Association of Short-Term Increases in Ambient Fine Particulate Matter With Hospitalization for Asthma or COPD During Wildfire Season and Other Time Periods.

BACKGROUND: Short-term increases in air pollution are associated with poor asthma and COPD outcomes. Short-term elevations in fine particulate matter (PM2.5) due to wildfire smoke are becoming more common. RESEARCH QUESTION: Are short-term increases in PM2.5 and ozone in wildfire season and in winter inversion season associated with a composite of emergency or inpatient hospitalization for asthma and COPD? STUDY DESIGN AND METHODS: Case-crossover analyses evaluated 63,976 and 18,514 patients hospitalized for primary discharge diagnoses of asthma and COPD, respectively, between January 1999 and March 2022. Patients resided on Utah's Wasatch Front where PM2.5 and ozone were measured by Environmental Protection Agency-based monitors. ORs were calculated using Poisson regression adjusted for weather variables. RESULTS: Asthma risk increased on the same day that PM2.5 increased during wildfire season (OR, 1.057 per + 10 µg/m3; 95% CI, 1.019-1.097; P = .003) and winter inversions (OR, 1.023 per +10 µg/m3; 95% CI, 1.010-1.037; P = .0004). Risk decreased after 1 week, but during wildfire season risk rebounded at a 4-week lag (OR, 1.098 per +10 µg/m3; 95% CI, 1.033-1.167). Asthma risk for adults during wildfire season was highest in the first 3 days after PM2.5 increases, but for children, the highest risk was delayed by 3 to 4 weeks. PM2.5 exposure was weakly associated with COPD hospitalization. Ozone exposure was not associated with elevated risks. INTERPRETATION: In a large urban population, short-term increases in PM2.5 during wildfire season were associated with asthma hospitalization, and the effect sizes were greater than for PM2.5 during inversion season.

Periodic Fasting and Acute Cardiac Events in Patients Evaluated for COVID-19: An Observational Prospective Cohort Study.

BACKGROUND: Periodic fasting was previously associated with greater longevity and a lower incidence of heart failure (HF) in a pre-pandemic population. In patients with coronavirus disease 2019 (COVID-19), periodic fasting was associated with a lower risk of death or hospitalization. This study evaluated the association between periodic fasting and HF hospitalization and major adverse cardiovascular events (MACEs). METHODS: Patients enrolled in the INSPIRE registry from February 2013 to March 2020 provided periodic fasting information and were followed into the pandemic (n = 5227). Between March 2020 and February 2023, N = 2373 patients were studied, with n = 601 COVID-positive patients being the primary study population (2836 had no COVID-19 test; 18 were excluded due to fasting <5 years). A Cox regression was used to evaluate HF admissions, MACEs, and other endpoints through March 2023, adjusting for covariables, including time-varying COVID-19 vaccination. RESULTS: In patients positive for COVID-19, periodic fasting was reported by 180 (30.0% of 601), who periodically fasted over 43.1 ± 19.2 years (min: 7, max: 83). HF hospitalization (n = 117, 19.5%) occurred in 13.3% of fasters and 22.1% of non-fasters [adjusted hazard ratio (aHR) = 0.63, CI = 0.40, 0.99; p = 0.044]. Most HF admissions were exacerbations, with a prior HF diagnosis in 111 (94.9%) patients hospitalized for HF. Fasting was also associated with a lower MACE risk (aHR = 0.64, CI = 0.43, 0.96; p = 0.030). In n = 1772 COVID-negative patients (29.7% fasters), fasting was not associated with HF hospitalization (aHR = 0.82, CI = 0.64, 1.05; p = 0.12). In COVID-positive and negative patients combined, periodic fasting was associated with lower mortality (aHR = 0.60, CI = 0.39, 0.93; p = 0.021). CONCLUSIONS: Routine periodic fasting was associated with less HF hospitalization in patients positive for COVID-19.

