Toxicity of low dose bisphenols in human iPSC-derived cardiomyocytes and human cardiac organoids - Impact on contractile function and hypertrophy.

Bisphenol A (BPA) and its analogs are common environmental chemicals with various adverse health impacts, including cardiac toxicity. In this study, we examined the long term effect of low dose BPA and three common BPA analogs, bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF), in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) based models. HiPSC-CMs and human cardiac organoids were exposed to these chemicals for 4-5 or 20 days. 1 nM BPA, BPS, and BPAF, but not BPF, resulted in suppressed myocyte contractility, retarded contraction kinetics, and aberrant Ca2+ transients in hiPSC-CMs. In cardiac organoids, BPAF and BPA, but not the other bisphenols, resulted in suppressed contraction and Ca2+ transients, and aberrant contraction kinetics. The order of toxicities was BPAF > BPA>∼BPS > BPF and the toxicities of BPAF and BPA were more pronounced under longer exposure. The impact of BPAF on myocyte contraction and Ca2+ handling was mediated by reduction of sarcoplasmic reticulum Ca2+ load and inhibition of L-type Ca2+ channel involving alternation of Ca2+ handling proteins. Impaired myocyte Ca2+ handling plays a key role in cardiac pathophysiology and is a characteristic of cardiac hypertrophy; therefore we examined the potential pro-hypertrophic cardiotoxicity of these bisphenols. Four to five day exposure to BPAF did not cause hypertrophy in normal hiPSC-CMs, but significantly exacerbated the hypertrophic phenotype in myocytes with existing hypertrophy induced by endothelin-1, characterized by increased cell size and elevated expression of the hypertrophic marker proBNP. This pro-hypertrophic cardiotoxicity was also occurred in cardiac organoids, with BPAF having the strongest toxicity, followed by BPA. Our findings demonstrate that long term exposures to BPA and some of its analogs cause contractile dysfunction and abnormal Ca2+ handling, and have potential pro-hypertrophic cardiotoxicity in human heart cells/tissues, and suggest that some bisphenol chemicals may be a risk factor for cardiac hypertrophy in human hearts.

Association between serum copper levels and stroke in the general population: A nationally representative study.

OBJECTIVES: The objective was to explore the association between serum copper levels and the prevalence of stroke. METHODS: Data were obtained from 3 consecutive National Health and Nutrition Examination Survey (NHANES) cycles (2011-2016). Weighted multivariable logistic regression analysis was conducted to evaluate the association between serum copper levels and self-reported stroke. RESULTS: A total of 5,151 adults met the inclusion criteria. A total of 181 (3.51%) stroke patients were identified. In comparison to individuals with serum copper levels in the lowest tertile (<16.4 µmol/l), those with levels in the middle tertile (16.4-19.8 µmol/l) had an odds ratio (OR) of 0.99 (95% confidence interval [CI]: 0.44-2.25), while those with levels in the highest tertile (>19.8 µmol/l) had an OR of 2.36 (95% CI: 1.01-5.52). Furthermore, each standard deviation (SD) increase in serum copper was found to be positively associated with the prevalence of stroke, with an OR of 1.44 (95% CI: 1.11-1.86). Dose‒response analysis showed a positive linear association between serum copper levels and stroke (Pnonlinearity=0.554). CONCLUSIONS: This cross-sectional study suggested a positive association between serum copper levels and stroke among American adults.

Toxicity of environmentally relevant concentration of PFAS chemicals in Lumbriculus variegatus (Oligochaeta, Lumbriculidae) - A multi-bioindicator study.

