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To provide updated reference standards for cardiorespiratory fitness (CRF) for the United States derived from cardiopulmonary exercise (CPX) testing when using a treadmill or cycle ergometer.Thirty-four laboratories in the United States contributed data to the Fitness Registry and the Importance of Exercise National Database. Analysis included 22,379 tests (16,278 treadmill and 6101 cycle ergometer) conducted between January 1, 1968, through March 31, 2021, from apparently healthy adults (aged 20 to 89 years). Percentiles of peak oxygen consumption for men and women were determined for each decade from 20 through 89 years of age for treadmill and cycle exercise modes, as well as when defining maximal effort as respiratory exchange ratio (RER) greater than or equal to 1.0 or RER greater than or equal to 1.1.For both men and women, the 50These updated cardiorespiratory fitness reference standards improve the representativeness of the US population compared with the original standards.

Importance: The COVID-19 pandemic saw one of the fastest developments of vaccines in an effort to combat an out-of-control pandemic. The 2 most common COVID-19 vaccine platforms currently in use, messenger RNA (mRNA) and adenovirus vector, were developed on the basis of previous research in use of this technology. Postauthorization surveillance of COVID-19 vaccines has identified safety signals, including unusual cases of thrombocytopenia with thrombosis reported in recipients of adenoviral vector vaccines. One of the devastating manifestations of this syndrome, termed vaccine-induced immune thrombotic thrombocytopenia (VITT), is cerebral venous sinus thrombosis (CVST). This review summarizes the current evidence and indications regarding biology, clinical characteristics, and pharmacological management of VITT with CVST. Observations: VITT appears to be similar to heparin-induced thrombocytopenia (HIT), with both disorders associated with thrombocytopenia, thrombosis, and presence of autoantibodies to platelet factor 4 (PF4). Unlike VITT, HIT is triggered by recent exposure to heparin. Owing to similarities between these 2 conditions and lack of high-quality evidence, interim recommendations suggest avoiding heparin and heparin analogues in patients with VITT. Based on initial reports, female sex and age younger than 60 years were identified as possible risk factors for VITT. Treatment consists of therapeutic anticoagulation with nonheparin anticoagulants and prevention of formation of autoantibody-PF4 complexes, the latter being achieved by administration of high-dose intravenous immunoglobin (IVIG). Steroids, which can theoretically inhibit the production of new antibodies, have been used in combination with IVIG. In severe cases, plasma exchange should be used for clearing autoantibodies. Monoclonal antibodies, such as rituximab and eculizumab, can be considered when other therapies fail. Routine platelet transfusions, aspirin, and warfarin should be avoided because of the possibility of worsening thrombosis and magnifying bleeding risk. Conclusions and Relevance: Adverse events like VITT, while uncommon, have been described despite vaccination remaining the most essential component in the fight against the COVID-19 pandemic. While it seems logical to consider the use of types of vaccines (eg, mRNA-based administration) in individuals at high risk, treatment should consist of therapeutic anticoagulation mostly with nonheparin products and IVIG.

Which came first, the chicken or the egg? This causality dilemma was first proposed by the Greek biographer Plutarch in the 1st century CE. While the cause-effect relationship between lifestyle behaviors and chronic disease is not always a certainty, and genetic predisposition can independently lead to premature chronic disease, the likelihood of developing one or more chronic conditions is significantly higher in those who: (1) lead sedentary lifestyles; (2) consume unhealthy diets; (3) smoke; or (4) have excess body mass. Recently, the Royal College of General Practitioners issued an apology for the title of an online event that suggested the coronavirus disease 2019 (COVID-19) is a lifestyle disease. We feel that this was the correct course of action as leading an unhealthy lifestyle is certainly not the cause for an individual contracting COVID-19 (ie, effect). However, a body of evidence has demonstrated that unhealthy lifestyle behaviors and characteristics as well as being diagnosed with one or more chronic diseases does significantly increase the risk for a complicated medical course in individuals infected with COVID-19. Moreover, the cause-effect relationship between lifestyle behaviors and characteristics and COVID-19 may eventually prove to go both ways, as the pandemic may lead to a higher prevalence of unhealthy lifestyle behaviors and characteristics over the long term that eventually leads to a higher prevalence of chronic disease. As such, health living medicine must be widely practiced and prescribed to all individuals globally.

Introduction: The Elevation Training Mask 2.0 (ETM) has been introduced as a novel tool to allow for respiratory muscle training and altitude exposure during exercise that can improve performance and hematological markers in elite and well-trained athletes. Thus, the aim of the present study was to assess the effect of wearing ETM while training on erythropoietin (EPO), vascular endothelial growth factor (VEGF), peak oxygen consumption (VO2max), lactate, and 1000-m kayaking performance in elite Kayaking girls. Methods: Thirty elite Kayaking girls (14 to 18-year-old) were equally and randomly assigned into mask, no mask, and control groups. The mask and no-mask groups completed 8 weeks of repeated sprint training, while the control group performed their routine kayaking training programs. Pre- and post-training tests included EPO, VEGF, VO2max, lactate, and 1000-m kayaking performance. Results: 1000-m time trial significantly decreased for mask (p < 0.001) and control (p = 0.035) groups, and was significantly lower in mask group than control (p = 0.014) and no mask (p = 0.009) groups. EPO did not show any significant changes for all groups. VEGF was increased significantly for mask (p = 0.04) and no mask (p = 0.014) groups. Lactate was decreased significantly for mask group (p = 0.025). VO2max increased significantly for no mask group (p = 0.021). Conclusion: Wearing the ETM while participating in 8 weeks of repeated sprint training might improve specific blood markers and endurance performance, especially anaerobic pathways. Performing repeated sprint training while wearing ETM has the potential to enhance performance in Kayak racing.