Associations of air pollution with acute coronary syndromes based on A/B/AB versus O blood types: case-crossover study.

Short-term exposure to air pollutants may contribute to an increased risk of acute coronary syndrome (ACS). This study assessed the role of short-term exposure to fine particulate matter (PM2.5) as well as fine and coarse PM (PM10) air pollution in ACS events and the effect of blood groups on this phenomenon. A retrospectively collected database of 9026 patients was evaluated. The study design was a case-crossover using a conditional logistic regression model. The main analysis focused on PM2.5 levels with a 1 day lag until the ACS event, using threshold-modelled predictor for all patients. Secondary analyses utilized separate threshold-modelled predictors for 2-7-days moving averages and for patients from specific ABO blood groups. Additional analysis was performed with the non-threshold models and for PM10 levels. Short-term exposure to increased PM2.5 and PM10 levels at a 1-day lag was associated with elevated risks of ACS (PM2.5: OR = 1.012 per + 10 µg/m3, 95% CI 1.003, 1.021; PM10: OR = 1.014 per + 10 µg/m3, CI 1.002, 1.025) for all patients. Analysis showed that exposure to PM2.5 was associated with increased risk of ACS at a 1-day lag for the A, B or AB group (OR = 1.012 per + 10 µg/m3, CI 1.001, 1.024), but not O group (OR = 1.011 per + 10 µg/m3, CI 0.994, 1.029). Additional analysis showed positive associations between exposure to PM10 and risk of ACS, with 7-days moving average models stratified by blood group revealing that exposures to PM2.5 and PM10 were associated with elevated risk of ACS for patients with group O. Short-term exposures to PM2.5 and PM10 were associated with elevated risk of ACS. Short-term exposure to PM2.5 was positively associated with the risk of ACS for patients with A, B, or AB blood groups for a 1-day lag, while risk in O group was delayed to 7 days.

Contemporary Predictors of Major Adverse Cardiovascular Events Following Percutaneous Coronary Intervention: A Nationally Representative US Sample.

Background: Patient outcomes after percutaneous coronary intervention (PCI) have improved over the last 30 years due to better techniques, therapies, and care processes. This study evaluated contemporary predictors of post-PCI major adverse cardiovascular events (MACE) and summarized risk in a parsimonious risk prediction model. Methods: The Cardiovascular Patient-Level Analytical Platform (CLiPPeR) is an observational dataset of baseline variables and longitudinal outcomes from the American College of Cardiology's CathPCI Registry® and national claims data. Cox regression was used to evaluate 2-6 years of patient follow-up (mean: 2.56 years), ending in December 2017, after index PCI between 2012 and 2015 (N = 1,450,787), to examine clinical and procedural predictors of MACE (first myocardial infarction, stroke, repeat PCI, coronary artery bypass grafting, and mortality). Cox analyses of post-PCI MACE were landmarked 28 days after index PCI. Results: Overall, 12.4% (n = 179,849) experienced MACE. All variables predicted MACE, with cardiogenic shock, cardiac arrest, four diseased coronary vessels, and chronic kidney disease having hazard ratios (HRs) ≥ 1.50. Other major predictors of MACE were in-hospital stroke, three-vessel disease, anemia, heart failure, and STEMI presentation. The index revascularization and discharge prescription of aspirin, P2Y12 inhibitor, and lipid-lowering medication had HR ≤ 0.67. The primary Cox model had c-statistic c = 0.761 for MACE versus c = 0.701 for the parsimonious model and c = 0.752 for the parsimonious model plus treatment variables. Conclusions: In a nationally representative US sample of post-PCI patients, predictors of longitudinal MACE risk were identified, and a parsimonious model efficiently encapsulated them. These findings may aid in assessing care processes to further improve care post-PCI outcomes.

The impact of multimorbidity and functional limitation on quality of life in patients with heart failure: A multi-site study.