PFAS, or per- and polyfluoroalkyl substances, are a family of man-made chemicals found in a variety of products from non-stick cookware and food wrappers to firefighting foams. PFAS are persistent and widely distributed in the environment, including aquatic environments. In this study we examined the impact of PFAS chemicals on the physiological and behavioral endpoints of Lumbriculus variegatus (i.e., blackworms). Lumbriculus variegatus is a species of freshwater annelid worm that plays key roles in shallow freshwater ecosystems. At an environmentally relevant concentration of 1 µg/L, 12-day aqueous exposure to long chain PFAS, including PFOA, PFOS and PFDA, each markedly slowed the pulse rate of the dorsal blood vessel in L. variegatus, indicating a suppressive effect on blood circulation. The mean pulse rate was reduced from 9.6 beats/minute to 6.2 and 7.0 beats/min in PFOA and PFOS, respectively (P < 0.0001). Further, PFOA, PFOS and PFDA reduced the escape responsiveness of L. variegatus to physical stimulation. The percentage of worms showing normal escape behavior was reduced from 99.0% in control to 90.6% in the PFOS exposed group (P < 0.01). In a chronic (4 week) growth study, exposure to overlying water and sediment spiked with PFOA, PFOS or PFDA reduced the total biomass and the number of worms, indicating a suppressive effect on worm population growth. For instance, PFOA and PFDA reduced the total dry biomass by 26.3% and 28.5%, respectively, compared to the control (P < 0.05). The impact of PFAS on blackworm physiology is accompanied by an increase in lipid peroxidation. The level of malondialdehyde (MDA), an indicator of lipid peroxidation, and catalase, a major antioxidant enzyme, were markedly increased in PFOA, PFOS and PFDA exposed groups. Interestingly, exposure to PFHxA, a short chain PFAS, had no detectable effect on any of the measured endpoints. Our results demonstrate that L. variegatus is highly sensitive to the toxic impact of long chain PFAS chemicals as measured by multiple endpoints including blood circulation, behavior, and population growth. Such toxicity may have a detrimental impact on L. variegatus and the freshwater ecosystems where it resides.

Clinical Outcomes with GLP-1 Receptor Agonists in Patients with Heart Failure: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, there remains uncertainty about the efficiency of GLP-1 RAs in patients with heart failure (HF). METHODS: Randomized placebo-controlled trials (RCTs) that reported the effect of GLP-1 RAs on prognosis in patients with HF were identified by searching databases. The primary outcome was defined as MACE. Trail Sequential Analysis (TSA) was used to evaluate the reality and authenticity. RESULTS: Nine RCTs involving 8920 patients with HF were included. GLP-1 RAs significantly reduced the risk of MACE compared with placebo (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.77-0.98) in HF coexisting with T2DM. The benefit was not observed in all-cause death (HR 0.99, 95% CI 0.84-1.15), hospitalization for heart failure (HR 1.04, 95% CI 0.89-1.22), cardiovascular death (HR 0.95, 95% CI 0.79-1.16), myocardial infarction (HR 0.88, 95% CI 0.71-1.08), stroke (HR 1.03, 95% CI 0.75-1.43) and death or hospitalization for HF (HR 1.07, 95% CI 0.78-1.46). GLP-1 RAs did not improve the change in LVEF (mean difference [MD]): - 0.86, p = 0.12, left-ventricular end-diastolic volume (LVEDV) (MD: 3.54, p = 0.11), left-ventricular end-systolic volume (LVESV) (MD: 2.78, p = 0.07) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) (MD: - 140.36, p = 0.08). However, GLP-1 RAs significantly increased the change in the 6-min walk test (MWT) distance (MD: 19.74, p = 0.002). In the subgroup analyses, human GLP-1 RAs, but not nonhuman GLP-1 RAs, reduced the risk of MACE in patients with HF (p interaction = 0.11). Grading of Recommendations Assessment, Development and Evaluation (GRADE) showed moderate certainty for MACE, all-cause death and hospitalization for HF. Trail Sequential Analysis revealed that there may be a high possibility of false positive results for MACE. CONCLUSION: Compared with placebo, GLP-1 RAs may reduce the risk of MACE in patients with HF coexisting with T2DM, with a more significant efficiency of human GLP-1 RAs. More RCTs are needed to assess the cardiovascular benefits of GLP-1 RAs in HF, regardless of T2DM. REGISTRATION: The protocol for this meta-analysis is registered on PROSPERO [CRD42022357886].

Association of the Triglyceride-Glucose Index With Risk of Alzheimer's Disease: A Prospective Cohort Study.