The net clinical benefit of percutaneous coronary intervention (PCI) compared with medical therapy (MT) alone for the treatment of stable coronary artery disease (CAD) remains uncertain. We conducted an updated meta-analysis of randomized controlled trials (RCTs) to compare PCI with MT for the treatment of patients with stable CAD.RCTs of PCI vs MT in patients with stable CAD were identified from MEDLINE, the Cochrane Library, and manual search of bibliographies to March 2020. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) were pooled for the composite of all-cause mortality, myocardial infarction (MI), revascularizations, rehospitalizations, or stroke and its individual components.Eleven unique RCTs comprising 9629 patients were included. PCI reduced the overall risk of the composite outcome of allcause mortality, MI, revascularizations, rehospitalizations, or stroke (RR, 0.63; 95% CI, 0.46-0.87); unplanned revascularization (RR, 0.58; 95% CI, 0.44-0.77); and fatal MI (RR, 0.69; 95% CI, 0.52-0.92). There were no significant differences in overall risk of all-cause mortality and other cardiovascular events comparing PCI with MT. The composite outcome of all-cause mortality, MI, revascularizations, rehospitalizations, or stroke was reduced with PCI at 2-5 years.In patients with stable CAD, overall, short-term and intermediate-term risks of all-cause mortality are not significantly different between PCI and MT. However, PCI may reduce the overall and intermediate-term risk of the combined outcome of all-cause mortality, MI, revascularizations, rehospitalizations, or stroke.

The mechanisms occurring during sepsis that produce an increased risk of cardiovascular (CV) disease (CVD) are poorly understood. Even less information exists regarding CV dysfunction as a complication of sepsis, particularly for sepsis-induced cardiomyopathy. However, recent research has demonstrated that non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, play a crucial role in genetic reprogramming, gene regulation, and inflammation during the development of CVD. Here we describe experimental findings showing the importance of non-coding RNAs mediating relevant mechanisms underlying CV dysfunction after sepsis, so contributing to sepsis-induced cardiomyopathy. Importantly, non-coding RNAs are critical novel regulators of CVD risk factors. Thus, they are potential candidates to improve diagnostics and prognosis of sepsis-induced cardiomyopathy and other CVD events occurring after sepsis and set the basis to design novel therapeutic strategies.

During the ongoing COVID-19 pandemic caused by SARS-CoV-2 virus, the vast majority of patients have a mild to moderate illness that does not necessitate hospitalization and are appropriately treate...

Background Cinnamon has been used as a traditional herbal medication for decades. Several studies have investigated cinnamon consumption and cardiovascular risk. So far, the evidence remains inconclusive. Thus, we aim to systematically review the currently available literature and quantify the evidence, if possible. Methods We systematically searched Ovid MEDLINE, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science from database inception in 1966 through December 2020. The exposure of interest was cinnamon consumption, the outcome was cardiovascular risk defined as hemoglobin A1C, low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c). Two investigators independently reviewed the data. Conflicts were resolved through consensus. Random-effects meta-analyses were used. Results Of 23 studies (1070 subjects), the included studies were heterogeneous, generally of very poor quality. We found no difference in LDL-c levels in patients who consumed cinnamon vs those who did not, with a weighted mean difference (WMD) of 0.38 (confidence interval [CI], −6.07-6.83). We also found no difference in HDL-c between the 2 groups with WMD 0.40 (CI, −1.14-1.94). In addition, we found no statistical differences in hemoglobin A1C between the 2 groups with WMD of 0.0 (CI, −0.44-0.45). Conclusions Our meta-analysis suggests that there is no association between cinnamon consumption and differences in LDL-c, HDL-c, and hemoglobin A1C levels. Further randomized control trials studies using a robust design with long-term cinnamon consumption are needed to further investigate any potential effect.

Inflammation is a marker of arterial disease stemming from cholesterol-dependent to -independent molecular mechanisms. In recent years, the role of inflammation in atherogenesis has been underpinned by pharmacological approaches targeting systemic inflammation that have led to a significant reduction in cardiovascular disease (CVD) risk. Although the use of nutraceuticals to prevent CVD has largely focused on lipid-lowering (e.g, red-yeast rice and omega-3 fatty acids), there is growing interest and need, especially now in the time of coronavirus pandemic, in the use of nutraceuticals to reduce inflammatory markers, and potentially the inflammatory CVD burden, however, there is still not enough evidence to confirm this. Indeed, diet is an important lifestyle determinant of health and can influence both systemic and vascular inflammation, to varying extents, according to the individual nutraceutical constituents. Thus, the aim of this Position Paper is to provide the first attempt at recommendations on the use of nutraceuticals with effective anti-inflammatory properties.

To investigate whether specific social determinants of health could be a "health barrier" toward achieving blood pressure (BP) control and to further evaluate any differences between Black patients and White patients.We conducted a retrospective cohort study of 3305 patients with elevated BP who were enrolled in a hypertension digital medicine program for at least 60 days and followed up for up to 1 year. Patients were managed virtually by a dedicated hypertension team who provided guideline-based medication management and lifestyle support to achieve goal BP.Compared with individuals without any health barriers, the addition of 1 barrier was associated with lower probability of control at 1 year from 0.73 to 0.60 and to 0.55 in those with 2 or more barriers. Health barriers were more prevalent in Black patients than in those who were White (44.6% [482 of 1081] vs 31.3% [674 of 2150]; P.001). There was no difference at all in BP control between Black individuals and those who were White if 2 or more barriers were present.Patient-related health barriers are associated with BP control. Black patients with poorly controlled hypertension have a higher prevalence of health barriers than their White counterparts. When 2 or more health barriers were present, there was no differences in BP control between White and Black individuals.

