Showing papers in "Journal of the American Heart Association in 2016"
TL;DR: It was shown that activation of nuclear factor‐κB signaling was necessary for TMAO to induce inflammatory gene expression in both of these relevant cell types as well as endothelial cell adhesion of leukocytes, which suggests a likely contributory mechanism for T MAO‐dependent enhancement in atherosclerosis and cardiovascular risks.
Abstract: Background The choline‐derived metabolite trimethylamine N‐oxide (TMAO) has been demonstrated to contribute to atherosclerosis and is associated with coronary artery disease risk.
Methods and Results We explored the impact of TMAO on endothelial and smooth muscle cell function in vivo, focusing on disease‐relevant outcomes for atherogenesis. Initially, we observed that aortas of LDLR−/− mice fed a choline diet showed elevated inflammatory gene expression compared with controls. Acute TMAO injection at physiological levels was sufficient to induce the same inflammatory markers and activate the well‐known mitogen‐activated protein kinase, extracellular signal–related kinase, and nuclear factor‐κB signaling cascade. These observations were recapitulated in primary human aortic endothelial cells and vascular smooth muscle cells. We also found that TMAO promotes recruitment of activated leukocytes to endothelial cells. Through pharmacological inhibition, we further showed that activation of nuclear factor‐κB signaling was necessary for TMAO to induce inflammatory gene expression in both of these relevant cell types as well as endothelial cell adhesion of leukocytes.
Conclusions Our results suggest a likely contributory mechanism for TMAO‐dependent enhancement in atherosclerosis and cardiovascular risks.
538 citations
TL;DR: Effect sizes were generally similar for CVD and T2DM, and suggested that the greatest gain in health is associated with moving from inactivity to small amounts of PA.
Abstract: Background The relationships between physical activity (PA) and both cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) have predominantly been estimated using categorical measures of PA, masking the shape of the dose‐response relationship. In this systematic review and meta‐analysis, for the very first time we are able to derive a single continuous PA metric to compare the association between PA and CVD/T2DM, both before and after adjustment for a measure of body weight.
Methods and Results The search was applied to MEDLINE and EMBASE electronic databases for all studies published from January 1981 to March 2014. A total of 36 studies (3 439 874 participants and 179 393 events, during an average follow‐up period of 12.3 years) were included in the analysis (33 pertaining to CVD and 3 to T2DM). An increase from being inactive to achieving recommended PA levels (150 minutes of moderate‐intensity aerobic activity per week) was associated with lower risk of CVD mortality by 23%, CVD incidence by 17%, and T2DM incidence by 26% (relative risk [RR], 0.77 [0.71–0.84]), (RR, 0.83 [0.77–0.89]), and (RR, 0.74 [0.72–0.77]), respectively, after adjustment for body weight.
Conclusions By using a single continuous metric for PA levels, we were able to make a comparison of the effect of PA on CVD incidence and mortality including myocardial infarct (MI), stroke, and heart failure, as well as T2DM. Effect sizes were generally similar for CVD and T2DM, and suggested that the greatest gain in health is associated with moving from inactivity to small amounts of PA.
398 citations
TL;DR: Adherence to anticoagulation is poor in practice and may be modestly improved with NOACs, whereas the benefits of antICOagulation may not outweigh the harms in patients with CHA 2 DS 2‐VASc score 0 or 1.
Abstract: Background In comparison to warfarin, non–vitamin K antagonist oral anticoagulants (NOACs) have the advantages of ease of dosing, fewer drug interactions, and lack of need for ongoing monitoring. We sought to evaluate whether these advantages translate to improved adherence and whether adherence is associated with improved outcomes in patients with atrial fibrillation. Methods and Results We performed a retrospective cohort analysis by using a large US commercial insurance database to identify 64 661 patients with atrial fibrillation who initiated warfarin, dabigatran, rivaroxaban, or apixaban treatment between November 1, 2010, and December 31, 2014. During a median of 1.1 y of follow‐up, 47.5% of NOAC patients had a proportion of days covered of ≥80%, compared with 40.2% in warfarin patients ( P 2 DS 2 ‐VASc (risk based on the presence of congestive heart failure, hypertension age 65–74 y, age ≥75 y, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, sex category) score ≥4 were at increased risk of stroke when they were not taking anticoagulation ≥1 month versus P 2 DS 2 ‐VASc score 2 or 3 were at increased risk of stroke when they were not taking anticoagulation ≥6 months (HR 2.73, P 2 DS 2 ‐VASc score ≥2, nonadherence was not associated with intracranial hemorrhage. Among patients with CHA 2 DS 2 ‐VASc score 0 or 1, time not taking anticoagulation was not associated with stroke, but not taking anticoagulation ≥3 months was associated with a significant reduction of bleeding. Conclusions Adherence to anticoagulation is poor in practice and may be modestly improved with NOACs. Adherence to therapy appears to be most important in patients with CHA 2 DS 2 ‐VASc score ≥2, whereas the benefits of anticoagulation may not outweigh the harms in patients with CHA 2 DS 2 ‐VASc score 0 or 1.
342 citations
TL;DR: In patients with nonvalvular atrial fibrillation, apixaban was associated with lower risks of both stroke and major bleeding, dabigatran was associated as with similar risk of stroke but lower risk of major bleed, and rivaroxaban wasassociated with similar risks ofBoth stroke andMajor bleeding in comparison to warfarin.
Abstract: BackgroundThe introduction of non–vitamin K antagonist oral anticoagulants has been a major advance for stroke prevention in atrial fibrillation; however, outcomes achieved in clinical trials may n...