INTRODUCTION: Triglyceride-glucose index (TyG) is a reliable surrogate marker of insulin resistance, and insulin resistance has been implicated in Alzheimer's disease pathophysiology. However, the relationship between the TyG index and Alzheimer's disease remains unclear. This study aimed to evaluate the association of the TyG index with the risk of Alzheimer's disease. METHODS: This prospective study included 2,170 participants free of Alzheimer's disease from the Framingham Heart Study Offspring Cohort Exam 7 (1998-2001), whose follow-up data were collected until 2018. The TyG index was calculated as Ln(fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The association of the TyG index with Alzheimer's disease was evaluated by competing risk regression model. Statistical analyses were performed in 2023. RESULTS: During a median follow-up of 13.8 years, 163 (7.5%) participants developed Alzheimer's disease. When compared with the reference (TyG index ≤8.28), a significantly elevated risk of Alzheimer's disease was seen in the group with a triglyceride-glucose index of 8.68-9.09 (adjusted hazard ratio=1.69, 95% CI=1.02, 2.81). When the TyG index was considered as a continuous variable, each unit increment in the TyG index was not significantly associated with the risk of Alzheimer's disease (adjusted hazard ratio=1.32, 95% CI=0.98, 1.77). CONCLUSIONS: This study showed that moderately elevated TyG index was independently associated with a higher incidence of Alzheimer's disease. TheTyG index might be used to define a high-risk population of Alzheimer's disease.

The regulation of circRNA and lncRNAprotein binding in cardiovascular diseases: Emerging therapeutic targets.

Noncoding ribonucleic acids (ncRNAs) are a class of ribonucleic acids (RNAs) that carry cellular information and perform essential functions. This class encompasses various RNAs, such as small nuclear ribonucleic acids (snRNA), small interfering ribonucleic acids (siRNA) and many other kinds of RNA. Of these, circular ribonucleic acids (circRNAs) and long noncoding ribonucleic acids (lncRNAs) are two types of ncRNAs that regulate crucial physiological and pathological processes, including binding, in several organs through interactions with other RNAs or proteins. Recent studies indicate that these RNAs interact with various proteins, including protein 53, nuclear factor-kappa B, vascular endothelial growth factor, and fused in sarcoma/translocated in liposarcoma, to regulate both the histological and electrophysiological aspects of cardiac development as well as cardiovascular pathogenesis, ultimately leading to a variety of genetic heart diseases, coronary heart disease, myocardial infarction, rheumatic heart disease and cardiomyopathies. This paper presents a thorough review of recent studies on circRNA and lncRNAprotein binding within cardiac and vascular cells. It offers insight into the molecular mechanisms involved and emphasizes potential implications for treating cardiovascular diseases.

Association of Body Mass Index and Abdominal Obesity with Incidence of Atrial Fibrillation in Heart Failure with Preserved Ejection Fraction.

INTRODUCTION: The association between obesity and atrial fibrillation (AF) incidence in heart failure with preserved ejection fraction (HFpEF) patients is currently unclear. Our analyses and results are based on the whole Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial (placebo and spironolactone). METHOD: A total of 2138 subjects without baseline AF were included in the trial. Kaplan-Meier (K-M) curves and Cox regression with hazard ratios (HRs) and confidence intervals (CIs) were used to assess the incidence of AF with obesity. Of 2138 HFpEF patients without baseline AF, 1165 were obese (body mass index [BMI]≥30 kg/m2). RESULT: The K-M curve showed obese patients developed AF more than overweight (25≤ BMI ≤29.9 kg/m2) patients (p=0.013), confirmed by multivariable analysis, while there's no statistical difference between overweight and normal weight (18.5≤ BMI ≤24.9 kg/m2) patients. The occurrence of AF increased by 3% for every kg/m2 increase in BMI (adjusted HR, aHR: 1.03; 95% CI: 1.00-1.06), with a positive linear association (p for nonlinear: 0.145). Obesity was associated with AF incidence (aHR: 1.62; 95% CI: 1.05-2.50) compared with non-obesity (including overweight and normal-weight patients). CONCLUSION: Abdominal obesity was associated with increased AF incidence (aHR: 1.70; 95% CI: 1.04-2.77), and AF incidence rose by 18% per centimeter in circumference (aHR: 1.18; 95% CI: 1.04-1.34). Obesity and abdominal obesity increase the incidence of AF in HFpEF patients. Further studies need to determine whether there is a difference in AF in response to spironolactone across obese HFpEF pheno groups.

