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Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov , NCT03310125. Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI –0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, –0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93–1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54–5·22). In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong. [ABSTRACT FROM AUTHOR]

Background: The authors previously reported that perioperative aspirin and/or clonidine does not prevent a composite of death or myocardial infarction 30 days after noncardiac surgery. Moreover, aspirin increased the risk of major bleeding and clonidine caused hypotension and bradycardia. Whether these complications produce harm at 1 yr remains unknown.Methods: The authors randomized 10,010 patients with or at risk of atherosclerosis and scheduled for noncardiac surgery in a 1:1:1:1 ratio to clonidine/aspirin, clonidine/aspirin placebo, clonidine placebo/aspirin, or clonidine placebo/aspirin placebo. Patients started taking aspirin or placebo just before surgery; those not previously taking aspirin continued daily for 30 days, and those taking aspirin previously continued for 7 days. Patients were also randomly assigned to receive clonidine or placebo just before surgery, with the study drug continued for 72 h.Results: Neither aspirin nor clonidine had a significant effect on the primary 1-yr outcome, a composite of death or nonfatal myocardial infarction, with a 1-yr hazard ratio for aspirin of 1.00 (95% CI, 0.89 to 1.12; P = 0.948; 586 patients [11.8%] vs. 589 patients [11.8%]) and a hazard ratio for clonidine of 1.07 (95% CI, 0.96 to 1.20; P = 0.218; 608 patients [12.1%] vs. 567 patients [11.3%]), with effect on death or nonfatal infarction. Reduction in death and nonfatal myocardial infarction from aspirin in patients who previously had percutaneous coronary intervention at 30 days persisted at 1 yr. Specifically, the hazard ratio was 0.58 (95% CI, 0.35 to 0.95) in those with previous percutaneous coronary intervention and 1.03 (95% CI, 0.91to 1.16) in those without (interaction P = 0.033). There was no significant effect of either drug on death, cardiovascular complications, cancer, or chronic incisional pain at 1 yr (all P > 0.1).Conclusions: Neither perioperative aspirin nor clonidine have significant long-term effects after noncardiac surgery. Perioperative aspirin in patients with previous percutaneous coronary intervention showed persistent benefit at 1 yr, a plausible sub-group effect. [ABSTRACT FROM AUTHOR]

Background: Patients with atrial fibrillation (AF) have an increased risk of cognitive decline, potentially resulting from clinically unrecognized vascular brain lesions.Objectives: This study sought to assess the relationships between cognitive function and vascular brain lesions in patients with AF.Methods: Patients with known AF were enrolled in a multicenter study in Switzerland. Brain magnetic resonance imaging (MRI) and cognitive testing using the Montreal Cognitive Assessment (MoCA) were performed in all participants. Large noncortical or cortical infarcts (LNCCIs), small noncortical infarcts (SNCIs), microbleeds, and white matter lesions were quantified by a central core laboratory. Clinically silent infarcts were defined as infarcts on brain MRI in patients without a clinical history of stroke or transient ischemic attack.Results: The study included 1,737 patients with a mean age of 73 ± 8 years (28% women, 90% taking oral anticoagulant agents). On MRI, LNCCIs were found in 387 patients (22%), SNCIs in 368 (21%), microbleeds in 372 (22%), and white matter lesions in 1715 (99%). Clinically silent infarcts among the 1,390 patients without a history of stroke or transient ischemic attack were found in 201 patients with LNCCIs (15%) and 245 patients with SNCIs (18%). The MoCA score was 24.7 ± 3.3 in patients with and 25.8 ± 2.9 in those without LNCCIs on brain MRI (p < 0.001). The difference in MoCA score remained similar when only clinically silent LNCCIs were considered (24.9 ± 3.1 vs. 25.8 ± 2.9; p < 0.001). In a multivariable regression model including all vascular brain lesion parameters, LNCCI volume was the strongest predictor of a reduced MoCA (β = -0.26; 95% confidence interval: -0.40 to -0.13; p < 0.001).Conclusions: Patients with AF have a high burden of LNCCIs and other brain lesions on systematic brain MRI screening, and most of these lesions are clinically silent. LNCCIs were associated with worse cognitive function, even among patients with clinically silent infarcts. Our findings raise the question of MRI screening in patients with AF. [ABSTRACT FROM AUTHOR]

Background: Long-term continuous monitoring detects short-lasting, subclinical atrial fibrillation (SCAF) in approximately one-third of older individuals with cardiovascular conditions. The relationship between SCAF, its progression, and the development of heart failure (HF) is unclear.Objectives: This study examined the relationship between progression from shorter to longer SCAF episodes and HF hospitalization.Methods: Subjects in ASSERT (Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial) were ≥65 years old, had history of hypertension, no prior clinical AF, and an implanted pacemaker or defibrillator. We examined patients whose longest SCAF episode during the first year after enrollment was >6 min but ≤24 h (n = 415). Using time-dependent Cox models, we evaluated the relationship between subsequent development of SCAF >24 h or clinical AF and HF hospitalization.Results: Over a mean follow-up of 2 years, 65 patients (15.7%) progressed to having SCAF episodes >24 h or clinical AF (incidence 8.8% per year). Older age, greater body mass index, and longer SCAF duration within the first year were independent predictors of SCAF progression. The rate of HF hospitalization among patients with SCAF progression was 8.9% per year compared with 2.5% per year for those without progression. After multivariable adjustment, SCAF progression was independently associated with HF hospitalization (hazard ratio [HR]: 4.58; 95% confidence interval [CI]: 1.64 to 12.80; p = 0.004). Similar results were observed when we excluded patients with prior history of HF (HR: 7.06; 95% CI: 1.82 to 27.30; p = 0.005) or when SCAF progression was defined as development of SCAF >24 h alone (HR: 3.68; 95% CI: 1.27 to 10.70; p = 0.016).Conclusions: In patients with a pacemaker or defibrillator, SCAF progression was strongly associated with HF hospitalization. [ABSTRACT FROM AUTHOR]

Background: Some but not all prior studies have shown that women receiving a primary prophylactic implantable cardioverter defibrillator (ICD) have a lower risk of death and appropriate shocks than men. Purpose: To evaluate the effect of gender on the risk of appropriate shock, all-cause mortality and inappropriate shock in contemporary studies of patients receiving a primary prophylactic ICD. Data Source: PubMed, LIVIVO, Cochrane CENTRAL between 2010 and 2016. Study Selection: Studies providing at least 1 gender-specific risk estimate for the outcomes of interest. Data Extraction: Abstracts were screened independently for potentially eligible studies for inclusion. Thereby each abstract was reviewed by at least two authors. Data Synthesis: Out of 680 abstracts retained by our search strategy, 20 studies including 46’657 patients had gender-specific information on at least one of the relevant endpoints. Mean age across the individual studies varied between 58 and 69 years. The proportion of women enrolled ranged from 10% to 30%. Across 6 available studies, women had a significantly lower risk of first appropriate shock compared with men (pooled multivariable adjusted hazard ratio 0.62 (95% CI [0.44; 0.88]). Across 14 studies reporting multivariable adjusted gender-specific hazard ratio estimates for all-cause mortality, women had a lower risk of death than men (pooled hazard ratio 0.75 (95% CI [0.66; 0.86]). There was no statistically significant difference for the incidence of first inappropriate shocks (3 studies, pooled hazard ratio 0.99 (95% CI [0.56; 1.73]). Limitations: Individual patient data were not available for most studies. Conclusion: In this large contemporary meta-analysis, women had a significantly lower risk of appropriate shocks and death than men, but a similar risk of inappropriate shocks. These data may help to select patients who benefit from primary prophylactic ICD implantation. [ABSTRACT FROM AUTHOR]