332 citations
TL;DR: With current clinical standards, Bazett overestimated the number of patients with potential dangerous QTc prolongation, which could lead to unnecessary safety measurements as withholding the patient of first‐choice medication.
Abstract: BackgroundDrug safety precautions recommend monitoring of the corrected QT interval. To determine which QT correction formula to use in an automated QT‐monitoring algorithm in our electronic medica...
277 citations
TL;DR: RAO is a common complication of transradial access and maintenance of radial patency should be an integral part of all procedures undertaken through the radial approach, and high‐dose heparin along with shorter compression times and patent hemostasis is recommended in reducing RAO.
Abstract: Background Radial artery occlusion (RAO) may occur posttransradial intervention and limits the radial artery as a future access site, thus precluding its use as an arterial conduit. In this study, we investigate the incidence and factors influencing the RAO in the current literature.
Methods and Results We searched MEDLINE and EMBASE for studies of RAO in transradial access. Relevant studies were identified and data were extracted. Data were synthesized by meta‐analysis, quantitative pooling, graphical representation, or by narrative synthesis. A total of 66 studies with 31 345 participants were included in the analysis. Incident RAO ranged between 1 week follow‐up). The most efficacious measure in reducing RAO was higher dose of heparin, because lower doses of heparin were associated with increased RAO (risk ratio 0.36, 95% CI 0.17–0.76), whereas shorter compression times also reduced RAO (risk ratio 0.28, 95% CI 0.05–1.50). Several factors were found to be associated with RAO including age, sex, sheath size, and diameter of radial artery, but these factors were not consistent across all studies.
Conclusions RAO is a common complication of transradial access. Maintenance of radial patency should be an integral part of all procedures undertaken through the radial approach. High‐dose heparin along with shorter compression times and patent hemostasis is recommended in reducing RAO.
266 citations
TL;DR: Gut microbiota facilitate AngII‐induced vascular dysfunction and hypertension, at least in part, by supporting an MCP‐1/IL‐17 driven vascular immune cell infiltration and inflammation.
Abstract: Background The gut microbiome is essential for physiological host responses and development of immune functions. The impact of gut microbiota on blood pressure and systemic vascular function, processes that are determined by immune cell function, is unknown.
Methods and Results Unchallenged germ‐free mice (GF) had a dampened systemic T helper cell type 1 skewing compared to conventionally raised (CONV‐R) mice. Colonization of GF mice with regular gut microbiota induced lymphoid mRNA transcription of T‐box expression in T cells and resulted in mild endothelial dysfunction. Compared to CONV‐R mice, angiotensin II (AngII; 1 mg/kg per day for 7 days) infused GF mice showed reduced reactive oxygen species formation in the vasculature, attenuated vascular mRNA expression of monocyte chemoattractant protein 1 (MCP‐1), inducible nitric oxide synthase (iNOS) and NADPH oxidase subunit Nox2, as well as a reduced upregulation of retinoic‐acid receptor‐related orphan receptor gamma t (Rorγt), the signature transcription factor for interleukin (IL)‐17 synthesis. This resulted in an attenuated vascular leukocyte adhesion, less infiltration of Ly6G+ neutrophils and Ly6C+ monocytes into the aortic vessel wall, protection from kidney inflammation, as well as endothelial dysfunction and attenuation of blood pressure increase in response to AngII. Importantly, cardiac inflammation, fibrosis and systolic dysfunction were attenuated in GF mice, indicating systemic protection from cardiovascular inflammatory stress induced by AngII.
Conclusion Gut microbiota facilitate AngII‐induced vascular dysfunction and hypertension, at least in part, by supporting an MCP‐1/IL‐17 driven vascular immune cell infiltration and inflammation.
266 citations
TL;DR: Medication adherence should be addressed in regular follow‐up visits with HF patients, and interventions to improve adhere should be a key part of HF self‐care programs.
Abstract: Background Poor adherence to medications is a common problem among heart failure (HF) patients. Inadequate adherence leads to increased HF exacerbations, reduced physical function, and higher risk for hospital admission and death. Many interventions have been tested to improve adherence to HF medications, but the overall impact of such interventions on readmissions and mortality is unknown.
Methods and Results We conducted a comprehensive search and systematic review of intervention studies testing interventions to improve adherence to HF medications. Mortality and readmission outcome effect sizes (ESs) were calculated from the reported data. ESs were combined using random‐effects model meta‐analysis methods, because differences in true between‐study effects were expected from variation in study populations and interventions. ES differences attributed to study design, sample, and intervention characteristics were assessed using moderator analyses when sufficient data were available. We assessed publication bias using funnel plots. Comprehensive searches yielded 6665 individual citations, which ultimately yielded 57 eligible studies. Overall, medication adherence interventions were found to significantly reduce mortality risk among HF patients (relative risk, 0.89; 95% CI, 0.81, 0.99), and decrease the odds for hospital readmission (odds ratio, 0.79; 95% CI, 0.71, 0.89). Heterogeneity was low. Moderator analyses did not detect differences in ES from common sources of potential study bias.
Conclusions Interventions to improve medication adherence among HF patients have significant effects on reducing readmissions and decreasing mortality. Medication adherence should be addressed in regular follow‐up visits with HF patients, and interventions to improve adherence should be a key part of HF self‐care programs.
227 citations
TL;DR: The results indicate a possible role of the NLRP3 inflammasome and its genetic variants in the pathogenesis of atherosclerosis.