Prevalence estimates of the insulin resistance and associated prevalence of heart failure among United Status adults.

BACKGROUND: The triglyceride glucose (TyG) index, a metric for estimating insulin resistance (IR), is linked with cardiovascular disease (CVD) morbidity and mortality among the population regardless of diabetic status. However, IR prevalence and the association between the TyG index and heart failure (HF) in Americans is unclear. METHODS: The Nation Health and Nutrition Examination Survey (NHANES) (2009-2018) dataset was used. IR was defined by homeostatic model assessment of insulin resistance (HOMA-IR) > 2.0 and 1.5. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. A weighted logistic regression was applied to evaluate the association between the TyG index and the prevalence of HF. RESULTS: This study comprised 12,388 people, including 322 (2.6%) individuals with HF. The average prevalence of IR was found to be 13.9% and 22.7% for cutoff values greater than 2.0 and 1.5, respectively. HOMA-IR and the TyG index showed a moderate correlation (r = 0.30). There is a significant positive association between the TyG index and HF prevalence (per 1-unit increment; adjusted OR [aOR]: 1.34; 95% confidence interval [CI]: 1.02-1.76). Patients with higher TyG values were associated with a prevalence of HF (OR:1.41; 95% CI: 1.01,1.95) (quartiles 4 vs 1-3). The TyG index is associated with a higher prevalence of dyslipidemia, coronary heart disease, and hypertension but not a stroke (cerebrovascular disease). CONCLUSIONS: Our results show that IR does not considerably increase from 2008 to 2018 in American adults. A moderate correlation is noted between HOMA-IR and the TyG index. TyG index is associated with the prevalence of HF, as were other cardiovascular diseases.

Association between triglyceride glucose index and arterial stiffness and coronary artery calcification: a systematic review and exposure-effect meta-analysis.

BACKGROUND: The triglyceride and glucose (TyG) index has been linked to various cardiovascular diseases. However, it's still unclear whether the TyG index is associated with arterial stiffness and coronary artery calcification (CAC). METHODS: We conducted a systematic review and meta-analysis of relevant studies until September 2022 in the PubMed, Cochrane Library, and Embase databases. We used a random-effects model to calculate the pooled effect estimate and the robust error meta-regression method to summarize the exposure-effect relationship. RESULTS: Twenty-six observational studies involving 87,307 participants were included. In the category analysis, the TyG index was associated with the risk of arterial stiffness (odds ratio [OR]: 1.83; 95% CI 1.55-2.17, I2 = 68%) and CAC (OR: 1.66; 95% CI 1.51-1.82, I2 = 0). The per 1-unit increment in the TyG index was also associated with an increased risk of arterial stiffness (OR: 1.51, 95% CI 1.35-1.69, I2 = 82%) and CAC (OR: 1.73, 95% CI 1.36-2.20, I2 = 51%). Moreover, a higher TyG index was shown to be a risk factor for the progression of CAC (OR = 1.66, 95% CI 1.21-2.27, I2 = 0, in category analysis, OR = 1.47, 95% CI 1.29-1.68, I2 = 41% in continuity analysis). There was a positive nonlinear association between the TyG index and the risk of arterial stiffness (Pnonlinearity < 0.001). CONCLUSION: An elevated TyG index is associated with an increased risk of arterial stiffness and CAC. Prospective studies are needed to assess causality.

Is There a Sex Difference in the Prognosis of Hypertrophic Cardiomyopathy? A Systematic Review and Meta-Analysis.

