Search

Background Plasma levels of natriuretic peptides (NP) have been inversely related to hemoglobin (Hb) concentration in prior studies. However, the mechanism underlying this association remains unclear. We aimed to obtain further insights into potential mechanisms for this correlation in a cohort of healthy adults. Methods A population-based study was performed among 2113 healthy adults aged 25–41 years. Relationships of N-Terminal fragment of Pro-B-Type Natriuretic Peptide (NT-proBNP) or copeptin with volume-dependent (Hb, hematocrit (Hct), erythrocyte count (EC), mean corpuscular Hb concentration (MCHC)) and volume-independent (mean corpuscular volume (MCV), mean corpuscular Hb (MCH)) erythrocyte-related parameters were assessed using sex-specific multivariable linear regression analyses. Results The median age was 36.7 years. Median NT-proBNP (ng/L) levels were 49.5 and 20 among women and men, respectively (p < 0.0001). Mean (standard deviation) Hb (g/L) levels were 130.1(9.1) and 149.7(8.6) among women and men, respectively (p < 0.0001). Among men, multivariable adjusted β-coefficients (95% confidence interval) for NT-proBNP were − 1.68 (− 2.36; − 1.01), p < 0.0001 for Hb; − 0.38 (− 0.57; − 0.20), p < 0.0001 for Hct; − 0.06 (− 0.09; − 0.04), p < 0.0001 for EC; − 0.78 (− 1.50; − 0.07), p = 0.03 for MCHC; 0.26 (− 0.04; 0.56), p = 0.09 for MCV; and 0.03 (− 0.08; 0.14), p = 0.61 for MCH. For copeptin, these relationships were 1.36 (0.39; 2.32), p = 0.006; 0.41 (0.15; 0.68), p = 0.002; 0.06 (0.02; 0.09), p = 0.002; − 0.17 (− 1.19; 0.86), p = 0.75; − 0.12 (− 0.55; 0.31), p = 0.58 and − 0.05 (− 0.21; 0.10), p = 0.52. Similar results were observed among women. Conclusions We found significant relationships of NT-proBNP and copeptin with volume-dependent but not volume-independent erythrocyte-related parameters, suggesting that hemodilution may at least in part explain these associations. [ABSTRACT FROM AUTHOR]

Background Elevated blood pressure (BP) is a leading cardiovascular risk factor and a major determinant of left ventricular mass. Te aim of this study was to assess electrocardiographic (ECG) changes associated with hypertension in a large cohort of young and healthy adults. Methods Healthy individuals aged 25–41 years without known cardiovascular disease were enrolled in a population based cohort study. Resting 12-lead ECG and ambulatory 24-hour BP measurement were obtained using validated devices. Multivariable logistic regression models were constructed to assess the relationships between ECG parameters and daytime hypertension, defined as systolic daytime BP ≥ 140, diastolic BP ≥ 90 mmHg or use of antihypertensive treatment. Results Daytime hypertension was present among 430 of 2070 (21%) participants. Significant linear relationships were observed between daytime hypertension with RR interval (odds ratio (OR) 95% confidence interval (CI) 0.84 (0.78; 0.92)), R-wave amplitude in leads I and II (OR (95% CI) 2.04 (1.30; 3.19) and 1.61 (1.15; 2.24), and S-wave amplitudes in leads aVR, V1 and V2 with ORs (95% CI) of 3.28 (1.93; 5.59), 2.15 (1.51; 3.08) and 1.47 (1.18; 1.83), respectively. We also observed linear associations between daytime hypertension and T-wave amplitudes in leads V1 (OR (95% CI) 4.83 (2.35; 9.91)), V2 (2.18 (1.43; 3.32)), V4 (0.48 (0.29; 0.80)) and V5 (0.37 (0.19; 0.72)). Conclusion Several ECG parameters are independently associated with daytime hypertension among young and healthy adults. This is one of the first studies to show significant relationships between T wave amplitude and hypertension. [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]

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]