BACKGROUND: Multimorbidity and functional limitation are associated with poor outcomes in heart failure (HF). However, the individual and combined effect of these on health-related quality of life in patients with HF is not well understood. METHODS: Patients aged ≥30 years with two or more HF diagnostic codes and one or more HF-related prescription drugs from four U.S. institutions were mailed a survey to measure patient-centric factors including functional status (activities of daily living [ADLs]) and health-related quality of life (PROMIS-29 Health Profile). Patients with HF from January 1, 2013 to February 1, 2018 were included. Multimorbidity was defined as ≥2 non-cardiovascular comorbidities; functional limitation as any limitation in at least one of eight ADLs. Patients were categorized into four groups by multimorbidity (Yes/No) and functional limitation (Yes/No). We dichotomized the PROMIS-29 sub-scale scores at the median and calculated odd ratios for the four multimorbidity/functional limitation groups. RESULTS: A total of 3330 patients with HF returned the survey (response rate 31%); 3020 completed the questions of interest and were retained. Among these patients (45% female; mean age 73 [standard deviation: 12] years), 29% had neither multimorbidity nor functional limitation, 24% had multimorbidity only, 22% had functional limitation only, and 25% had both. After adjustment, having functional limitation only was associated with higher anxiety (odds ratio [OR]: 3.44, 95% confidence interval [CI]: 2.66-4.45), depression (OR: 3.11, 95% CI: 2.39-4.06), and fatigue (OR: 4.19, 95% CI: 3.25-5.40); worse sleep (OR: 2.14, 95% CI: 1.69-2.72) and pain (OR: 6.73, 95% CI: 5.15-8.78); and greater difficulty with social activities (OR: 9.40, 95% CI: 7.19-12.28) compared with having neither. Results were similar for having both multimorbidity and functional limitation. CONCLUSION: Patients with only functional limitation have similar poor health-related quality of life scores as those with both multimorbidity and functional limitation, underscoring the important role that physical functioning plays in the well-being of patients with HF.

Cardiovascular morbidity and mortality following hypertensive disorders of pregnancy.

OBJECTIVES: To determine whether hypertensive disorders of pregnancy (HDP) are associated with maternal coronary artery disease (CAD) and other cardiovascular (CV) diseases within 10-20 years following delivery. STUDY DESIGN: Retrospective cohort including all women who delivered ≥ 1 pregnancy ≥ 20 weeks' gestation within a single health system from 1998 to 2008. We excluded those with CV risk factors preceding first delivery or with no follow-up after delivery. The exposure of interest was any HDP, determined by ICD coding. MAIN OUTCOME MEASURES: The primary outcome was a composite of ICD codes for CAD, peripheral vascular disease, and CV events (myocardial infarction, stroke, and death). Multivariable Cox proportional hazards estimated the association between exposure and outcomes. A nested cohort of women who underwent cardiac catheterization had a primary outcome of angiographic CAD, and multivariable logistic regression estimated the association between HDP and CAD. RESULTS: Of 33,959 women included, 2,385 women had HDP. HDP was associated with the composite outcome (adjusted HR 1.50, 95 % CI 1.11, 2.03). There was a significant difference in event-free survival between groups (p = 0.003) with a median follow-up of 17.3 years. 592 women (1.7 %) underwent cardiac catheterization: 20 of 90 women with HDP had CAD (22.2 %) on angiography vs 49 of 502 without HDP (9.8 %, p < 0.001). HDP was associated with angiographic CAD (adjusted OR 2.08, 95 % CI 1.05, 4.11). CONCLUSIONS: Women with HDP had twice the incidence of CAD on angiography compared to parous women without HDP. Obstetric history may inform the decision to perform cardiac catheterization in relatively young women.

A large, multi-center survey assessing health, social support, literacy, and self-management resources in patients with heart failure.

