Physical Activity, Cardiorespiratory Fitness, and the Obesity Paradox with Consideration for Racial and/or Ethnic Differences: A Broad Review and Call to Action.

Despite decades of extensive research and clinical insights on the increased risk of all-cause and disease-specific morbidity and mortality due to obesity, the obesity paradox still presents a unique perspective, i.e., having a higher body mass index (BMI) offers a protective effect on adverse health outcomes, particularly in people with known cardiovascular disease (CVD). This protective effect may be due to modifiable factors that influence body weight status and health, including physical activity (PA) and cardiorespiratory fitness (CRF), as well as non-modifiable factors, such as race and/or ethnicity. This article briefly reviews the current knowledge surrounding the obesity paradox, its relationship with PA and CRF, and compelling considerations for race and/or ethnicity concerning the obesity paradox. As such, this review provides recommendations and a call to action for future precision medicine to consider modifiable and non-modifiable factors when preventing and/or treating obesity.

Impact of Cardiorespiratory Fitness on COVID-19-Related Outcomes: The Exercise Testing and Health Outcomes Study (ETHOS).

OBJECTIVE: To assess the association between cardiorespiratory fitness (CRF) and COVID-19-related health outcomes including mortality, hospitalization, and mechanical ventilation. PATIENTS AND METHODS: In a retrospective analysis of 750,302 patients included in the Exercise Testing and Health Outcomes Study, we identified 23,140 who had a positive result on COVID-19 testing between March 2020 and September 2021 and underwent a maximal exercise test in the Veterans Affairs Health Care System between October 1, 1999 to September 3, 2020. The association between CRF and risk for severe COVID-19 outcomes, including mortality, hospitalization due to COVID-19, and need for intubation was assessed after adjustment for 15 covariates. Patients were stratified into 5 age-specific CRF categories (Least-Fit, Low-Fit, Moderate-Fit, Fit, and High-Fit), based on peak metabolic equivalents achieved. RESULTS: During a median of follow-up of 100 days, 1643 of the 23,140 patients (7.1%) died, 4995 (21.6%) were hospitalized, and 927 (4.0%) required intubation for COVID-19-related reasons. When compared with the Least-Fit patients (referent), the Low-Fit, Moderate-Fit, Fit, and High-Fit patients had hazard ratios for mortality of 0.82 (95% CI, 0.72 to 0.93), 0.73 (95% CI, 0.63 to 0.86), 0.61 (95% CI, 0.53 to 0.72), and 0.54 (95% CI, 0.45 to 0.65), respectively. Patients who were more fit also had substantially lower need for hospital admissions and intubation. Similar patterns were observed for elderly patients and subgroups with comorbidities including hypertension, diabetes, cardiovascular disease, and chronic kidney disease; for each of these conditions, those in the High-Fit category had mortality rates that were roughly half those in the Low-Fit category. CONCLUSION: Among patients positive for COVID-19, higher CRF had a favorable impact on survival, need for hospitalization, and need for intubation regardless of age, body mass index, or the presence of comorbidities.

Clinical implications of combination proton pump inhibitor and triple therapies in patients with atrial fibrillation following percutaneous intervention: a guide for clinicians.

INTRODUCTION: Patients on systemic oral anticoagulation with vitamin K antagonists (VKA) or non-vitamin K oral anticoagulants (NOAC) often require triple therapy following percutaneous coronary intervention, substantially increasing the risk of bleeding. Gastroprotective agents like proton pump inhibitors (PPI) are often employed to mitigate this risk, despite potential competitive inhibition between P2Y12-receptor inhibitors, NOACs, and VKAs. While the interactions and clinical outcomes of PPIs and DAPT have been frequently explored in literature, not many studies have evaluated the same outcomes for triple therapy. AREAS COVERED: This comprehensive narrative review of three studies on PPIs and triple from the PubMed/MEDLINE database supplemented by 23 other relevant studies aims to use the available literature to analyze the potential interactions between PPIs and triple therapy while shedding light on their mechanisms, clinical implications, and areas for optimization. EXPERT OPINION: If triple therapy is indicated following PCI, then patients at high-risk for bleeding may benefit from transition to apixaban and a PPI to lower the risk of gastrointestinal bleeding. More research is needed to determine the role of PPIs in triple therapies in prevention of gastrointestinal bleeding or potentiation of other adverse outcomes.