Objective Glucagon-like peptide 1 ( GLP-1)-related pathways may partially explain the strong relationship between obesity and type 2 diabetes. We therefore aimed to evaluate the relationships between fasting GLP-1 levels, body fat mass and other obesity markers in a large sample of young and healthy adults. Design and Patients Our population-based study included 2096 individuals aged 24-44. Exclusion criteria were prevalent cardiovascular disease, diabetes or a body mass index ( BMI) >35 kg/m2. Body fat mass was obtained by bioelectrical impedance analysis. Multivariable linear regression models were constructed to assess the relationships of GLP-1 with various measures of body composition. Results Median age of our population was 37 years, median BMI 24·1 kg/m2 and median body fat 25·1%. A strong positive correlation was observed in age-adjusted models between GLP-1 and fat mass in men (β (95% confidence interval) 1·38 (0·69; 2·07), P < 0·001) and women (1·27 (0·65; 1·89), P < 0·001) as well as fully adjusted models including BMI in men [0·87 (0·27; 1·46), P < 0·01] but not women [0·29 (−0·07; 0·64), P = 0·11]. The relationships of GLP-1 with BMI for men and women [0·00 (−0·34; 0·34), P = 0·99] [−0·02 (−0·28; 0·25), P = 0·91] and waist circumference [0·43 (−0·45; 1·30), P = 0·34] [0·37 (−0·44; 1·18), P = 0·37], respectively, were not significant after multivariable adjustment including fat mass. Conclusion Among young and healthy adults, GLP-1 levels are strongly and independently related to body fat mass especially in men but not BMI or waist circumference. These results raise the hypothesis that GLP-1 may be implicated in body fat mass regulation. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is common in patients with heart failure (HF). Real-world data about long-term outcomes and rhythm control interventions use in AF patients with and without HF remain scarce. AF patients from two prospective, multicentre studies were classified based on the HF status at baseline into: HF with preserved ejection fraction (HFpEF), HF with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF), and no HF. The prespecified primary outcome was risk of HF hospitalisation. Other outcomes of interest included mortality, cardiovascular events, AF progression, and quality of life. A total of 1265 patients with AF were analysed (mean age 69.6 years, women 27.4%) with a median follow-up of 5.98 years. Patients with HFpEF (n = 126) had a 2.69-fold and patients with HFrEF/HFmrEF (n = 308) had a 2.12-fold increased risk of HF hospitalisation compared to patients without HF (n = 831, p < 0.001). Similar results applied for all-cause and cardiovascular mortality. The risk for AF progression was higher for patients with HFpEF and HFrEF/HFmrEF (6.30 and 6.79 per 100 patient-years, respectively) compared to patients without HF (4.20). The use of rhythm control strategies during follow-up was least in the HFpEF population (4.56 per 100 patient-years) compared to 7.74 in HFrEF/HFmrEF and 8.03 in patients with no HF. With regards to quality of life over time, this was worst among HFpEF patients. The presence of HFpEF among patients with AF carried a high risk of HF hospitalisations and AF progression, and worse quality of life. Rhythm control interventions were rarely offered to HFpEF patients. These results uncover an unmet need for enhanced therapeutic interventions in patients with AF and HFpEF. • Atrial fibrillation (AF) and heart failure (HF) are highly prevalent and closely intertwined. • There is a scarcity of data on clinical characteristics and long-term outcomes in AF patients with different HF phenotypes. • This study reveals that all HF phenotypes in AF are associated with worse outcomes compared to patients without HF. • Patients with HFpEF have a higher risk of AF progression, lower utilization of rhythm control, and worse quality of life. • These findings emphasize the need for novel therapies tailored to address the challenges faced by AF patients with HF. [ABSTRACT FROM AUTHOR]

