Potential Confounders Research Articles

Differences in symptoms of anxiety and depression among out-of-hospital cardiac arrest survivors and their relatives, paired results from the DANCAS survey

Abstract Background It is well known that out-of-hospital cardiac arrest (OHCA) survivors, as well as their relatives, struggle with symptoms of anxiety and depression, but less is known about the potential differences in paired outcomes. Purpose To describe differences in symptoms of anxiety and depression among OHCA survivors and their relatives (paired) and to investigate characteristics associated with these symptoms among both groups. Methods A national cross-sectional survey (DANCAS) was conducted with OHCA survivors combined with a survey for their closest relatives. The Hospital Anxiety and Depression Scale (HADS) was included in both surveys. Paired t-tests were used to examine potential differences in HADS mean scores among survivors and relatives. Associations between characteristics (demographic and other self-reported outcomes) and symptoms of anxiety (HADS-A ≥8) and depression (HADS-D ≥8) were examined using multivariable logistic regression models, presented as odds ratios (OR) with 95% confidence intervals (CI), adjusted for potential confounders. Results In total, 526 pairs of OHCA survivors and their relatives both responded, with 447 (85%) of the survivors being men, a median age of 67 years (IQR 59-75) and 462 (88%) of the relatives being women with a median age of 64 years (IQR 55-70). Most relatives (85%) were spouses or unmarried partners. In the paired analyses, relatives had significantly higher scores of anxiety compared to survivors (mean 5.6 SD 4.0 vs 3.5 SD 3.8; p<0.001). On the contrary, survivors had significantly worse scores of depression (mean 3.1 SD 2.8 vs 2.4 SD 3.2; p>0.001). Several characteristics (demographic and self-reported) were associated with symptoms of anxiety and depression among both survivors and relatives, Table 1 & 2. Conclusion Following OHCA, relatives report worse scores of anxiety while, in contrast, survivors report worse scores of depression, indicating psychological interventions should be tailored differently for the two groups. Further investigation of the reasons for these findings are needed, including whether fatigue might be a symptom of depression or a confounder.

Circadian heart rate fluctuations predict 21-year cardiovascular and all-cause mortality in type 2 and type 1 diabetes

Abstract Background Alterations in circadian heart rate (HR) fluctuations have been associated with cardiovascular events in the general population. This study aimed at defining their long-term prognostic value for cardiovascular and all-cause mortality in patients with diabetes. Methods We examined a cohort of 349 patients with type 2 or type 1 diabetes (52% women, age 57.1±11.9 years, BMI 29.4±5.9 kg/m2, HbA1c 8.6±2.1%, 81% type 2 diabetes) who underwent 24h ambulatory blood pressure and HR monitoring (ABPM) and assessment of diabetic microvascular complications. The median standard deviation (SD) value of ABPM-derived HR measurements was used to define patients with low daily HR fluctuations (low 24h-HR SD), while a <10% decline in average night-time vs day-time HR identified patients with blunted nocturnal HR dip (n=107, 31%). The clinical features and time-dependent prognostic impact of these conditions were evaluated over a 21-year observational follow-up. Results Low 24h-HR SD and blunted nocturnal HR dip were associated with an adverse cardiometabolic risk profile and high prevalence of cardiac autonomic neuropathy and nephropathy. After 6,251 person-years of follow-up (21.0 [14.0-21.0] years), a total of 136 (39%) deaths occurred, of which 100 (68%) of cardiovascular cause. After adjustment for potential confounders, the low 24h-HR SD group had a higher risk for both cardiovascular (hazard ratio 1.99, 95% CI 1.29–3.06, p=0.002) and all-cause mortality (hazard ratio 1.50, 95% CI 1.03–2.18, p=0.033), compared with high 24h-HR SD. Consistently, patients with blunted nocturnal HR dip had a higher adjusted risk for cardiovascular (1.61, 95% CI 1.07–2.43, p=0.023) and all-cause mortality (1.61, 95% CI 1.11–2.34, p=0.012), compared with those with preserved nocturnal HR dip. Conclusions Impaired circadian HR fluctuations are frequent in patients with long-standing diabetes and are associated with microvascular disease and increased long-term cardiovascular and all-cause mortality. Identifying these conditions via 24h-ABPM may provide a cost-effective risk stratification tool in this high-risk population.Kaplan-Meier curves

Association between warfarin and direct oral anticoagulants users and risk of mortality: cohort studies in England and Hong Kong