COVID-19 susceptibility causally related to stroke risk: Using SARS-CoV-2 infection as a natural test of disease predisposition?

The COVID-19 pandemic, caused by SARS-CoV-2, has sparked recurring outbreaks and remains endemic, posing ongoing health risks. In addition to its immediate effects, COVID-19 has been linked to cardiovascular complications, including stroke. However, it remains unclear whether COVID-19 causally increases future stroke risk. This study used Mendelian randomization (MR) analysis to explore the causal link between COVID-19 susceptibility and stroke risk. By analyzing genome-wide association study (GWAS) data, genetically determined susceptibility to COVID-19 was identified and linked to various stroke subtypes, including cardioembolic, small-vessel, and large-artery ischemic stroke. Results indicated a significant association between COVID-19 susceptibility and increased stroke risk, particularly for large-artery ischemic stroke. These findings suggest that SARS-CoV-2 infection could serve as a natural indicator of disease predisposition, revealing inherent cardiovascular vulnerabilities. This revolutionizes the way we view pathogen infections-not only as harmful threats, but also as opportunities to assess individual health risks. By analyzing how people respond to infections, we can gain valuable insights into their predisposition to other diseases later in life, offering an analytical framework for early diagnosis and prevention. This perspective-using pathogen infections as natural tests of disease predisposition-offers a transformative way to view human diseases as a continuum. Instead of merely treating infections as isolated diseases, we can exploit natural infections to assess broader population health, thus paving the way for precision medicine and personalized healthcare interventions.

Temporal Trends and Outcomes of Peripheral Artery Disease and Critical Limb Ischemia in the United States.

INTRODUCTION: Peripheral arterial disease (PAD) is a progressive, systemic atherosclerotic disease that is associated with an increased risk of coronary artery disease (CAD), cerebrovascular disease (CVD), and critical limb ischemia (CLI). CLI represents the most severe stage of PAD, characterized by progressive endothelial dysfunction and arterial narrowing. We hypothesized that the incidence of CLI and PAD would increase over the study period and that the rates of in-hospital mortality and major amputations among patients admitted with CLI would rise correspondingly. METHODS: We utilized the National Inpatient Sample (NIS) database from year 2016 to 2021 using the ICD-10-CM codes. Patients with a primary or secondary diagnoses of PAD were initially selected and subsequently hospitalization with CLI were appropriately identified. Cochran Armitage test was used to describe the trend of outcomes across the years. All statistical analyses were conducted using the software Stata version 17.0. RESULTS: From 2016-2021, there were 2,930,639 admissions for critical limb ischemia. 65% of these patients were over the age of 60 and 35.8% of these patients were women. Most of these individuals were white (64.7%), followed by African Americans (15.8%) and Hispanics (12.6%). In-hospital mortality rates varied by revascularization method, with hybrid revascularization showing the highest rate at 2.6%, followed by endovascular revascularization at 1.8%, and surgical revascularization at 1.6%. Additionally, hospitalization costs were highest for patients undergoing hybrid revascularization ($46,257 ± $36,417), compared to endovascular ($36,924 ± $27,945) and surgical revascularization ($35,672 ± $27,127). Endovascular revascularization rates seemed to increase while surgical revascularization rates decreased during this time period. CONCLUSION: PAD is a progressive, systemic atherosclerotic disease that is associated with an increased risk of CAD, CVD, and CLI. Our data showed that the rates of PAD and CLI hospitalizations has remained relatively stable from 2016-2021, but there seems to be a trend towards doing more revascularization via an endovascular approach as compared to a surgical approach.

Landscape of stroke comorbidities: A disease-wide association study.

