Longevity is a relevant cardiovascular (CV) endpoint because survival integrates incident CV disease (CVD), competing non-CVD risks, and the physiological reserve that determines resilience to aging and chronic illness. Two related constructs, physical activity (PA; a modifiable behavior) and cardiorespiratory fitness (CRF; an integrative phenotype reflecting habitual PA, genetics, cardiopulmonary function, skeletal muscle oxidative capacity, and comorbidity), are consistently associated with lower all-cause and CVD mortality across diverse populations. In this invited narrative review, we synthesize evidence linking PA and CRF to longevity, highlight the dose-response nature of benefits and the importance of activity domain and intensity, and explain why CRF generally outperforms self-reported PA for risk prediction. We address challenges in causal inference, residual confounding variables, reverse causation, and selection/measurement bias, and emphasize approaches that strengthen inference, including device-based PA assessment (e.g., accelerometry), repeated measures, and triangulation with mechanistic and trial evidence. Mechanistic pathways plausibly linking PA and CRF to survival include favorable effects on blood pressure, glycemia and insulin sensitivity, adiposity and body composition, vascular reactivity, autonomic balance, inflammation and immune function, thrombosis, and preservation of skeletal muscle and mitochondrial reserve. We review evidence in particularly relevant subgroups and discuss the "extreme exercise hypothesis", distinguishing mortality from risks, such as atrial fibrillation and accelerated coronary calcification, in endurance athletes. We conclude with practical actions for clinicians and health systems, such as prescribing activities based on the frequency, intensity, time, and type (FITT) principles, incorporating resistance training, treating CRF as a vital sign, and addressing common implementation barriers.

To evaluate the effects of aerobic exercise (AE) versus resistance training (RT) on cardiometabolic health-related outcomes in patients with type 2 diabetes mellitus and concurrent obesity (diabesity). Systematic review and meta-analysis of randomized controlled trials (RCTs). PubMed, Web of Science, Scopus, ScienceDirect, Cochrane Library, and Google Scholar databases were searched from inception up to April 2026. RCTs comparing AE and RT for a minimum duration of two weeks. Participants were adults with diabesity. A total of 23 RCTs qualified, involving 1, 184 patients (58/42 women/men ratio; age range: 30-70 years; body mass index: 32.1 ± 6.6 kg/m2). AE appears to be more efficacious than RT in reducing fasting blood glucose (mean differences (MD) = -0.89 mmol/L, 95% CI: -1.62 to -0.16; I2 = 0%) and increasing cardiorespiratory fitness (MD = 1.78 mL/kg/min, 95% CI: 0.38 to 3.18; I2 = 66%). However, AE led to a greater increase in body fat (MD = 0.34%, 95% CI: 0.10 to 0.57; I2 = 1%) and less fat-free mass retention (MD = -0.86 kg, 95% CI: -1.46 to -0.26; I2 = 37%) compared with RT. For selected cardiometabolic health-related outcomes, including anthropometrics, blood lipids, and hemodynamics, no statistically significant between-group difference was detected. The overall certainty of the evidence across outcomes ranged from high to very low, with most being moderate. In adults with diabesity, AE appears to provide greater benefits for FBG and CRF, whereas RT appears more favorable for preserving FFM and improving BF. For the majority of cardiometabolic outcomes, the two modalities exhibit analogous effects. The present findings support a goal-directed and complementary approach to exercise prescription, as opposed to a one-modality-fits-all model, for the improvement of cardiometabolic health in patients with diabesity.