BACKGROUND: Most patients with heart failure (HF) have multimorbidity which may cause difficulties with self-management. Understanding the resources patients draw upon to effectively manage their health is fundamental to designing new practice models to improve outcomes in HF. We describe the rationale, conceptual framework, and implementation of a multi-center survey of HF patients, characterize differences between responders and non-responders, and summarize patient characteristics and responses to the survey constructs among responders. METHODS: This was a multi-center cross-sectional survey study with linked electronic health record (EHR) data. Our survey was guided by the Chronic Care Model to understand the distribution of patient-centric factors, including health literacy, social support, self-management, and functional and mental status in patients with HF. Most questions were from existing validated questionnaires. The survey was administered to HF patients aged ≥ 30 years from 4 health systems in PCORnet® (the National Patient-Centered Clinical Research Network): Essentia Health, Intermountain Health, Mayo Clinic, and The Ohio State University. Each health system mapped their EHR data to a standardized PCORnet Common Data Model, which was used to extract demographic and clinical data on survey responders and non-responders. RESULTS: Across the 4 sites, 10,662 patients with HF were invited to participate, and 3330 completed the survey (response rate: 31%). Responders were older (74 vs. 71 years; standardized difference (95% CI): 0.18 (0.13, 0.22)), less racially diverse (3% vs. 12% non-White; standardized difference (95% CI): -0.32 (-0.36, -0.28)), and had higher prevalence of many chronic conditions than non-responders, and thus may not be representative of all HF patients. The internal reliability of the validated questionnaires in our survey was good (range of Cronbach's alpha: 0.50-0.96). Responders reported their health was generally good or fair, they frequently had cardiovascular comorbidities, > 50% had difficulty climbing stairs, and > 10% reported difficulties with bathing, preparing meals, and using transportation. Nearly 80% of patients had family or friends sit with them during a doctor visit, and 54% managed their health by themselves. Patients reported generally low perceived support for self-management related to exercise and diet. CONCLUSIONS: More than half of patients with HF managed their health by themselves. Increased understanding of self-management resources may guide the development of interventions to improve HF outcomes.

Vaccine Effectiveness Against Long COVID in Children.

OBJECTIVES: Vaccination reduces the risk of acute coronavirus disease 2019 (COVID-19) in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5 to 17 years. METHODS: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record program for visits after vaccine availability. We examined both probable (symptom-based) and diagnosed long COVID after vaccination. RESULTS: The vaccination rate was 67% in the cohort of 1 037 936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, whereas diagnosed long COVID was 0.8%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5-44.7) against probable long COVID and 41.7% (15.0-60.0) against diagnosed long COVID. VE was higher for adolescents (50.3% [36.6-61.0]) than children aged 5 to 11 (23.8% [4.9-39.0]). VE was higher at 6 months (61.4% [51.0-69.6]) but decreased to 10.6% (-26.8% to 37.0%) at 18-months. CONCLUSIONS: This large retrospective study shows moderate protective effect of severe acute respiratory coronavirus 2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including electronic health record sources and prospective data.

Developing 60-Day Readmission Risk Score among Home Healthcare Patients with Heart Failure.

Heart failure (HF) readmissions are common, costly, and often preventable. Despite the implementation of HF programs across clinical settings, rehospitalization is still common. Efforts to identify risk factors for 60-day rehospitalization among HF patients exist, but risk scoring has not been utilized in home healthcare. The purpose of this study was to develop a 60-day rehospitalization risk score for home care patients with HF. This study is a secondary data analysis of a retrospective cross-sectional dataset that was composed of data using the Outcome Assessment Information Set (OASIS)-C version for patients with HF. We computed the Charlson Comorbidity Index (CCI) to use as a confounder. The risk score was computed from the final logistic regression model regression coefficients. The median age was 78 years old, 45.4% were male, and 81.0% were White. We identified 10 significant risk factors including CCI score. The risk score achieved a c-statistic of 0.70 in this patient sample. This risk score could prove useful in clinical practice for guiding attention and decision-making for personalized care of patients with unrecognized or under-treated health needs.