Background It is still unclear whether there is a sex difference in the prognosis of patients with hypertrophic cardiomyopathy (HCM). Therefore, we performed a meta-analysis to elucidate the association between sex and adverse outcomes in patients with HCM. Methods and Results The PubMed, Cochrane Library, and Embase databases were used to search for studies on sex differences in prognosis in patients with HCM up to August 17, 2021. Summary effect sizes were calculated using a random effects model. The protocol was registered in PROSPERO (International prospective register of systematic reviews) (registration number- CRD42021262053). A total of 27 cohorts involving 42 365 patients with HCM were included. Compared with male subjects, female subjects had a higher age at onset (mean difference=5.61 [95% CI, 4.03-7.19]), a higher left ventricular ejection fraction (standard mean difference=0.09 [95% CI, 0.02-0.15]) and a higher left ventricular outflow tract gradient (standard mean difference=0.23 [95% CI, 0.18-0.29]). The results showed that compared with male subjects with HCM, female subjects had higher risks of HCM-related events (risk ratio [RR]=1.61 [95% CI, 1.33-1.94], I2=49%), major cardiovascular events (RR=3.59 [95% CI, 2.26-5.71], I2=0%), HCM-related death (RR=1.57 [95% CI, 1.34-1.82], I2=0%), cardiovascular death (RR=1.55 [95% CI, 1.05-2.28], I2=58%), noncardiovascular death (RR=1.77 [95% CI, 1.46-2.13], I2=0%) and all-cause mortality (RR=1.43 [95% CI, 1.09-1.87], I2=95%), but not atrial fibrillation (RR=1.13 [95% CI, 0.95-1.35], I2=5%), ventricular arrhythmia (RR=0.88 [95% CI, 0.71-1.10], I2=0%), sudden cardiac death (RR=1.04 [95% CI, 0.75-1.42], I2=38%) or composite end point (RR=1.24 [95% CI, 0.96-1.60], I2=85%). Conclusions Based on current evidence, our results show significant sex-specific differences in the prognosis of HCM. Future guidelines may emphasize the use of a sex-specific risk assessment for the diagnosis and management of HCM.

U-shaped association between the triglyceride-glucose index and atrial fibrillation incidence in a general population without known cardiovascular disease.

OBJECTIVE: The triglyceride-glucose (TyG) index has been shown to be a new alternative measure for insulin resistance. However, no study has attempted to investigate the association of the TyG index with incident atrial fibrillation (AF) in the general population without known cardiovascular diseases. METHODS: Individuals without known cardiovascular diseases (heart failure, coronary heart disease, or stroke) from the Atherosclerosis Risk in Communities (ARIC) cohort were recruited. The baseline TyG index was calculated as the Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The association between the baseline TyG index and incident AF was examined using Cox regression. RESULTS: Of 11,851 participants, the mean age was 54.0 years; 6586 (55.6%) were female. During a median follow-up of 24.26 years, 1925 incidents of AF cases (0.78/per 100 person-years) occurred. An increased AF incidence with a graded TyG index was found by Kaplan‒Meier curves (P < 0.001). In multivariable-adjusted analysis, both < 8.80 (adjusted hazard ratio [aHR] = 1.15, 95% confidence interval [CI] 1.02, 1.29) and > 9.20 levels (aHR 1.18, 95% CI 1.03, 1.37) of the TyG index were associated with an increased risk of AF compared with the middle TyG index category (8.80-9.20). The exposure-effect analysis confirmed the U-shaped association between the TyG index and AF incidence (P = 0.041). Further sex-specific analysis showed that a U-shaped association between the TyG index and incident AF still existed in females but not in males. CONCLUSIONS: A U-shaped association between the TyG index and AF incidence is observed in Americans without known cardiovascular diseases. Female sex may be a modifier in the association between the TyG index and AF incidence.

Insights into monkeypox pathophysiology, global prevalence, clinical manifestation and treatments.

On 23rd July 2022, the World Health Organization (WHO) recognized the ongoing monkeypox outbreak as a public medical crisis. Monkeypox virus (MPV), the etiological agent of monkeypox, is a zoonotic, linear, double-stranded DNA virus. In 1970, the Democratic Republic of the Congo reported the first case of MPV infection. Human-to-human transmission can happen through sexual contact, inhaled droplets, or skin-to-skin contact. Once inoculated, the viruses multiply rapidly and spread into the bloodstream to cause viremia, which then affect multiple organs, including the skin, gastrointestinal tract, genitals, lungs, and liver. By September 9, 2022, more than 57,000 cases had been reported in 103 locations, especially in Europe and the United States. Infected patients are characterized by physical symptoms such as red rash, fatigue, backache, muscle aches, headache, and fever. A variety of medical strategies are available for orthopoxviruses, including monkeypox. Monkeypox prevention following the smallpox vaccine has shown up to 85% efficacy, and several antiviral drugs, such as Cidofovir and Brincidofovir, may slow the viral spread. In this article, we review the origin, pathophysiology, global epidemiology, clinical manifestation, and possible treatments of MPV to prevent the propagation of the virus and provide cues to generate specific drugs.