Atrial fibrillation is an increasingly common arrhythmia associated with substantial but largely preventable risk of ischemic stroke. There has been an exponential increase in research related to atrial fibrillation in recent years, resulting in some major advances in the therapeutic management. Novel oral anticoagulant agents have become available and require thorough assessment of risk-to-benefit ratio. While the knowledge is rapidly accumulating, the basic principles of atrial fibrillation management remain proper recognition, risk stratification, and appropriate prevention of thromboembolic complications. This review highlights some common misconceptions about atrial fibrillation. [ABSTRACT FROM AUTHOR]

Background: The association between growth differentiation factor-15 concentrations and cardiovascular disease has been well described. The study hypothesis was that growth differentiation factor-15 may help cardiac risk stratification in noncardiac surgical patients, in addition to clinical evaluation. Methods: The objective of the study was to determine whether preoperative serum growth differentiation factor-15 is associated with the composite primary outcome of myocardial injury after noncardiac surgery and vascular death at 30 days and can improve cardiac risk prediction in noncardiac surgery. This is a prospective cohort study of patients 45 yr or older having major noncardiac surgery. The association between preoperative growth differentiation factor-15 and the primary outcome was determined after adjusting for the Revised Cardiac Risk Index. Preoperative N-terminal-pro hormone brain natriuretic peptide was also added to compare predictive performance with growth differentiation factor-15. Results: Between October 27, 2008, and October 30, 2013, a total of 5,238 patients were included who had preoperative growth differentiation factor-15 measured (median, 1,325; interquartile range, 880 to 2,132 pg/ml). The risk of myocardial injury after noncardiac surgery and vascular death was 99 of 1,705 (5.8%) for growth differentiation factor-15 less than 1,000 pg/ml, 161 of 1,332 (12.1%) for growth differentiation factor-15 1,000 to less than 1,500 pg/ml, 302 of 1476 (20.5%) for growth differentiation factor-15 1,500 to less than 3,000 pg/ml, and 247 of 725 (34.1%) for growth differentiation factor-15 concentrations 3,000 pg/ml or greater. Compared to patients who had growth differentiation factor-15 concentrations less than 1,000 pg/ml, the corresponding adjusted hazard ratio for each growth differentiation factor-15 category was 1.93 (95% CI, 1.50 to 2.48), 3.04 (95% CI, 2.41 to 3.84), and 4.8 (95% CI, 3.76 to 6.14), respectively. The addition of growth differentiation factor-15 improved cardiac risk classification by 30.1% (301 per 1,000 patients) compared to Revised Cardiac Risk Index alone. It also provided additional risk classification beyond the combination of preoperative N-terminal-pro hormone brain natriuretic peptide and Revised Cardiac Risk Index (16.1%; 161 per 1,000 patients). Conclusions: Growth differentiation factor-15 is strongly associated with 30-day risk of major cardiovascular events and significantly improved cardiac risk prediction in patients undergoing noncardiac surgery. This study used clinical data and serum samples from 5,238 patients enrolled in a multisite cohort study (Vascular Events in Noncardiac Surgery Evaluation study; VISION). The authors assessed the association between increased preoperative serum growth differentiation factor-15 and the primary study outcome of 30-day risk of myocardial injury after noncardiac surgery and vascular death. A preoperative growth differentiation factor-15 concentration 1,500 pg/ml or greater was associated with a 24.9% risk of myocardial injury after noncardiac surgery and vascular death. In the subset of patients who had preoperative N-terminal-pro hormone brain natriuretic peptide results available (n = 4,246), the incidence of myocardial injury after noncardiac surgery and vascular death was 606 patients (14.3%). In a multivariable model that included preoperative Revised Cardiac Risk Index score and preoperative N-terminal-pro hormone brain natriuretic peptide categories, both preoperative growth differentiation factor-15 and N-terminal-pro hormone brain natriuretic peptide remained independently associated with myocardial injury after noncardiac surgery and vascular death and vascular mortality at 30 days. [ABSTRACT FROM AUTHOR]

Uncertainty exists around management of long-term antihypertensive medications around the time of noncardiac surgery and intraoperative blood pressures to target. This trial assigned patients to hypotension-avoidance versus hypertension-avoidance strategies in the preoperative setting and assessed differences in vascular death, nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest. Visual Abstract. Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery: Uncertainty exists around management of long-term antihypertensive medications around the time of noncardiac surgery and intraoperative blood pressures to target. This trial assigned patients to hypotension-avoidance versus hypertension-avoidance strategies in the preoperative setting and assessed differences in vascular death, nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest. Background: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively. Objective: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery. Design: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723) Setting: 110 hospitals in 22 countries. Patients: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications. Intervention: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin–angiotensin–aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery. Measurements: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment. Results: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P  = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term. Limitation: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels. Conclusion: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications. Primary Funding Source: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong. [ABSTRACT FROM AUTHOR]

Abstract: Background: Left atrial (LA) enlargement facilitates induction and/or maintenance of atrial fibrillation (AF). However, little is known about risk factors for AF with normal LA size. Methods: We prospectively followed 34713 initially healthy women for incident AF. Information on echocardiographic LA size at first AF diagnosis was abstracted from medical charts during AF confirmation. LA enlargement was defined as LA diameter >40mm. Using a competing risk approach, we constructed Cox proportional-hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI) of risk factors for incident AF with and without LA enlargement, respectively. Results: Among 796 women with incident AF and available LA size, 328 (41%) had LA enlargement. In multivariable competing risk models, the relationship between age and incident AF was stronger in those with (HR 1.12, 95% CI 1.10–1.14) versus without (HR 1.08, 95% CI 1.06–1.09) LA enlargement (p for difference <0.0001). Body weight was associated with AF only in the presence of LA enlargement (HR per 10kg 1.34, 95% CI 1.26-1.43; versus 1.07, 95% CI 0.998–1.14, p for difference<0.0001). Hypertension and height were significantly associated with AF both in the presence (HR 1.99, 95% CI 1.49–2.65; and HR per 10cm 1.36, 95% CI 1.13–1.63) and absence (1.55, 1.25–1.92 and 1.29, 1.10–1.50) of LA enlargement (p for difference 0.17 and 0.66, respectively). Conclusions: These data suggest that LA enlargement explains much of the increased AF risk associated with obesity and age. In contrast, height and hypertension appear to also influence AF risk through other mechanisms besides LA enlargement. [Copyright &y& Elsevier]

Menichelli and colleagues' trial results suggest that reduced-dose prasugrel for elderly or underweight patients with ACS is effective and safe. The editorialists discuss the findings and the need for better strategies to reduce risk and adequately powered head-to-head comparisons to treatment strategies. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. The close relationship between acute excesses of alcohol and the occurrence of AF even in healthy individuals has been known for several decades. More recently, a significant relationship has been consistently observed between elevated consumption of alcoholic beverages on a regular basis and an increased risk of developing AF. However, the amount of alcohol needed to confer an increased risk of AF is rather elevated, approximately two alcoholic beverages per day in women and four to five alcoholic beverages per day in men, suggesting that on a population level, alcohol is not a major contributor to the global AF epidemic. [ABSTRACT FROM AUTHOR]

