Citations

Background: Stroke is a major health burden and the second leading cause of death globally, only after ischemic heart disease. While observational studies have elaborated on the effect of physical activity (PA) and sedentary behavior (SB) on stroke risk, their findings remain inconsistent and are often influenced by confounding factors and reverse causation. Mendelian randomization (MR) can help overcome these shortcomings and assess potential causal relationships using genetic variants as proxies for exposures. Methods: We conducted a systematic review and meta-analysis of MR studies investigating the effects of PA and SB on stroke risk. Following PRISMA guidelines, we searched PubMed and Google Scholar through May 2025. Eligible studies used two-sample MR designs to estimate the impact of moderate-to-vigorous physical activity (MVPA) and sedentary leisure behavior (SLB) on stroke outcomes. MVPA exposures included self-reported activity and accelerometer-derived measures (e.g., leisure time MVPA ≥425 mg), while SLB included television, screen time, sitting, etc. Key outcomes of interest were any stroke and ischemic stroke events. Random-effects models were used for meta-analysis and heterogeneity was assessed with the I2 statistic. Leave-one-out sensitivity analyses were performed to ensure robustness of the results. Results: Six studies met inclusion criteria. Genetically predicted MVPA was associated with a lower risk of stroke (pooled OR = 0.73; 95% CI: 0.53–1.01; p = 0.06), though the result was not statistically significant (I2= 79.5%). In contrast, SLB showed a significant association with increased stroke risk (pooled OR = 1.15; 95% CI: 1.01–1.31; p = 0.03; I2 = 89.9%). Sensitivity analyses confirmed that findings were not influenced by any single study. Conclusion: These findings support a causal association between SLB and increased stroke risk, with suggestive but non-significant evidence for MVPA’s protective role. Despite significant association, high heterogeneity warrants conscious interpretation of findings. Further MR studies using standardized exposure definitions and updated genetic data are needed to strengthen the results.

Background: Cardiac rehabilitation (CR) is emerging as an essential aspect of secondary prevention in patients recovering from acute myocardial infarction (AMI) or coronary artery disease (CAD). Exercise-based rehabilitation involves high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), and maximum intensity interval training (MIIT). These are integral to improving cardiopulmonary fitness, cardiovascular outcomes, and affect health-related quality of life (HRQoL). HIIT is presumed to show better outcomes, though comparative evidence across exercise types remains inconsistent. Clarifying the differential impact of HIIT, MIIT, and MICT on physical and psychosocial outcomes is vital for optimizing CR. Methods: 5 studies involving 650 post-AMI adults enrolled in CR were included. Most studies compared HIIT and MICT; one study also included maximal-intensity interval training (MIIT), and all others used usual care as a control. Outcomes included cardiorespiratory fitness (VO2 max), functional capacity (6-minute walk test [6MWT]), HRQoL (EQ-5D-5L, MacNew), mental health (PHQ, vitality), sleep quality (PSQI), fatigue (FSS), and physiological measures (blood pressure (BP), lipid profile, stroke volume, VE_peak). A qualitative synthesis of findings was performed due to heterogeneity across studies. Results: All 5 studies indicated that structured exercise improved outcomes. HIIT led to greater gains in VO2max compared to MICT. MIIT, assessed in one study, showed the largest VO2max improvements. HRQoL improved in all modalities across EQ-5D-5L, MacNew, PHQ, and visual analog scales. Functional metrics (6MWT, PPO) and cardiovascular parameters (HDL-C, HR recovery) improved more with HIIT. BP, BMI, and HbA1c improved similarly across groups. In several studies, HIIT had a stronger effect on physical functioning and emotional health. Only HIIT led to a significant drop in depression scores. HDL cholesterol improved more with HIIT. Conclusion: HIIT provides superior gains in cardiorespiratory fitness and physical function compared to MICT or MIIT in CR participants, without compromising safety/quality of life. Mental health, HRQoL, and physiological parameters improve comparably across exercise modalities. These findings support that HIIT is an effective, time-efficient option in contemporary CR planning. Future standardized, large-scale, and long-term studies are needed to assess sustained clinical impact and cardiovascular event reduction.