Abstract: Background: The NLR family, pyrin domain containing 3 (NLRP3) inflammasome is an interleukin (IL)-1β and IL-18 cytokine processing complex that is activated in inflammatory conditions. The role of ...
208 citations
TL;DR: Age has a greater influence on major bleeding than thromboembolic risk in patients with atrial fibrillation, and treatment of elderly patients with edoxaban provides an even greater absolute reduction in safety events over warfarin, compared to treatment with Edoxaban versus warFarin in younger patients.
Abstract: Background Elderly patients with atrial fibrillation are at higher risk of both ischemic and bleeding events compared to younger patients. In a prespecified analysis from the ENGAGE AF‐TIMI 48 trial, we evaluate clinical outcomes with edoxaban versus warfarin according to age.
Methods and Results Twenty‐one thousand one‐hundred and five patients enrolled in the ENGAGE AF‐TIMI 48 trial were stratified into 3 prespecified age groups: <65 (n=5497), 65 to 74 (n=7134), and ≥75 (n=8474) years. Older patients were more likely to be female, with lower body weight and reduced creatinine clearance, leading to higher rates of edoxaban dose reduction (10%, 18%, and 41% for the 3 age groups, P <0.001). Stroke or systemic embolic event (1.1%, 1.8%, and 2.3%) and major bleeding (1.8%, 3.3%, and 4.8%) rates with warfarin increased across age groups ( P trend<0.001 for both). There were no interactions between age group and randomized treatment in the primary efficacy and safety outcomes. In the elderly (≥75 years), the rates of stroke/systemic embolic event were similar with edoxaban versus warfarin (hazard ratio 0.83 [0.66–1.04]), while major bleeding was significantly reduced with edoxaban (hazard ratio 0.83 [0.70–0.99]). The absolute risk difference in major bleeding (−82 events/10 000 pt‐yrs) and in intracranial hemorrhage (−73 events/10 000 pt‐yrs) both favored edoxaban over warfarin in older patients.
Conclusions Age has a greater influence on major bleeding than thromboembolic risk in patients with atrial fibrillation. Given the higher rates of bleeding and death with increasing age, treatment of elderly patients with edoxaban provides an even greater absolute reduction in safety events over warfarin, compared to treatment with edoxaban versus warfarin in younger patients.
Clinical Trial Registration URL: . Unique identifier: NCT00781391.
206 citations
TL;DR: Elevated plasma TMAO levels portended higher long‐term mortality risk among patients with stable coronary artery disease managed with optimal medical treatment, and provided significant incremental prognostic value for all‐cause mortality.
Abstract: BackgroundTrimethylamine‐N‐oxide (TMAO), a metabolite derived from gut microbes and dietary phosphatidylcholine, is linked to both coronary artery disease pathogenesis and increased cardiovascular ...
TL;DR: The Cardiio Rhythm smartphone PPG application provides an accurate and reliable means to detect atrial fibrillation in patients at risk of developing AF and has the potential to enable population‐based screening for AF.
Abstract: Background Diagnosing atrial fibrillation (AF) before ischemic stroke occurs is a priority for stroke prevention in AF. Smartphone camera–based photoplethysmographic (PPG) pulse waveform measurement discriminates between different heart rhythms, but its ability to diagnose AF in real‐world situations has not been adequately investigated. We sought to assess the diagnostic performance of a standalone smartphone PPG application, Cardiio Rhythm, for AF screening in primary care setting. Methods and Results Patients with hypertension, with diabetes mellitus, and/or aged ≥65 years were recruited. A single‐lead ECG was recorded by using the AliveCor heart monitor with tracings reviewed subsequently by 2 cardiologists to provide the reference standard. PPG measurements were performed by using the Cardiio Rhythm smartphone application. AF was diagnosed in 28 (2.76%) of 1013 participants. The diagnostic sensitivity of the Cardiio Rhythm for AF detection was 92.9% (95% CI] 77–99%) and was higher than that of the AliveCor automated algorithm (71.4% [95% CI 51–87%]). The specificities of Cardiio Rhythm and the AliveCor automated algorithm were comparable (97.7% [95% CI: 97–99%] versus 99.4% [95% CI 99–100%]). The positive predictive value of the Cardiio Rhythm was lower than that of the AliveCor automated algorithm (53.1% [95% CI 38–67%] versus 76.9% [95% CI 56–91%]); both had a very high negative predictive value (99.8% [95% CI 99–100%] versus 99.2% [95% CI 98–100%]). Conclusions The Cardiio Rhythm smartphone PPG application provides an accurate and reliable means to detect AF in patients at risk of developing AF and has the potential to enable population‐based screening for AF.
University of Alabama at Birmingham1, Mashhad University of Medical Sciences2, University of Milan3, University College London4, Veterans Health Administration5, New York Medical College6, University of Birmingham7, Erasmus University Rotterdam8, University of California, Irvine9, Medical University of Łódź10
TL;DR: The results of the meta‐analysis showed a statistically significant effect of quercetin supplementation in the reduction of BP, possibly limited to, or greater with dosages of >500 mg/day.
Abstract: Background Quercetin, the most abundant dietary flavonol, has antioxidant effects in cardiovascular disease, but the evidence regarding its effects on blood pressure (BP) has not been conclusive. We assessed the impact of quercetin on BP through a systematic review and meta‐analysis of available randomized controlled trials.