The Effects of a High-Carbohydrate versus a High-Fat Shake on Biomarkers of Metabolism and Glycemic Control When Used to Interrupt a 38-h Fast: A Randomized Crossover Study.

This study aimed to determine the impact of various fast-interrupting shakes on markers of glycemic control including glucose, ß-hydroxybutyrate (BHB), insulin, glucagon, GLP-1, and GIP. Twenty-seven sedentary adults (twelve female, fifteen male) with overweight or obesity completed this study. One condition consisted of a 38-h water-only fast, and the other two conditions repeated this, but the fasts were interrupted at 24 h by either a high carbohydrate/low fat (HC/LF) shake or an isovolumetric and isocaloric low carbohydrate/high fat (LC/HF) shake. The water-only fast resulted in 135.3% more BHB compared to the HC/LF condition (p < 0.01) and 69.6% more compared to the LC/HF condition (p < 0.01). The LC/HF condition exhibited a 38.8% higher BHB level than the HC/LF condition (p < 0.01). The area under the curve for glucose was 14.2% higher in the HC/LF condition than in the water condition (p < 0.01) and 6.9% higher compared to the LC/HF condition (p < 0.01), with the LC/HF condition yielding 7.8% more glucose than the water condition (p < 0.01). At the 25-h mark, insulin and glucose-dependent insulinotropic polypeptide (GIP) were significantly elevated in the HC/LF condition compared to the LC/HF condition (p < 0.01 and p = 0.02, respectively) and compared to the water condition (p < 0.01). Furthermore, insulin, GLP-1, and GIP were increased in the LC/HF condition compared to the water condition at 25 h (p < 0.01, p = 0.015, and p < 0.01, respectively). By the 38-h time point, no differences were observed among the conditions for any of the analyzed hormones. While a LC/HF shake does not mimic a fast completely, it does preserve some of the metabolic changes including elevated BHB and glucagon, and decreased glucose and insulin compared to a HC/LF shake, implying a potential for improved metabolic health.

Sex-dependent regulation of social avoidance by oxytocin signaling in the ventral tegmental area.

It has been hypothesized that oxytocin increases the salience of social stimuli, whether the valence is positive or negative, through its interactions with the ventral tegmental area (VTA). Indeed, oxytocin neurons project to the VTA and activate dopamine neurons that are necessary for social experiences with positive valence. Surprisingly, though, there has not been an investigation of the role of oxytocin in the VTA in mediating social experiences with negative valence (e.g., social stress). Given that there are sex differences in how oxytocin regulates the salience of positively-valenced social interactions, we hypothesized that oxytocin acting in the VTA also alters the salience of social stress in a sex-dependent manner. To test this, female and male Syrian hamsters were site-specifically infused with either saline, oxytocin (9 µM), or oxytocin receptor antagonist (90 µM) into the VTA. Subjects were then exposed to either no defeat or a single, 15 min defeat by one RA. The day following social defeat, subjects underwent a 5 min social avoidance test. There was an interaction between sex and drug treatment, such that the oxytocin antagonist increased social avoidance compared to saline treatment in socially stressed females, while oxytocin decreased social avoidance compared to saline treatment in socially stressed males. Contrary to expectations, these results suggest that oxytocin signaling generally acts to decrease social avoidance, regardless of sex. These sex differences in the efficacy of oxytocin and oxytocin receptor antagonists to alter negatively-valenced social stimuli, however, should be considered when guiding pharmacotherapies for disorders involving social deficits.

Vaccine Effectiveness Against Long COVID in Children: A Report from the RECOVER EHR Cohort.