Premature atrial contractions (PACs) are independent predictors of atrial fibrillation, stroke, and death. However, little is known about PAC frequency in the general population and its association with other cardiovascular risk factors. We performed a cross-sectional analysis among participants of the population-based Swiss cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA). 24-hour Holter electrocardiograms to assess PAC prevalence and frequency were performed in a random sample of 1742 participants aged ≽50 years. The median (interquartile range) number of PACs per hour was 0.8 (0.4-1.8), 1.1 (0.5-2.4), 1.4 (0.7-4.6), 2.3 (0.8-6.9), and 2.6 (1.2-6.5) among participants aged 50 to 55, 55 to 60, 60 to 65, 65 to 70, and ≽70 years, respectively (PcO.OOOl). Only 18 (1.0%) participants did not have at least 1 PAC during Holter monitoring. In multivariable negative binomial regression models, PAC frequency was significantly associated with age (risk ratio [RR] per SD 1.80; P<0.0001), height (RR per SD 1.52; PC0.0001), prevalent cardiovascular disease (RR 2.40; P<0.0001), log-transformed N-terminal pro B-type natriuretic peptides (RR per SD 1.27; P<0.0001), physical activity ≽2 hours per day (RR 0.69; P=0.002), and high-density lipoprotein cholesterol (RR per SD 0.80; /J=0.0002). Hypertension and body mass index were not significantly related to PAC frequency. our knowledge, this is the first study to assess risk factors for PAC frequency in the general population aged ≽50 years. PACs are common, and their frequency is independently associated with age, height, history of cardiovascular disease, natriuretic peptide levels, physical activity, and high-density lipoprotein cholesterol. The underlying mechanisms of these relationships need to be addressed in future studies. [ABSTRACT FROM AUTHOR]

Background: Smoking has a well-documented detrimental effect on risk for myocardial infarction and stroke, but less information is available regarding peripheral artery disease (PAD), particularly among women. Objective: To prospectively assess the association of current smoking status, cumulative smoking exposure, and smoking cessation with incident symptomatic PAD in women. Design: Prospective cohort study. Setting: U.S. female health care professionals in the Women's Health Study. Participants: 39 825 women with no cardiovascular disease who were prospectively followed for a median of 12.7 years. Measurements: Incidence of symptomatic PAD. Cox proportional hazards models were used to compare PAD risk across smoking categories. Results: 178 confirmed PAD events occurred. Across the 4 smoking categories (never, former, <15 cigarettes/d, and ⩾15 cigarettes/d), age-adjusted incidence rates were 0.12, 0.34, 0.95, and 1.63 per 1000 person-years of follow-up, respectively. Multivanate adjustment had little effect on this relationship (adjusted hazard ratios [HRs], 3.14 [95% Cl, 2.01 to 4.90], 8.93 [Cl, 5.02 to 15.89], and 16.95 [Cl, 10.77 to 26.67], respectively, vs. women who never smoked). Additional adjustment for high-sensitivity C-reactive protein and soluble intercellular adhesion molecule-i levels among women with available blood samples (28 314 participants, 117 events) attenuated risk estimates (HR. 5.58 [I, 2.61 to 11.93] for smoking <15 cigarettes/d and 9.52 [Cl, 5.17 to 17.53] for smoking ⩾15 cigarettes/d). Lifetime exposure showed a strong dose-response relationship; fully adjusted HRs for smoking abstinence of fewer than 10, 10 to 29, and 30 or more pack-years were 2.52 (Cl, 1.49 to 4.25), 6.75 (Cl, 4.33 to 10.52), and 11.09 (Cl, 6.94 to 17.72), respectively. Compared with current smokers, the adjusted HRs for fewer than 10 years, 10 to 20 years, more than 20 years, or lifelong abstinence were 0.39 (Cl, 0.24 to 0.66), 0.28 (Cl, 0.17 to 0.46), 0.16 (Cl, 0.10 to 0.26), and 0.08 (Cl, 0.05 to 0.12), respectively. Limitation: The use of symptomatic PAD as the a priori primary end point excludes asymptomatic disease. Conclusion: Among initially healthy women, smoking is a potent risk factor for symptomatic PAD and was associated with subclinical inflammation. Smoking cessation substantially reduces risk for PAD, but an increased occurrence of PAD persists even among former smokers who maintain abstinence. [ABSTRACT FROM AUTHOR]

The article discusses a research study which investigated the link between incident atrial fibrillation (AF) and mortality in initially healthy women and evaluates the effect of associated cardiovascular co-morbidities on risk. The study revealed that new-onset AF among a group of healthy women was independently related to all-cause, cardiovascular, and noncardiovascular mortality, with some of the risk potentially explained by nonfatal cardiovascular events. Incidence rates per 1,000 person-years among women with and without AF were 10.8 and 3.1 for all-cause mortality, 4.3 and 0.57 for cardiovascular mortality, and 6.5 and 2.5 for noncardiovascular mortality, respectively.

Elevated levels of γ-glutamyltransferase (GGT) have been associated with elevated blood pressure (BP) and diabetes. However, the causality of these relations has not been addressed. The authors performed a cross-sectional analysis (2003–2006) among 4,360 participants from the population-based Cohorte Lausannoise (CoLaus) Study (Lausanne, Switzerland). The rs2017869 variant of the γ-glutamyltransferase 1 (GGT1) gene, which explained 1.6% of the variance in GGT levels, was used as an instrument for Mendelian randomization (MR). Sex-specific GGT quartiles were strongly associated with both systolic and diastolic BP (all P’s < 0.0001). After multivariable adjustment, these relations were attenuated but remained significant. Using MR, the authors observed no positive association of GGT with BP (systolic: β −5.68, 95% confidence interval (CI): −11.51, 0.16 (P = 0.06); diastolic: β = −2.24, 95% CI: −5.98, 1.49 (P = 0.24)). The association of GGT with insulin was also attenuated after multivariable adjustment but persisted in the fully adjusted model (β = 0.07, 95% CI: 0.04, 0.09; P < 0.0001). Using MR, the authors also observed a positive association of GGT with insulin (β = 0.19, 95% CI: 0.01, 0.37; P = 0.04). In conclusion, the authors found evidence for a direct causal relation of GGT with fasting insulin but not with BP. [ABSTRACT FROM PUBLISHER]

Objectives: The purpose of this study was to characterize the relationship between changes in body mass index (BMI) and incident atrial fibrillation (AF) in a large cohort of women. Background: Obesity and AF are increasing public health problems. The importance of dynamic obesity-associated AF risk is uncertain, and mediators are not well characterized. Methods: Cases of AF were confirmed by medical record review in 34,309 participants in the Women''s Health Study. Baseline and updated measures of BMI were obtained from periodic questionnaires. Results: During 12.9 ± 1.9 years of follow-up, 834 AF events were confirmed. BMI was linearly associated with AF risk, with a 4.7% (95% confidence interval [CI]: 3.4 to 6.1, p < 0.0001) increase in risk with each kilogram per square meter. Adjustment for inflammatory markers minimally attenuated this risk. When updated measures of BMI were used to estimate dynamic risk, overweight (hazard ratio [HR]: 1.22; 95% CI: 1.02 to 1.45, p = 0.03), and obesity (HR: 1.65; 95% CI: 1.36 to 2.00; p < 0.0001) were associated with adjusted short-term increases in AF risk. Participants becoming obese during the first 60 months had a 41% adjusted increase in risk of the development of AF (p = 0.02) compared with those maintaining BMI <30 kg/m2. The prevalence of overweight and obesity increased over time. The adjusted proportion of incident AF attributable to short-term elevations in BMI was substantial (18.3%). Conclusions: In this population of apparently healthy women, BMI was associated with short- and long-term increases in AF risk, accounting for a large proportion of incident AF independent of traditional risk factors. A strategy of weight control may reduce the increasing incidence of AF. (Women''s Health Study [WHS]: A Randomized Trial of Low-Dose Aspirin and Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer; NCT00000479). [Copyright &y& Elsevier]

The article presents a medical research study which examined the association between regular alcohol consumption and the incident of atrial fibrillation among women. Participants were initially healthy women older than 45 years and free of atrial fibrillation at baseline. Questionnaires were used to assess alcohol consumption at baseline and at 48 months. Atrial fibrillation was reported by the participants via yearly questionnaires. The time to the first episode of atrial fibrillation was the main outcome measure. Consumption of up to two alcoholic beverages per day was found not to be associated with increased risk of incident atrial fibrillation among healthy middle-aged women. A small but statistically significant increased risk was found for consumption of two or more drinks per day.