Methods and Results We searched PUBMED, Cochrane Library, Scopus, and EMBASE up to January 31, 2015 to identify placebo‐controlled randomized controlled trials investigating the effect of quercetin on BP. Meta‐analysis was performed using either a fixed‐effects or random‐effect model according to I2 statistic. Effect size was expressed as weighted mean difference (WMD) and 95% CI. Overall, the impact of quercetin on BP was reported in 7 trials comprising 9 treatment arms (587 patients). The results of the meta‐analysis showed significant reductions both in systolic BP (WMD: −3.04 mm Hg, 95% CI: −5.75, −0.33, P =0.028) and diastolic BP (WMD: −2.63 mm Hg, 95% CI: −3.26, −2.01, P <0.001) following supplementation with quercetin. When the studies were categorized according to the quercetin dose, there was a significant systolic BP and diastolic BP‐reducing effect in randomized controlled trials with doses ≥500 mg/day (WMD: −4.45 mm Hg, 95% CI: −7.70, −1.21, P =0.007 and −2.98 mm Hg, 95% CI: −3.64, −2.31, P <0.001, respectively), and lack of a significant effect for doses <500 mg/day (WMD: −1.59 mm Hg, 95% CI: −4.44, 1.25, P =0.273 and −0.24 mm Hg, 95% CI: −2.00, 1.52, P =0.788, respectively), but indirect comparison tests failed to significant differences between doses.
Conclusions The results of the meta‐analysis showed a statistically significant effect of quercetin supplementation in the reduction of BP, possibly limited to, or greater with dosages of >500 mg/day. Further studies are necessary to investigate the clinical relevance of these results and the possibility of quercetin application as an add‐on to antihypertensive therapy.
TL;DR: Critical limb ischemia (CLI) is at the end of the peripheral artery disease (PAD) spectrum and is associated with excessively high risk for cardiovascular events, including myocardial infarction, and death.
Abstract: Critical limb ischemia (CLI), which is at the end of the peripheral artery disease (PAD) spectrum, is associated with excessively high risk for cardiovascular events, including myocardial infarction, and death.[1][1], [2][2], [3][3] Mortality rates as high as 20% within 6 months from diagnosis and
TL;DR: In a rat myocardial infarction model, MSC exosome–preconditioned CSCs had significantly better survival, enhanced capillary density, reduced cardiac fibrosis, and restored long‐term cardiac function.
Abstract: Background Exosomes derived from mesenchymal stem cells (MSCs) were proved to boost cell proliferation and angiogenic potency. We explored whether cardiac stem cells (CSCs) preconditioned with MSC exosomes could survive and function better in a myocardial infarction model.
Methods and Results DiI‐labeled exosomes were internalized with CSCs. They stimulated proliferation, migration, and angiotube formation of CSCs in a dose‐dependent manner. In a rat myocardial infarction model, MSC exosome–preconditioned CSCs had significantly better survival, enhanced capillary density, reduced cardiac fibrosis, and restored long‐term cardiac function. MicroRNA profiling analysis revealed that a set of microRNAs were significantly changed in CSCs after MSC exosome treatment.
Conclusions Pretreatment of CSCs with MSC exosomes provided a promising strategy to improve survival and angiogenic potency of CSCs.
TL;DR: CAA z‐score at diagnosis was highly predictive of outcomes, which may be improved by early IVIG treatment and adjunctive therapies, and factors associated with major adverse cardiac events (MACE) and CAA regression were identified.
Abstract: Background The natural history of coronary artery aneurysms (CAA) after intravenous immunoglobulin (IVIG) treatment in the United States is not well described. We describe the natural history of CAA in US Kawasaki disease (KD) patients and identify factors associated with major adverse cardiac events (MACE) and CAA regression.
Methods and Results We evaluated all KD patients with CAA at 2 centers from 1979 to 2014. Factors associated with CAA regression, maximum CA z ‐score over time ( z Max), and MACE were analyzed. We performed a matched analysis of treatment effect on likelihood of CAA regression. Of 2860 KD patients, 500 (17%) had CAA, including 90 with CAA z ‐score >10. Most (91%) received IVIG within 10 days of illness, 32% received >1 IVIG, and 27% received adjunctive anti‐inflammatory medications. CAA regression occurred in 75%. Lack of CAA regression and higher CAA z Max were associated with earlier era, larger CAA z ‐score at diagnosis, and bilateral CAA in univariate and multivariable analyses. MACE occurred in 24 (5%) patients and was associated with higher CAA z ‐score at diagnosis and lack of IVIG treatment. In a subset of patients (n=132) matched by age at KD and baseline CAA z ‐score, those receiving IVIG plus adjunctive medication had a CAA regression rate of 91% compared with 68% for the 3 other groups (IVIG alone, IVIG ≥2 doses, or IVIG ≥2 doses plus adjunctive medication).
Conclusions CAA regression occurred in 75% of patients. CAA z ‐score at diagnosis was highly predictive of outcomes, which may be improved by early IVIG treatment and adjunctive therapies.
TL;DR: The BEST‐CLI trial is the first randomized controlled trial comparing endovascular therapy to open surgical bypass in patients with CLI to be carried out in North America and aims to provide Level I data to clarify the appropriate role for both treatment strategies and help define an evidence‐based standard of care for this challenging patient population.
Abstract: Background Critical limb ischemia (CLI) is increasing in prevalence, and remains a significant source of mortality and limb loss. The decision to recommend surgical or endovascular revascularization for patients who are candidates for both varies significantly among providers and is driven more by individual preference than scientific evidence.