Objective To evaluate the nature, magnitude and specificity of the association between handgrip strength (HGS) and heart failure (HF) risk as these aspects of the association in the general population are uncertain.Patients and Methods Handgrip strength was assessed at baseline from March 01, 1998 to December 31, 2001 using a hand dynamometer in the Finnish Kuopio Ischemic Heart Disease prospective population-based cohort of 770 men and women aged 61-74 years without a history of HF. Relative HGS was obtained by dividing the absolute value by body weight. Hazard ratios (HRs) (95% confidence intervals, CIs) were estimated using Cox regression models. We used multiple imputation to account for missing data.Results During a median (interquartile range) follow-up of 17.1 (11.3-18.3) years, 177 HF events were recorded. Handgrip strength was continually associated with risk of HF, consistent with a curvilinear shape. On adjustment for several established risk factors and other potential confounders, the HR (95% CIs) for HF was 0.73 (0.59-0.91) per 1 standard deviation increase in relative HGS. Comparing the top versus bottom tertiles of relative HGS, the corresponding adjusted HR was 0.55 (0.38-0.81). The association remained similar across several clinical subgroups. Imputed results were broadly similar to the observed results.Conclusions Relative HGS is inversely and continually associated with the future risk of HF in the general population. Studies are warranted to evaluate if HGS may be a useful prognostic tool for HF in the general population, and to determine if resistance exercise training may lower the risk of HF.

Coronavirus disease 2019 (COVID-19) continues to have a devastating effect on a global scale. COVID-19 variants continue to arise and counteract vaccination efficacy. As such, preventative health measures, such as social distancing and stay at home mandates, will continue for the foreseeable future. Evidence on those at greatest risk for poor outcomes if infected with COVID-19 has rapidly come to light. It has become clear that those with unhealthy lifestyle characteristics, chronic disease risk factors and/or a confirmed diagnosis of one or more chronic conditions are at greatest risk for hospitalization, intensive care unit admission, mechanical ventilation, and death if infected with COVID-19. The cytokine storm is a phenomenon that has been posited as a pathophysiologic response to COVID-19 infection that leads to poor outcomes. The current graphical review illustrates the association between unhealthy lifestyle characteristics and increased vulnerability to the cytokine storm as well as the physiologic mechanisms healthy living behaviors elicit and decrease risk for the cytokine storm. Through this graphical review, we will demonstrate unhealthy lifestyle characteristics, chronic disease risk factors and diagnoses, and COVID-19 outcomes are intricately linked, creating a new global syndemic. It is also clear that a primary way to uncouple this syndemic is through increasing healthy living behaviors, as illustrated in this graphical review. Moving forward, healthy living medicine should be practiced with renewed vigor to improve human resiliency to health threats posed by both chronic disease and viral infections.

Author(s): Rizk, John G; Kalantar-Zadeh, Kamyar; Mehra, Mandeep R; Lavie, Carl J; Rizk, Youssef; Forthal, Donald N

There continues to be controversy regarding the use of menopausal therapy for women, with considerable evidence supporting the benefits of oestrogen for women,1 but with recent guidelines from the American Heart Association stating that hormone replacement therapy (HRT) and selective oestrogen-receptor modulators should not be used for the primary or secondary prevention of cardiovascular (CV) disease (CVD).2 Nevertheless, there is substantial data to support that premature menopause is associated with increased risk of coronary heart disease (CHD) and CVD events.3 The reason for this, however, remains uncertain, including the adverse effects of earlier loss of oestrogen on CHD risk factors or loss of other beneficial effects of oestrogen on the CV system. In their Heart paper, O'Keeffe and colleagues4 use data from the large United Kingdom Medical Research Counsel National Survey of Health and Development to examine the association between age at cessation of menstrual period and trajectory of CHD risk factors from ages 53–69 years in over 2500 women, where approximately 1670 had data available on blood pressure and body composition and approximately 1500 had data on lipids and glucose metabolism. These results did not demonstrate a clear impact of cessation of period on conventional CHD and CVD risk factors, therefore, suggesting that the reason for the increased CHD and CVD risk in these women with early menopause likely comes from other factors. Whether or not a woman enters menopause at age 50 or 53 years may not have a great deal of differential impact on her overall CV status by the time she reaches age 69. There is, however, no doubt that with the arrival of menopause, the progression of the insidious diseases of ageing, and of CV dysfunction, …

OBJECTIVE: To determine the association between cost-sharing and adherence to cardiac rehabilitation (CR). PATIENTS AND METHODS: We collected detailed cost-sharing information for patients enrolled in CR at Baystate Medical Center in Springfield, MA, including the presence/absence and amounts of copays and deductibles. We evaluated the association between cost-sharing and the total number of CR sessions attended, as well as the influence of household income on CR attendance. RESULTS: In 2015, 603 patients enrolled in CR had complete cost-sharing information. In total, 235 (39%) had some form of cost-sharing. Of these, 82% had copays [median copay $20 (IQR 10, 32)] and 50% had an unmet deductible [median $500 (IQR 250, 1800)]. The presence of any amount or form of cost-sharing was associated with 6 fewer sessions of CR [16 (IQR 4 to 36) vs. 10 (IQR 4 to 27), P < .001]. Patients hospitalized in November or December with deductibles that renewed in January attended 4.5 fewer sessions of CR [8.5 (3.25 to 12.5) vs. 13 (5.25 to 36) P = .049]. After adjustment for differences in baseline characteristics, every $10 increase in copay was associated with 1.5 (95% CI −2.3 to −0.7) fewer sessions of CR (P < .001). Household income did not moderate these relationships. CONCLUSION: Cost-sharing was associated with lower CR attendance and exhibited a dose-response relationship such that higher cost-sharing was associated with lower CR attendance. Given that CR is cost-effective and underutilized, insurance companies and other payers should re-evaluate their cost-sharing policies for CR.