ABSTRACT Objective To compare cardiovascular risk among women with high normal blood pressure (130-9/85-9 mm Hg) against those with normal blood pressure (120-9/75- 84 mm Hg) and those with baseline hypertension. Design Prospective cohort study. Setting Women's health study, United States. Participants 39 322 initially healthy women classified into four categories according to self reported baseline blood pressure and followed for a median of 10.2 years. Main outcome measures Time to cardiovascular death, myocardial infarction, or stroke (major cardiovascular event-primary end point); progression to hypertension. Results 982 (2.5%) women developed a major cardiovascular event, and 8686 (30.1%) women without baseline hypertension progressed to hypertension. The age adjusted event rate for the primary end point was 1.6/1000 person years among women with normal blood pressure, 2.9/1000 person years among those with high normal blood pressure, and 4.3/1000 person years amongthose with baseline hypertension. Compared with women with high normal blood pressure (reference group), those with normal blood pressure had a lower risk of a major cardiovascular event (adjusted hazard ratio 0.61, 95% confidence interval 0.48 to 0.76) and of incident hypertension (0.42, 0.40 to 0.44). The hazard ratio for a major cardiovascular event in women with baseline hypertension was 1.30 (1.08 to 1.57). Women who progressed to hypertension (reference group) during the first 48 months of the study had a higher cardiovascular risk than those who remained normotensive (adjusted hazard ratio 0.64, 0.50 to 0.81). Women with high normal blood pressure at baseline who progressed to hypertension (reference group) had similar outcome rates to women with baseline hypertension (adjusted hazard ratio 1.17, 0.88 to 1.55). Conclusion The cardiovascular risk of women with high normal blood pressure is higher than that of women with normal blood pressure. The cardiovascular risk of women who progress to hyp [ABSTRACT FROM AUTHOR]

Objectives: This study sought to determine the clinical course and predictors of long-term outcome in patients with documented amiodarone-induced thyrotoxicosis (AIT). Background: Amiodarone-induced thyrotoxicosis is a condition that is difficult to manage, in particular because of the long half-life of amiodarone. Data on optimal treatment for AIT are scarce. Methods: We performed a retrospective review among patients with documented AIT at a tertiary care center. Baseline characteristics, treatment received, laboratory parameters, and events during follow-up were evaluated. The predefined composite end point consisted of the following AIT-associated complications: death, heart transplantation, hospitalization for heart failure, myocardial infarction, stroke, hospitalization for arrhythmia management, or hospitalization for treatment complications. Results: Eighty-four patients were included in the present analysis; 27 patients received prednisone for AIT. There was no difference in time to normalization of free thyroxine between those receiving and those not receiving prednisone. Long-term follow-up showed high morbidity and mortality; 47 patients (56%) reached the primary end point. Patients receiving prednisone had a worse outcome than those not receiving prednisone (p = 0.003). Although patients received prednisone for 84 ± 65 days, curves started to separate only 12 months after the initial diagnosis. Conclusions: Patients with AIT have a high event rate during follow-up. Prednisone had no effect on time to normalization of thyroxine levels and was associated with an increased event rate. Importantly, AIT-related problems must be expected late, at a time when thyroid function is under control. [Copyright &y& Elsevier]

Abstract: Background: The administration of radiographic contrast agents is an important cause of acute renal failure. We hypothesised that hypertension is an independent risk factor for the development of contrast nephropathy in patients undergoing percutaneous coronary intervention. Methods: 1383 consecutive patients scheduled for elective or emergency percutaneous coronary intervention were randomly assigned to receive isotonic or half-isotonic hydration. Contrast nephropathy was defined as a rise in serum creatinine of at least 44 μmol/l (0.5 mg/dl) within 48 h of the procedure. Hypertension was defined as self-reported history of treated or untreated diagnosed high blood pressure. Results: The prevalence of hypertension was 63%. Patients with hypertension were significantly older, were more often female, smoked less and had a higher incidence of 3-vessel disease than patients without hypertension. The estimated glomerular filtration rate was slightly lower in hypertensive patients. There was no difference in preventive hydration regimen, type and quantity of contrast medium used, or quantity of intravenous fluids given. Contrast nephropathy developed in 17 of 874 hypertensive patients (2%) compared to 2 of 509 patients (0.4%) without hypertension (p =0.016). When contrast nephropathy was defined as a 25% rise in baseline creatinine, the disease developed in 103 patients (12%) with and 36 patients (7%) without hypertension (p =0.005). After adjustment for confounders, arterial hypertension remained an independent predictor of contrast nephropathy (odds ratio 4.6, 95% CI 1.0–20.5, p =0.046). Conclusion: Hypertension is an independent risk factor for the development of contrast nephropathy. Further preventive strategies to lower the incidence of contrast nephropathy in hypertensive patients are warranted. [Copyright &y& Elsevier]

Aim: Diagnosis of early stages of arrhythmogenic right ventricular cardiomyopathy (ARVC) with minimal structural abnormalities is challenging. The purpose of this study was to assess the value of repeated cardiac magnetic resonance imaging (CMR) in patients referred for right ventricular arrhythmias and clinical suspicion of ARVC. Methods and Results: Prospective follow-up study of 18 patients (8 females) studied with CMR for suspected ARVC. Patients with implanted defibrillators (ICD) were excluded. Mean follow-up was 37 ± 16 (12–59) months. Patients were assigned to 2 categories (ARVC likely or ARVC unlikely) according to a CMR-score based on right ventricular abnormalities. Clinical follow-up revealed no disease progression in 17 patients (94%). In 1 patient, an ICD was implanted because of disease progression. Of 9 patients with initial findings suggestive of ARVC, follow-up CMR remained positive in 3 and was diagnosed as normal in 6, mainly due to the inability to confirm the presence of fatty infiltrates at follow-up (5 of 6 patients). Initially, 9 patients had a normal CMR and 8 of those remained normal during follow-up. Conclusion: Repeated CMR after an average follow-up of 3 years was normal in 6 of 9 patients with clinical findings consistent with early stages of ARVC at the time of baseline CMR. Thus, CMR diagnosis of early stage ARVC is difficult and should be made with caution. [ABSTRACT FROM AUTHOR]

The diagnosis of left ventricular (LV) hypertrophy, an independent predictor of death and cardiovascular events, is difficult without using echocardiography. This study tested the hypothesis whether C-reactive protein (CRP) and B-type natriuretic peptide (BNP) would be useful to exclude echocardiographic LV hypertrophy. Consecutive hypertensive outpatients were asked to participate. Exclusion criteria were overt heart failure, severe renal insufficiency or any other severe concomitant illness. A venous blood sample was taken to measure plasma CRP and BNP concentrations. Echocardiographic LV hypertrophy was defined as LV mass ≥125 g/m2 for men and ≥110 g/m2 for women. In total, 320 patients were studied, and 37 patients (12%) had echocardiographic LV hypertrophy. Patients with LV hypertrophy were significantly older and had higher CRP and BNP concentrations and higher systolic blood pressure than those without LV hypertrophy. The optimal cut-off points for the diagnosis of LV hypertrophy were 35 pg/ml for BNP (sensitivity 73%, specificity 72%) and 2.5 mg/L for CRP (sensitivity 68%, specificity 59%). Only 1 of 123 patients with values of BNP and CRP less than the optimal cut-off point had echocardiographic LV hypertrophy, resulting in a high negative predictive value of 99% for the 2 blood tests combined to exclude LV hypertrophy. In conclusion, in hypertensive patients, echocardiographic LV hypertrophy can be excluded on the basis of a single blood sample for the determination of BNP and CRP. [Copyright &y& Elsevier]