Introduction: Atrial fibrillation (AF) poses a significant risk of stroke. Left atrial appendage occlusion (LAAO) is an alternative for patients with contraindications to oral anticoagulation (OAC) or with high risk of bleeding. This study aims to compare the outcomes of LAAO versus conventional stroke prevention in high-risk AF-patients. Methods: This secondary analysis incorporates data from the prospective Swiss-AF and Beat-AF cohorts, and the Zurich LAAO Registry. Cardinality matching was performed to create two comparable cohorts: conventional treatment (92% OAC) and LAAO. The primary endpoint was a composite of stroke, cardiovascular (CV) death, and clinically relevant bleeding. Kaplan-Meier method with competing risk analysis was used. Results: Each group included 468 patients (age 76.4 [70.5, 82.0] years, 33% female). The LAAO group exhibited higher baseline bleeding risk (HAS BLED 2.0 [1.0–3.0] versus 3.0 [3.0–4.0]; p < 0.001). Median follow-up time: 6.0 (4.7–7.0) years in conventional treatment group and 4.0 (1.5–6.1) in LAAO group. No significant difference in the primary composite endpoint (HR 0.87, 95% CI: 0.72–1.06, p = 0.18), stroke risk (HR 1.14, 95% CI: 0.66–1.97, p = 0.64), or CV mortality (HR 1.08, 95% CI: 0.82–1.42, p = 0.60) was observed between groups. LAAO correlated with a significantly lower risk of clinically relevant bleeding (HR 0.61, 95% CI: 0.47–0.80, p < 0.001). Conclusion: In this cardinality matched analysis with long-term follow-up, LAAO showed similar stroke and CV death rates but lower clinically relevant bleeding risk compared to conventional therapy in high-risk AF-patients. [ABSTRACT FROM AUTHOR]

Background: Inflammation plays an important role in the initiation and progression of atrial fibrillation (AF), but data about the relationship between subclinical inflammation and recurrence of AF after catheter ablation remains poorly studied. We aimed to assess whether plasma levels of C-reactive protein (CRP) are associated with long-term AF recurrence following catheter ablation.Methods: Prior to the intervention, plasma CRP concentrations were measured in patients who underwent first catheter ablation for AF. AF recurrence was evaluated after 12 months and defined as any AF episode longer than 30 s recorded on either 12-lead electrocardiogram, 24-h Holter or 7-day Holter monitoring. Multivariable adjusted Cox models were constructed to examine the association of CRP levels and AF recurrence.Results: Of the 711 patients (mean age: 61 years, 25% women) included in this study, 247 patients (35%) experienced AF recurrence after ablation. Patients who were in the highest CRP quartile had a higher rate of recurrent AF compared to those who were in the lowest quartile (53.4 vs. 33.1% at 1 year of follow-up; P = 0.004). The adjusted hazard ratios (aHR) of recurrent AF across increasing quartiles of CRP were 1.0 (reference), 1.26 (95% confidence interval [CI], 0.86-1.84), 1.15 (95% CI, 0.78-1.70) and 1.60 (95% CI, 1.10-2.34) (P trend = 0.015). A similar effect was observed when CRP was analyzed as continuous variable (aHR per unit increase, 1.21; 95% CI, 1.05-1.39; P = 0.009). When a predefined CRP cut-off of 3 mg/l was applied, patients with CRP levels of 3 mg/l or above had a higher risk of AF recurrence than those with levels below (aHR, 1.44; 95% CI, 1.06-1.95; P = 0.019).Conclusions: Increasing pre-interventional CRP levels are associated with a higher risk of AF recurrence in patients undergoing catheter ablation for AF.Trail Registration: ClinicalTrials.gov identifier, NCT03718364. [ABSTRACT FROM AUTHOR]

Considering sex as a biological variable in modern digital health solutions, we investigated sex-specific differences in the trajectory of four physiological parameters across a COVID-19 infection. A wearable medical device measured breathing rate, heart rate, heart rate variability, and wrist skin temperature in 1163 participants (mean age = 44.1 years, standard deviation [SD] = 5.6; 667 [57%] females). Participants reported daily symptoms and confounders in a complementary app. A machine learning algorithm retrospectively ingested daily biophysical parameters to detect COVID-19 infections. COVID-19 serology samples were collected from all participants at baseline and follow-up. We analysed potential sex-specific differences in physiology and antibody titres using multilevel modelling and t-tests. Over 1.5 million hours of physiological data were recorded. During the symptomatic period of infection, men demonstrated larger increases in skin temperature, breathing rate, and heart rate as well as larger decreases in heart rate variability than women. The COVID-19 infection detection algorithm performed similarly well for men and women. Our study belongs to the first research to provide evidence for differential physiological responses to COVID-19 between females and males, highlighting the potential of wearable technology to inform future precision medicine approaches. [ABSTRACT FROM AUTHOR]