Objective To examine the association between physical activity (PA) and the risk for metabolically unhealthy obesity (MUO) or metabolically healthy obesity (MHO) in Asian adults. Patients and Methods Data were obtained from 205,745 healthy individuals 18 years or older. Individuals were classified as inactive, lower or upper insufficiently active, active, and high active. Metabolically unhealthy was defined as having 1 or more of the metabolic syndrome criteria, excluding the abdominal obesity criterion. Results The percentages of metabolically healthy normal-weight (MHNW), metabolically healthy overweight (MHOW), MHO, and MUO in our cohort were 30.8% (63,408 of 205,745), 5.8% (12,002 of 205,745), 4.1% (8329 of 205,745), and 20.7% (42,564 of 205,745), respectively. During a mean follow-up of 6 (range, 0.5-19) years, among 63,408 MHNW participants, 1890 (3.0%) and 1174 (1.9%) developed MUO and MHO, respectively. Among 12,002 MHOW participants, 3404 (28.4%) developed MUO and 2734 (22.8%) developed MHO. A total of 5506 of 8329 (66.1%) participants moved from MHO to MUO, and 5675 of 42,564 (13.3%) moved from MUO to MHO. Compared with being inactive, MHNW individuals who were active or high active showed lower risk for MUO. Among those with MHOW, being high active was associated with reduced risk for MUO and MHO. Although among MHO participants, PA was not associated with incident MUO, being active or high active was linked to a greater likelihood of moving from MUO to MHO. Conclusion PA may prevent the development of both MHO and MUO. PA also helps increase the transition from MUO to MHO, which may contribute to reduce the subsequent development of type 2 diabetes mellitus and major cardiovascular disease complications.

In the past five decades, cardiorespiratory fitness (CRF) has become fairly established as an important risk factor or marker for cardiovascular disease (CVD), as well as CVD - and all-cause mortality. Substantial evidence supports a strong inverse association between baseline levels of CRF and the risk of developing CVD risk factors, including dyslipidemia. Additionally, accumulating evidence also supports that maintaining or improving a certain level of CRF over time leads to a lower rate of developing CVD risk factors, such as dyslipidemia, and also improves survival. Recent evidence also supports the role of resistance exercise and muscular strength to reduce the development of metabolic syndrome and hypercholesterolemia and potentially reduce development of diabetes as well, in addition to improving survival. Therefore, great efforts are needed to increase both CRF and muscle strength with aerobic exercise and resistance exercise in the primary and secondary prevention of CVD.

Physical inactivity and psychosocial stress are prevalent in residents of the United States. The purpose of this article is to review the interaction between these 2 conditions and examine the effects of exercise on stress and cardiovascular (CV) health. A query of scientific references between 1974 to 2018 was performed using the PubMed search engine accessing the MEDLINE database using the search terms psychosocial stress, CV disease (CVD), physical activity, exercise, cardiac rehabilitation, and team sports. Psychosocial stress is a strong independent risk factor for adverse CV events. Conversely, people who experience CV events subsequently have drastically elevated rates of new-onset mental health disorders, including depression and anxiety. Psychosocial stress and CVD often trigger self-reinforcing feedback loops that can worsen mental health and cardiac prognosis. Exercise predictably improves CV health and prognosis and also is effective at lowering levels of psychosocial stress. Group exercise in particular seems to provide social support while at the same time boosting fitness levels and, thus, may be the single most important intervention for patients with concomitant CVD and emotional stress. Collaborative physical activity, such as group exercise, team sports, interactive physical play, and cardiac rehabilitation programs, have the potential to improve mental health and CV prognosis.

Obesity is associated with increased prevalence of cardiovascular (CV) disease (CVD) risk factors, which may adversely impact CV structure and function and may increase the prevalence of most CVD, particularly heart failure (HF) and coronary heart disease (CHD). Physical activity (PA), exercise training (ET) and cardiorespiratory fitness (CRF) are all associated with marked reductions in most CVD, including HF and CHD. Additionally, PA/ET and, especially CRF, markedly alter the relationship between adiposity and subsequent major CVD outcomes and dramatically impact the "obesity paradox," which are all reviewed, including attention to the debate regarding "fitness versus fatness" for long-term prognosis, including in patients with established CVD.

The epidemic of obesity contributes to the burden of type 2 diabetes mellitus (T2DM) in the United States and worldwide. Importantly, obesity is not only preventable but can be treated, particularly with lifestyle modifications to forestall T2DM in those with excess adiposity. The mechanisms linking obesity to T2DM are numerous and involve adipose tissue remodeling as a result of unhealthy behaviors, including unhealthy diet, reduced physical activity (PA) and exercise training (ET), and increased sedentary behaviors. Taken together, these factors markedly reduce cardiorespiratory fitness (CRF), one of the strongest predictors for cardiovascular outcomes and all-cause mortality in the general population, but also in those with T2DM. In this review we describe the mechanisms leading to adipose tissue remodeling resulting in obesity, as well as the mechanisms linking excess adiposity to insulin resistance and, in turn, T2DM. We then present the therapeutic strategies that can be implemented in obesity to prevent T2DM, with a brief discussion on weight loss, and greater emphasis on PA and ET. We finally present the evidence to support the beneficial effects of such strategies in patients with established T2DM and discuss the importance of achieving improvements in CRF in this population to potentially improve clinical outcomes.

Diabetes causes cardiomyopathy and increases the risk of heart failure independent of hypertension and coronary heart disease. This condition called "Diabetic Cardiomyopathy" (DCM) is becoming a well- known clinical entity. Recently, there has been substantial research exploring its molecular mechanisms, structural and functional changes, and possible development of therapeutic approaches for the prevention and treatment of DCM. This review summarizes the recent advancements to better understand fundamental molecular abnormalities that promote this cardiomyopathy and novel therapies for future research. Additionally, different diagnostic modalities, up to date screening tests to guide clinicians with early diagnosis and available current treatment options has been outlined.