Objective: Smoking cessation interventions are underutilized in the surgical setting. We aimed to systematically identify the barriers and facilitators to smoking cessation in the surgical setting. Methods: Following the Joanna Briggs Institute (JBI) framework for scoping reviews, we searched 5 databases (MEDLINE, Embase, Cochrane CENTRAL, CINAHL, and PsycINFO) for quantitative or qualitative studies published in English (since 2000) evaluating barriers and facilitators to perioperative smoking cessation interventions. Data were analyzed using thematic analysis and mapped to the theoretical domains framework (TDF). Results: From 31 studies, we identified 23 unique barriers and 13 facilitators mapped to 11 of the 14 TDF domains. The barriers were within the domains of knowledge (e.g., inadequate knowledge of smoking cessation interventions) in 23 (74.2%) studies; environmental context and resources (e.g., lack of time to deliver smoking cessation interventions) in 19 (61.3%) studies; beliefs about capabilities (e.g., belief that patients are nervous about surgery/diagnosis) in 14 (45.2%) studies; and social/professional role and identity (e.g., surgeons do not believe it is their role to provide smoking cessation interventions) in 8 (25.8%) studies. Facilitators were mainly within the domains of environmental context and resources (e.g., provision of quit smoking advice as routine surgical care) in 15 (48.4%) studies, reinforcement (e.g., surgery itself as a motivator to kickstart quit attempts) in 8 (25.8%) studies, and skills (e.g., smoking cessation training and awareness of guidelines) in 5 (16.2%) studies. Conclusion: The identified barriers and facilitators are actionable targets for future studies aimed at translating evidence informed smoking cessation interventions into practice in perioperative settings. More research is needed to evaluate how targeting these barriers and facilitators will impact smoking outcomes. [ABSTRACT FROM AUTHOR]

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to evaluate serial measurements of B-type natriuretic peptide (BNP) and NT-proBNP levels in the detection of myocardial ischemia. A total of 62 consecutive male patients referred for stress echocardiography in a tertiary care cardiology center were enrolled. Inducible myocardial ischemia was detected in 15 patients (24%). BNP and NT-proBNP levels were significantly lower in patients with ischemia compared to those without ischemia throughout exercise testing and during recovery (p <0.05 for all comparisons). Major differences in baseline characteristics including age and higher incidence of comorbidities including hypertension and kidney disease in patients without ischemia apparently outweighed myocardial ischemia as trigger for BNP and NT-proBNP secretion. The same factors may have induced a selection bias in the decision to offer direct coronary angiography or initial stress testing. In conclusion, BNP and NT-proBNP are not helpful in the evaluation of male patients with suspected myocardial ischemia in a tertiary care cardiology center with rapid access to coronary angiography. [Copyright &y& Elsevier]

Background: For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes.Methods: The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization.Discussion: Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality.Trial Registration: ClinicalTrials.gov NCT03505723. Registered on 23 April 2018. [ABSTRACT FROM AUTHOR]

Randomized controlled trials of pulmonary vein isolation (PVI) for treating atrial fibrillation (AF) have proven the procedure's efficacy. Studies assessing its empirical cost-effectiveness outside randomized trial settings are lacking. We aimed to evaluate the effectiveness and cost-effectiveness of PVI versus medical therapy for AF. We followed a target trial approach using the Swiss-AF cohort, a prospective observational cohort study that enrolled patients with AF between 2014 and 2017. Resource utilization and cost information were collected through claims data. Quality of life was measured with EQ-5D-3L utilities. We estimated incremental cost-effectiveness ratios (ICERs) from the perspective of the Swiss statutory health insurance system. Patients undergoing PVI compared with medical therapy had a 5-year overall survival advantage with a hazard ratio of 0.75 (95% CI 0.46-1.21; P =.69) and a 19.8% SD improvement in quality of life (95% CI 15.5-22.9; P <.001), at an incremental cost of 29 604 Swiss francs (CHF) (95% CI 16 354-42 855; P <.001). The estimated ICER was CHF 158 612 per quality-adjusted life-year (QALY) gained within a 5-year time horizon. Assuming similar health effects and costs over 5 additional years changed the ICER to CHF 82 195 per QALY gained. Results were robust to the sensitivity analyses performed. Our results show that PVI might be a cost-effective intervention within the Swiss healthcare context in a 10-year time horizon, but unlikely to be so at 5 years, if a willingness-to-pay threshold of CHF 100 000 per QALY gained is assumed. Given data availability, we find target trial designs are a valuable tool for assessing the cost-effectiveness of healthcare interventions outside of randomized controlled trial settings. • What is the real-world cost-effectiveness of pulmonary vein isolation (PVI) compared with standard medical therapy for patients with atrial fibrillation? • In this economic evaluation designed with a target trial approach including 2379 patients with real-world clinical, quality of life, and costing data, we estimate the incremental cost-effectiveness ratio of PVI compared with standard medical therapy to be 158 612 Swiss francs per quality-adjusted life-year gained (1 US dollar ∼ 0.93 Swiss francs) at 5 years and 82 195 per quality-adjusted life-year at 10 years. • In our target trial emulation-based cost-effectiveness assessment, PVI for the management of atrial fibrillation might be cost-effective over a 10-year period. [ABSTRACT FROM AUTHOR]

Introduction: Atrial fibrillation (AF) adversely impacts right ventricular (RV) and right atrial (RA) structure and function. There are limited data on these changes after electrical cardioversion (ECV) and the relative contribution of heart rate to evaluate the immediate (1–2 h) and short-term (4–6 weeks) changes in right cardiac chamber dimensions and RV function after ECV in patients with persistent AF. Methods: Right cardiac chamber dimensions and RV function were measured in 64 patients using transthoracic echocardiography 1–2 h before, immediately after, and 4–6 weeks after ECV. Associations between changes in right-heart measures and rhythm status at follow-up were assessed using linear regression models. Results: For patients who remained in sinus rhythm 4–6 weeks after ECV (n = 48), median fractional area change (FAC) at baseline, immediately after ECV, and 4–6 weeks after ECV were 39 (Q1:35, Q3:42) %, 42 (Q1:39, Q3:46) %, 46 (Q1:43, Q3:49) % (p < 0.01); median tricuspid annular plane systolic excursion (TAPSE) values at the same time points were 18 (Q1:17, Q3:20) mm, 20 (Q1:18, Q3:23) mm, and 24 (Q1:22, Q3:26) mm (p < 0.01), respectively. There was no significant difference in RV end systolic area and RA volume index before and after ECV. However, RV end systolic area and RA volume index decreased significantly after 4–6 weeks from a median of 10 (Q1:8, Q3:13) cm2 to 8 (Q1:7, Q3:10) cm2 (p < 0.01), and from a median of 30 (Q1:24, Q3:36) mL/m2 to 24 (Q1:20, Q3:27) mL/m2 (p < 0.01). Changes in TAPSE were significantly associated with sinus rhythm at follow-up (p = 0.027), changes in FAC showed a strong trend to association with sinus rhythm (p = 0.053), and this was not true for RA measures (p = 0.64). Conclusions: Among AF patients who remained in sinus rhythm after ECV, RV function improved immediately after ECV with further improvement at 4–6 weeks following sinus rhythm restoration. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is often detected for the first time in patients who are hospitalized for another reason. Management of patients whose AF resolves before discharge is not always clear. In this matched cohort study, the authors examined the risks for AF recurrence among patients with new AF who were hospitalized for another surgical or medical diagnosis and whose AF resolved before discharge. Visual Abstract. Atrial Fibrillation Recurrence in Patients With Transient New-Onset Atrial Fibrillation Detected During Hospitalization for Noncardiac Surgery or Medical Illness: Atrial fibrillation (AF) is often detected for the first time in patients who are hospitalized for another reason. Management of patients whose AF resolves before discharge is not always clear. In this matched cohort study, the authors examined the risks for AF recurrence among patients with new AF who were hospitalized for another surgical or medical diagnosis and whose AF resolved before discharge. Background: Atrial fibrillation (AF) is often detected for the first time in patients who are hospitalized for another reason. Long-term risks for AF recurrence in these patients are unclear. Objective: To estimate risk for AF recurrence in patients with new-onset AF during a hospitalization for noncardiac surgery or medical illness compared with a matched population without AF. Design: Matched cohort study. (ClinicalTrials.gov: NCT03221777) Setting: Three academic hospitals in Hamilton, Ontario, Canada. Participants: The study enrolled patients hospitalized for noncardiac surgery or medical illness who had transient new-onset AF. For each participant, an age- and sex-matched control participant with no history of AF from the same hospital ward was recruited. All participants left the hospital in sinus rhythm. Measurements: 14-day electrocardiographic (ECG) monitor at 1 and 6 months and telephone assessment at 1, 6, and 12 months. The primary outcome was AF lasting at least 30 seconds on the monitor or captured by ECG 12-lead during routine care at 12 months. Results: Among 139 participants with transient new-onset AF (70 patients with medical illness and 69 surgical patients) and 139 matched control participants, the mean age was 71 years (SD, 10), the mean CHA 2 DS 2 -VASc score was 3.0 (SD, 1.5), and 59% were male. The median duration of AF during the index hospitalization was 15.8 hours (IQR, 6.4 to 49.6 hours). After 1 year, recurrent AF was detected in 33.1% (95% CI, 25.3% to 40.9%) of participants in the transient new-onset AF group and 5.0% (CI, 1.4% to 8.7%) of matched control participants; after adjustment for the number of ECG monitors worn and for baseline clinical differences, the adjusted relative risk was 6.6 (CI, 3.2 to 13.7). After exclusion of participants who had electrical or pharmacologic cardioversion during the index hospitalization (n = 40) and their matched control participants and limiting to AF events detected by the patch ECG monitor, recurrent AF was detected in 32.3% (CI, 23.1% to 41.5%) of participants with transient new-onset AF and 3.0% (CI, 0% to 6.4%) of matched control participants. Limitations: Generalizability is limited, and the study was underpowered to evaluate subgroups and clinical predictors. Conclusion: Among patients who have transient new-onset AF during a hospitalization for noncardiac surgery or medical illness, approximately 1 in 3 will have recurrent AF within 1 year. Primary Funding Source: Peer-reviewed grants. [ABSTRACT FROM AUTHOR]