Introduction: The natural course of atrial fibrillation (AF) is unkown. Hypothesis: We aimed to investigate the change in AF-burden over time using yearly 7-day Holter-ECG recordings and its association with clinical parameters. Methods: Fifty-four participants with recently documented paroxysmal or persistent AF were prospectively enrolled. Main exclusion criteria were permanent AF and scheduled or previous catheter ablation for AF. AF episodes >30sec were assessed using annual 7 day Holter-ECG monitoring and AF-burden was calculated by time with AF divided by total recording time. A relative change ≥10% or an absolute change >0.5% of AF-burden over time was considered significant. Mixed effect models were built to investigate the relation of AF-burden over time with clinical, laboratory and echocardiographic parameters. Results: Mean age was 66.5 (±8.2) years and 72.2% were men. At baseline, AF was recorded in 25 (46.3%) participants. In subsequent 7 day Holter-ECG monitorings 9 (16.7%) participants showed a decrease and 11 (20.3%) participants an increase in AF-burden (Fig. A). The proportion of patients with no recorded AF increased from 53.7 to 78.6% after 4 years of follow-up (Fig. B). In separate multivariable, mixed effect models AF-burden over time was associated with prior stroke (β 42.59, CI (23.40; 61.77); p<0.0001), brain natriuretic peptide (BNP) levels (β 0.05, CI (0.02; 0.09); p=0.005), minimal (β 0.49, CI (0.23; 0.74); p=0.0003) as well as maximal (β 0.25, CI (0.05; 0.46); p=0.02) left atrial volume, left atrial ejection fraction (β -0.43, CI (-0.76; -0.10); p=0.01), E wave (β 36.67, CI (12.96; 60.38); p=0.003) and deceleration time (β -0.1, CI (-0.16; -0.05); p=0.0002). In a combined, mixed-effect model, including all significantly associated variables from the separate models, only history of a prior stroke (β 29.93, CI (2.95; 56.93); p=0.03) and BNP levels (β 0.05, CI (0.01; 0.08); p=0.006) remained significantly associated with AF-burden. Conclusions: In the majority of participants no AF could be recorded in yearly 7-day Holter-ECG monitorings. Several participants showed a decrease in AF-burden over time. AF-burden was independently, positively associated with a history of prior stroke and BNP levels. [ABSTRACT FROM AUTHOR]

Background: Patients with atrial fibrillation (AF) face a high risk of heart failure (HF) hospitalizations. Unfortunately, little data is currently available on the underlying mechanisms of this relationship. Insulin-Like Growth Factor-Binding Protein-7 (IGFBP7) has been associated with worsening HF and cardiac hypertrophy, and is therefore an interesting target in this context. Methods: We performed a prospective multicenter observational cohort study of 1484 patients with documented AF. Information on personal characteristics and co-morbidities was obtained through standardized questionnaires. Baseline IGFBP7 levels were measured from frozen plasma samples. The primary endpoint of this analysis was hospitalization for acute HF, and all events were independently confirmed. Multivariable adjusted Cox regression analyses were constructed to assess the relationship of IGFBP7 levels with incident HF and to adjust for covariates. Results: Mean age was 69±12 years, 435 (29.3%) were females and 302 (20.4%) had a history of HF at baseline. During a mean follow-up of 4.3±1.6 years, 144 confirmed cases of HF hospitalizations occurred. The rate of HF hospitalizations across increasing IGFBP7 quartiles was 5, 6, 20 and 74 per 1000 patient-years of follow-up. The multivariable adjusted hazard ratios [95% CI] across increasing quartiles of IGFBP7 were 0.9 [0.4; 2.1], 2.0 [0.9; 4.5], and 5.3 [2.5; 11.6] (p for trend <0.0001) (Table). Among patients without HF at baseline, the hazard ratios [95% CI] across increasing quartiles of IGFBP7 were 1.0 [0.4; 2.6], 0.7 [0.3; 2.1], and 3.3 [1.3; 8.1] (p for trend <0.0001) (Table). The corresponding incidence rates were 5, 6, 7 and 51 per 1000 patients-years of follow-up. Conclusion: Increasing levels of IGFBP7 were strongly and independently associated with HF hospitalizations in patients with AF, suggesting that cardiac hypertrophy is a major factor in the tight relationship between AF and HF. Given the strength of the association, IGFBP7 may become a useful marker to identify AF patients at increased risk of incident HF. [ABSTRACT FROM AUTHOR]