Type 2 Diabetes (T2D) is a growing public health threat that is evolving into a global pandemic with debilitating, expensive and often lethal complications. Even when hemoglobin A1c (HbA1C) levels are well controlled, and concomitant cardiovascular (CV) risk factors are effectively treated, two out of every three patients with T2D are destined to die from CV complications. Several large randomized controlled trials (RCT) indicate that two classes of glucose-lowering medications, oral sodium-glucose cotransporter type 2 inhibitors (SGLT2-i) and injectable glucagon-like peptide-1 receptor agonists (GLP-1RA), confer significant CV benefits, including reductions in: hospitalizations for heart failure (HF), progression of diabetic kidney disease, atherosclerotic CV events, and (with some agents) CV death. These CV benefits appear to be independent of the glucose-lowering effects of these agents. These compelling findings are triggering a fundamental paradigm shift in T2D management whereby the focus is no longer on HbA1c alone, but instead on implementing a comprehensive CV risk reduction strategy prioritizing the use of these evidence-based therapies (along with other evidence-based treatment strategies) with the objective of reducing the risk of morbid complications, and improving the quantity and quality of life of patients with T2D. Cardiologists are uniquely positioned to become more involved in the management of T2D and established CV disease, which at this time should include initiation (either by prescribing or by making recommendations) of agents proven to reduce CV risk. Specifically, SGLT2-is and/or GLP-1RA have now been shown to have a favorable risk-benefit balance, and are being increasingly emphasized by the practice guidelines as preferable treatment options in vulnerable patients with T2D. The cardiology community should collaborate with other care providers to ensure that when and where appropriate these new T2D therapies are used along with other evidence-based therapies to improve patient outcomes.

Exercise intolerance is the cardinal symptom of heart failure (HF) and is of crucial relevance, because it is associated with a poor quality of life and increased mortality. While impaired cardiac reserve is considered to be central in HF, reduced exercise and functional capacity are the result of key patient characteristics and multisystem dysfunction, including aging, impaired pulmonary reserve, as well as peripheral and respiratory skeletal muscle dysfunction. We herein review the different modalities to quantify exercise intolerance, the pathophysiology of HF, and comorbid conditions as they lead to reductions in exercise and functional capacity, highlighting the fact that distinct causes may coexist and variably contribute to exercise intolerance in patients with HF.

Obesity is associated with an increased risk of developing cardiovascular disease (CVD), particularly heart failure (HF) and coronary heart disease (CHD). The mechanisms through which obesity increases CVD risk involve changes in body composition that can affect hemodynamics and alters heart structure. Pro-inflammatory cytokines produced by the adipose tissue itself which can induce cardiac dysfunction and can promote the formation of atherosclerotic plaques. When obesity and HF or CHD coexist, individuals with class I obesity present a more favorable prognosis compared to individuals who are normal or underweight. This phenomenon has been termed the "obesity paradox." Obesity is defined as an excess fat mass (FM), but individuals with obesity typically also present with an increased amount of lean mass (LM). The increase in LM may explain part of the obesity paradox as it is associated with improved cardiorespiratory fitness (CRF), a major determinant of clinical outcomes in the general population, but particularly in those with CVD, including HF. While increased LM is a stronger prognosticator in HF compared to FM, in patients with CHD excess FM can exert protective effects particularly when not associated with increased systemic inflammation. In the present review, we discuss the mechanisms through which obesity may increase the risk for CVD, and how it may exert protective effects in the setting of established CVD, with a focus on body composition. We also highlight the importance of measuring or estimating CRF, including body composition-adjusted measures of CRF (ie, lean peak oxygen consumption) for an improved risk status stratification in patients with CVD and finally, we discuss the potential non-pharmacologic therapeutics, such as exercise training and dietary interventions, aimed at improving CRF and perhaps clinical outcomes.

To summarize current non-exercise prediction models to estimate cardiorespiratory fitness (CRF), cross-validate these models, and apply them to predict health outcomes. PubMed search was up to August 2018 for eligible publications. The current review was comprised of three steps. The first step was to search the literature on non-exercise prediction models. The key words combined non-exercise, CRF and one among prediction, prediction model, equation, prediction equation and measurement. The second step was to search the literature about cross-validation of non-exercise equations. The key words included non-exercise, CRF and one among validation, cross-validation and validity. The last step was to search for application of CRF assessed from non-exercise equations. The key words were non-exercise, CRF, mortality, all-cause mortality, cardiovascular disease (CVD) mortality and cancer mortality. Sixty non-exercise equations were identified. Age, gender, percent body fat, body mass index, weight, height and physical activity status were commonly used in the equations. Several researchers cross-validated non-exercise equations and proved their validity. In addition, non-exercise estimated CRF was significantly associated with all-cause mortality and fatal and nonfatal CVD. Measurement of CRF from non-exercise models is practical and viable when exercise testing is not feasible. Despite the limitations of equations, application of CRF from non-exercise methods showed accuracy and predictive ability.