Objective: Vaccination reduces the risk of acute COVID-19 in children, but it is less clear whether it protects against long COVID. We estimated vaccine effectiveness (VE) against long COVID in children aged 5-17 years. Methods: This retrospective cohort study used data from 17 health systems in the RECOVER PCORnet electronic health record (EHR) Program for visits between vaccine availability, and October 29, 2022. Conditional logistic regression was used to estimate VE against long COVID with matching on age group (5-11, 12-17) and time period and adjustment for sex, ethnicity, health system, comorbidity burden, and pre-exposure health care utilization. We examined both probable (symptom-based) and diagnosed long COVID in the year following vaccination. Results: The vaccination rate was 56% in the cohort of 1,037,936 children. The incidence of probable long COVID was 4.5% among patients with COVID-19, while diagnosed long COVID was 0.7%. Adjusted vaccine effectiveness within 12 months was 35.4% (95 CI 24.5 - 44.5) against probable long COVID and 41.7% (15.0 - 60.0) against diagnosed long COVID. VE was higher for adolescents 50.3% [36.3 - 61.0]) than children aged 5-11 (23.8% [4.9 - 39.0]). VE was higher at 6 months (61.4% [51.0 - 69.6]) but decreased to 10.6% (-26.8 - 37.0%) at 18-months. Discussion: This large retrospective study shows a moderate protective effect of SARS-CoV-2 vaccination against long COVID. The effect is stronger in adolescents, who have higher risk of long COVID, and wanes over time. Understanding VE mechanism against long COVID requires more study, including EHR sources and prospective data. Article Summary: Vaccination against COVID-19 has a protective effect against long COVID in children and adolescents. The effect wanes over time but remains significant at 12 months. What's Known on This Subject: Vaccines reduce the risk and severity of COVID-19 in children. There is evidence for reduced long COVID risk in adults who are vaccinated, but little information about similar effects for children and adolescents, who have distinct forms of long COVID. What This Study Adds: Using electronic health records from US health systems, we examined large cohorts of vaccinated and unvaccinated patients <18 years old and show that vaccination against COVID-19 is associated with reduced risk of long COVID for at least 12 months. Contributors' Statement: Drs. Hanieh Razzaghi and Charles Bailey conceptualized and designed the study, supervised analyses, drafted the initial manuscript, and critically reviewed and revised the manuscript.Drs. Christopher Forrest and Yong Chen designed the study and critically reviewed and revised the manuscript.Ms. Kathryn Hirabayashi, Ms. Andrea Allen, and Dr. Qiong Wu conducted analyses, and critically reviewed and revised the manuscript.Drs. Suchitra Rao, H Timothy Bunnell, Elizabeth A. Chrischilles, Lindsay G. Cowell, Mollie R. Cummins, David A. Hanauer, Benjamin D. Horne, Carol R. Horowitz, Ravi Jhaveri, Susan Kim, Aaron Mishkin, Jennifer A. Muszynski, Susanna Nagie, Nathan M. Pajor, Anuradha Paranjape, Hayden T. Schwenk, Marion R. Sills, Yacob G. Tedla, David A. Williams, and Ms. Miranda Higginbotham critically reviewed and revised the manuscript.All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Authorship statement: Authorship has been determined according to ICMJE recommendations.

Intermittent fasting and changes in clinical risk scores: Secondary analysis of a randomized controlled trial.