Purpose: The exercise heart rate (HR)/oxygen uptake (VO2) relationship, expressed as beats/metabolic equivalent (MET), represents chronotropic efficiency (CE), a widely cited “normal value” ~10 beats/MET. This analysis examined the range of beats/MET values observed at peak oxygen uptake (VO2peak) in patients with and without heart failure and the impact of superimposed atrial fibrillation (AF) versus sinus rhythm (SR). Methods: From Medline and Google Scholar searches, a database of 100 studies for SR and 46 for AF was identified. Study requirements included: 1. HRrest, 2. HRpeak and 3. Measured peak oxygen uptake i.e. VO2peak. From these data, the following were determined: (a) HR reserve (HRR) [HRpeak – HRrest], (b) For VO2peak, beats/MET equalled HRR/(peak METs -1) and (c) HR index (HRI) [HRpeak/HRrest]. Results: VO2peak, expressed as METs, was grouped from <4 METs to a maximum of >14 METs. For SR, beats/MET ranged from 14.9 ± 3.8 for VO2peak <4 METs to 8.9 ± 0.8 for VO2peak > 14 METs. For AF, beats/MET ranged from 20.5 ± 5.9 for VO2peak<4 METs to 15.1 ± 2.0 for a VO2peak range of 6.0–7.9 METs. For comparable MET ranges, beats/MET were 21% to 38% higher for AF than SR. Conclusions: These unique findings establish a range of beats/MET, reflecting the considerable variability in CE in health and disease for VO2peak. The most compromised group was AF with heart failure, >20 beats/MET, compared with <9 beats/MET for elite endurance athletes. Future studies are needed to clarify the potential clinical utility and/or prognostic significance of this metric.

INTRODUCTION:Coronary collaterals are vascular connections that bridge epicardial arteries and supply blood to the oxygen-deprived myocardium in patients with coronary artery disease (CAD). This comprehensive review aimed to identify and evaluate potential interventions that may enhance the growth of coronary collateral vessels. METHODS:We conducted a scoping review of five databases to identify relevant studies that focused on interventions that may promote coronary collateral circulation in patients with CAD. RESULTS:Our search identified 23 studies that met our inclusion criteria. Studies (n = 7) using pharmacologic agents (i.e., angiotensin-converting enzyme inhibitors, granulocyte macrophage colony stimulating factor, statins, human recombinant basic fibroblast growth factor, and granulocyte macrophage colony stimulating factor) were found to improve collateralization, as did the non-pharmacologic studies (n = 13) (i.e., exercise training, electrical stimulation, and enhanced external counterpulsation), which formed most of the studies. Three studies found benefits of a combination of exercise and heparin. Improvements were seen in collateralization as measured by the coronary flow index and Rentrop scores across all interventions. Effect sizes from randomized trials with pharmacologic, non-pharmacologic, and exercise-based interventions ranged between 0.4 and 0.7. CONCLUSION:This review provides a comprehensive overview and update of the existing literature on interventions that may promote coronary collateralization (CC). In summary, we observed a few pharmacological and non-pharmacological (exercise, electrical stimulation, and enhanced external counterpulsation) interventions that have shown a positive effect on CC. These data provide a framework for more robust trials regarding the proliferation and clinical significance of enhanced CC in cardiovascular outcomes in patients with known or occult CAD.