Abstract Background The evidence of the association between warfarin and risk of mortality compared with direct oral anticoagulants (DOACs) has been mixed in current literature. Purpose To investigate the association between all-cause mortality and warfarin, compared with DOACs. Methods Population-based cohort studies were conducted using the data from the Hong Kong Clinical Data Analysis and Reporting System (CDARS) and United Kingdom Clinical Practice Research Datalink (CPRD) Aurum. People with atrial fibrillation aged ≥18 years who initiated warfarin or a DOAC during the study period (1st Jan 2014 - 31st Dec 2019) were identified. Follow-up started from the first date of oral anticoagulant prescription and ended at earliest of the date of death, the day before drug switching (between warfarin and DOACs), transferring out of the practice (CPRD Aurum only), last data collection date for the practice (CPRD Aurum only) or the end of study period. We estimated propensity score (PS) based on the list of potential confounders including demographics, co-morbidities, co-medications and polypharmacy. Cox proportional hazards regression model with PS-weighting was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Among 227,190 new oral anticoagulant users, 54,367 (23.93%) died. The median follow-up was 2.96 and 2.45 years in CPRD and CDARS, respectively. Compared with DOAC use, a lower hazard of all-cause mortality was found in warfarin use (PS-weighted hazard ratio [HR]=0.94, 95% confidence interval [CI]=0.89-0.99) in CPRD; while a higher hazard was observed in warfarin users (PS-weighted HR=1.31, 95% CI=1.24-1.39) in CDARS, versus DOAC users. Consistent results were seen in both databases when stratified warfarin users by Time in Therapeutic Range (TTR). We observed a lower hazard of all-cause mortality in warfarin users with TTR≥65% (PS-weighted HR=0.90, 95% CI=0.85-0.94 in CPRD; 0.87, 0.79-0.96 in CDARS) and increased hazard in warfarin users with TTR<65% (PS-weighted HR=1.37, 95% CI=1.25-1.49 in CPRD; 1.57, 1.48-1.66 in CDARS), versus DOAC users. Conclusions The hazard of all-cause mortality associated with warfarin compared with DOACs were found to be conflicting across databases. However, both databases consistently showed that an increased hazard of all-cause mortality was only found in warfarin users with TTR<65% but not in those with TTR≥65%, suggesting that the differences in hazard of all-cause mortality associated with warfarin compared with DOAC, in part may depend on anticoagulation control in warfarin users. We recommend that warfarin users with poor INR control warrant closer clinical attention and could be considered for a switch to DOACs.

Influence of hospital ownership on patient outcomes in STEMI-induced cardiogenic shock undergoing revascularization: a retrospective cohort study

Abstract Background Investor-owned hospitals constitute an expanding segment of healthcare enterprises that frequently eschew the provision of non-profitable services. The implications of this disparity in costs on the mortality rates of patients experiencing cardiogenic shock (CS) subsequent to ST-Elevation Myocardial Infarction (STEMI) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) or bare-metal stents (BMS) remain unknown. Methods In this retrospective analysis, data from the National Inpatient Sample (NIS) were examined, including acute care admissions for patients aged 18 years and above admitted due to cardiogenic shock secondary to ST-Elevation Myocardial Infarction (STEMI) who underwent percutaneous coronary intervention (PCI) with the placement of either drug-eluting stents (DES) or bare-metal stents (BMS) between 2016 and 2020. Multivariable logistic regression, multilinear regression, chi-square tests, and t-tests were used to compare mortality rates, length of stay (LOS), and healthcare costs, adjusting for potential confounders. The total charges were adjusted for inflation using the Consumer Price Index (CPI) from the Bureau of Labor Statistics to ensure consistency in financial evaluations. Results We analyzed 66,180 patients and divided them into two cohorts: admitted to investor-owned vs nonprofit institutions. The findings revealed no significant difference in mortality rates, with an adjusted odds ratio (aOR) of 1.03 (P=0.60; 95% CI: 0.91-1.16). However, treatment in investor-owned hospitals was associated with significantly higher healthcare costs, with a coefficient of 120,921 (P<0.001; 95% CI: 106,658.6–135,184.7), but without a significant difference in length of stay (LOS) (coefficient 0.04; P=0.81; 95% CI: -0.33 to 0.41). Key predictors of mortality included age, with each additional year increasing the odds of mortality by 3% (P<0.001; 95% CI: 1.02-1.03), and uninsured status, which was linked to a higher mortality risk (aOR 1.40; P<0.001; 95% CI: 1.16-1.70). Disparities in healthcare costs were observed across different races and insurance types, notably affecting Hispanic patients and those covered by Medicaid. A significant difference was noted in the average adjusted hospital charges between non-profit and investor-owned hospitals; the average charge at investor-owned hospitals was $314,633, compared to $220,227 at non-profit hospitals (P<0.01), marking a net difference of $94,406. Conclusion This retrospective cohort analysis demonstrated that investor-owned hospitals incurred, on average, over $94,406 more in healthcare costs than nonprofit hospitals, with no significant difference in mortality rates and only a marginal difference in length of stay (LOS). Higher expenses at investor-owned hospitals did not translate into improved patient outcomes, challenging the notion that increased healthcare spending necessarily results in better healthcare delivery.

The impact of intimate partner violence on adverse birth outcomes in 20 sub-Saharan African countries: propensity score matching analysis

BackgroundIntimate partner violence (IPV) is a significant public health problem, with serious consequences on women's physical, mental, sexual, and reproductive health, as well as birth outcomes. Women who encounter IPV are more likely to experience adverse birth outcomes such as low birth weight, premature delivery, and stillbirth. Although numerous studies are exploring the association between IPV and adverse birth outcomes, they merely used classical models and could not control for potential confounders. The purpose of this study was to ascertain whether there was a causation between IPV and adverse birth outcomes in sub-Saharan Africa (SSA) using a quasi-experimental statistical technique [i.e., propensity score matching (PSM) analysis].MethodThis study used the most recent (2015–22) Demographic and Health Survey (DHS) data from 20 SSA countries. A total weighted sample of 13,727 women was included in this study. IPV (i.e., sexual, physical, emotional, and at least one form of IPV) was the exposure/treatment variable and adverse birth outcomes (preterm delivery, low birth weight, stillbirth, and macrosomia) were the outcome variables of this study. PSM was employed to estimate the impact of IPV on adverse birth outcomes.ResultsThe average treatment effects (ATE) of sexual, physical, emotional, and at least one form of IPV were 0.031, 0.046, 0.084, and 0.025, respectively. Sexual, physical, emotional, and at least one form of IPV increased adverse birth outcomes by 3.1%, 4.6%, 8.4%, and 2.5%, respectively. Findings from the average treatment effect on treated (ATT) showed that women who experienced sexual, physical, emotional, and at least one form of IPV had an increased risk of adverse birth outcomes by 3.6%, 3.7%, 3.3%, and 3.0%, respectively, among treated groups.ConclusionThis study demonstrates a causal relationship between IPV and adverse birth outcomes in SSA countries, indicating a need for programs and effective interventions to mitigate the impact of IPV during pregnancy to reduce related adverse pregnancy outcomes. Furthermore, we suggest further research that investigates the causal effect of IPV on adverse birth outcomes by incorporating additional proximal variables not observed in this study.