Methods and Results The Best Endovascular Versus Best Surgical Therapy for Patients With Critical Limb Ischemia (BEST‐CLI) Trial is a prospective, randomized, multidisciplinary, controlled, superiority trial designed to compare treatment efficacy, functional outcomes, quality of life, and cost in patients undergoing best endovascular or best open surgical revascularization. Approximately 140 clinical sites in the United States and Canada will enroll 2100 patients with CLI who are candidates for both treatment options. A pragmatic trial design requires consensus on patient eligibility by at least 2 investigators, but leaves the choice of specific procedural strategy within the assigned revascularization approach to the individual treating investigator. Patients with suitable single‐segment of saphenous vein available for potential bypass will be randomized within Cohort 1 (n=1620), while patients without will be randomized within Cohort 2 (n=480). The primary efficacy end point of the trial is Major Adverse Limb Event–Free Survival. Key secondary end points include Re‐intervention and Amputation‐Free‐Survival and Amputation Free‐Survival.
Conclusions The BEST‐CLI trial is the first randomized controlled trial comparing endovascular therapy to open surgical bypass in patients with CLI to be carried out in North America. This landmark comparative effectiveness trial aims to provide Level I data to clarify the appropriate role for both treatment strategies and help define an evidence‐based standard of care for this challenging patient population.
Clinical Trial Registration URL: . Unique identifier: NCT02060630.
TL;DR: A greater benefit for CVD was observed among participants with lower plasma folate levels and without preexisting CVD and in studies with larger decreases in homocysteine levels, while folic acid supplementation had no significant effect on risk of coronary heart disease.
Abstract: Background Results from observational and genetic epidemiological studies suggest that lower serum homocysteine levels are associated with lower incidence of cardiovascular disease (CVD). Numerous randomized controlled trials have investigated the efficacy of lowering homocysteine with folic acid supplementation for CVD risk, but conflicting results have been reported.
Methods and Results Three bibliographic databases (Medline, Embase, and the Cochrane Database of Systematic Reviews) were searched from database inception until December 1, 2015. Of the 1933 references reviewed for eligibility, 30 randomized controlled trials involving 82 334 participants were included in the final analysis. The pooled relative risks of folic acid supplementation compared with controls were 0.90 (95% CI 0.84–0.96; P =0.002) for stroke, 1.04 (95% CI 0.99–1.09; P =0.16) for coronary heart disease, and 0.96 (95% CI 0.92–0.99; P =0.02) for overall CVD. The intervention effects for both stroke and combined CVD were more pronounced among participants with lower plasma folate levels at baseline (both P <0.02 for interaction). In stratified analyses, a greater beneficial effect for overall CVD was seen in trials among participants without preexisting CVD ( P =0.006 for interaction) or in trials with larger reduction in homocysteine levels ( P =0.009 for interaction).
Conclusions Our meta‐analysis indicated a 10% lower risk of stroke and a 4% lower risk of overall CVD with folic acid supplementation. A greater benefit for CVD was observed among participants with lower plasma folate levels and without preexisting CVD and in studies with larger decreases in homocysteine levels. Folic acid supplementation had no significant effect on risk of coronary heart disease.
TL;DR: Although overall stroke hospitalizations declined in the United States, the reduction was more pronounced among older individuals, women, Hispanics, and whites and renewed efforts at targeting risk factor control among vulnerable individuals may be warranted.
Abstract: Background Population‐based studies have revealed declining acute ischemic stroke (AIS) hospitalization rates in the United States, but no study has assessed recent temporal trends in race/ethnic‐, age‐, and sex‐specific AIS hospitalization rates.
Methods and Results Temporal trends in hospitalization for AIS from 2000 to 2010 were assessed among adults ≥25 years using the Nationwide Inpatient Sample. Age‐, sex‐, and race/ethnic‐specific and age‐adjusted stroke hospitalization rates were calculated using the weighted number of hospitalizations and US census data. From 2000 to 2010, age‐adjusted stroke hospitalization rates decreased from 250 to 204 per 100 000 (overall rate reduction 18.4%). Age‐specific AIS hospitalization rates decreased for individuals aged 65 to 84 years (846 to 605 per 100 000) and ≥85 years (2077 to 1618 per 100 000), but increased for individuals aged 25 to 44 years (16 to 23 per 100 000) and 45 to 64 years (149 to 156 per 100 000). Blacks had the highest age‐adjusted yearly hospitalization rates, followed by Hispanics and whites (358, 170, and 155 per 100 000 in 2010). Age‐adjusted AIS hospitalization rates increased for blacks but decreased for Hispanics and whites. Age‐adjusted AIS hospitalization rates were lower in women and declined more steeply compared to men (272 to 212 per 100 000 in women versus 298 to 245 per 100 000 in men).
Conclusions Although overall stroke hospitalizations declined in the United States, the reduction was more pronounced among older individuals, women, Hispanics, and whites. Renewed efforts at targeting risk factor control among vulnerable individuals may be warranted.
TL;DR: Novel circulating metabolites reflecting impaired or dysregulated fatty acid oxidation that are independently associated with HF and differentially elevated in HFpEF and HFrEF are identified and suggest a shared metabolic mechanism in HF along the LVEF spectrum.
Abstract: Background Metabolic impairment is an important contributor to heart failure (HF) pathogenesis and progression. Dysregulated metabolic pathways remain poorly characterized in patients with HF and preserved ejection fraction (HFpEF). We sought to determine metabolic abnormalities in HFpEF and identify pathways differentially altered in HFpEF versus HF with reduced ejection fraction (HFrEF).