Obesity has been linked with increased incidence of atrial fibrillation (AF), but impact of presence of obesity on outcomes of hospitalizations for AF has not been investigated. We used the National Inpatient Sample database 2010 to 2014 to identify all adult hospitalizations aged >= 18 years with a primary diagnosis of AF. Obese patients were identified using the co-morbidity variable for obesity, as defined in National Inpatient Sample databases. Multivariable logistic regression was used to compare in-hospital outcomes (mortality, acute stroke events) between obese and non-obese patients with AF. Of 431, 734 hospitalizations for AF, 66,138 (15.3%) were obese. Obese patients were younger and more likely to be African-Americans compared with non-obese patients. Despite being younger, obese patients had significantly higher prevalence of cardiovascular co-morbidities such - as hypertension, diabetes mellitus, dyslipidemia, smoking, heart failure, and chronic renal failure (p

Background and purpose: Although several studies have assessed the importance of traditional risk factors in predicting stroke, none have concurrently addressed the stroke-predicting ability of these risk factors across the lifespan of subjects without a hypertension (HTN) diagnosis. Thus, this study aimed to assess the importance of blood-pressure-related risk indicators, cardiorespiratory fitness (CRF), weight status, diabetes mellitus (DM), and lifestyle factors as predictors of stroke in different stages of life among non-hypertensive subjects.Materials and methods: This study was a long-term follow-up study including 33,254 men and 10,598 women from the Aerobics Center Longitudinal Study (ACLS) who were 18-100 years old and did not have a HTN diagnosis at baseline. Logistic regression models were constructed using forward selection procedures for each age category, with stroke occurrence as the dependent variable, and pulse pressure (PP), mean arterial pressure (MAP), systolic blood pressure (SBP), smoking status, CRF, drinking behavior, DM status, and weight status as potential predictors.Results: In total, 507 subjects had a stroke during an average follow-up period of 17 years (range= 1-34 years). Logistic regression models showed that MAP values (P=0.043) in those aged 19-39 years; SBP (P < 0.001), CRF (P=0.001), weight status (P=0.005), and alcohol consumption (P=0.001) in those 40-60 years old; and CRF (P=0.002), weight status (P=0.005), and DM status (P=0.037) in those over 60 years old were predictors of stroke.Conclusion: These findings suggest that, among individuals without a baseline HTN diagnosis, classic modifiable risk factors for stroke change across different stages of life.

Obesity is associated with several cardiac structural, functional, hemodynamic, and neurohormonal changes, resulting in increased risk for cardiovascular diseases (CVDs). Particularly, obesity is associated with greater risk for heart failure, hypertension, coronary heart disease, atrial fibrillation, and more recently, pulmonary arterial hypertension. Once such diseases have been diagnosed, however, patients with obesity present a more favorable prognosis compared to leaner patients. Such a phenomenon has been defined as “the obesity paradox.” The mechanisms leading to improved outcomes in obese patients are still largely unknown; however, most of the studies investigating the role of obesity on the development and progression of CVD were limited by the use of the body mass index, which does not distinguish between different body composition (BC) compartments, which have distinctive effects on the CV system. In this review, we will discuss the increased risk of CVD in patients with obesity and the mechanisms through which obesity and particularly BC compartments (e.g., skeletal muscle mass) may confer protection once CVDs have been diagnosed. We will then review the impact of cardiorespiratory fitness in modulating the effects of obesity in patients with CVD and the role of unintentional and intentional weight loss in such conditions. Finally, we will discuss the potential beneficial effects of therapeutics targeting BC compartments in determining prognosis in patients with established CVD.

Inflammation has proven in multiple studies to be responsible for the progression of cardiometabolic diseases and malignancies. The interleukin family has been critically associated with progression of atherosclerosis, insulin resistance, and various malignancies. Given the advent of pharmacologic interleukin-1 (IL-1) inhibition, this pathway can potentially be targeted to improve outcomes. In the recently concluded Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) trial, investigators looked at the potential role of IL-1 (especially IL-1β) inhibition in halting the progression of atherosclerosis. In the subset analysis of the data from this trial, IL-1β inhibition with canakinumab was found to have beneficial effects in other cardiometabolic diseases characterized by inflammation, like diabetes, stroke, and chronic kidney disease, and also in patients with lung cancer. In this article, we will try to review the current literature on the role of canakinumab in the treatment of cardiometabolic diseases and malignancies.

Sedentary behavior and physical inactivity are among the leading modifiable risk factors worldwide for cardiovascular disease and all-cause mortality. The promotion of physical activity and exercise training (ET) leading to improved levels of cardiorespiratory fitness is needed in all age groups, race, and ethnicities and both sexes to prevent many chronic diseases, especially cardiovascular disease. In this state-of-the-art review, we discuss the negative impact of sedentary behavior and physical inactivity, as well as the beneficial effects of physical activity /ET and cardiorespiratory fitness for the prevention of chronic noncommunicable diseases, including cardiovascular disease. We review the prognostic utility of cardiorespiratory fitness compared with obesity and the metabolic syndrome, as well as the increase of physical activity /ET for patients with heart failure as a therapeutic strategy, and ET dosing. Greater efforts at preventing sedentary behavior and physical inactivity while promoting physical activity, ET, and cardiorespiratory fitness are needed throughout the healthcare system worldwide and particularly in the United States in which the burden of cardiometabolic diseases remains extremely high.

PURPOSE: Resistance exercise (RE) can improve many cardiovascular disease (CVD) risk factors, but specific data on the effects on CVD events and mortality are lacking. We investigated the associations of RE with CVD and all-cause mortality, and further examined the mediation effect of body mass index between RE and CVD outcomes. METHODS: We included 12,591 participants (mean age 47 years) who received at least two clinical examinations 1987–2006. RE was assessed by a self-reported medical history questionnaire. RESULTS: During a mean follow-up of 5.4 and 10.5 years, 205 total CVD events (morbidity and mortality combined) and 276 all-cause deaths occurred, respectively. Compared with no RE, weekly RE frequencies of one, two, three times or total amount of 1–59 minutes were associated with approximately 40–70% decreased risk of total CVD events, independent of aerobic exercise (AE) (all p-values