Temporal Trends in Dementia Incidence in Sweden: Insights from NEAR Data

Abstract Background This study investigates the temporal trends of dementia incidence in Sweden over a span of 35 years, drawing on data from the National E-Infrastructure for Aging Research (NEAR). Methods Our comprehensive analysis encompassed over 10,000 participants aged 50 and above. We estimated dementia incidence rates across the study period, considering birth cohort, age, and sex while controlling for potential confounders. Additionally. We explored potential modifiers influencing the estimated trend of dementia incidence. Results The analysis reveals a notable decline in dementia incidence rates, particularly among individuals born in more recently. Octogenarians born in the 1920-1930 cohort had a 74% lower dementia incidence rate compared to their counterparts born before 1900. Similarly, nonagenarians born in the 1910-1920 cohort experienced a 45% lower incidence rate. We further investigate determinants influencing this declining trend, shedding light on various factors shaping the observed patterns. Conclusions The incidence rate of dementia in Sweden has shown a consistent decline over the past 35 years, with a notable birth cohort effect indicating lower rates among individuals born more recently. This finding suggests evolving factors in lifestyle, healthcare, or environmental conditions contributing to improved cognitive health outcomes. Key Messages • These findings underscore the importance of proactive public health measures aimed at sustaining and enhancing cognitive health outcomes among aging populations. • Understanding the temporal dynamics and underlying factors driving these trends can inform strategies for promoting healthy aging and improving the quality of life for older adults.

Prior fecal immunochemical test positivity is associated with adverse prognosis in patients with acute ST-segment elevation myocardial infarction

Abstract Backgrounds While fecal immunochemical testing (FIT) is commonly used for disease screening, its significance in other conditions, particularly in patients with ST-segment elevation myocardial infarction (STEMI), is not extensively researched. Purpose This study aimed to investigate the impact of prior positive FIT results on the clinical prognosis of patients with STEMI. Methods The data for this study were derived from the Health and Medical Big Data Superplatform, comprising a retrospective cohort of patients discharged from 72 hospitals from 2010 to 2023. A total of 76,157 patients with acute STEMI patients were enrolled. Positive FIT was defined as "+-" or higher on the fecal occult blood test. Propensity score matching (PSM) was employed to balance differences between the two groups. Kaplan-Meier analysis with log-rank tests compared endpoint risks between groups, and a multivariable Cox regression model adjusted for potential confounders. The primary endpoint was Net Adverse Clinical Event (NACE), including cardiac death, recurrent myocardial infarction, revascularization, stroke, cerebral hemorrhage, and gastrointestinal bleeding. Results After 1:3 PSM,2,148acute STEMI patients were included, with 537 having prior positive FIT and 1,611 without. Patients with prior positive FIT were more likely to have comorbidities such as hyperlipidemia, prior malignancy, post-coronary artery bypass grafting, renal insufficiency, and prior cerebral hemorrhage. The prior positive FIT group had a higher proportion of prior clopidogrel and indobufen usage, while aspirin use during follow-up was lower. Kaplan-Meier analysis demonstrated a significantly higher risk of NACE in acute STEMI patients with prior positive FIT (before PSM: log-rank P = 0.001, after PSM: log-rank P = 0.005, Figure 1）, as well as increased rates of Major Adverse Cardiac and Cerebral Events (MACCE), all-cause death, and gastrointestinal bleeding (log-rank P < 0.05 for all). Multivariate Cox-proportional hazard analysis adjusted for age, sex, percutaneous coronary intervention during hospitalization, diabetes, hypertension, ischemic stroke, atrial fibrillation, medication during hospitalization, and follow-up showed similar results (Figure 2). Conclusions This study reveals a significant association between prior positive FIT and higher rates of NACE, MACCE, all-cause death, and gastrointestinal bleeding in STEMI patients within 1 year. A history of positive FIT results could serve as a prognostic indicator in this specific patient population.