Background: An increased risk of intracranial hemorrhage (ICH) associated with statins has been reported, but data on the relationship between statin use and cerebral microbleeds (CMBs) in patients with atrial fibrillation (AF), a population at high bleeding and cardiovascular risk, are lacking. Aims: To explore the association between statin use and blood lipid levels with the prevalence and progression of CMBs in patients with AF with a particular focus on anticoagulated patients. Methods: Data of Swiss-AF, a prospective cohort of patients with established AF, were analyzed. Statin use was assessed during baseline and throughout follow-up. Lipid values were measured at baseline. CMBs were assessed using magnetic resonance imagining (MRI) at baseline and at 2 years follow-up. Imaging data were centrally assessed by blinded investigators. Associations of statin use and low-density lipoprotein (LDL) levels with CMB prevalence at baseline or CMB progression (at least one additional or new CMB on follow-up MRI at 2 years compared with baseline) were assessed using logistic regression models; the association with ICH was assessed using flexible parametric survival models. Models were adjusted for hypertension, smoking, body mass index, diabetes, stroke/transient ischemic attack, coronary heart disease, antiplatelet use, anticoagulant use, and education. Results: Of the 1693 patients with CMB data at baseline MRI (mean ± SD age 72.5 ± 8.4 years, 27.6% women, 90.1% on oral anticoagulants), 802 patients (47.4%) were statin users. The multivariable adjusted odds ratio (adjOR) for CMBs prevalence at baseline for statin users was 1.10 (95% CI = 0.83–1.45). AdjOR for 1 unit increase in LDL levels was 0.95 (95% CI = 0.82–1.10). At 2 years, 1188 patients had follow-up MRI. CMBs progression was observed in 44 (8.0%) statin users and 47 (7.4%) non-statin users. Of these patients, 64 (70.3%) developed a single new CMB, 14 (15.4%) developed 2 CMBs, and 13 developed more than 3 CMBs. The multivariable adjOR for statin users was 1.09 (95% CI = 0.66–1.80). There was no association between LDL levels and CMB progression (adjOR 1.02, 95% CI = 0.79–1.32). At follow-up 14 (1.2%) statin users had ICH versus 16 (1.3%) non-users. The age and sex adjusted hazard ratio (adjHR) was 0.75 (95% CI = 0.36–1.55). The results remained robust in sensitivity analyses excluding participants without anticoagulants. Conclusions: In this prospective cohort of patients with AF, a population at increased hemorrhagic risk due to anticoagulation, the use of statins was not associated with an increased risk of CMBs. [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]