Proarrhythmic toxicity of low dose bisphenol A and its analogs in human iPSC-derived cardiomyocytes and human cardiac organoids through delay of cardiac repolarization.

Bisphenol A (BPA) and its analogs are common environmental chemicals with many potential adverse health effects. The impact of environmentally relevant low dose BPA on human heart, including cardiac electrical properties, is not understood. Perturbation of cardiac electrical properties is a key arrhythmogenic mechanism. In particular, delay of cardiac repolarization can cause ectopic excitation of cardiomyocytes and malignant arrhythmia. This can occur as a result of genetic mutations (i.e., long QT (LQT) syndrome), or cardiotoxicity of drugs and environmental chemicals. To define the impact of low dose BPA on electrical properties of cardiomyocytes in a human-relevant model system, we examined the rapid effects of 1 nM BPA in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) using patch-clamp and confocal fluorescence imaging. Acute exposure to BPA delayed repolarization and prolonged action potential duration (APD) in hiPSC-CMs through inhibition of the hERG K+ channel. In nodal-like hiPSC-CMs, BPA acutely increased pacing rate through stimulation of the If pacemaker channel. Existing arrhythmia susceptibility determines the response of hiPSC-CMs to BPA. BPA resulted in modest APD prolongation but no ectopic excitation in baseline condition, while rapidly promoted aberrant excitations and tachycardia-like events in myocytes that had drug-simulated LQT phenotype. In hiPSC-CM-based human cardiac organoids, the effects of BPA on APD and aberrant excitation were shared by its analog chemicals, which are often used in "BPA-free" products, with bisphenol AF having the largest effects. Our results reveal that BPA and its analogs have repolarization delay-associated pro-arrhythmic toxicity in human cardiomyocytes, particularly in myocytes that are prone to arrhythmias. The toxicity of these chemicals depends on existing pathophysiological conditions of the heart, and may be particularly pronounced in susceptible individuals. An individualized approach is needed in risk assessment and protection.

Depressive symptoms, anxiety and social stress are associated with diminished cardiovascular reactivity in a psychological treatment-naive population.

BACKGROUND: There is now an increasing appreciation of how psychological health can contribute to cardiovascular disease, called the mind-heart connection. A blunted cardiovascular reactivity to depression and anxiety may be responsible for the potential mechanism, however, with inconsistent results. Anti-psychological drugs have an effect on the cardiovascular system and, thus, may disturb their relationship. However, in treatment-naive individuals with psychological symptoms, no research has specifically evaluated the relationship between psychological state and cardiovascular reactivity. METHODS: We included 883 treatment-naive individuals who came from a longitudinal cohort study of Midlife in the United States. Symptoms of depression, anxiety, and stress were assessed by the Center for Epidemiologic Studies Depression Scale (CES-D), Spielberger Trait Anxiety Inventory (STAI), the Liebowitz Social Anxiety scale (LSAS) and the Perceived Stress Scale (PSS), respectively. Cardiovascular reactivity was measured using standardized, laboratory-based stressful tasks. RESULTS: Treatment-naive individuals with depressive symptoms (CES-D ≥ 16), anxiety symptoms (STAI ≥ 54), and higher stress levels (PSS ≥ 27) had lower cardiovascular reactivity as assessed by systolic blood pressure (SBP) reactivity, diastolic blood pressure (DBP) reactivity and heart rate (HR) reactivity (P < 0.05). Pearson analyses showed that psychological symptoms were correlated with lower SBP reactivity, DBP reactivity, and heart rate reactivity (P < 0.05). Multivariate linear regression showed that depression and anxiety were negatively related to lower cardiovascular reactivity (SBP, DBP and HR reactivity) after full adjustments (P < 0.05). Stress was associated with reduced SBP and DBP reactivity but with a nonsignificant association with HR reactivity (P = 0.056). CONCLUSION: Depression, anxiety, and stress symptoms are associated with blunted cardiovascular reactivity in treatment-naive adult Americans. These findings suggest that blunted cardiovascular reactivity is an underlying mechanism linking psychological health and cardiovascular diseases.