Stroke is a leading cause of death and disability worldwide, with diverse comorbidities that influence its clinical outcomes. However, a comprehensive understanding of the short- and long-term patterns of stroke-related comorbidities remains limited. To address this gap, we conducted a disease-wide association study (DWAS) to systematically explore the landscape of stroke comorbidities in a population-based cohort. Using data from the FinnGen cohort, which included 337,194 participants and 27,496 ischemic stroke cases, we analyzed 1,757 medical events as potential stroke comorbidities. We employed Cox proportional hazards regression, adjusting for sex and age, to identify significant associations between stroke and these medical events. Comorbidities were classified into pre- and post-stroke categories, and their temporal patterns were analyzed over a 1- to 15-year follow-up period. Our findings revealed that stroke comorbidities span multiple disease taxonomies, with significant enrichment in the circulatory, digestive, and musculoskeletal systems. Notably, the study identified distinct pre-stroke and post-stroke comorbidities that persist or evolve over time, supporting the concept of a disease continuum. These temporal patterns suggest that stroke risk and outcomes are shaped by sequential comorbidities rather than simultaneous occurrences. This study provides the most comprehensive profile of stroke comorbidities to date, highlighting the interconnected nature of diseases. By mapping the progression of comorbidities across time and disease categories, DWAS offers valuable insights for early intervention and long-term treatment. Our findings emphasize the importance of viewing stroke as part of a broader disease continuum, offering new opportunities for prevention, diagnosis, and treatment strategies tailored to individual risk profiles.

Antegrade Approach versus Retrograde Approach Percutaneous Coronary Intervention for Chronic Total Occlusion: An updated Meta-Analysis.

BACKGROUND: Retrograde approach has notably improved success rates of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). However, longer procedural time, increase use of fluoroscopy and contrast dye have been reported in retrograde techniques in CTO PCI. We aimed to study in-hospital and long-term outcomes of retrograde approach versus antegrade approach in CTO PCI. METHODS: We searched PubMed, Scopus, WOS, and Cochrane Central until June, 2023 to include all relevant studies that compared retrograde approach versus antegrade approach in patients with CTO PCI. We synthesized the outcome data using a random-effects model, expressing the effect estimates as odds ratios (OR) or mean difference (MD) with corresponding 95% confidence intervals (CI). RESULTS: A total of 18 studies comprising 18,830 patients were included in the analysis. Regarding in-hospital outcomes, antegrade approach was associated with lower odds of MACE (OR= 0.34, 95% CI: 0.23 to 0.51), all-cause mortality (OR= 0.35, 95% CI: 0.19 to 0.64), MI (OR= 0.36, 95% CI: 0.25 to 0.53), urgent pericardiocentesis (OR= 0.27, 95% CI: 0.16 to 0.46), CIN (OR= 0.46, 95% CI: 0.33 to 0.65), procedural complications (OR= 0.52, 95% CI: 0.33 to 0.83), target vessel perforation (OR= 0.45, 95% CI: 0.32 to 0.64). while antegrade was associated with higher success rates (OR= 1.16, 95% CI: 1.1 to 1.22). CONCLUSION: Compared to antegrade technique, retrograde was associated with higher risk for in-hospital and long-term adverse events, and preferably should be performed in more complex CTO lesions.

Healthy Lifestyle and Cardiac Rehabilitation for Weight Loss.

PURPOSE OF REVIEW: Considerable current interest is directed at pharmacological agents for producing significant weight loss. However, healthy lifestyle choices can also lead to clinically meaningful weight loss and improvements in cardiovascular disease (CVD) risk factors. RECENT FINDINGS: In this review, we summarize the recent research from our PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) randomized controlled trial and review previous data on the potential benefits of cardiac rehabilitation and exercise training (CRET) programs to produce weight loss and improvements in CVD risk factors. Although obesity medications are becoming extremely attractive for secondary and even primary CVD prevention, high-intensity non-pharmacological therapies with healthy lifestyle choices reviewed herein can also lead to substantial health improvements in patients with obesity, including improvements in body weight and other body composition parameters as well as overall CVD risk.

Exploring the Molecular Adaptations, Benefits, and Future Direction of Exercise Training: Updated Insights into Cardiovascular Health.