Background: Studies in the past have demonstrated an association between sarcoidosis and pulmonary embolism (PE), but little is known about its impact, especially in young adults. We aim to determine the burden and impact of PE in young adults hospitalized with sarcoidosis. Methods: This study investigates the prevalence and consequences of PE in young adults aged 18–44 years hospitalized with sarcoidosis using data from the National Inpatient Sample (2016–2020) with relevant International Classification of Diseases (ICD)-10 codes. This study aims to address the primary outcomes of the burden and trends of PE and its associated impact on in-hospital mortality. Additionally, it explores secondary outcomes such as healthcare resource utilization and discharge patterns. Results: Among 50,385 young adults (median age 37 years) hospitalized with sarcoidosis, 1120 had PE, showing a linear increase from 2% in 2016 to 2.9% ( P < 0.001) in 2020. The sarcoidosis–PE+ group, predominantly in young blacks, exhibited a higher prevalence of comorbidities such as obesity, smoking, drug use, peripheral vascular disease, hypothyroidism and prior history of venous thrombus embolism. In contrast, the sarcoidosis–PE− group had a higher prevalence of diabetes (with/without chronic complication), hyperlipidemia and chronic pulmonary disease. Multivariable regression analysis adjusted for all potential sociodemographic and comorbid variables showed higher odds of all-cause mortality (odds ratio [OR]: 2.92, 95% confidence interval [CI]: 1.18–7.24, P < 0.02) in the sarcoidosis–PE+ group as compared to the sarcoidosis–PE− group. The sarcoidosis–PE+ group also had higher hospital costs and length of stay. Conclusion: The higher odds of in-hospital mortality with an increased length of stay and hospital cost observed in the sarcoidosis–PE+ group highlight the often underreported complications of sarcoidosis, particularly in a younger demographic. The relevance of this study stems from its potential to uncover trends that could lead to improved diagnostic and therapeutic strategies.

Purpose: Obesity is a risk factor for sepsis complications in older adults. We assessed the impact of metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO) on outcomes in septic shock. Methods: We conducted a retrospective analysis using the National Inpatient Sample (2016-2020) to identify a cohort of 1,737,075 patients aged 65 years and older who were hospitalized with septic shock, as defined by ICD-10 diagnosis codes. Obese patients without hypertension, diabetes, or hyperlipidemia were classified as MHO; those with ≥1 risk factor as MUHO. Baseline demographics and hospital characteristics were compared using χ² and Mann–Whitney U tests. Multivariable logistic regression adjusted for age, sex, race, comorbidity index, and hospital factors estimated odds ratios (ORs) for respiratory failure, mechanical ventilation, in-hospital mortality, and cardiac arrest. Secondary endpoints included length of stay (LOS) and hospitalization cost. Results: Among 268 050 obese patients, 23 915 (1.4%) were classified as MHO and 244 135 (14.1%) as MUHO. Both phenotypes were more prevalent in females and least common among Asian patients. MHO prevalence was highest among Native Americans, while MUHO was most common among Hispanics in 2020. From 2016 to 2019, the prevalence of both phenotypes remained stable, with modest increases observed during the 2020 sepsis surge. Respiratory failure occurred most frequently in the MHO group (∼70%), followed by MUHO (∼65%) and non-obese patients (∼60%). After adjusting for confounders, both MHO and MUHO groups had higher odds of respiratory failure and mechanical ventilation compared to non-obese patients. In-hospital mortality increased across all groups in 2020; however, MUHO patients had lower adjusted mortality risk. Cardiac arrest rates remained unchanged, while length of stay and hospitalization costs were highest among MHO patients. Conclusions: MHO and MUHO both confer higher respiratory failure and ventilation risk; lower mortality in MUHO warrants further study. Clinical Implications Phenotypic obesity classification may improve sepsis risk stratification and inform metabolic-specific management.