Key Points The validity and reliability of existing and/or underdevelopment fitness apps should be further investigated. Physiological signals should be incorporated into fitness apps, such as heart rate measures using a smartphone camera, during or after exercise testing. There is a need to develop interoperable fitness apps (e.g., different languages, apps integrated into both app markets, data that is device-independent). Fitness apps should incorporate evidence-based cutpoints of CRF, allowing interpretation of fitness testing results, We are grateful to Ms Carmen Sainz-Quinn for assistance with the English language., Background Cardiorespiratory fitness (CRF) assessment provides key information regarding general health status that has high clinical utility. In addition, in the sports setting, CRF testing is needed to establish a baseline level, prescribe an individualized training program and monitor improvement in athletic performance. As such, the assessment of CRF has both clinical and sports utility. Technological advancements have led to increased digitization within healthcare and athletics. Nevertheless, further investigation is needed to enhance the validity and reliability of existing fitness apps for CRF assessment in both contexts. Objectives The present review aimed to (1) systematically review the scientific literature, examining the validity and reliability of apps designed for CRF assessment; and (2) systematically review and qualitatively score available fitness apps in the two main app markets. Lastly, this systematic review outlines evidence-based practical recommendations for developing future apps that measure CRF. Data Sources The following sources were searched for relevant studies: PubMed, Web of Science®, ScopusTM, and SPORTDiscus, and data was also found within app markets (Google Play and the App Store). Study Eligibility Criteria Eligible scientific studies examined the validity and/or reliability of apps for assessing CRF through a field-based fitness test. Criteria for the app markets involved apps that estimated CRF. Study Appraisal and Synthesis Methods The scientific literature search included four major electronic databases and the timeframe was set between 01 January 2000 and 31 October 2018. A total of 2796 articles were identified using a set of fitness-related terms, of which five articles were finally selected and included in this review. The app market search was undertaken by introducing keywords into the search engine of each app market without specified search categories. A total of 691 apps were identified using a set of fitness-related terms, of which 88 apps were finally included in the quantitative and qualitative synthesis. Results Five studies focused on the scientific validity of fitness tests with apps, while only two of these focused on reliability. Four studies used a sub-maximal fitness test via apps. Out of the scientific apps reviewed, the SA-6MWTapp showed the best validity against a criterion measure (r = 0.88), whilst the InterWalk app showed the highest test–retest reliability (ICC range 0.85–0.86). Limitations Levels of evidence based on scientific validity/reliability of apps and on commercial apps could not be robustly determined due to the limited number of studies identified in the literature and the low-to-moderate quality of commercial apps. Conclusions The results from this scientific review showed that few apps have been empirically tested, and among those that have, not all were valid or reliable. In addition, commercial apps were of low-to-moderate quality, suggesting that their potential for assessing CRF has yet to be realized. Lastly, this manuscript has identified evidence-based practical recommendations that apps might potentially offer to objectively and remotely assess CRF as a complementary tool to traditional methods in the clinical and sports settings.

Substantial evidence shows that physical inactivity (PI) and sedentary behavior (SB) increases the risk of many chronic diseases and shortens life expectancy. We describe evidence that certain domains of physical activity (PA) in the United States (US) population have declined substantially over 5 decades. The prevalence of PI is very high worldwide, which has contributed to 6%-10% of the burden of many chronic diseases and premature mortality. Reduction or elimination of PI would likely produce substantial increases in life expectancy of the world's population. Great efforts are needed to reduce PI and SB and increase levels of PA in the US and worldwide.

To investigate the association between cardiorespiratory fitness and risk of cardiovascular disease, cancer, and all-cause mortality in men with musculoskeletal conditions.Participants were 12,728 men (mean age 47.0 [9.3] y) with a history of musculoskeletal conditions (including joint pain, low back pain, stiff joints, arthritis, osteoporosis, or gout) and were followed for all-cause mortality to December 31, 2003. Fitness was quantified by maximal treadmill exercise test and was categorized for analysis as low, moderate, and high performance. Cox proportional hazards regression was used to calculate hazard ratios and 95% confidence intervals.Overall, the multivariable-adjusted hazard ratios and 95% confidence intervals for mortality across incremental fitness categories were 1.00 (reference), 0.45 (0.30-0.68) and 0.35 (0.22-0.53), linear trend P .01 for all-cause, 0.50 (0.23-1.10) and 0.29 (0.12-0.71), linear trend P = .02 for cardiovascular disease, and 0.38 (0.20-0.74) and 0.40 (0.20-0.80), linear trend P = .01 for cancer mortality.Among men with musculoskeletal conditions, higher fitness is associated with lower risk of death by cardiovascular disease, cancer, or any cause, independent of other risk factors.

Purpose: Cardiac rehabilitation (CR) is associated with significant reductions in mortality and morbidity, but few women are included in trials. Therefore, a meta-Analysis of the effects of CR in women is warranted. Methods: Randomized controlled trials from recent systematic reviews that included women attending comprehensive CR and reporting the outcomes of mortality and morbidity (hospitalization, myocardial infarction, bypass surgery, percutaneous coronary intervention) were considered for inclusion. An updated search of the literature was performed from the end date of the last search, based on the Cochrane strategy. Authors were contacted to provide results on women where none were reported. Results: On the basis of 2 recent systematic reviews, 80 trials were identified. Fifty (62.5%) were excluded, most commonly due to lack of inclusion of women (n = 18; 22.5%). One trial was identified through the search update. Of 31 potential trials meeting inclusion criteria, 1 reported results on women and many were old, and hence data by sex were no longer available. Ultimately, data for women were available in 2 trials. Therefore, it was deemed inappropriate to undertake this meta-Analysis. Conclusions: This review corroborates the dearth of data on CR in women despite the fact that cardiovascular disease is the leading cause of death in women. Given the totality of evidence, including reductions in mortality and morbidity in nonrandomized studies, and evidence of benefit for other important outcomes such as functional capacity and quality of life, women should continue to be referred to CR.