Asymmetric outcomes in bilateral maxillary impacted tooth extractions: A case report

BACKGROUND The extraction of maxillary impacted teeth is a common procedure in oral surgery, frequently complicated by oroantral communications. For less-experienced clinicians, accurately assessing the difficulty and associated risks of maxillary third molar extractions remain a significant challenge. CASE SUMMARY We present a case involving disparate outcomes following bilateral extraction of maxillary third molars. Using cone-beam computed tomography and three-dimensional software, we conducted a digital assessment of the factors contributing to extraction difficulty and risk, controlling for potential confounders. Key variables analyzed included alveolar bone volume, bone quality, crown-root angulation, and maxillary sinus mucosal thickness. Additionally, we introduce the novel concept of "tegmen bone" to quantitatively evaluate the bone mass between the teeth and the maxillary sinus. This unique case, with differing outcomes on opposite sides of the same patient, provided an opportunity to minimize extraneous variables and focus on the local anatomical factors influencing the procedures, thereby improving the precision of our analysis. CONCLUSION This case highlights the potential utility of predictive analysis in guiding the management of complex tooth extractions.

C-reactive protein after discharge and infarct size in patients with ST segment elevation myocardial infarction

Abstract Background C-reactive protein (CRP) peaks at 2 days in patients with ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) and can predict final infarct size. It is, however, unknown whether CRP level after discharge, indicative of prolonged inflammation, plays a prognostic role in myocardial damage. Purpose To investigate the prevalence of high CRP level within 3 months after discharge in patients with STEMI and its association with myocardial damage. Methods In the current study, all patients were identified through the xx database and treated with timely PCI at xx hospital from 2011 to 2014. Blood samples were retrieved within 3 months after discharge. High CRP level was defined as CRP >=3 mg/L. Only patients with a cardiac magnetic resonance (CMR) at baseline or follow-up were recruited. The primary outcome was final infarct size. Multiple regression was performed to adjust for potential confounders using any baseline variable with P<0.10 for the difference between groups. Results Of the 1603 patients from xx, 273 patients had CRP measured following discharge and at least one CMR measured. Of them, 200 (73.3%) had high CRP level after discharge. There was no difference in period from PCI to CRP testing between patients with high CRP and those with low CRP [11 days, interquartile range (IQR) (4, 40) vs. 21 days, IQR (4, 42), P=0.31]. Patients with high CRP level showed larger final infarct size [12.5% left ventricle (LV) vs. 7.0% LV, P <0.001] and larger acute infarct size [15.2% LV vs. 10.6% LV, p=0.004] compared with those with low CRP level. Patients with high CRP level also had lower final myocardial salvage index (MSI) (0.67 vs. 0.75, P=0.003) and lower acute MSI (0.47 vs. 0.61, P=0.006). The results persisted after adjusting for potential confounders in multiple regression. Conclusions A large proportion of patients with STEMI undergoing PCI persisted high CRP within 3 months after discharge. High CRP level after discharge was associated with larger acute and final infarct size as well as lower acute and final MSI level.

Effects of prognostic nutritional index and obesity on 1-year mortality in patients with acute heart failure

Abstract Background Increased body mass index (BMI) has paradoxically been linked to improved survival rates among patients with acute heart failure (AHF). However, the impact of different nutritional statuses on this obesity paradox on 1-year mortality remains unclear. The prognostic nutritional index (PNI) is a simple tool to assess nutrition status. Recently, landmark findings such as the STEP-HFpEF (Semaglutide Treatment Effect in People With Obesity and HFpEF) trial showed at 1-year, semaglutide not only reduced weight considerably, but also significantly improved health-related quality of life, functional status, and CRP levels. Also, the semaglutide effects on heart disease and stroke in patients with overweight or obesity (SELECT) trial demonstrated a 20% reduction in cardiovascular outcomes. Purpose To investigate the association between obesity and AHF on all-cause mortality according to nutritional status. Methods The cohort study comprised 7258 patients with a cardiopulmonary condition, all of whom were admitted and included on-site at the Emergency Department (ED) in a large University Hospital in Denmark, between March 2020 and March 2022. The follow-up time was at least 365 days. 408 patients with AHF were identified by chart review by trained cardiologists for analysis. PNI was calculated according to the formula: 10×serum albumin (g/ dL) + 5×total lymphocyte count×109/L. A value ≥ 38 is considered well-nourished, and a value < 38 is considered malnourished. Patients were divided into High-PNI (≥38) and Low-PNI (<38) according to cut-off value of PNI. The Kaplan-Meier (KM) curves were used to analyze cumulative survival in each subgroup, and the log-rank test was used to compare differences between groups. Cox regression models were used to analyze associa­tions between BMI, nutritional status and outcomes, expressed as hazard ratios (HR) and relative 95% confi­dence intervals (CI). Results Amongst 408 hospitalized AHF patients, 384 (mean age 75.6 ±11.7) with available PNI scores were enrolled into this study. 55.7% (n=214) were male, 56.4% (n=93) died in the Low-PNI group and 34.2% (n=75) died in the High-PNI group within 1 year. After adjusting for potential confounders in the High-PNI population, compared with the under/normal and overweight BMI group, obesity was negatively associated with 1-year mortality, with adjusted HR of 0.47, 95% CI (0.24–0.94), P = 0.033. However, this correlation disappeared in the Low-PNI group (obese BMI: HR 1.2, 95% CI 0.71–2.1, P = 0.457). In addition, those who were overweight in the Low-PNI group had an 80% increase in 1-year risk of death. Conclusion Obesity (BMI>30) was associated with reduced 1-year mortality only in AHF-patients with good nutritional status. However, this association disappeared in malnourished patients. Consequently, additional research is essential to formulate weight loss recommendations for malnourished obese patients with AHF.