Methods and Results We identified HFpEF cases, HFrEF controls, and no‐HF controls from the CATHGEN study of sequential patients undergoing cardiac catheterization. HFpEF cases (N=282) were defined by left ventricular ejection fraction (LVEF) ≥45%, diastolic dysfunction grade ≥1, and history of HF; HFrEF controls (N=279) were defined similarly, except for having LVEF <45%. No‐HF controls (N=191) had LVEF ≥45%, normal diastolic function, and no HF diagnosis. Targeted mass spectrometry and enzymatic assays were used to quantify 63 metabolites in fasting plasma. Principal components analysis reduced the 63 metabolites to uncorrelated factors, which were compared across groups using ANCOVA. In basic and fully adjusted models, long‐chain acylcarnitine factor levels differed significantly across groups ( P< 0.0001) and were greater in HFrEF than HFpEF ( P =0.0004), both of which were greater than no‐HF controls. We confirmed these findings in sensitivity analyses using stricter inclusion criteria, alternative LVEF thresholds, and adjustment for insulin resistance.
Conclusions We identified novel circulating metabolites reflecting impaired or dysregulated fatty acid oxidation that are independently associated with HF and differentially elevated in HFpEF and HFrEF. These results elucidate a specific metabolic pathway in HF and suggest a shared metabolic mechanism in HF along the LVEF spectrum.
TL;DR: In a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in10 deaths were caused by nonhemorrhagic stroke or systemic embolism, suggesting Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.
Abstract: The ROCKET AF trial was sponsored by Johnson & Johnson Pharmaceutical Research & Development (Raritan, NJ) and Bayer HealthCare AG (Leverkusen, Germany).
TL;DR: The MRC refractory VF/VT protocol is feasible and led to a high functionally favorable survival rate with few complications, and no significant ECMO‐related complications were encountered.
Abstract: Background In 2015, the Minnesota Resuscitation Consortium (MRC) implemented an advanced perfusion and reperfusion life support strategy designed to improve outcome for patients with out‐of‐hospital refractory ventricular fibrillation/ventricular tachycardia (VF/VT). We report the outcomes of the initial 3‐month period of operations.
Methods and Results Three emergency medical services systems serving the Minneapolis–St. Paul metro area participated in the protocol. Inclusion criteria included age 18 to 75 years, body habitus accommodating automated Lund University Cardiac Arrest System (LUCAS) cardiopulmonary resuscitation (CPR), and estimated transfer time from the scene to the cardiac catheterization laboratory of ≤30 minutes. Exclusion criteria included known terminal illness, Do Not Resuscitate/Do Not Intubate status, traumatic arrest, and significant bleeding. Refractory VF/VT arrest was defined as failure to achieve sustained return of spontaneous circulation after treatment with 3 direct current shocks and administration of 300 mg of intravenous/intraosseous amiodarone. Patients were transported to the University of Minnesota, where emergent advanced perfusion strategies (extracorporeal membrane oxygenation; ECMO), followed by coronary angiography and primary coronary intervention (PCI), were performed, when appropriate. Over the first 3 months of the protocol, 27 patients were transported with ongoing mechanical CPR. Of these, 18 patients met the inclusion and exclusion criteria. ECMO was placed in 83%. Seventy‐eight percent of patients had significant coronary artery disease with a high degree of complexity and 67% received PCI. Seventy‐eight percent of patients survived to hospital admission and 55% (10 of 18) survived to hospital discharge, with 50% (9 of 18) achieving good neurological function (cerebral performance categories 1 and 2). No significant ECMO‐related complications were encountered.
Conclusions The MRC refractory VF/VT protocol is feasible and led to a high functionally favorable survival rate with few complications.
TL;DR: CAC improves discrimination and risk reclassification for major coronary heart disease and CVD beyond risk factors in asymptomatic community‐dwelling persons and accurately reclassifies two‐thirds of the intermediate‐risk population.
Abstract: Background We determined whether vascular and valvular calcification predicted incident major coronary heart disease, cardiovascular disease (CVD), and all‐cause mortality independent of Framingham risk factors in the community‐based Framingham Heart Study.
Methods and Results Coronary artery calcium (CAC), thoracic and abdominal aortic calcium, and mitral or aortic valve calcium were measured by cardiac computed tomography in participants free of CVD. Participants were followed for a median of 8 years. Multivariate Cox proportional hazards models were used to determine association of CAC, thoracic and abdominal aortic calcium, and mitral and aortic valve calcium with end points. Improvement in discrimination beyond risk factors was tested via the C‐statistic and net reclassification index. In this cohort of 3486 participants (mean age 50±10 years; 51% female), CAC was most strongly associated with major coronary heart disease, followed by major CVD, and all‐cause mortality independent of Framingham risk factors. Among noncoronary calcifications, mitral valve calcium was associated with major CVD and all‐cause mortality independent of Framingham risk factors and CAC. CAC significantly improved discriminatory value beyond risk factors for coronary heart disease (area under the curve 0.78–0.82; net reclassification index 32%, 95% CI 11–53) but not for CVD. CAC accurately reclassified 85% of the 261 patients who were at intermediate (5–10%) 10‐year risk for coronary heart disease based on Framingham risk factors to either low risk (n=172; no events observed) or high risk (n=53; observed event rate 8%).
Conclusions CAC improves discrimination and risk reclassification for major coronary heart disease and CVD beyond risk factors in asymptomatic community‐dwelling persons and accurately reclassifies two‐thirds of the intermediate‐risk population.
TL;DR: The diagnostic accuracy of E/è to identify/exclude elevated LVFP and DD/HFpEF is limited and requires further validation in a well‐designed prospective clinical trial.