A healthy lifestyle is associated with a lower risk of cardiovascular events and mortality, but underlying mechanisms are not fully understood. The aim of our study was to investigate the relationships between a healthy lifestyle and glucagon-like peptide-1 (GLP-1), an incretin hormone with both glycemic and cardiovascular properties. Healthy participants aged 25-41years without cardiovascular disease, diabetes or a body mass index (BMI) >35kg/m2 were enrolled in a population-based study. The following metrics were used to build a lifestyle score ranging from 0 to 7 (a higher score indicating a healthier lifestyle): blood pressure (BP) (<120/80mmHg), plasma levels of glycated hemoglobin (<5.7%), total cholesterol levels (<200mg/dl), BMI (<25kg/m2), not smoking cigarettes, moderate (≥150min/week) or vigorous (≥75min/week) physical activity and a healthy diet. Among 2133 participants median age was 36.7years and 53.3% were female. GLP-1 levels decreased significantly from 39.5 to 30.9ng/l (p<0.0001) across increasing lifestyle score categories. This linear relationship persisted in multivariable adjusted linear regression models (B for GLP-1 per 1-unit increase of the lifestyle score -0.06; 95% confidence intervals -0.07, -0.04; p<0.0001). Individual health metrics that were significantly associated with GLP-1 were a normal BMI (-0.07; -0.12, -0.03; p=0.001), low total cholesterol levels (-0.07; -0.12, -0.03; p=0.001), normal BP (-0.05; -0.10, -0.00; p=0.047) and not smoking (-0.06; -0.10, -0.01; p=0.01). A healthy lifestyle is strongly associated with lower GLP-1 levels in young and healthy adults. [ABSTRACT FROM AUTHOR]

Background Kidney injury molecule-1 (KIM-1) has been associated with kidney damage in patients with preexisting renal disease. However, little is known about the relationships of KIM-1 with renal function and cardiovascular risk factors in healthy individuals from the general population. Methods Healthy individuals aged 25–41 years were enrolled in a population-based study. Main exclusion criteria were a BMI > 35 kg/m 2 , preexisting kidney disease or established cardiovascular disease. KIM-1 was measured from frozen plasma samples using a high-sensitivity assay. Multivariable linear regression models were constructed to assess the relationships of KIM-1 with renal function and various cardiovascular risk factors. Results We included 2060 individuals (47% men, median (interquartile range) age: 37 (31–40) years) in this analysis. Median KIM-1 levels were 82.5 (IQR 59.4–112.7) pg/ml. We found no significant relationship of KIM-1 with creatinine (adjusted β-coefficient (95% confidence interval) 0.0005 (− 0.002; 0.003), p = 0.61) and cystatin C (− 0.02 (− 0.21; 0.17), p = 0.84). There were significant linear relationships of log-transformed KIM-1 with systolic blood pressure (adjusted β-coefficient (95% confidence interval) 0.07 (0.04; 0.09), p < 0.0001), diastolic blood pressure (0.04 (0.02; 0.07), p = 0.001), low-density lipoprotein cholesterol (0.09 (0.06; 0.11), p < 0.0001), high-density lipoprotein cholesterol (0.07 (0.05; 0.1), p < 0.0001), high-sensitivity C-reactive protein (0.05 (0.03; 0.07), p < 0.0001), age (0.09 (0.07; 0.11), p < 0.0001), BMI (0.04 (0.01; 0.06), p = 0.005) and current smoking (0.12 (0.07; 0.17), p < 0.0001). Conclusion Among healthy adults from the general population, plasma levels of KIM-1 were not associated with renal function but were independently related to multiple cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background A longer QTc interval has been associated with more adverse cardiovascular events and death in the general population. Little evidence is available on these relationships among patients with atrial fibrillation (AF). Methods We performed a prospective observational multicenter cohort study of 1413 patients with AF. A resting 12‑lead electrocardiogram (ECG) was performed at baseline. QT interval was corrected for heart rate using the Bazett formula (QTc). Endpoints for this study included hospitalizations for congestive heart failure (CHF), a combination of cardiovascular death, myocardial infarction, stroke, systemic arterial embolism (MACE) and all-cause mortality. Results Mean age of our population was 68 ± 12 years and 420 (30%) participants were female. Median QTc was 432 ms (interquartile range 409; 457). The mean follow-up time was 3.6 ± 1.5 years. After multivariable adjustment, there was a linear increase in risk with increasing QTc interval for incident CHF (hazard ratio (HR) per 1-SD increase in QTc 1.3 [95% CI 1.1; 1.6], p = 0.008), MACE (HR 1.2 [1.0; 1.4], p = 0.02) and all-cause mortality (HR 1.3 [1.0; 1.6], p = 0.002). Results were consistent whether or not patients were in sinus rhythm on the baseline ECG (HR for CHF 1.7 versus 1.3, p interaction 0.08; HR for MACE 1.3 versus 1.2, p interaction 0.9; HR for all-cause mortality 1.4 versus 1.4, p interaction 0.9). Conclusions In this large well-characterized cohort of AF patients, QTc interval was independently associated with adverse outcomes. These results were independent of the rhythm on the baseline ECG. [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]