The soluble urokinase plasminogen activator receptor (suPAR), as a correlate of chronic low-grade inflammation, may be used to predict individual cardiovascular risk. Since chronic low-grade inflammation is thought to be associated with the development of cardiovascular disease, this study aimed to evaluate if suPAR plasma levels are correlated with cardiovascular risk factors in young and healthy adults (aged 25–41 years). Consequently, data from the GAPP (genetic and phenotypic determinants of blood pressure and other cardiovascular risk factors) study were used to investigate suPAR plasma levels in relation to the following cardiovascular risk factors and laboratory parameters: BMI, physical activity, alcohol consumption, smoking status, blood pressure parameters, glucose status, and lipid levels. Additionally, suPAR was compared to the healthy lifestyle score and the Framingham score representing the overall cardiovascular risk profile. These associations were assessed using two different statistical approaches. Firstly, all cardiovascular risk factors and scores were compared amongst sex-specific suPAR plasma levels with ANOVA analysis. Secondly, sex-specific multivariable linear regressions were performed. Female participants had higher plasma suPAR levels than male participants (1.73 ng/mL versus 1.50 ng/mL; p < 0.001). A significant inverse correlation between suPAR plasma levels and HDL cholesterol was found in men (p = 0.001) and women (p < 0.001). Furthermore, male (p < 0.001) and female participants (p < 0.001) who smoked showed significantly higher plasma levels of suPAR (p < 0.001). For male participants, an inverse correlation of the healthy lifestyle score with suPAR plasma levels (p = 0.001) and a positive correlation of the Framingham score with suPAR plasma levels (p < 0.001) were detected. In women, no such correlation was found. The cholesterol levels (p = 0.001) and HbA1c (p = 0.008) correlated significantly with plasma suPAR levels in female participants. suPAR plasma levels were found to be strongly associated with certain cardiovascular risk factors; however, sex-specific differences were found. These sex-specific differences might be explained by the higher prevalence of cardiovascular risk factors in men resulting in a stronger correlation of suPAR as a marker of low-grade inflammation, since the existence of the risk factors already led to subclinical damage in men. Further research on suPAR levels in an older study population is needed. [ABSTRACT FROM AUTHOR]

Background: Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery; it is associated with morbidity and mortality. We undertook this review to compare the effects of rhythm vs. rate control in this population. Methods: We searched MEDLINE, Embase and CENTRAL to March 2023. We included randomized trials and observational studies comparing rhythm to rate control in cardiac surgery patients with POAF. We used a random-effects model to meta-analyze data and rated the quality of evidence using GRADE. Results: From 8,110 citations, we identified 8 randomized trials (990 patients). Drug regimens used for rhythm control included amiodarone in four trials, other class III anti-arrhythmics in one trial, class I anti-arrhythmics in four trials and either a class I or III anti-arrhythmic in one trial. Rhythm control compared to rate control did not result in a significant difference in length of stay (mean difference −0.8 days; 95% CI −3.0 to +1.4, I2 = 97%), AF recurrence within 1 week (130 events; risk ratio [RR] 1.1; 95%CI 0.6–1.9, I2 = 54%), AF recurrence up to 1 month (37 events; RR 0.9; 95%CI 0.5–1.8, I2 = 0%), AF recurrence up to 3 months (10 events; RR 1.0; 95%CI 0.3–3.4, I2 = 0%) or mortality (25 events; RR 1.6; 95%CI 0.7–3.5, I2 = 0%). Effect measures from seven observational studies (1428 patients) did not differ appreciably from those in randomized trials. Conclusions: Although atrial fibrillation is common after cardiac surgery, limited low-quality data guide its management. Limited available evidence suggests no clear advantage to either rhythm or rate control. A large-scale randomized trial is needed to inform this important clinical question. [ABSTRACT FROM AUTHOR]

It is unknown whether neurological symptoms are associated with brain injury after SARS-CoV-2 infections and whether brain injury and related symptoms also emerge in Long-COVID patients. Biomarkers such as serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) can be used to elucidate neuro-axonal and astroglial injuries. We investigated whether these biomarkers are associated with COVID-19 infection status, associated symptoms and Long-COVID. From 146 individuals of the general population with a post-acute, mild-to-moderate SARS-CoV-2 infection, sNfL and sGFAP were measured before, during and after (five and ten months) the infection. Individual symptoms and Long-COVID status were assessed using questionnaires. Neurological associated symptoms were described for individuals after a mild and moderate COVID-19 infection; however, sNfL (p = 0.74) and sGFAP (p = 0.24) did not change and were not associated with headache (p = 0.51), fatigue (p = 0.93), anosmia (p = 0.77) or ageusia (p = 0.47). In Long-COVID patients, sGFAP (p = 0.038), but not sNfL (p = 0.58), significantly increased but was not associated with neurological associated symptoms. Long-COVID status, but not post-acute SARS-CoV-2 infections, may be associated with astroglial injury/activation, even if neurological associated symptoms were not correlated. [ABSTRACT FROM AUTHOR]