BACKGROUND: Studies in the past have demonstrated an association between sarcoidosis and pulmonary embolism but little is known about its impact, especially in young adults. We aim to determine the burden and impact of pulmonary embolism (PE) in young adults hospitalized with sarcoidosis. METHOD: The study investigates the prevalence and consequences of PE in young adults aged 18-44 years hospitalized with sarcoidosis using data from the National Inpatient Sample (2016-2020) with relevant ICD-10 codes. This study aims to address the primary outcomes of the burden and trends of PE and its associated impact on in-hospital mortality. Additionally, it explores secondary outcomes such as healthcare resource utilization and discharge patterns. RESULT: Among 50,385 young adults (median age 37 years) hospitalized with sarcoidosis, 1120 had PE, showing a linear increase from 2% in 2016 to 2.9% (p<0.001) in 2020. Sarcoidosis-PE+ group, predominantly in young blacks, exhibited a higher prevalence of comorbidities such as obesity, smoking, drug use, peripheral vascular disease, hypothyroidism, and prior history of VTE. In contrast, the sarcoidosis-PE- group had a higher prevalence of diabetes (with/without chronic complication), hyperlipidemia, and chronic pulmonary disease. Multivariable regression analysis adjusted for all potential sociodemographic and comorbid variables showed higher odds of all-cause mortality (OR: 2.92, 95% CI: 1.18-7.24, p <0.02) in the sarcoidosis-PE+ group as compared to sarcoidosis-PE- group. The sarcoidosis-PE+ group also had higher hospital costs and length of stay. CONCLUSION: The higher odds of in-hospital mortality with an increased length of stay and hospital cost observed in the sarcoidosis-PE+ group highlight the often underreported complications of sarcoidosis, particularly in a younger demographic. The relevance of this study stems from its potential to uncover trends that could lead to improved diagnostic and therapeutic strategies.

Background With the increase in popularity of cannabis and its use and the lack of large‐scale data on cannabis use and venous thromboembolism and pulmonary embolism (PE), we used a nationally representative cohort of young adults (aged 18–44 years) to compare the odds of admissions and in‐hospital mortality of PE with and without cannabis use disorder (CUD). Methods and Results Identified patients with PE using the National Inpatient Sample (2018) were compared for baseline, comorbidities, and outcomes. Multivariable regression analysis, adjusted for covariates, was used to compare the odds of PE in young patients with CUD (CUD+) versus those without (CUD−) and those with prior venous thromboembolism. Propensity score–matched analysis (1:6) was also performed to assess in‐hospital outcomes. A total of 61 965 (0.7%) of 8 438 858 young adult admissions in 2018 were PE related, of which 1705 (0.6%) had CUD+. On both unadjusted (odds ratio, 0.80 [95% CI, 0.71–0.90]; P <0.001) and adjusted regression analyses, the CUD+ cohort had a lower risk of PE admission. The CUD+ cohort had fewer routine discharges (58.3% versus 68.3%) and higher transfers to short‐term (7.9% versus 4.8%) and nursing/intermediate care (12.6% versus 9.5%) ( P <0.001). The PE‐CUD+ cohort of in‐hospital mortality did not differ from the CUD− cohort. Propensity score–matched (1:6) analysis revealed comparable mortality odds with higher median hospital stay and cost in the CUD+ cohort. Conclusions Young adults with CUD demonstrated lower odds of PE hospitalizations without any association with subsequent in‐hospital mortality. The median hospital stay of the CUD+ cohort was longer, they were often transferred to other facilities, and they had a higher cost.

Introduction: Obesity is a known risk factor and causes worse cardiovascular outcomes in obstructive sleep apnea. With the growing use of cannabis in the US, so we aimed to assess the impact of cannabis use disorder (CUD) on risk of atrial tachyarrhythmias (atrial fibrillation, AF; atrial fibrillation, AFL) and stroke in young patients with obesity-associated obstructive sleep apnea (OOSA). Methods: The National Inpatient Sample (2015Oct-2017) with relevant ICD-10 codes were used to identify admissions among young adults (18-44 years) with OOSA. We then matched (1:1) two cohorts of cannabis use disorder (CUD+) vs. without (CUD-) with controlling potential sociodemographic confounders. Primary outcomes of interest were frequency and risk of atrial tachyarrhythmias and stroke assessed by multivariable analysis. Results: Of 7470 demographically-matched OOSA admissions, CUD+ and CUD- cohorts had 3735 hospitalizations in each cohort. Both cohorts were comparable mean age of 38 years and CUD+ cohort more frequently included male (66.6% vs. 53.5%), African American (40.0% vs. 30.1%) patients admitted non-electively (92.3% vs. 84.5%). Rates of drug abuse, hypertension, smoking and chronic pulmonary disease were higher but diabetes mellitus, hyperlipidemia, and renal failure were lower in CUD+ cohort vs. CUD- cohort (p<0.001). The frequency of AF/AFL (5.7% vs 7.4%) related admissions were lower; however, the risk of AF/AFL (OR:1.64, 95%CI:1.17-2.30, p=0.004) and stroke (OR:4.41, 95%CI:1.41-13.77, p<0.011) admissions were significantly higher in the OOSA-CUD+ cohort vs. CUD- cohort in the multivariable analysis controlled for relevant cardiovascular/extracardiac comorbidities and concomitant alcohol/drug abuse and smoking. Conclusions: This propensity-matched analysis highlights that recreational cannabis use in young patients with OOSA may alarmingly increase emergency hospitalizations and independently increase the risk of AF/AFL and stroke.