In the United States, the prevalence of high cholesterol, hypertension, and cigarette smoking together with ageadjusted cardiovascular deaths has declined over the last several decades. On the other hand, the prevalence of diabetes has risen steadily, largely because of an epidemic of obesity and adiposity and our increasingly inactive lifestyle (see also Chapters 1 and 5). These trends will likely mitigate further reductions in cardiovascular mortality and even reverse the decline in cardiovascular disease (CVD) incidence. Using 2010 as the baseline, the estimated direct and indirect costs of CVD are expected to triple by the year 2030, making this a critical medical and societal issue. These sobering projections and other recent data suggest that effective preventive strategies are needed if we are to limit the growing burden of CVD (see also Chapters 5 and 6). The current reactive-based health care model, in which patients are seen when they become ill, typically during outpatient visits or hospitalizations, often fails to proactively improve health, because so many health outcomes are explained by individual behaviors and the lifestyle choices people make on a daily basis. Unfortunately, many patients as well as individuals in the medical community continue to rely on costly coronary revascularization procedures and/or cardioprotective medications as a first-line strategy to stabilize or favorably modify established risk factors and the course of coronary heart disease (CHD). However, these therapies do not address the root of the problem, that is, the most proximal risk factors for CHD, including poor dietary practices, physical inactivity, and cigarette smoking, as shown in Figure 12-1. Unhealthy lifestyle habits strongly influence not only conventional risk factors (e.g., blood pressure, lipid and lipoprotein levels, glucose-insulin homeostasis) but also novel or emerging risk factors such as endothelial function, inflammation (e.g., C-reactive protein), thrombosis and coagulation, arrhythmias, and other disease modulators (e.g., psychosocial stressors), even among users of lipid-lowering and antihypertensive medications. Collectively, these data suggest it is time to change our emphasis from disease management to disease prevention, focusing on the foundational causes of CVD by reengineering prevention into the U.S. health care system. This chapter emphasizes the role of lifestyle interventions in the prevention and treatment of CVD in patients with diabetes, with specific reference to weight management and energy balance, dietary intake and cardiometabolic risk, smoking cessation, exercise and physical activity, cardiorespiratory fitness, and research-based psychosocial

Purpose: Heart rate (HR)-derived variables (HR reserve [HRpeak - HRrest], chronotropic indices [attenuated HR response to exercise], HR recovery [attenuated HR response to exercise recovery], and peak HR index [HRpeak/HRrest]) together with peak oxygen uptake (VO2peak) are potential prognostic variables for cardiovascular and all-cause mortality. However, heart rate index (HRI) has not been established as a surrogate for VO2peak, whether measured (Meas) or estimated (Est), during cycle ergometry (CE) and/or treadmill testing (TT). Methods: HR-derived prognostic variables to assess cardiovascular outcomes were identified from 150 studies obtained from MEDLINE and Google Scholar searches. The Meas CE/TT-VO2peak was reported in 81 studies (21 773 participants) and Est CE/TT-VO2peak in 69 studies (331 435 participants). Using the HRI equation with metabolic equivalent (METs) = 6 x HRI - 5 (where HRI = peak HR/resting HR), HRI-VO2peak was calculated from HR data reported in the 150 studies. The HRI-VO2peak was then compared against group mean data for both Meas CE/TT-VO2peak and Est CE/TT-VO2peak. Results: The difference between Meas CE/TT-VO2peak and HRI-VO2peak was 1% (7.15 +/- 3.25 METs vs 7.08 +/- 3.02 METs [P = .833], respectively). By comparison, the difference between Est CE/TT-VO2peak and HRI-VO2peak was 25.6% (8.94 +/- 2.36 METs vs 7.12 +/- 2.27 METs [P < .001], respectively). Moreover, HRI equation estimation of VO2peak showed greater overprediction for TT, 26.6%, than for CE, 11.9%. Conclusions: The Meas-VO2peak and HRI-VO2peak agreed closely. When compared with HRI-VO2peak, Est-VO2peak from currently used exercise-based equations shows significant overprediction. Use of HRI and/or Fitness Registry and the Importance of Exercise National Database (FRIEND) registry equations warrant consideration for more accurately estimating VO2peak.