This review emphasizes the globally accepted physical activity guidelines and explores the various molecular adaptations that occur with continuous exercise. It is essential to highlight the critical roles of cardiorespiratory fitness, muscular strength, and muscle mass in reducing mortality and enhancing quality of life. It has been shown in various studies that there are certainly substantial reductions in cardiovascular and all-cause mortality among individuals with high cardiorespiratory fitness levels. Resistance training is also examined, which, likewise, reveals significant mortality benefits, even with minimal weekly engagement. When delving into the molecular mechanisms, it is apparent that exercise training favorably influences certain cardiovascular conditions, mostly owing to its effect on enhanced lipid metabolism, improvement in glucose regulation, ability to modulate inflammation and oxidative processes, and induction of other cardioprotective effects like improved sympathetic tone and left ventricular remodeling. Cardiovascular diseases and malignancy also share the same risk factors, which explains why exercise can also mitigate the risk of developing many types of cancers. But despite these advancements in research, cardiovascular diseases continue to be prevalent, which may suggest the need to devise other means of promoting physical activity involvement. These approaches may include a greater emphasis on the societal benefits of increased exercise adherence, facilitated by community involvement and technological advancements in fitness tracking devices. We conclude that the future directions for exercise research should emphasize the need for personalized or tailored exercise programs to make it more engaging, accessible, and inclusive for a diverse set of people.

Racial disparities in trend, clinical characteristics and outcomes in Takotsubo syndrome.

INTRODUCTION: Takotsubo syndrome (TTS) is an acute transient nonischemic cardiomyopathy often characterized by its hallmark feature of left ventricular apical ballooning. The correlation between racial backgrounds and the prognosis of individuals with TTS remains poorly defined. Our study aimed to explore the influence of race on the trends, clinical presentations, and outcomes in patients diagnosed with TTS. METHODS: We queried the National Inpatient Sample (NIS) database from 2016 to 2020 and identified hospitalizations with TTS. We compared the clinical features and outcomes across three different races - non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic population. The primary outcome was in-hospital mortality. RESULTS: 76,505 weighted hospitalizations for TTS were identified, of which 65,495 (85.6%) were non-Hispanic White, 5,830 (7.6%) were non-Hispanic Black, and 5,180 (6.8%) were Hispanics. After propensity-score matching, NHB patients had higher odds of acute kidney injury (OR: 1.49, 95% CI: 1.21-1.84, p < 0.001) and mechanical ventilation (OR: 1.33, 95% CI: 1.04-1.68, p = 0.02). Hispanic patients had a higher incidence of acute kidney injury requiring dialysis when compared to NHW patients (OR: 2.53, 95% CI: 1.11-5.77, p = 0.027). There was no significant difference in terms of in-hospital mortality between NHB and Hispanic patients when compared to NHW patients. Notably, Hispanic populations experienced a higher mortality rate during the COVID-19 period. CONCLUSION: Our study suggested significant differences in the outcomes of TTS across different racial groups. Hispanic populations experienced a higher mortality rate with TTS during the COVID-19 era. Further research should emphasize discovering the factors contributing to the observed disparities.

Obesity and Weight Loss Strategies for Patients With Heart Failure.

Obesity is a common comorbidity among patients with heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF), with the strongest pathophysiologic link of obesity being seen for HFpEF. Lifestyle measures are the cornerstone of weight loss management, but sustainability is a challenge, and there are limited efficacy data in the heart failure (HF) population. Bariatric surgery has moderate efficacy and safety data for patients with preoperative HF or left ventricular dysfunction and has been associated with reductions in HF hospitalizations and medium-term mortality. Antiobesity medications historically carried concerns for cardiovascular adverse effects, but the safety and weight loss efficacy seen in general population trials of glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide/GLP-1 agonists are highly encouraging. Although there are safety concerns regarding GLP-1 agonists in advanced HFrEF, trials of the GLP-1 agonist semaglutide for treatment of obesity have confirmed safety and efficacy in patients with HFpEF.