Background and purpose: Vascular brain lesions, such as ischemic infarcts, are common among patients with atrial fibrillation (AF) and are associated with impaired cognitive function. The role of physical activity (PA) in the prevalence of brain lesions and cognition in AF has not been investigated. Methods: Patients from the multicenter Swiss‐AF cohort study were included in this cross‐sectional analysis. We assessed regular exercise (RE; at least once weekly) and minutes of weekly PA using a validated questionnaire. We studied associations with ischemic infarcts, white matter hyperintensities, cerebral microbleeds, and brain volume on brain magnetic resonance imaging and with global cognition measured with a cognitive construct (CoCo) score. Results: Among 1490 participants (mean age = 72 ± 9 years), 730 (49%) engaged in RE. In adjusted regression analyses, RE was associated with a lower prevalence of ischemic infarcts (odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.63–0.98, p = 0.03) and of moderate to severe white matter hyperintensities (OR = 0.78, 95% CI = 0.62–0.99, p = 0.04), higher brain volume (β‐coefficient = 10.73, 95% CI = 2.37–19.09, p = 0.01), and higher CoCo score (β‐coefficient = 0.08, 95% CI = 0.03–0.12, p < 0.001). Increasing weekly PA was associated with higher brain volume (β‐coefficient = 1.40, 95% CI = 0.65–2.15, p < 0.001). Conclusions: In AF patients, RE was associated with a lower prevalence of ischemic infarcts and of moderate to severe white matter disease, with larger brain volume, and with better cognitive performance. Prospective studies are needed to investigate whether these associations are causal. Until then, our findings suggest that patients with AF should be encouraged to remain physically active. [ABSTRACT FROM AUTHOR]

The article highlights a study which examined the link between mortality and new-onset atrial fibrillation (AF) in initially healthy women. The results of the study showed that new-onset AF is independently associated with cardiovascular, all-cause and non-cardiovascular mortality in initially healthy women.

A letter to the editor is presented in response to the article "Feasibility of Treating Prehypertension With an Angiotensin-Receptor Blocker," by S. Julius, S. D. Nesbitt, B. M. Egan et al. in the April 20, 2006 issue.

Abstract: Purpose: Countless blood pressure measurements are performed every day for almost every hospitalized patient. We analyzed the value of routine blood pressure measurements on patient care in an unselected group of hospitalized patients. Methods: The study included 639 patients who were admitted to the hospital with a broad range of medical conditions. Two independent investigators reviewed the medical charts of the patients. Routine blood pressure values were abstracted from the patient charts and evaluated with respect to the occurrence of adverse clinical events in the study group. Changes in blood pressure between the last measurement just before adverse clinical events and the mean blood pressure values 72 hours before the adverse events were calculated and compared with mean normal day-to-day variations in blood pressure. Results: In every patient, a mean of 1.6 ± 0.6 routine blood pressure measurements per day were performed. Of the 639 patients in the study, 122 (19%) had clinical complications. The most commonly occurring complications were gastrointestinal bleeding (n = 15), falls (n = 13), other bleeding (n = 12) and pneumonia (n = 8). In patients who experienced clinical complications, pre-event systolic and diastolic blood pressure changes of at least 10 mm Hg occurred in 41% and 24% of the group, respectively, but this was not different from the normal day-to-day variations observed in patients who had no clinical complications. The results also were similar for patients who died or who had a severe adverse event that required admission to an intensive care unit. Conclusion: Routine blood pressure measurements in a general hospital patient population do not predict clinical adverse events. [Copyright &y& Elsevier]

Background: Tobacco smoking is a leading preventable cause of death and increases perioperative risk. Determinants of smoking abstinence after noncardiac surgery and the association between smoking and 1-yr vascular outcomes are not fully elucidated.Methods: We did a prospective cohort study of 40 004 patients, aged ≥45 yr, enrolled between August 2007 and November 2013, and followed for 1 yr after surgery. Patients were categorised as never smokers, ex-smokers (quit >4 weeks preoperatively), and current smokers (smoking ≤4 weeks preoperatively). Primary outcome was abstinence at 1 yr. Secondary outcome was a composite of all-cause death, non-fatal myocardial infarction, and non-fatal stroke at 1 yr.Results: Of 4658 current smokers, 1838 (39.5%) were abstinent 1 yr after surgery. Median (inter-quartile range) time to resumption was 7 (3-23) days post-surgery. Perioperatively, 7.2% of current smokers obtained smoking cessation pharmacotherapy. Older age (adjusted risk ratio [aRR] 1.21; 95% confidence interval [CI]: 1.12-1.32); having recent coronary artery disease (aRR 1.41; 95% CI: 1.29-1.55); cancer (aRR 1.37; 95% CI: 1.18-1.59); and undergoing major vascular (aRR 1.20; 95% CI: 1.02-1.41), urgent/emergent (aRR 1.14; 95% CI: 1.05-1.23), or thoracic (aRR 1.41; 95% CI: 1.26-1.56) surgeries increased abstinence. One-year abstinence was less likely when patients stopped smoking 0-1 day (aRR 0.53; 95% CI: 0.43-0.66) and 2-14 days (aRR 0.76; 95% CI: 0.71-0.82) before surgery compared with >14 days before surgery. Current smokers (adjusted hazard ratio [aHR] 1.14; 95% CI: 1.01-1.29) and ex-smokers (aHR 1.11; 95% CI: 1.03-1.21) had higher risk of the 1-yr vascular outcome compared with never smokers.Conclusions: Long-term tobacco abstinence is more likely after major surgery in those with serious medical comorbidities. Interventions to prevent smoking resumption after surgery remain a priority. Clinical trial registration NCT00512109. [ABSTRACT FROM AUTHOR]

Aims: To examine clinical and social correlates of health‐related quality of life (HRQL) in patients with heart failure (HF) from high‐ (HIC), upper middle‐ (UMIC), lower middle‐ (LMIC) and low‐income (LIC) countries. Methods and results: Between 2017 and 2020, 23 292 patients with HF (32% inpatients, 61% men) from 40 countries were enrolled in the Global Congestive Heart Failure study. HRQL was recorded at baseline using the Kansas City Cardiomyopathy Questionnaire (KCCQ)‐12. In a cross‐sectional analysis, we compared age‐ and sex‐adjusted mean KCCQ‐12 summary scores (SS: 0–100, higher = better) between patients from different country income levels. We used multivariable linear regression examining correlations (estimated coefficients) of KCCQ‐12‐SS with sociodemographic, comorbidity, treatment and symptom covariates. The adjusted model (37 covariates) was informed by univariable findings, clinical importance and backward selection. Mean age was 63 years and 40% of patients were in New York Heart Association (NYHA) class III–IV. Average HRQL was 55 SD 27. It was 62.5 (95% confidence interval [CI] 62.0–63.1) in HIC, 56.8 (56.1–57.4) in UMIC, 48.6 (48.0–49.3) in LMIC, and 38.5 (37.3–39.7) in LICs (p < 0.0001). Strong correlates (estimated coefficient [95% CI]) of KCCQ‐12‐SS were NYHA class III versus class I/II (−12.1 [−12.8 to −11.4] and class IV versus class I/II (−16.5 [−17.7 to −15.3]), effort dyspnoea (−9.5 [−10.2 to −8.8]) and living in LIC versus HIC (−5.8 [−7.1 to −4.4]). Symptoms explained most of the KCCQ‐12‐SS variability (partial R2 = 0.32 of total adjusted R2 = 0.51), followed by sociodemographic factors (R2 = 0.12). Results were consistent in populations across income levels. Conclusion: The most important correlates of HRQL in HF patients relate to HF symptom severity, irrespective of country income level. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is one of the most common complications after cardiac surgery. New-onset post-operative AF may signal an elevated risk of AF and associated outcomes in long-term follow-up. We aimed to estimate the rate of AF recurrence as detected by an implantable loop recorder (ILR) in patients experiencing post-operative AF within 30 days after cardiac surgery. We searched MEDLINE, Embase and Cochrane CENTRAL to April 2023 for studies of adults who did not have known AF, experienced new-onset AF within 30 days of cardiac surgery and received an ILR. We pooled individual participant data on timing of AF recurrence using a random-effects model with a frailty model applied to a Cox proportional hazard analysis. From 8671 citations, 8 single-centre prospective cohort studies met eligibility criteria. Data were available from 185 participants in 7 studies, with a median follow-up of 1.7 (IQR: 1.3–2.8) years. All included studies were at a low risk of bias. Pooled AF recurrence rates following 30 post-operative days were 17.8% (95% CI 11.9%–23.2%) at 3 months, 24.4% (17.7%–30.6%) at 6 months, 30.1% (22.8%–36.7%) at 12 months and 35.3% (27.6%–42.2%) at 18 months. In patients who experience new-onset post-operative AF after cardiac surgery, AF recurrence lasting at least 30 s occurs in approximately 1 in 3 in the first year after surgery. The optimal frequency and modality to use for monitoring for AF recurrence in this population remain uncertain. • 1/3 with new-onset POAF experience recurrence within 1 year of cardiac surgery. • This is the largest cardiac surgery patient series with new-onset POAF and ILRs. • Future studies are needed to establish cut-offs of clinically important AF durations. [ABSTRACT FROM AUTHOR]