Abstract: Background Tissue Doppler index E/e' is used clinically and in multidisciplinary research for estimation of left ventricular filling pressure (LVFP) and diastolic dysfunction (DD)/heart failure with preserved ejection fraction (HFpEF). Its diagnostic accuracy is not well studied.
Methods and Results From the PubMed, Scopus, Embase, and Cochrane databases, we identified 24 studies reporting E/e' and invasive LVFP in preserved EF (≥50%). In random‐effects models, E/e' had poor to mediocre linear correlation with LVFP. Summary sensitivity and specificity (with 95% CIs) for the American Society of Echocardiography–recommended E/e' cutoffs (lateral, mean, and septal, respectively) to identify elevated LVFP was estimated by using hierarchical summary receiver operating characteristic analysis. Summary sensitivity was 30% (9–48%), 37% (13–61%), and 24% (6–46%), and summary specificity was 92% (82–100%), 91% (80–99%), and 98% (92–100%). Positive likelihood ratio (LR+) was 10 for septal E/e' obtained from 4 studies (cumulative sample size <220). For excluding elevated LVFP, summary sensitivity for E/e' (lateral, mean, and septal, respectively) was 64% (38–86%), 36% (3–74%), and 50% (14–81%), while summary specificity was 73% (54–89%), 83% (49–100%), and 89% (66–100%). Because of data set limitations, meaningful inference for identifying HFpEF by using E/e' could not be drawn. With the use of quality assessment tool for diagnostic accuracy studies (Quality Assessment of Diagnostic Accuracy Studies questionnaire), we found substantial risks of bias and/or applicability.
Conclusions There is insufficient evidence to support that E/e' can reliably estimate LVFP in preserved EF. The diagnostic accuracy of E/e' to identify/exclude elevated LVFP and DD/HFpEF is limited and requires further validation in a well‐designed prospective clinical trial.
TL;DR: The link between obesity and HF was stronger than those for other CVD subtypes and was uniquely unexplained by traditional risk factors.
Abstract: BackgroundObesity is a risk factor for various subtypes of cardiovascular disease (CVD), including coronary heart disease (CHD), heart failure (HF), and stroke. Nevertheless, there are limited comp...
TL;DR: In this prospective pilot study, the baseline NIHSS score was essential for prediction of acute ischemic stroke outcomes, followed by age; whereas traditional comorbidity index contributed little to the overall model.
Abstract: Background Stroke is among the leading causes of morbidity and mortality worldwide. Without reliable prediction models and outcome measurements, comparison of care systems is impossible. We analyzed prospectively collected data from 4 countries to explore the importance of stroke severity in outcome prediction.
Methods and Results For 2 months, all acute ischemic stroke patients from the hospitals participating in the Global Comparators Stroke GOAL (Global Outcomes Accelerated Learning) collaboration received a National Institutes of Health Stroke Scale (NIHSS) score on admission and a modified Rankin Scale score at 30 and 90 days. These data were added to the administrative data set, and risk prediction models including age, sex, comorbidity index, and NIHSS were derived for in‐hospital death within 7 days, all in‐hospital death, and death and good outcome at 30 and 90 days. The relative importance of each variable was assessed using the proportion of explained variation. Of 1034 admissions for acute ischemic stroke, 614 had a full set of NIHSS and both modified Rankin Scale values recorded; of these, 507 patients could be linked to administrative data. The marginal proportion of explained variation was 0.7% to 4.0% for comorbidity index, and 11.3 to 25.0 for NIHSS score. The percentage explained by the model varied by outcome (16.6–29.1%) and was highest for good outcome at 30 and 90 days. There was high agreement between 30‐ and 90‐day modified Rankin Scale scores (weighted κ=0.82).
Conclusions In this prospective pilot study, the baseline NIHSS score was essential for prediction of acute ischemic stroke outcomes, followed by age; whereas traditional comorbidity index contributed little to the overall model. Future studies of stroke outcomes between different care systems will benefit from including a baseline NIHSS score.
TL;DR: For nonwhite adult samples with hypertension, dynamic RT may elicit BP reductions that are comparable to or greater than those reportedly achieved with AE training, and dynamic RT should be further investigated as a viable stand‐alone therapeutic exercise option for adult populations with high BP.
Abstract: Background Aerobic exercise (AE) is recommended as first‐line antihypertensive lifestyle therapy based on strong evidence showing that it lowers blood pressure (BP) 5 to 7 mm Hg among adults with hypertension. Because of weaker evidence showing that dynamic resistance training (RT) reduces BP 2 to 3 mm Hg among adults with hypertension, it is recommended as adjuvant lifestyle therapy to AE training. Yet, existing evidence suggests that dynamic RT can lower BP as much or more than AE. Methods and Results We meta‐analyzed 64 controlled studies (71 interventions) to determine the efficacy of dynamic RT as stand‐alone antihypertensive therapy. Participants (N=2344) were white (57%), middle‐aged (47.2±19.0 years), and overweight (26.8±3.4 kg/m 2 ) adults with prehypertension (126.7±10.3/76.8±8.7 mm Hg); 15% were on antihypertensive medication. Overall, moderate‐intensity dynamic RT was performed 2.8±0.6 days/week for 14.4±7.9 weeks and elicited small‐to‐moderate reductions in systolic BP (SBP; d + =−0.31; 95% CIs, −0.43, −0.19; −3.0 mm Hg) and diastolic BP (DBP; d + =−0.30; 95% CIs, −0.38, −0.18; −2.1 mm Hg) compared to controls ( P s P s Conclusions Our results indicate that for nonwhite adult samples with hypertension, dynamic RT may elicit BP reductions that are comparable to or greater than those reportedly achieved with AE training. Dynamic RT should be further investigated as a viable stand‐alone therapeutic exercise option for adult populations with high BP.