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]

Direct oral anticoagulants (DOACs) have a favourable risk-benefit profile compared to vitamin K-antagonists (VKAs) in atrial fibrillation (AF). Dosing is based on age, weight and renal function, without need of routine monitoring. In two prospective, multicentre AF cohorts (Swiss-AF, BEAT-AF) patients were stratified as receiving VKAs or adequately-, under- or overdosed DOACs, according to label. Primary outcome was a composite of major adverse clinical events (MACE), defined as cardiovascular death, myocardial infarction (MI), ischaemic stroke and systemic embolism. Secondary outcomes included major bleeding. Adjustment for confounding was performed. Median follow-up was 4 years. Of 3236 patients, 1875 (58%) were on VKAs and 1361 (42%) were on DOACs, of which 1137 (83%) were adequately-, 134 (10%) over- and 90 (7%) under-dosed. Compared to adequately dosed individuals, overdosed patients were more likely to be older and female. Underdosing correlated with concomitant aspirin therapy and coronary artery disease. Both groups had higher CHA 2 DS 2 -VASc scores. Patients on overdosed DOACs had higher incidence of MACE (HR 1.75; CI 1.10–2.79; adjusted-HR: 1.22) and major bleeding (HR 1.99; CI 1.14–3.48; adjusted-HR: 1.51). Underdosing was not associated with a higher incidence of MACE (HR 0.94; CI 0.46–1.92; adjusted-HR 0.61) or major bleeding (HR 1.07; CI 0.46–2.46; adjusted-HR 0.82). After adjustment, all CIs crossed 1.0. Inappropriate DOAC-dosing was more prevalent in multimorbid patients, but did not correlate with higher risks of adverse events after adjusting for confounders. DOAC prescription should follow label. [ABSTRACT FROM AUTHOR]

Background and Aims: The role of biomarkers in diagnosing pulmonary hypertension (PH) and distinguishing between pre- and post-capillary PH remains poorly understood. We aimed to identify biomarkers with a strong association with mean pulmonary arterial pressure, mPAP (PH diagnosis) and pulmonary vascular resistance, PVR (pre-capillary component), but not with pulmonary arterial wedge pressure, PAWP (post-capillary component)., Methods: Blood samples were collected in patients undergoing right heart catheterization within a prospective cross-sectional study. Biomarkers measured included BMP10, NT-proBNP, ANG2, ESM1/endocan, FGF23, GDF15, IGFBP7, IL6, MyBPC3, proC3, and proC6/endotrophin. Primary outcomes were mPAP, PVR, and PAWP, while secondary outcomes included PH diagnosis (mPAP > 20 mmHg) and elevated PVR (> 2 Wood units). Multivariable linear and logistic regression models were used to assess the relationship between biomarkers and outcomes., Results: Of the 127 patients included (age 66 ± 13 years, 54% female), 73% were diagnosed with PH. BMP10, NT-proBNP, ANG2, MyBPC3, and FGF23 showed a strong association with mPAP (p < 0.001). BMP10 and NT-proBNP were strongly associated with PVR (p < 0.001), while NT-proBNP and ANG2 were strongly associated with PAWP (p < 0.001). NT-proBNP had the strongest association with the diagnosis of PH (area under the curve = 0.76). BMP10 was the only biomarker associated with elevated PVR (OR 1.60, 95%CI 1.01-2.54, p = 0.04) but not with PAWP (p = 0.86)., Conclusions: Several biomarkers were strongly associated with mPAP, PAWP, and PVR. BMP10 was the only biomarker strongly associated with mPAP and PVR, but not with PAWP, thus reflecting the pre-capillary PH component. Measurement of BMP10 along with NT-proBNP may aid in diagnosing PH., (© 2024. The Author(s).)