Background: Intermittent fasting may increase longevity and lower cardiometabolic risk. This study evaluated whether fasting modifies clinical risk scores for mortality [i.e., Intermountain Mortality Risk Score (IMRS)] or chronic diseases [e.g., Pooled Cohort Risk Equations (PCRE), Intermountain Chronic Disease score (ICHRON)]. Methods and results: Subjects (N = 71) completing the WONDERFUL trial were aged 21-70 years, had ≥1 metabolic syndrome criteria, elevated cholesterol, and no anti-diabetes medications, statins, or chronic diseases. The intermittent fasting arm underwent 24-h water-only fasting twice-per-week for 4 weeks and once-per-week for 22 weeks (26 weeks total). Analyses examined the IMRS change score at 26 weeks vs. baseline between intermittent fasting (n = 38) and ad libitum controls (n = 33), and change scores for PCRE, ICHRON, HOMA-IR, and a metabolic syndrome score (MSS). Age averaged 49 years; 65% were female. Intermittent fasting increased IMRS (0.78 ± 2.14 vs. controls: -0.61 ± 2.56; p = 0.010) but interacted with baseline IMRS (p-interaction = 0.010) to reduce HOMA-IR (but not MSS) more in subjects with higher baseline IMRS (median HOMA-IR change: fasters, -0.95; controls, +0.05) vs. lower baseline IMRS (-0.29 vs. -0.32, respectively). Intermittent fasting reduced ICHRON (-0.92 ± 2.96 vs. 0.58 ± 3.07; p = 0.035) and tended to reduce PCRE (-0.20 ± 0.22 vs. -0.14 ± 0.21; p = 0.054). Conclusions: Intermittent fasting increased 1-year IMRS mortality risk, but decreased 10-year chronic disease risk (PCRE and ICHRON). It also reduced HOMA-IR more in subjects with higher baseline IMRS. Increased IMRS suggests fasting may elevate short-term mortality risk as a central trigger for myriad physiological responses that elicit long-term health improvements. Increased IMRS may also reveal short-term fasting-induced safety concerns.

Higher docosahexaenoic acid levels lower the protective impact of eicosapentaenoic acid on long-term major cardiovascular events.

Introduction: Long-chain omega-3 polyunsaturated fatty acids (OM3 PUFA) are commonly used for cardiovascular disease prevention. High-dose eicosapentaenoic acid (EPA) is reported to reduce major adverse cardiovascular events (MACE); however, a combined EPA and docosahexaenoic acid (DHA) supplementation has not been proven to do so. This study aimed to evaluate the potential interaction between EPA and DHA levels on long-term MACE. Methods: We studied a cohort of 987 randomly selected subjects enrolled in the INSPIRE biobank registry who underwent coronary angiography. We used rapid throughput liquid chromatography-mass spectrometry to quantify the EPA and DHA plasma levels and examined their impact unadjusted, adjusted for one another, and fully adjusted for comorbidities, EPA + DHA, and the EPA/DHA ratio on long-term (10-year) MACE (all-cause death, myocardial infarction, stroke, heart failure hospitalization). Results: The average subject age was 61.5 ± 12.2 years, 57% were male, 41% were obese, 42% had severe coronary artery disease (CAD), and 311 (31.5%) had a MACE. The 10-year MACE unadjusted hazard ratio (HR) for the highest (fourth) vs. lowest (first) quartile (Q) of EPA was HR = 0.48 (95% CI: 0.35, 0.67). The adjustment for DHA changed the HR to 0.30 (CI: 0.19, 0.49), and an additional adjustment for baseline differences changed the HR to 0.36 (CI: 0.22, 0.58). Conversely, unadjusted DHA did not significantly predict MACE, but adjustment for EPA resulted in a 1.81-fold higher risk of MACE (CI: 1.14, 2.90) for Q4 vs. Q1. However, after the adjustment for baseline differences, the risk of MACE was not significant for DHA (HR = 1.37; CI: 0.85, 2.20). An EPA/DHA ratio ≥1 resulted in a lower rate of 10-year MACE outcomes (27% vs. 37%, adjusted p-value = 0.013). Conclusions: Higher levels of EPA, but not DHA, are associated with a lower risk of MACE. When combined with EPA, higher DHA blunts the benefit of EPA and is associated with a higher risk of MACE in the presence of low EPA. These findings can help explain the discrepant results of EPA-only and EPA/DHA mixed clinical supplementation trials.

Predicting post-discharge venous thromboembolism and bleeding among medical patients: External validation of a novel risk score utilizing ubiquitous biomarkers.