PURPOSE:This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of aerobic exercise on cardiometabolic health-related indices in patients with type 2 diabetes and concurrent overweight/obesity (diabesity). METHODS:PubMed, Web of Science, Scopus, Science Direct, Cochrane Library, and Google Scholar databases were searched from inception to October 2024. The search strategy included the following keywords: diabetes, aerobic exercise, and endurance training. RCTs comparing aerobic exercise training ≥2 weeks in duration to standard treatment were considered eligible. Participants were adults with diabesity. RESULTS:A total of 1391 middle-aged/older adult patients (55 % females) were included in 34 RCTs. Body mass index [standardized mean differences (SMD) -0.18 kg/m2, 95 % confidence intervals (CI) -0.36 to -0.01]. waist circumference (SMD -0.23 cm, 95 % CI -0.44 to -0.03), body fat (SMD -0.30 %, 95 % CI -0.59 to -0.01), fasting blood glucose (SMD -0.49 mmol/L, 95 % CI -0.72 to -0.27), glycated hemoglobin (SMD -0.79 %, 95 % CI -1.17 to -0.41), fasting insulin (SMD -0.44 mIU/L, 95 % CI -0.72 to -0.15), homeostatic model assessment for insulin resistance (SMD -0.72, 95 % CI -1.09 to -0.35), high-density lipoprotein cholesterol (SMD 0.32 mg/dL, 95 % CI 0.01 to 0.63), triglycerides (SMD -0.33 mg/dL, 95 % CI -0.63 to -0.04), and total cholesterol (SMD -0.28 mg/dL, 95 % CI -0.47 to -0.10) improved compared with standard treatment. CONCLUSIONS:These results underscore the beneficial role of aerobic exercise as a non-pharmacological intervention in managing and treating patients with diabesity when compared to standard treatment, despite the presence of considerable uncertainty in several outcomes.

OBJECTIVE:To evaluate the effects of resistance training on cardiometabolic health-related outcomes in patients with type 2 diabetes mellitus (T2DM) and overweight/obesity. DESIGN:Systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES:PubMed, Web of Science, Scopus, Science Direct, Cochrane Library and Google Scholar databases were searched from inception up to May 2024. The search strategy included the following keywords: diabetes, resistance exercise and strength training. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:RCTs published in English comparing resistance training alone with non-exercising standard treatment. Participants were adults diagnosed with T2DM and concurrent overweight/obesity (body mass index (BMI) ≥25 kg/m2). RESULTS:A total of 18 RCTs qualified involving 1180 patients (48.6/51.4 female/male ratio; 63.3±7.0 years; 29.3±4.3 kg/m2). Waist circumference (standardised mean differences (SMD) -0.85 cm, 95% CI -1.66 to -0.04), waist-to-hip ratio (SMD -0.72, 95% CI -1.30 to -0.15), high-density lipoprotein cholesterol (SMD +0.40 mg/dL, 95% CI 0.07 to -0.72), triglycerides (SMD -0.54 mg/dL, 95% CI -1.06 to -0.02), fasting blood glucose (SMD -0.65 mmol/L, 95% CI -1.19 to -0.12), fasting insulin (SMD -0.74 uIU/mL, 95% CI -1.12 to -0.36) and glycated haemoglobin (SMD -0.32%, 95% CI -0.63 to -0.01) improved compared with standard treatment. The risk of bias was low to unclear, and the quality of evidence was very low to moderate. CONCLUSIONS:Resistance training as a standalone exercise intervention in the management and treatment of T2DM with concurrent overweight/obesity is associated with many cardiometabolic benefits when compared with standard treatment without exercise. PROSPERO REGISTRATION NUMBER:CRD42022355612.

Elmer, Steven J. PhD; Wedig, Isaac J. PhD; Lennox, Isaac M. MS; Franklin, Barry A. PhD Author Information