Empirical dietary inflammatory pattern could increase the odds of breast cancer: a case-control study

BackgroundIt has been shown that chronic inflammation is a significant factor in cancer development and progression. The current study aimed to investigate whether a higher score on the empirical dietary inflammatory pattern (EDIP), which indicates a more pro-inflammatory diet, is related to higher odds of breast cancer in Iranian women.MethodsIn the present case-control study, subjects in the case (n = 133) and control (n = 265) groups were chosen from the hospitals in Tehran, Iran. The cases consisted of women with newly diagnosed breast cancer, while the controls were selected from other parts of the same hospital and had no history of cancer or hormone therapy. Individuals whose reported energy intake deviated by three standard deviations above or below the mean energy intake of the population were excluded from the study. A reliable and valid semi-quantitative food frequency questionnaire was used to determine the participants’ dietary intake. Additionally, the association between breast cancer and EDIP was evaluated by logistic regression analysis in both crude and adjusted models.ResultsThe median scores of EDIP in the case and control groups were 0.65 and 0.61, respectively. The findings also indicated that, in the adjusted model, the odds of developing breast cancer significantly increased in the last tertile of EDIP compared to the first tertile (odds ratio (OR) = 1.859; 95% confidence interval (CI): 1.059–3.265; P = 0.031). Additionally, after adjusting for potential confounders, higher odds of breast cancer were observed in the last tertile of EDIP compared to the first tertile in postmenopausal women (OR = 2.516; 95% CI: 1.081–5.856; P = 0.033).ConclusionsThe current study indicated that individuals with a higher pro-inflammatory diet score were more likely to develop breast cancer.

Impact of body mass index on aortic valve stenosis and its clinical outcomes in early adulthood: a long-term study of young men

Abstract Aims Studies investigating associations between body mass index (BMI), incidence of aortic valve stenosis (AVS), and clinical outcomes in AVS patients are scarce. Purpose To investigate the relationship between BMI in youth and subsequent diagnosis of AVS. A secondary aim was to determine the role of obesity in clinical outcomes in individuals diagnosed with AVS. Methods This was a nationwide, register-based cohort study of 1 701 390 men (mean age, 18.3 ±0.8 years) enrolled in compulsory conscription for military service in Sweden from 1969 through 2005. Anthropometrics, blood pressure, fitness, muscle strength and IQ were recorded at baseline. AVS cases and cardiovascular outcomes were identified according to the International Classification of Diseases (ICD)-10 registered in the National patient register and Cause of Death Register through the Swedish 12-digit personal identification number. BMI (kg/m2) was categorized as <18.5, 18.5–<20, 20–<22.5, 22.5–<25, 25–<27.5, 27.5 <30, 30–<35, and 35–<50 kg/m2. Cox proportional hazard models were used to estimate the association between adolescent BMI and future hospitalization for AVS while adjusting for potential confounders. The BMI reference was set as 20–<22.5. Those who developed AVS formed a subcohort that was followed until a first clinical cardiovascular outcome of death, cardiovascular mortality, Heart failure, Atrial fibrillation, myocardial infarction, or ischaemic stroke. Results During a median follow-up of 32 years (IQR, 24-41 years), 5766 cases (mean age 54.7±9.4 years) of AVS were diagnosed. After adjustment, underweight subjects with a BMI of <18.5 kg/m2, compared to those with a low-normal BMI (20.0–<22.5 kg/m2) showed lower risk (HR 0.70; 95% CI 0.61–0.80) of AVS. The multivariable-adjusted HR for AVS increased from HR 1.28; 95% CI 1.17–1.39 for BMI 22.5–<25 kg/m2 to HR 1.91; 95% CI 1.12–3.25 for those with BMI 35–50 kg/m2. Further on, individuals diagnosed with AVS were followed for a median of ~5.5 years. The multivariable-adjusted HR for all-cause mortality, cardiovascular mortality, and heart failure for obese (BMI 30–50 kg/m2), compared to BMI <20.0 kg/m2 in men diagnosed with AVS, were 4.69 (95% CI 2.61–8.44), 4.09 (95% CI 1.72–9.73), and 2.76 (95% CI, 1.36–5.60), respectively. Conclusions Elevated BMI in youth, even within the normal range, is associated with increased risk of developing AVS, while subnormal BMI was protective. Excess weight in youth diagnosed with AVS is associated with higher risk of subsequent clinical outcomes. These findings are novel, generating new questions as to potential mechanisms and implying more vigilant monitoring of patients with AVS and a history of obesity in youth.Figure 1Figure 2

Comparison between coronary calcium score and segment involvement score when used in clinical routine