Substances use and risk of hypertension before midlife in military young adults: CHIEF cohort study, 2014-2020.

BACKGROUND: The use of substances, e.g., tobacco and betel nut, are prevalent among military personnel in Taiwan, whereas some specific substances such as alcohol use are forbidden in military base. There were inconsistent findings for the incidence of hypertension with habitual substances use in diverse populations, while no studies were carried out in the military. METHODS: A total of 2419 Taiwanese military personnel, aged 18-39 years, who were not taking any antihypertensive agents and did not have a baseline systolic blood pressure (SBP) ≥130 mmHg and/or diastolic blood pressure (DBP) ≥80 mmHg were followed for incidence of hypertension from baseline (2014) through the end of 2020. Alcohol, tobacco and betel nut use status (active vs. former/never) were self-reported by each participant at baseline. New-onset hypertension of each participant was defined by an average of two resting BP measurements in the annual health examinations (2015-2020). Multivariable Cox regression analysis with adjustments for baseline BP and other potential covariates were performed to determine the risk of incident hypertension with each substance use. Five-year absolute changes in BP level with specific substance use were compared using analysis of covariance (ANCOVA). RESULTS: There were 867 active smokers (35.8 %), 237 active betel nut chewers (9.8 %) and 961 active alcohol consumers (39.7 %) at baseline. During a median follow-up of 5.8 years, 911 new-onset hypertension events (37.7 %) were observed. While compared to those without any substances use, merely active holiday alcohol users had a significantly lower risk of incident hypertension [hazard ratio (HR) and 95 % confidence interval: 0.72 (0.58-0.89)]. The 5-year diastolic BP increase (mmHg) was borderline significantly lower in active alcohol users on holidays as compared to former/never alcohol users (4.02 (standard deviation =9.01) and 4.76 (9.42), p = 0.07). The risk of incident hypertension was not significant in active smokers and active betel nut users, while the 5-year BP increase level was significantly greater in active smokers than former/never smokers (5.60 (9.96) vs. 4.42 (9.22), p = 0.03). CONCLUSION: Our findings suggest that military young personnel consuming alcohol only allowed on holidays had a lower incidence of new-onset hypertension. On the contrary, the 5-year BP change may increase greater with habitual smoking, though the risk of new-onset hypertension was not affected.

Relationship between epicardial adipose tissue and coronary atherosclerosis by CCTA in young adults (18-45).

Objective: Epicardial adipose tissue (EAT) is implicated in the pathogenesis and progression of coronary artery disease (CAD). Limited data exists on the interplay between EAT and atherosclerosis in young individuals. Our study aims to explore the relationship between EAT and CAD in a young cohort. Methods: All young (18-45 years) patients without prior CAD, referred for coronary computed tomography angiography (CCTA) from 2016 to 2022 were included. EAT volume and coronary artery calcium (CAC) were calculated from dedicated non-contrast scans. Coronary plaque presence, extent, and volume were quantified from CCTA. Multivariable logistic regression models for the presence of CAD, defined as any coronary atherosclerosis, were performed. Results: Overall, 712 patients (39±4.8 years, 54 % female) with 45 % Hispanic, and 21 % non-Hispanic Black were included. Patients with CAD had higher EAT volume than those without (80.80 mL ± 36.00 vs 55.16 mL ± 27.92; P < 0.001). In those with CAC=0, higher EAT was associated with the presence of CAD compared to lower EAT volume (P < 0.001). An EAT volume >76 mL was associated with higher CAC (P < 0.001), segment involvement score (P < 0.001), and quantitative total, non-calcified, and low-attenuation plaque volumes (P < 0.002). At multivariable analysis, EAT volume (per 10 mL, OR: 1.21; 95 %CI: 1.12-1.30; P < 0.0001) was independently associated with the presence of CAD. Conclusion: In a diverse cohort of young adults without history of CAD and undergoing a clinically indicated CCTA, EAT volume was independently associated with the presence of CAD. Our findings highlight EAT potential as a novel marker for CAD risk-assessment and a potential therapeutic target in young patients.

