinicos Latinoamerica, Rosario, Argentina.

Background: Previous studies reported an association of renal impairment with stroke, but there are uncertainties underpinning this association.

Aims: We explored if the association is explained by shared risk factors or is independent and whether there are regional or stroke subtype variations.

Methods: INTERSTROKE is a case-control study and the largest international study of risk factors for first acute stroke, completed in 27 countries. We included individuals with available serum creatinine values and calculated estimated glomerular filtration rate (eGFR). Renal impairment was defined as eGFR <60 mL/min/1.73 m2. Multivariable conditional logistic regression was used to determine the association of renal function with stroke.

Results: Of 21,127 participants, 41.0% were female, the mean age was 62.3 ± 13.4 years, and the mean eGFR was 79.9 ± 23.5 mL/min/1.73 m2. The prevalence of renal impairment was higher in cases (22.9% vs. 17.7%, p < 0.001) and differed by region (p < 0.001). After adjustment, lower eGFR was associated with increased odds of stroke. Renal impairment was associated with increased odds of all stroke (OR 1.35; 95% CI: 1.24-1.47), with higher odds for intracerebral hemorrhage (OR 1.60; 95% CI: 1.35-1.89) than ischemic stroke (OR 1.29; 95% CI: 1.17-1.42) (pinteraction 0.12). The largest magnitudes of association were seen in younger participants and those living in Africa, South Asia, or South America (pinteraction < 0.001 for all stroke). Renal impairment was also associated with poorer clinical outcome (RRR 2.97; 95% CI: 2.50-3.54 for death within 1 month).

Conclusion: Renal impairment is an important risk factor for stroke, particularly in younger patients, and is associated with more severe stroke and worse outcomes.
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http://dx.doi.org/10.1159/000515239DOI Listing
May 2021

COVID-19 Vaccination Prioritization on the Basis of Cardiovascular Risk Factors and Number Needed to Vaccinate to Prevent Death.

Can J Cardiol 2021 07 29;37(7):1112-1116. Epub 2021 Apr 29.

The Population Health Research Institute, McMaster University and Hamilton Health Sciences, and the Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.

The supply limitations of COVID-19 vaccines have led to the need to prioritize vaccine distribution. Obesity, diabetes, and hypertension have been associated with an increased risk of severe COVID-19 infection. Approximately half as many individuals with a cardiovascular risk factor need to be vaccinated against COVID-19 to prevent related death compared with individuals without a risk factor. Adults with body mass index ≥ 30, diabetes, or hypertension should be of a similar priority for COVID-19 vaccination to adults 10 years older with a body mass index of 20 to < 30, no diabetes, and no hypertension.
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http://dx.doi.org/10.1016/j.cjca.2021.04.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084283PMC
July 2021

Polypill in Persons without Cardiovascular Disease. Reply.

N Engl J Med 2021 04;384(17):1676-1677

St. John's Medical College, Bangalore, India.

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http://dx.doi.org/10.1056/NEJMc2102972DOI Listing
April 2021

Health-Related Quality of Life and Mortality in Heart Failure: The Global Congestive Heart Failure Study of 23 000 Patients From 40 Countries.

Circulation 2021 Jun 28;143(22):2129-2142. Epub 2021 Apr 28.

Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada (I.J., P.J., K.B., B.F., K.T., A.G., T.M., S.Y.).

Background: Poor health-related quality of life (HRQL) is common in heart failure (HF), but there are few data on HRQL in HF and the association between HRQL and mortality outside Western countries.

Methods: We used the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) to record HRQL in 23 291 patients with HF from 40 countries in 8 different world regions in the G-CHF study (Global Congestive Heart Failure). We compared standardized KCCQ-12 summary scores (adjusted for age, sex, and markers of HF severity) among regions (scores range from 0 to 100, with higher score indicating better HRQL). We used multivariable Cox regression with adjustment for 15 variables to assess the association between KCCQ-12 summary scores and the composite of all-cause death, HF hospitalization, and each component over a median follow-up of 1.6 years.