Cardiovascular disease is a leading cause of morbidity, mortality and financial burden to the United States health system. A change in focus towards preventive medicine along with advances in pharmacologic and invasive therapies, has led to improved cardiac death rates. These benefits however, come with increased prevalence of heart failure and soaring readmission rates. Reducing burden of hospitalizations has therefore, been a focus of clinicians and researchers over the years. An improvement in clinical outcomes has been demonstrated in multiple trials investigating HF therapies, however, execution of guideline recommendations has been trailing. Over the past decade, 2 classes of hypoglycemic agents, the glucagon-like peptide-1 (GLP-1) receptor agonists and the sodium-glucose cotransporter 2 (SGLT-2) inhibitors have been recognized for their cardiovascular morbidity and mortality benefits. Studies have shown that there has been a steady increase in prescription rates of these medications, however, overall usage remains quite low. Various patient, physician and system-based factors have been identified that cause barriers to translation of trial data to real-world clinical outcomes. A strategy focused on physician and patient education, quality improvement, multi-disciplinary team approach, and patient centered care is essential to meet treatment goals.

Objective To evaluate the differential improvements in life expectancy associated with participation in various sports. Patients and Methods The Copenhagen City Heart Study (CCHS) is a prospective population study that included detailed questionnaires regarding participation in different types of sports and leisure-time physical activity. The 8577 participants were followed for up to 25 years for all-cause mortality from their examination between October 10, 1991, and September 16, 1994, until March 22, 2017. Relative risks were calculated using Cox proportional hazards models with full adjustment for confounding variables. Results Multivariable-adjusted life expectancy gains compared with the sedentary group for different sports were as follows: tennis, 9.7 years; badminton, 6.2 years; soccer, 4.7 years; cycling, 3.7 years; swimming, 3.4 years; jogging, 3.2 years; calisthenics, 3.1 years; and health club activities, 1.5 years. Conclusion Various sports are associated with markedly different improvements in life expectancy. Because this is an observational study, it remains uncertain whether this relationship is causal. Interestingly, the leisure-time sports that inherently involve more social interaction were associated with the best longevity—a finding that warrants further investigation.

Physical inactivity is one of the leading modifiable risk factors for global mortality, with an estimated 20% to 30% increased risk of death compared with those who are physically active. The “behavior” of physical activity (PA) is multifactorial, including social, environmental, psychological, and genetic factors. Abundant scientific evidence has demonstrated that physically active people of all age groups and ethnicities have higher levels of cardiorespiratory fitness, health, and wellness, and a lower risk for developing several chronic medical illnesses, including cardiovascular disease, compared with those who are physically inactive. Although more intense and longer durations of PA correlate directly with improved outcomes, even small amounts of PA provide protective health benefits. In this state-of-the-art review, the authors focus on “healthy PA” with the emphasis on the pathophysiological effects of physical inactivity and PA on the cardiovascular system, mechanistic/triggering factors, the role of preventive actions through personal, education/environment, and societal/authoritative factors, as well as factors to provide guidance for caregivers of health promotion regarding PA. Sustainable and comprehensive programs to increase PA among all individuals need to be developed and implemented at local, regional, national, and international levels to effect positive changes and improve global health, especially the reduction of cardiovascular disease.

Heart failure with preserved ejection fraction (HFpEF) is common, increasing in prevalence, and refractory to available pharmacotherapies. Our understanding of HFpEF has evolved from a disorder of diastolic dysfunction to a constellation of physiologic impairments that lead to elevated left ventricular filling pressures and exercise intolerance. Accordingly, the therapeutic and preventive focus has shifted to identifying lifestyle factors that may have more pleotropic effects on the pathophysiologic mechanisms that define HFpEF. Recent studies have demonstrated that physical inactivity, low fitness, and obesity are potential modifiable targets for prevention as well as management of HFpEF. In this review, we have discussed the emerging epidemiological, mechanistic, and clinical evidence that support the role of these lifestyle factors as key determinants of development and progression of HFpEF. We also summarize the available evidence and major knowledge gaps with regard to developing exercise training and weight loss as unique and effective therapeutic strategies for management of HFpEF.

There is an escalating debate over the value and validity of self-reported dietary intake as estimated by Food Frequency Questionnaires and other forms of memory-based dietary assessment methods. Proponents argue that despite limitations, memory-based methods provide valid and valuable information about consumed foods and beverages and therefore can be used to assess diet-disease relations. In fact, over the past 60 years, thousands of memory-based dietary research reports were used to inform public policy and establish the Dietary Guidelines for Americans. Yet, despite this impressive history, our position is that memory-based dietary assessment methods are invalid and inadmissible for scientific research and therefore cannot be used in evidence-based policy making. Herein, we present the empirical evidence and theoretic and philosophic perspectives that render data derived from memory-based methods both fatally flawed and pseudoscientific. First, the use of memory-based methods is founded upon two inter-related logical fallacies: a category error and reification. Second, human memory and recall are not valid instruments for scientific data collection. Third, in standard epidemiologic contexts, the measurement errors associated with self-reported data are nonfalsifiable because there is no way to ascertain if the reported foods and beverages match the respondent's actual consumption. Fourth, the assignment of nutrient and energy values to self-reported intake (i.e., the pseudoquantification of anecdotal data) is impermissible and violates the foundational tenets of measurement theory. Fifth, the proxy estimates created via pseudoquantification are often physiologically implausible and have little relation to actual nutrient and energy consumption. Finally, investigators engendered a fictional discourse on the health effects of dietary sugar, salt, fat and cholesterol when they failed to cite contrary evidence or address decades of research demonstrating the fatal measurement, analytic, and inferential flaws of memory-based dietary assessment methods.