Association of type 1 diabetes mellitus and risk of atrial fibrillation: Systematic review and meta-analysis.

AIM: Whether type 1 diabetes mellitus (T1DM) could be regarded as an independent risk factor for atrial fibrillation (AF) risk remains unclear, and thus we aimed to elaborate on this association in our meta-analysis. METHODS: We systematically searched the Pubmed, Embase, Cochrane Library and Web of Science databases up to August 2022 for studies that were related to T1DM and AF incidence. Hazard ratios (HRs) and 95% confidence intervals (CIs) from each study were pooled via a random-effects model. RESULTS: A total of four cohort studies were involved in our meta-analysis. Our pooled results suggested that T1DM patients had a higher AF risk (HR = 1.30, 95%CI 1.15-1.47) than the control group. In the subgroup analysis, a higher AF incidence was also found in female T1DM patients (HR = 1.50, 95%CI 1.26-1.79) than that in male patients. Compared with T1DM patients over 65 years, those with < 65 years showed an increased risk of AF (HR = 1.45, 95%CI 1.21-1.74). CONCLUSIONS: Our meta-analysis demonstrated that T1DM was an independent risk factor for AF development, but further studies should be performed to provide more convincing evidence.

Atrial fibrillation and breast cancer-Vicious twins? A systematic review and meta-analysis.

Background: Epidemiological studies suggest a bidirectional association between atrial fibrillation and breast cancer. This study aimed to conduct a meta-analysis to elucidate the prevalence of atrial fibrillation among breast cancer patients, and the bidirectional association between atrial fibrillation and breast cancer. Methods: PubMed, the Cochrane Library, and Embase were searched to identify studies reporting the prevalence, incidence, and bidirectional association between atrial fibrillation and breast cancer. The study was registered with PROSPERO (CRD42022313251). Levels of evidence and recommendations were assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: Twenty-three studies (17 retrospective cohort studies, 5 case-control studies and 1 cross-sectional study) involving 8,537,551 participants were included. Among patients with breast cancer, the prevalence of atrial fibrillation was 3% (11 studies; 95% CI: 0.6 to 7.1%) and the incidence was 2.7% (6 studies; 95% CI: 1.1 to 4.9%). Breast cancer was associated with increased risk of atrial fibrillation (5 studies; hazard ratio [HR]: 1.43, 95% CI: 1.12 to 1.82, I2 = 98%). Atrial fibrillation was also significantly associated elevated risk of breast cancer (5 studies HR: 1.18, 95% CI: 1.14 to 1.22, I2 = 0%). Grade assessment shown low certainty of the evidence for the risk of atrial fibrillation and moderate certainty of the evidence for the risk of breast cancer. Conclusion: Atrial fibrillation is not uncommon in patients with breast cancer and vice versa. There is a bidirectional association between atrial fibrillation (low certainty) and breast cancer (moderate certainty).

Association between weight loss and outcomes in patients undergoing atrial fibrillation ablation: a systematic review and dose-response meta-analysis.

BACKGROUND: Obesity is an strong risk factor for atrial fibrillation (AF), and obesity can affect the prognosis of AF. However, the role of weight loss on outcomes after ablation remains unclear. OBJECTIVES: This study aims to determine the relationship between weight loss and outcomes in patients with AF ablation, as well as the potential dose-response relationship. METHODS: The Cochrane Library, PubMed, and Embase databases were searched to identify studies that reported a relationship between weight loss and ablation up to August 17, 2021. Relative risks (RRs) were pooled using random-effects models. RESULTS: One randomized, open-labeled clinical trial and seven cohort studies involving 1283 patients were included. The mean body mass index of all included studies was over 30 kg/m2. The clinical trial showed a non-significant benefit of weight loss intervention on AF recurrence (Odd risk [OR] = 1.02, 95% confidence interval [CI] 0.70-1.47). Meta-analysis based on observational studies showed that the recurrence rate of AF after ablation was significantly reduced (RR = 0.43, 95% CI 0.22-0.81, I2 = 97%) in relatively obese patients with weight loss compared with the control group. Each 10% reduction in weight was associated with a decreased risk of AF recurrence after ablation (RR = 0.54, 95% CI 0.33-0.88) with high statistical heterogeneity (I2 = 76%). An inverse linear association (Pnon-linearity = 0.27) between AF relapse and increasing weight loss was found. CONCLUSIONS: Our results first suggest an inverse dose-response association between weight loss and risk of recurrent AF after ablation, with moderate certainty.