Abstract Data from a nationwide registry on coronary computer tomography angiography. Background The Coronary Artery Calcium Score (CACS) and segment involvement score (SIS) are crucial factors in assessing the severity of coronary artery disease (CAD) and determining the likelihood of future cardiovascular events. However, there are few large multicenter studies comparing the predictive value of CACS and SIS when used in the clinical routine. Objectives To compare CACS and SIS ability to predict cardiovascular outcomes when used in the clinical routine. Methods This retrospective cohort study included patients who underwent Coronary Computed Tomography Angiography (CCTA) for CAD evaluation between 2006-2022 in 29 different centers in Sweden. CACS was calculated using the Agatston method, and SIS was determined based on the number of coronary segments exhibiting plaque. For SIS, patients were categorized into SIS=0, SIS=1, SIS=2, SIS=3, SIS³4, for CACS patients were categorized into CACS=0, CACS=1-9, CACS=10-99, CACS=100-299, CACS³300. Patients were followed regarding the primary outcome of death or myocardial infarction. Multivariable Cox proportional hazards models were used for adjusting for potential confounders. Results A total of 23034 patients underwent CCTA and were followed for up to ten years. Median age (IQR) was 58 (49–67) years, 50% were women, 9% had diabetes mellitus, 42% had hypertension, 25% had hyperlipidemia, 5% had previously known CAD. There were 955 patients (4.1%) with myocardial infarction (MI) and 409 patients (2.2%) died during follow up. There was an increase in cardiovascular events with increasing SIS. When comparing SIS and presence of obstructive stenosis, SIS was a better predictor of outcome (Figure 1). There was also an increase cardiovascular events with increasing CACS (Figure 2). When adjusted for age, sex, risk factors, previous cardiovascular disease and intervention, both SIS and CACS were independently associated with outcome. When SIS and CACS were compared in a receiver operating characteristic curve, CACS had significantly larger AUC than SIS, (0.70[0.67-0.73] vs 0.62[0.60-0.63]). Conclusion Our findings show that both CACS and SIS are important and independent predictors of cardiovascular outcomes thereby offering a valuable tool for personalized risk stratification and management in clinical settings. When used in the clinical routine, CACS appears to be more strongly associated with outcome than SIS.Figure1 Survival SISFigure 2 Survival CACS

Risk score guided dual antiplatelet therapy duration in patients with acute coronary syndrome: insights from the FORCE-ACS registry

Abstract Background The use of risk scores to guide the duration of dual antiplatelet therapy(DAPT) in patients with acute coronary syndrome(ACS) is recommended in current guidelines, however clinical data on the impact of its prospective use is lacking. Purpose To compare risk-score guided DAPT duration to standard of care in ACS patients. Methods Since 2015, patients with ACS are enrolled in the prospective FORCE-ACS registry. In 2018, we implemented a risk score-guided approach for DAPT duration. In this analysis, we compared patients in which DAPT duration was guided by bleeding and ischemic risk assessment using PRECISE-DAPT-scores and DAPT-scores to a standard treatment group in a 1:4 ratio. In risk score-guided patients, high bleeding risk patients(HBR) were advised short DAPT(≤6 months); patients without HBR or high ischemic risk(HIR) were advised 12 months DAPT; and patients without HBR but with HIR were advised prolonged DAPT(≥30 months). In the standard treatment group DAPT duration was left at the discretion of the treating physician. Exclusion criteria included no DAPT or oral anticoagulation at discharge or implanted bio-vascular stents. Primary outcome was a composite of all-cause mortality, myocardial infarction(MI), stent thrombosis(ST), stroke and Bleeding Academic Research Consortium(BARC) 3 or 5 bleeding; a secondary composite ischemic outcome consisted of cardiovascular mortality, MI, ST and ischemic stroke. Kaplan-Meier plots with log-rank testing and Cox proportional hazard regression after adjustment of potential confounders were performed for the primary outcome. Sensitivity analyses were performed for patients included after implementation of the risk score-guided approach and for censoring events within the first six months. Results Between 2015 and 2020 8,009 patients were enrolled in the FORCE-ACS registry, of which 5,518 patients were included for analysis. The risk-score guided group(n=1,200) more often presented with ST-elevation MI, percutaneous coronary intervention or optimal medical therapy, while standard treatment patients(n=4,318) were older, more often had prior MI, prior revascularization, received coronary artery bypass grafting or conservative management. In the risk-score guided group, 15.7% had HBR, 46.4% were without HBR or HIR, and 37.9% showed HIR without HBR. The primary outcome was 6.3%(n=75) in risk score-guided patients versus 14.8%(n=637) in the standard treatment group (adjusted hazard ratio(HR) 0.47 [95%CI 0.36–0.61], p<0.001). These results remained consistent after sensitivity analyses (fig 1B). Both the composite ischemic outcome(HR 0.54 [95%CI 0.41–0.72] p<0.001) and BARC 3 or 5 bleeding (HR 0.23 [95%CI 0.08-0.63], p=0.004) were significantly lower in risk score-guided patients compared to the standard treatment group. Conclusion In this prospective analysis, risk-score guided DAPT duration showed a significant reduction of both ischemic and bleeding events compared to standard treatment.

Predictors of B-line count in hospitalized patients with COVID-19

Abstract Background B-lines on lung ultrasound (LUS) are non-specific signs of increased density within lung tissue, which can be secondary to pulmonary congestion, pneumonia, or fibrosis. LUS is recommended for managing acute heart failure (HF); however, its value in non-HF populations is less clear. Purpose To identify clinical, laboratory, and echocardiographic predictors of B-lines in a population with Coronavirus disease 2019 (COVID-19). Methods In the ECHOVID-19 study, hospitalized non-ICU patients ≥18 years with confirmed laboratory diagnosis of COVID-19 in Eastern Denmark underwent 8-zone LUS and echocardiography. We used trend and regression analyses to identify associations with the number of B-lines and adjusted for potential confounders (age, sex, body mass index, C-reactive protein, and pandemic wave). Results Among 270 (89%) patients with adequate LUS images, the mean age was 69±14 years, 58% were male and 11% had prior HF. Median time from hospital admission to LUS was 4 [2-8] days. In total, 263 (97%) had ≥1 B-line (median B-line number 14 [9-22]) and median left ventricular ejection fraction [LVEF] was 59 [54-63]). In adjusted models, more B-lines were associated with higher levels of C-reactive protein with an incidence rate ratio (IRR) of 16% (95%CI: 8%-24%) per log-unit increase (P<0.001) and higher Early Warning Score (IRR 5% [95%CI: 1%-0%] per point, P=0.02). Higher tricuspid regurgitation gradient was associated with more B-lines: IRR 2% (95%CI: 1%-3%) per mmHg, P<0.001) (Figure 1). Echocardiographic measures of left ventricular (LV) function (including LVEF and global longitudinal strain, left atrial volume, and LV filling pressures (E/e’)) and right ventricular function were not significantly associated with the number of B-lines. B-lines were not associated with N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations, even in patients with established HF. Lastly, B-lines were not associated with 30-day mortality. Conclusions Among hospitalized patients with COVID-19, B-lines on LUS are associated with markers of infectious disease severity and pulmonary hypertension but not with markers of left-sided HF.Figure1.Predictors of B-lines