BACKGROUND: Post-hospitalization thromboprophylaxis can reduce venous thromboembolism (VTE) risk for non-surgical patients but may carry bleeding risks. We aimed to externally validate the Intermountain Risk Scores for hospital-associated venous thromboembolism (HA-VTE IMRS) and major bleeding (HA-MB IMRS) for VTE and bleeding outcomes. METHODS: Retrospective cohort study of adult patients discharged alive from medical services between 2015 and 2019. HA-VTE IMRS and HA-MB IMRS were calculated at the time of hospital discharge and dichotomized as high- or low-risk as described in the derivation manuscript. 90-day post-discharge VTE outcomes were assessed from diagnostic radiology reports, and bleeding outcomes were assessed using ICD-10 codes and blood bank transfusion records. RESULTS: Among 113,578 patients in the study, 66,340 patients (58.4 %) had a low-risk HA-VTE IMRS <7, versus 47,238 (41.6 %) high-risk ≥7. For bleed prediction, 71,576 patients (63 %) had a low-risk HA-MB IMRS <8, versus 42,002 (37 %) high-risk ≥8. VTE incidence was 1.1 % and 0.6 % while major bleeding incidence was 1.3 % and 0.1 % in high-risk versus low-risk cohorts, respectively. AUCs for VTE and bleed outcome discrimination were 0.59 and 0.78, respectively. Patients with a combined high-risk VTE score and low-risk bleeding score comprised 14.5 % of the population. CONCLUSION: In this external validation study, the HA-VTE IMRS had poor discrimination for VTE but the HA-MB IMRS had good discriminatory ability for major bleeding events. A sizable minority of patients were categorized as high VTE risk with low bleed risk, a population which may have an optimal risk-benefit profile for post-hospital thromboprophylaxis.

Left ventricular functional improvement appears to contribute to lower rates of device thrombosis in patients on durable mechanical circulatory support.

By unloading the failing heart, left ventricular (LV) assist devices (LVADs) provide a favorable environment for reversing adverse structural and functional cardiac changes. Prior reports have suggested that an improved native LV function might contribute to the development of LVAD thrombosis. We used the Interagency Registry for Mechanically Assisted Circulatory Support and found that LV functional improvement is associated with a lower risk for device thrombosis. The risk for cerebrovascular accident and transient ischemic attack was comparable across post-LVAD LV function subgroups, while the risk of hemolysis was lower in subgroups of patients with better LV function on LVAD support.

A highly predictive cardiac positron emission tomography (PET) risk score for 90-day and one-year major adverse cardiac events and revascularization.

BACKGROUND: With the increase in cardiac PET/CT availability and utilization, the development of a PET/CT-based major adverse cardiovascular events, including death, myocardial infarction (MI), and revascularization (MACE-Revasc) risk assessment score is needed. Here we develop a highly predictive PET/CT-based risk score for 90-day and one-year MACE-Revasc. METHODS AND RESULTS: 11,552 patients had a PET/CT from 2015 to 2017 and were studied for the training and development set. PET/CT from 2018 was used to validate the derived scores (n = 5049). Patients were on average 65 years old, half were male, and a quarter had a prior MI or revascularization. Baseline characteristics and PET/CT results were used to derive the MACE-Revasc risk models, resulting in models with 5 and 8 weighted factors. The PET/CT 90-day MACE-Revasc risk score trended toward outperforming ischemic burden alone [P = .07 with an area under the curve (AUC) 0.85 vs 0.83]. The PET/CT one-year MACE-Revasc score was better than the use of ischemic burden alone (P < .0001, AUC 0.80 vs 0.76). Both PET/CT MACE-Revasc risk scores outperformed risk prediction by cardiologists. CONCLUSION: The derived PET/CT 90-day and one-year MACE-Revasc risk scores were highly predictive and outperformed ischemic burden and cardiologist assessment. These scores are easy to calculate, lending to straightforward clinical implementation and should be further tested for clinical usefulness.