TL;DR: Coexistence of atherosclerotic risk factors and platelet activation account for the increased risk of MI in AF, and identification of high‐risk AF patients is a needed first step to develop cost‐effective approaches for prevention.
Abstract: Background A growing body of evidence suggests that atrial fibrillation (AF) is associated with myocardial infarction (MI). However, incidence and management of MI in AF is still undefined.
Methods and Results We searched MEDLINE via PubMed and Cochrane database between 1965 and 2015. All observational clinical studies and interventional trials reporting 1‐year incidence of MI in AF were included. We also discussed pathophysiological mechanisms, predictors, and therapeutic approaches to reduce the risk of MI in AF. Twenty‐one observational studies and 10 clinical trials were included. The annual rate of MI in observational studies including AF patients ranged from 0.4% to 2.5%. Higher rates of MI were reported in AF patients with stable coronary artery disease (11.5%/year), vascular disease (4.47%/year), heart failure (2.9%/year), and in those undergoing coronary artery interventions (6.3%/year). However, lower annual rates have been described in AF patients from Eastern countries (0.2–0.3%/year), and in those enrolled in clinical trials (from 0.4 to 1.3%/year).
Conclusions AF patients had a significant residual risk of MI despite anticoagulant treatment. Coexistence of atherosclerotic risk factors and platelet activation account for the increased risk of MI in AF. Identification of high‐risk AF patients is a needed first step to develop cost‐effective approaches for prevention. A new score, the 2MACE score, has been recently developed to stratify MI risk in AF, and may help not only in allocating resources to high‐risk groups, but also in design of studies examining novel therapies for prevention of MI in AF.
TL;DR: In this article, the authors systematically search PubMed for studies evaluating the effect of Internet, mobile phone, personal sensors, or stand-alone computer software on diet, physical activity, adiposity, tobacco, or alcohol use.
Abstract: Background Novel interventions are needed to improve lifestyle and prevent noncommunicable diseases, the leading cause of death and disability globally. This study aimed to systematically review, synthesize, and grade scientific evidence on effectiveness of novel information and communication technology to reduce noncommunicable disease risk.
Methods and Results We systematically searched PubMed for studies evaluating the effect of Internet, mobile phone, personal sensors, or stand‐alone computer software on diet, physical activity, adiposity, tobacco, or alcohol use. We included all interventional and prospective observational studies conducted among generally healthy adults published between January 1990 and November 2013. American Heart Association criteria were used to evaluate and grade the strength of evidence. From 8654 abstracts, 224 relevant reports were identified. Internet and mobile interventions were most common. Internet interventions improved diet (N=20 studies) (Class IIa A), physical activity (N=33), adiposity (N=35), tobacco (N=22), and excess alcohol (N=47) (Class I A each). Mobile interventions improved physical activity (N=6) and adiposity (N=3) (Class I A each). Evidence limitations included relatively brief durations (generally <6 months, nearly always <1 year), heterogeneity in intervention content and intensity, and limited representation from middle/low‐income countries.
Conclusions Internet and mobile interventions improve important lifestyle behaviors up to 1 year. This systematic review supports the need for long‐term interventions to evaluate sustainability.
TL;DR: TMAO was not associated with measures of atherosclerosis: CAC incidence, CAC progression, or cIMT, which indicates that TMAO may not contribute significantly to advancing early atherosclerotic disease risk among healthy early‐middle‐aged adults.
Abstract: Background Clinical studies implicate trimethylamine N‐oxide (TMAO; a gut microbiota‐dependent nutrient metabolite) in cardiovascular disease risk. There is a lack of population‐based data on the role of TMAO in advancing early atherosclerotic disease. We tested the prospective associations between TMAO and coronary artery calcium (CAC) and carotid intima‐media thickness (cIMT).
Methods and Results Data were from the Coronary Artery Risk Development in Young Adults Study (CARDIA), a biracial cohort of US adults recruited in 1985–1986 (n=5115). We randomly sampled 817 participants (aged 33–55 years) who attended examinations in 2000–2001, 2005–2006, and 2010–2011, at which CAC was measured by computed tomography and cIMT (2005–2006) by ultrasound. TMAO was quantified using liquid chromotography mass spectrometry on plasma collected in 2000–2001. Outcomes were incident CAC, defined as Agatston units=0 in 2000–2001 and >0 over 10‐year follow‐up, CAC progression (any increase over 10‐year follow‐up), and continuous cIMT. Over the study period, 25% (n=184) of those free of CAC in 2000–2001 (n=746) developed detectable CAC. In 2000–2001, median (interquartile range) TMAO was 2.6 (1.8–4.2) μmol/L. In multivariable‐adjusted models, TMAO was not associated with 10‐year CAC incidence (rate ratio=1.03; 95% CI: 0.71–1.52) or CAC progression (0.97; 0.68–1.38) in Poisson regression, or cIMT (beta coefficient: −0.009; −0.03 to 0.01) in linear regression, comparing the fourth to the first quartiles of TMAO.
Conclusions In this population‐based study, TMAO was not associated with measures of atherosclerosis: CAC incidence, CAC progression, or cIMT. These data indicate that TMAO may not contribute significantly to advancing early atherosclerotic disease risk among healthy early‐middle‐aged adults.