Associations of Cardiorespiratory Fitness and Muscular Endurance Fitness With Pulmonary Function in Physically Active Young Adults.

RATIONALE: While the beneficial effects of physical fitness on general health are well-documented, the specific relationship between different types of physical fitness, particularly cardiorespiratory fitness (CRF) and muscular endurance fitness (MEF), and lung function in physically active young adults remains less explored. OBJECTIVE: This study investigated the relationship between CRF and MEF, and their correlation with lung function in physically active young adults. METHODS: This cross-sectional study involved a cohort of 1227 physically active young adults without lung diseases. Lung function was assessed using FEV1, FVC, and FEV1/FVC measurements. The 3000-m run was used to assess CRF, and the 2-min push-up and sit-up tests were used to assess MEF. Multivariable linear regression analysis was used to evaluate the relationships between these fitness measures and lung function, adjusting for potential covariates. RESULTS: Enhanced CRF was associated with superior FEV1 and FVC after adjusting for covariates (ß=-.078, p=.015 for FEV1; ß=-.086, p=.009 for FVC). Push-ups were positively associated with FEV1 (ß=.102, p=.014), but not with FVC. In contrast, sit-ups showed no significant correlation with lung function in the fully adjusted model. CONCLUSION: The study demonstrated a clear association between improved physical fitness and better lung function in physically active young adults, with various exercises showing distinct associations with lung metrics. Notably, push-ups were particularly associated with higher FEV1. A future prospective study is necessary to determine whether routine exercises, such as push-ups, might lead to greater lung function.

Comparing the efficacy and safety of endovascular therapy versus surgical revascularization for critical limb-threatening ischemia: A systematic review and Meta-analysis.

INTRODUCTION: Critical limb-threatening ischemia (CLTI) is a severe manifestation of peripheral artery disease (PAD) that can lead to limb amputation and significantly reduce quality of life. In addition to guideline-directed medical therapy (GDMT), endovascular therapy and surgical revascularization are the two revascularization options for CLTI. In recent years, there has been an ongoing debate about the best approach for CLTI patients. The purpose of this meta-analysis is to examine the current evidence and compare the clinical outcomes of endovascular therapy and surgical revascularization for CLTI. METHODS: We conducted a systematic search of electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) for studies comparing the outcomes of endovascular therapy versus surgery in patients with CLTI. The primary outcomes were major adverse limb events (MALE) and major adverse cardiovascular events (MACE), while secondary outcomes included risk of bleeding, wound complications, readmission, unplanned reoperation, acute renal failure, and length of hospital stay. Pooled data was analyzed using the fixed-effect model or the random-effect model in Review Manager 5.3. The Newcastle-Ottawa Scale and Cochrane risk of bias assessment tool were used to assess the bias of included studies. RESULTS: A total of 16 studies (47,609 patients) were included in this meta-analysis. The overall effect favors surgery over endovascular intervention in terms of MALE [odds ratio (OR) 1.13, 95% CI (1.01-1.28), P = 0.04]. Endovascular therapy is associated with lower MACE rates compared to surgery [OR 0.62, 95% CI (0.51-0.76), P < 0.00001]. Furthermore, the risk of bleeding, wound complications, readmission, unplanned reoperation, acute renal failure as well as the length of hospital stay was lower for endovascular intervention. Finally, there was no statistically significant difference in 30-day mortality between the two groups [OR 0.94, 95% CI 0.79-1.12, P = 0.52; Fig. 3i], and the pooled studies were homogeneous [P = 0.39; I2 = 5%]. CONCLUSION: Surgery may be the preferred treatment option for CLTI patients, as it is associated with a lower risk of MALE than endovascular therapy. However, endovascular therapy may be associated with a lower risk of MACE and lower rates of bleeding, wound complications, readmission, unplanned reoperation, acute renal failure, and shorter hospital stays. There was no statistically significant difference in 30-day mortality between the two groups. Ultimately, the decision to use endovascular therapy or surgery as the primary treatment strategy should be based on a multi-disciplinary team approach with careful consideration of patient characteristics and anatomy.