Acute exposure to low-dose bisphenol A delays cardiac repolarization in female canine heart - Implication for proarrhythmic toxicity in large animals.

Bisphenol A (BPA) is a common environmental chemical with a range of potential adverse health effects. The impact of environmentally-relevant low dose of BPA on the electrical properties of the hearts of large animals (e.g., dog, human) is poorly defined. Perturbation of cardiac electrical properties is a key arrhythmogenic mechanism. In particular, delay of ventricular repolarization and prolongation of the QT interval of the electrocardiogram is a marker for the risk of malignant arrhythmias. We examined the acute effect of 10-9 M BPA on the electrical properties of female canine ventricular myocytes and tissues. BPA rapidly delayed action potential repolarization and prolonged action potential duration (APD). The dose response curve of BPA on APD was nonmonotonic. BPA rapidly inhibited the IKr K+ current and ICaL Ca2+ current. Computational modeling indicated that the effect of BPA on APD can be accounted for by its suppression of IKr. At the tissue level, BPA acutely prolonged the QT interval in 4 left ventricular wedges. ERß signaling contributed to the acute effects of BPA on ventricular repolarization. Our results demonstrate that BPA has QT prolongation liability in female canine hearts. These findings have implication for the potential proarrhythmic cardiac toxicity of BPA in large animals.

Essen Stroke Risk Score Predicts Clinical Outcomes in Heart Failure Patients with Preserved Ejection Fraction: Evidence from the TOPCAT trial.

BACKGROUND: Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with increased risks of stroke and other adverse outcomes. AIMS: This study sought to determine whether the Essen Stroke Risk Score (ESRS) could predict the risks of adjudicated clinical outcomes in patients with HFpEF from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. METHODS: We evaluated associations of baseline ESRS with clinical outcomes by using the Cox proportional hazard model with competing risk regression. The diagnostic accuracy of the ESRS was assessed using the C-index and calibration data. RESULTS: Of 3,441 HFpEF patients with a mean follow-up of 3.3 years, the risk of stroke ranged from 0.32% per year at an ESRS of 1 to 2 points to 1.71% per year at a score of ≥6 points. Each point increase in ESRS was associated with increased risks of primary composite outcome (hazard ratios [HRs] = 1.31; 95% confidence intervals [CIs]: 1.23-1.40; C-index = 0.68), stroke (HR = 1.33 [95% CI: 1.16-1.53]; C-index = 0.68), myocardial infarction (HR = 1.60 [95% CI: 1.40-1.83]; C-index = 0.75), HF hospitalization (HR = 1.30 [95% CI: 1.20-1.41]; C-index = 0.71), any hospitalization (HR = 1.20, 95% CI: 1.15-1.26; C-index = 0.68), cardiovascular death (HR = 1.32 [95% CI: 1.20-1.44]; C-index = 0.68), and all-cause death (HR = 1.37, [95% CI: 1.28-1.48]; C-index = 0.68). The calibration curves showed that the ESRS had a better agreement between predicted and observed stroke risks compared with the R2CHADS2, CHADS2, or CHA2DS2-VASC stroke scores. CONCLUSION: The ESRS had modest discriminatory abilities for predicting stroke as well as other adverse outcomes including myocardial infarction, hospitalization, and death in HFpEF patients. ESRS might have better calibration performance than R2CHADS2, CHADS2, or CHA2DS2-VASC in HFpEF at high risk for stroke. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT00094302.