Self-reported health effects from wildfire smoke: A cross-sectional study in New York State

Abstract Background Wildfires and exposure to wildfire smoke (WFS) are forecasted to increase, in part driven by climate change. As witnessed in 2023, regions in Europe and North America are facing more sustained periods of poor air quality due to WFS. Growing evidence suggests average daily WFS correlates with morbidity and mortality, but the impact of prolonged WFS exposure remains understudied, especially in areas where WFS is a newer occurrence. We examine associations between consecutive days of WFS experienced and self-reported health symptoms in the northeastern United States. Methods This retrospective cross-sectional study explored New York State (NYS) residents’ experience with WFS in summer 2023 via an online survey. Participants reported the longest period of consecutive WFS days and symptoms experienced. Log-binomial regression models estimated prevalence ratios (PR) and 95% confidence intervals (CI). Results 553 NYS residents were included, representing a healthy, primarily female and White population, ranging from 18 to 86 years. 549 (99.3%) reported experiencing WFS, with the longest period of consecutive WFS days varying (≤3 days: n = 152; 4 to 6 days: n = 255; ≥7 days: n = 146). 490 (88.6%) reported ≥1 health symptom, with itchy/watery eyes, sore throat, and headache as the most frequent. Compared to ≤ 3 consecutive WFS days, symptom prevalence was 9.1% higher for those reporting 4 to 6 days (PR [95% CI]:1.09 [1.00, 1.19]) and 16.7% higher for ≥7 days (1.17 [1.07, 1.27]). The trend of increased symptom prevalence with longer WFS periods persisted and was pronounced for specific symptoms. Control for potential confounders did not appreciably change estimates. Conclusions Our findings suggest longer sustained WFS exposure associates with higher symptom prevalence, which may be precursors to more serious health conditions. As global populations face more WFS with climate change, public health professionals should prioritize strategies to mitigate prolonged exposure. Key messages • In a convenience sample of 553 primarily healthy New York State residents, 99.3% reported experiencing wildfire smoke and 88.6% reported at least 1 symptom of poor health during summer 2023. • Associations between consecutive days of wildfire smoke experienced and prevalence of any and specific symptoms tended to vary in a dose-response manner.

First trimester maternal infections and offspring congenital heart defects: a systematic review and meta-analysis

Abstract Background Maternal infections early in pregnancy have been proposed as playing a role in the development of congenital heart defects. We aimed to summarise contemporary evidence regarding the association between first-trimester maternal infection and risk of offspring congenital heart defects. Methods For this systematic review and meta-analysis, we searched Medline and Embase for studies reporting associations of at least one measure of maternal infection during pregnancy and offspring congenital heart disease in humans and published in English between January 1, 1990 and February 13, 2024. Studies were eligible for inclusion if they reported rates of offspring congenital heart defects among both infected and non-infected mothers, and included a minimum of 50 offspring with congenital heart defects. We stratified associations by type of infection and type of heart defect when data from at least two studies were available. We used inverse variance weighted random-effect meta-analyses to pool the estimates. In main analyses, we pooled crude estimates from studies reporting maternal infections during the first trimester of pregnancy. We performed sensitivity analyses to include studies that i) investigated infections later in pregnancy or at unspecified time-points, and ii) adjusted for potential confounders such as maternal age, socioeconomic status, or ethnicity. Findings: We identified 11 studies (7 case control studies, 4 cohort studies) with data from 1,805,115 pregnancies. Nine of these studies assessed maternal infectious status through self-reported questionnaires or medical records, two used laboratory antibody testing and three reported on specific infectious pathogens. Studies reported on various types of bacterial and viral infections, including influenza, urinary tract infections, cytomegalovirus, herpes simplex virus, or chlamydia, with varying effect sizes. Ten studies reported a positive association between maternal infection variables and offspring congenital heart defects, with a pooled odds ratio (OR) and 95% confidence interval of 1.56 (1.27, 1.91) across all types of infections. Associations differed by individual subtype of congenital heart defects, with ORs ranging from 1.28 (0.89, 1.85) for pulmonary atresia to 1.75 (1.23, 2.49) for ventricular septal defects. Sensitivity analyses that included infections measured later in pregnancy, or adjusted rates for potential confounders, showed broadly similar trends but attenuated effect sizes. Interpretation: First trimester maternal infections are associated with increased risk of congenital heart defects. Associations appear to vary by type of infection and type of congenital heart defect, and to extend beyond infections commonly tested for during routine pregnancy screening. Larger-scale studies are warranted to confirm these findings using laboratory antibody testing and investigating how these associations vary by specific pathogens and subtypes of congenital heart defects.