Results: The mean age of participants was 65 years; 61% were men; 40% had New York Heart Association class III or IV symptoms; and 46% had left ventricular ejection fraction ≥40%. Average HRQL differed between regions (lowest in Africa [mean± SE, 39.5±0.3], highest in Western Europe [62.5±0.4]). There were 4460 (19%) deaths, 3885 (17%) HF hospitalizations, and 6949 (30%) instances of either event. Lower KCCQ-12 summary score was associated with higher risk of all outcomes; the adjusted hazard ratio (HR) for each 10-unit KCCQ-12 summary score decrement was 1.18 (95% CI, 1.17-1.20) for death. Although this association was observed in all regions, it was less marked in South Asia, South America, and Africa (weakest association in South Asia: HR, 1.08 [95% CI, 1.03-1.14]; strongest association in Eastern Europe: HR, 1.31 [95% CI, 1.21-1.42]; interaction <0.0001). Lower HRQL predicted death in patients with New York Heart Association class I or II and III or IV symptoms (HR, 1.17 [95% CI, 1.14-1.19] and HR, 1.14 [95% CI, 1.12-1.17]; interaction =0.13) and was a stronger predictor for the composite outcome in New York Heart Association class I or II versus class III or IV (HR 1.15 [95% CI, 1.13-1.17] versus 1.09 [95% CI, [1.07-1.11]; interaction <0.0001). HR for death was greater in ejection fraction ≥40 versus <40% (HR, 1.23 [95% CI, 1.20-1.26] and HR, 1.15 [95% CI, 1.13-1.17]; interaction <0.0001).

Conclusion: HRQL is a strong and independent predictor of all-cause death and HF hospitalization across all geographic regions, in mildly and severe symptomatic HF, and among patients with preserved and reduced ejection fraction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03078166.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.050850DOI Listing
June 2021

Bariatric Surgery and Cardiovascular Outcomes in Patients With Obesity and Cardiovascular Disease:: A Population-Based Retrospective Cohort Study.

Circulation 2021 Apr 5;143(15):1468-1480. Epub 2021 Apr 5.

Division of General Surgery (A.G.D., Y.L., D.H., M.A.), McMaster University, Hamilton, Ontario, Canada.

Background: Bariatric surgery has been shown to significantly reduce cardiovascular risk factors. However, whether surgery can reduce major adverse cardiovascular events (MACE), especially in patients with established cardiovascular disease, remains poorly understood. The present study aims to determine the association between bariatric surgery and MACE among patients with cardiovascular disease and severe obesity.

Methods: This was a propensity score-matched cohort study using province-wide multiple-linked administrative databases in Ontario, Canada. Patients with previous ischemic heart disease or heart failure who received bariatric surgery were matched on age, sex, heart failure history, and a propensity score to similar controls from a primary care medical record database in a 1:1 ratio. The primary outcome was the incidence of extended MACE (first occurrence of all-cause mortality, myocardial infarction, coronary revascularization, cerebrovascular events, and heart failure hospitalization). Secondary outcome included 3-component MACE (myocardial infarction, ischemic stroke, and all-cause mortality). Outcomes were evaluated through a combination of matching via propensity score and subsequent multivariable adjustment.

Results: A total of 2638 patients (n=1319 in each group) were included, with a median follow-up time of 4.6 years. The primary outcome occurred in 11.5% (151/1319) of the surgery group and 19.6% (259/1319) of the controls (adjusted hazard ratio [HR], 0.58 [95% CI, 0.48-0.71]; <0.001). The association was notable for those with heart failure (HR, 0.44 [95% CI, 0.31-0.62]; <0.001; absolute risk difference, 19.3% [95% CI, 12.0%-26.7%]) and in those with ischemic heart disease (HR, 0.60 [95% CI, 0.48-0.74]; <0.001; absolute risk difference, 7.5% [95% CI, 4.7%-10.5%]). Surgery was also associated with a lower incidence of the secondary outcome (HR, 0.66 [95% CI, 0.52-0.84]; =0.001) and cardiovascular mortality (HR, 0.35 [95% CI, 0.15-0.80]; =0.001).

Conclusions: Bariatric surgery was associated with a lower incidence of MACE in patients with cardiovascular disease and obesity. These findings require confirmation by a large-scale randomized trial.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052386DOI Listing
April 2021
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