The effect of the ventricular repolarization heterogeneity has not been systematically assessed in patients with atrial fibrillation (AF). Aim of this study is to assess ventricular repolarization heterogeneity as predictor of cardiovascular (CV) death and/or other CV events in patients with AF. From the multicenter prospective Swiss-AF (Swiss Atrial Fibrillation) Cohort Study, we enrolled 1711 patients who were in sinus rhythm (995) or AF (716). Resting ECG recordings of 5-min duration were obtained at baseline. Parameters assessing ventricular repolarization were computed (QTc, Tpeak-Tend, J-Tpeak and V-index). During AF, the V-index was found repeatable (no differences when computed over the whole recording, on the first 2.5-min and on the last 2.5-min segments). During a mean follow-up time of 2.6 ± 1.0 years, 90 patients died for CV reasons. In bivariate Cox regression analysis (adjusted for age only), the V-index was associated with an increased risk of CV death, both in the subgroup of patients in sinus rhythm (SR) as well as those in AF. In multivariate analysis adjusted for clinical risk factors and medications, both prolonged QTc and V-index were independently associated with an increased risk of CV death (QTc: hazard ratio [HR] 2.78, 95% CI 1.79–4.32, p < 0.001; V-index: HR 1.73, 95% CI 1.12–2.69, p = 0.014). QTc and V-index, measured in a single 5-min ECG recording, were independent predictors of CV death in a cohort of patients with AF and might be a valuable tool for further risk stratification to guide patient management. Clinical Trial Identifier Swiss-AF study: NCT02105844 • The V-index can be assessed in routine ambulatory 5-min ECG in patients with AF. • V-index and QTc independent predictors of cardiovascular mortality in AF patients. • The largest study for prognostic implications of ventricular repolarization in AF. • Large ventricular repolarization heterogeneity identifies high-risk AF patients. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is a cardiac arrhythmia associated with an elevated risk of stroke, heart failure, and mortality. However, preventative therapies are needed with ancillary benefits on its cardiovascular comorbidities. Lipoprotein(a) (Lp[a]) is a recognized risk factor for atherosclerotic cardiovascular disease (ASCVD), which itself increases AF risk, but it remains unknown whether Lp(a) is a causal mediator of AF independent of ASCVD.Objectives: This study investigated the role of Lp(a) in AF and whether it is independent of ASCVD.Methods: Measured and genetically predicted Lp(a) levels were tested for association with 20,432 cases of incident AF in the UK Biobank (N = 435,579). Mendelian randomization analyses were performed by using summary-level data for AF from publicly available genome-wide association studies (N = 1,145,375).Results: In the UK Biobank, each 50 nmol/L (23 mg/dL) increase in Lp(a) was associated with an increased risk of incident AF using measured Lp(a) (HR: 1.03; 95% CI: 1.02-1.04 ; P = 1.65 × 10-8) and genetically predicted Lp(a) (OR: 1.03; 95% CI: 1.02-1.05; P = 1.33 × 10-5). Mendelian randomization analyses using independent data replicated the effect (OR: 1.04 per 50 nmol/L Lp[a] increase; 95% CI: 1.03-1.05 per 50 nmol/L Lp[a] increase; P = 9.23 × 10-10). There was no evidence of risk-conferring effect from low-density lipoprotein cholesterol or triglycerides, and only 39% (95% CI: 27%-73%) of Lp(a) risk was mediated through ASCVD, suggesting that Lp(a) partly influences AF independent of its known effects on ASCVD.Conclusions: Our findings implicate Lp(a) as a potential causal mediator in the development of AF which show that the effects of Lp(a) extend across myocardial tissues. Ongoing clinical trials for Lp(a)-lowering therapies should evaluate effects on AF prevention. [ABSTRACT FROM AUTHOR]

Background: Serum neurofilament light chain (sNfL) is a biomarker of neuronal damage that is used not only to monitor disease activity and response to drugs and to prognosticate disease course in people with multiple sclerosis on the group level. The absence of representative reference values to correct for physiological age-dependent increases in sNfL has limited the diagnostic use of this biomarker at an individual level. We aimed to assess the applicability of sNfL for identification of people at risk for future disease activity by establishing a reference database to derive reference values corrected for age and body-mass index (BMI). Furthermore, we used the reference database to test the suitability of sNfL as an endpoint for group-level comparison of effectiveness across disease-modifying therapies.Methods: For derivation of a reference database of sNfL values, a control group was created, comprising participants with no evidence of CNS disease taking part in four cohort studies in Europe and North America. We modelled the distribution of sNfL concentrations in function of physiological age-related increase and BMI-dependent modulation, to derive percentile and Z score values from this reference database, via a generalised additive model for location, scale, and shape. We tested the reference database in participants with multiple sclerosis in the Swiss Multiple Sclerosis Cohort (SMSC). We compared the association of sNfL Z scores with clinical and MRI characteristics recorded longitudinally to ascertain their respective disease prognostic capacity. We validated these findings in an independent sample of individuals with multiple sclerosis who were followed up in the Swedish Multiple Sclerosis registry.Findings: We obtained 10 133 blood samples from 5390 people (median samples per patient 1 [IQR 1-2] in the control group). In the control group, sNfL concentrations rose exponentially with age and at a steeper increased rate after approximately 50 years of age. We obtained 7769 samples from 1313 people (median samples per person 6·0 [IQR 3·0-8·0]). In people with multiple sclerosis from the SMSC, sNfL percentiles and Z scores indicated a gradually increased risk for future acute (eg, relapse and lesion formation) and chronic (disability worsening) disease activity. A sNfL Z score above 1·5 was associated with an increased risk of future clinical or MRI disease activity in all people with multiple sclerosis (odds ratio 3·15, 95% CI 2·35-4·23; p<0·0001) and in people considered stable with no evidence of disease activity (2·66, 1·08-6·55; p=0·034). Increased Z scores outperformed absolute raw sNfL cutoff values for diagnostic accuracy. At the group level, the longitudinal course of sNfL Z score values in people with multiple sclerosis from the SMSC decreased to those seen in the control group with use of monoclonal antibodies (ie, alemtuzumab, natalizumab, ocrelizumab, and rituximab) and, to a lesser extent, oral therapies (ie, dimethyl fumarate, fingolimod, siponimod, and teriflunomide). However, longitudinal sNfL Z scores remained elevated with platform compounds (interferons and glatiramer acetate; p<0·0001 for the interaction term between treatment category and treatment duration). Results were fully supported in the validation cohort (n=4341) from the Swedish Multiple Sclerosis registry.Interpretation: The use of sNfL percentiles and Z scores allows for identification of individual people with multiple sclerosis at risk for a detrimental disease course and suboptimal therapy response beyond clinical and MRI measures, specifically in people with disease activity-free status. Additionally, sNfL might be used as an endpoint for comparing effectiveness across drug classes in pragmatic trials.Funding: Swiss National Science Foundation, Progressive Multiple Sclerosis Alliance, Biogen, Celgene, Novartis, Roche. [ABSTRACT FROM AUTHOR]