Light Physical Activity Throughout the Day and Physical Function in Older Adults

Abstract Background Light physical activity (LPA) plays a crucial role in preventing muscle loss and disability in older adults. Since LPA makes up a significant portion of daily activity, understanding how the timing of LPA influences physical function is important for designing effective health interventions. Methods This cross-sectional study investigated the association between the timing of LPA and physical function among 200 older adults (mean age 76.3, 55.5% female) attending the geriatric outpatient clinic at National Taiwan University Hospital. LPA was objectively measured using wrist-worn accelerometers for seven consecutive days. Principal component analysis (PCA) was used to identify distinct patterns of LPA timing. Participants underwent assessments of grip strength, basic mobility, walking speed, and lower limb muscle strength. Multivariable linear regression models were adjusted for potential confounders, including gender, age, moderate-to-vigorous physical activity (MVPA), and accelerometer wear time. Results Our findings revealed that higher levels of LPA during the morning to noon period were positively associated with better performance across all four physical function tests. Moreover, after controlling for relevant confounders, increased LPA in the late afternoon and evening was positively associated with enhanced basic mobility, walking speed, and lower limb muscle strength. Conclusions This study highlights the importance of considering LPA timing when promoting physical function in older adults, independent of MVPA participation. Encouraging LPA, particularly during the morning to noon period, could be a valuable strategy for maintaining and improving physical capabilities in this population. These findings provide actionable insights for clinicians and health professionals when tailoring physical activity recommendations for older adults within geriatric care settings. Key messages • Morning LPA boosts physical function in seniors, enhancing grip, mobility, walking speed, and muscle strength. • Timing of light activity crucial for older adults’ physical health, with morning to noon activity showing most benefits.

Incremental prognostic value of combined information of arterial stiffness and the result of treadmill exercise test in patients with suspected coronary artery disease

Abstract Background The effectiveness of diagnostic tools can be enhanced by their combination. We aimed to investigate whether arterial stiffness data, obtained by brachial-ankle pulse wave velocity (baPWV) measurement, could improve prognostic value to exercise treadmill test (ETT) to predict future cardiovascular events. Methods A total of 1,788 consecutive subjects (mean age 55.8 ± 10.7 years, 59.1% men) with suspected of having coronary artery disease (CAD), who underwent ETT and baPWV on the same day were prospectively recruited. The study outcome was major adverse cardiac and cerebrovascular event (MACCE), a composite of cardiac death, non-fatal myocardial infarction, coronary revascularization and ischemic stroke. Results During a mean follow-up period of 875 days (interquartile range, 116–2,212 days), there were 88 cases of MACCE (4.9%). The elevated baPWV (≥ 1,440 cm/s) (hazard ratio [HR] 5.18; 95% confidence interval [CI] 2.68–10.0; P < 0.001) and positive ETT result (HR 2.81; 95% CI 1.77–4.47; P < 0.001) were associated with MACCE even after adjustment for potential confounders. The combination of baPWV to traditional risk factors and ETT result further stratified the subjects’ risk (low baPWV and negative ETT result vs. high baPVW and positive ETT result; HR 16.44; 95% CI 6.17–43.78; P < 0.001). Conclusions Arterial stiffness, assessed by baPWV, had incremental prognostic value to ETT result in patients with suspected of CAD. baPWV can serve as a useful clinical tool for risk stratification in this high-risk patient population.Kaplan-Meier survival curveMultivariable cox analysis

Life course cumulative PM2.5 exposure since childhood and albuminuria in midlife: a 30-year prospective cohort study

Abstract Background Previous studies have confirmed the adverse effect of ambient fine particulate matter (PM2.5) on kidney and cardiovascular diseases. However, the effects of long-term cumulative PM2.5 exposure on albuminuria, particularly from childhood to middle age, remains uncertain. Purposes We aimed to investigate the association between cumulative PM2.5 exposure and albuminuria across three distinct time frames using data from the 30-year population-based cohort study. Methods Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, 1643 children and adolescents were followed with 6 visits over 30 years. The annual mean PM2.5 concentration for the period 1987-2017, at the address of each participant, was obtained from the MERRA-2 and CHAP datasets in China. We assessed cumulative PM2.5 exposure as the area under the curve (AUC) and used the linear regression models to estimate the association between cumulative PM2.5 exposure and urinary albumin-to-creatinine ratio (uACR) in 2017. Results In full adjustment for potential confounders, childhood and life course cumulative PM2.5 exposure was positively associated with uACR in midlife [childhood: β=0.103 (95%CI: 0.003, 0.202); life course: β=0.078 (95%CI: 0.004, 0.153)]. However, the relationship between adulthood cumulative PM2.5 exposure and uACR in middle age was not statistically significant. In addition, the associations of adulthood and life course cumulative PM2.5 exposure with uACR in middle age were only observed in non-smokers [β=0.109 (95% CI: 0.002, 0.216)], but not in smokers. Conclusions Cumulative PM2.5 exposure during childhood and over the life course is associated with higher uACR in midlife, especially for children and non-smokers. Lowering PM2.5 pollution early in life could prevent the development of renal dysfunction and cardiovascular disease in later life.