ImportanceStroke is a leading cause of death and disability in the US. Accurate and updated measures of stroke burden are needed to guide public health policies.ObjectiveTo present burden estimates of ischemic and hemorrhagic stroke in the US in 2019 and describe trends from 1990 to 2019 by age, sex, and geographic location.Design, Setting, and ParticipantsAn in-depth cross-sectional analysis of the 2019 Global Burden of Disease study was conducted. The setting included the time period of 1990 to 2019 in the US. The study encompassed estimates for various types of strokes, including all strokes, ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs). The 2019 Global Burden of Disease results were released on October 20, 2020.ExposuresIn this study, no particular exposure was specifically targeted.Main Outcomes and MeasuresThe primary focus of this analysis centered on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100 000 individuals.ResultsIn 2019, the US recorded 7.09 million prevalent strokes (4.07 million women [57.4%]; 3.02 million men [42.6%]), with 5.87 million being ischemic strokes (82.7%). Prevalence also included 0.66 million ICHs and 0.85 million SAHs. Although the absolute numbers of stroke cases, mortality, and DALYs surged from 1990 to 2019, the age-standardized rates either declined or remained steady. Notably, hemorrhagic strokes manifested a substantial increase, especially in mortality, compared with ischemic strokes (incidence of ischemic stroke increased by 13% [95% uncertainty interval (UI), 14.2%-11.9%]; incidence of ICH increased by 39.8% [95% UI, 38.9%-39.7%]; incidence of SAH increased by 50.9% [95% UI, 49.2%-52.6%]). The downturn in stroke mortality plateaued in the recent decade. There was a discernible heterogeneity in stroke burden trends, with older adults (50-74 years) experiencing a decrease in incidence in coastal areas (decreases up to 3.9% in Vermont), in contrast to an uptick observed in younger demographics (15-49 years) in the South and Midwest US (with increases up to 8.4% in Minnesota).Conclusions and RelevanceIn this cross-sectional study, the declining age-standardized stroke rates over the past 3 decades suggest progress in managing stroke-related outcomes. However, the increasing absolute burden of stroke, coupled with a notable rise in hemorrhagic stroke, suggests an evolving and substantial public health challenge in the US. Moreover, the significant disparities in stroke burden trends across different age groups and geographic locations underscore the necessity for region- and demography-specific interventions and policies to effectively mitigate the multifaceted and escalating burden of stroke in the country.

Cerebral embolic protection devices (CEPD) during transcatheter aortic valve replacement (TAVR) have been shown to lower the risk of stroke during the procedure. However, their long-term and clinical effects on neuro-cognition are unknown. Therefore, we hypothesized the benefit of CEPD in TAVR patients with a prior history of stroke or transient ischemic attack (TIA). National Inpatient Sample (2019) and International Classification of Diseases, 10th Revision codes were used to identify patients undergoing TAVR with prior stroke or TIA. Propensity-matched analysis was performed to adjust for baseline characteristics and comorbidities. Primary outcome measures were postoperative stroke and all-cause mortality. Length of stay and hospital cost were secondary outcomes. Of 8450 unmatched TAVR patients with prior stroke or TIA in 2019, 1095 (13%) utilized CEPD. After propensity matching previous myocardial infarction (MI), coronary artery bypass grafting, and drug abuse were higher in the TAVR-only cohort. Postoperative stroke rate (1.4% vs 2.2%; P = 0.081) and odds [adjusted odds ratio (aOR), 0.48; 95% confidence interval (CI), 0.11–2.17; P = 0.341] were lower in the CEPD group. There was no difference in all-cause in-hospital mortality between the 2 groups (0.9% vs 1.0%). Length of stay (3 vs 2 days, P <0.001) and hospital expenditure ($172,711 vs $162,284; P = 0.002) were higher for the TAVR-only cohort. CEPD in TAVR patients with prior stroke or TIA did not show statistically significant postoperative stroke benefits. However, further larger-scale prospective studies are needed to evaluate the long-term neurocognitive benefits of CEPD in these patients. As the use of TAVR continues to expand, optimizing peri-procedural strategies such as the use of CEPD remains a critical area of research to improve patient outcomes.