BACKGROUND AND AIMS:Sex differences have been suggested in the association between baseline physical activity (PA) and cardiovascular outcomes, with women potentially benefiting more. This study evaluated sex differences in survival benefits of changes in moderate-to-vigorous physical activity (MVPA) before and after acute coronary syndrome (ACS). METHODS:We analyzed 30,840 patients with an ACS diagnosis (mean age 60 years; men: 25,069, women: 5771) from the National Health Insurance Service. Changes in MVPA before and after ACS were self-reported and categorized as persistently inactive, MVPA initiation, MVPA cessation, or MVPA continuation. Outcomes included all-cause and cardiovascular disease (CVD) mortality. RESULTS:Over a median follow-up of 5.8 years, 1349 CVD deaths and 4379 all-cause deaths occurred. MVPA initiation was associated with reduced all-cause mortality in men (Hazard Ratio [HR] = 0.77, 95 % Confidence Interval [CI] 0.64-0.93) and women (HR = 0.57, 95 % CI 0.42-0.79). MVPA continuation was associated with reduced all-cause mortality in men and women: (HR = 0.74, 95 % CI 0.63-0.88) and (HR = 0.58, 95 % CI 0.44-0.77). For CVD mortality, MVPA initiation yielded HRs of 0.84 (95 % CI 0.59-1.19) in men and 0.53 (95 % CI 0.31-0.91) in women; MVPA continuation rendered HRs of 0.71 (95 % CI 0.51-0.99) in men and 0.46 (95 % CI 0.29-0.75) in women. Interaction analyses did not suggest significant sex differences in these associations. CONCLUSIONS:Initiating or continuing MVPA post-ACS diagnosis is associated with a lower risk of all-cause and CVD mortality, with comparable benefits in men and women; this challenging the notion that women derive greater PA-induced mortality reductions than their male counterparts.

Background: The cardioprotective benefits and prognostic significance of regular moderate-to-vigorous physical activity (PA), increased cardiorespiratory fitness (CRF), or both are often underappreciated by the medical community and the patients they serve. Individuals with low CRF are two to three times more likely to die prematurely from atherosclerotic cardiovascular disease (CVD), than their fitter counterparts when matched for risk factor profile or coronary artery calcium (CAC) score. Accordingly, part 1 of this 2-part review examines these relations and the potential underlying mechanisms of benefit (e.g., exercise preconditioning) on atherosclerotic CVD, with specific reference to gait speed and mortality, CRF and PA as separate risk factors, and the relation between CRF and/or PA on attenuating the adverse impact of an elevated CAC score, as well as potentially favorably modifying CAC morphology, and on incident atrial fibrillation, all-cause and cardiovascular mortality, and on sudden cardiac death (SCD). Summary: We explore the underappreciated cardioprotective effects of regular PA and CRF. Part 1 examines how CRF and PA reduce the risk of premature death from atherosclerotic CVD by investigating their roles as separate risk factors, the potential underlying mechanisms of benefit, and their impact on gait speed, mortality, and atrial fibrillation. The review also addresses how CRF and PA may mitigate the adverse impact of an elevated CAC score, potentially modifying CAC morphology, and reduce the risk of SCD. Key Messages: Regular PA and high CRF are essential for reducing the risk of premature death from CVD and mitigating the negative impact of elevated CAC scores. Additionally, they provide significant protection against SCD and atrial fibrillation, emphasizing their broad cardioprotective effects.

Apply It! • Emphasize the Prevalence of Chronic Conditions: 52% of U.S. adults suffer from at least one chronic condition, underscoring the widespread need for exercise intervention in managing these diseases. • Advocate for Structured Exercise Programs: Stress the importance of structured exercise programs in managing chronic diseases, citing well-documented physical and mental health benefits associated with regular physical activity. • Educate on Exercise Thresholds: Educate clients on the exercise thresholds recommended by the World Health Organization, emphasizing the need for at least 150 to 300 minutes of moderate-intensity physical activity per week, complemented by resistance training and a reduction in sedentary behaviors. • Tailor Programs to Individual Readiness: Assess clients' readiness to change unhealthy lifestyle habits using models like the Transtheoretical Stages of Change Model, and tailor exercise prescriptions and counseling accordingly to increase the likelihood of successful behavior change.

Purpose: Patient- and disease-specific data on cardiac rehabilitation (CR) participation and changes over time are limited. The objective of this study was to describe time trends in CR participation between 2013 and 2019 and provides insights into the utilization of CR components. Methods: Patients with cardiovascular disease (CVD) with an indication for CR were enrolled between 2013 and 2019. Dutch health insurance claims data were used to identify CR participation and its components. Results: In total, 106 212 patients with CVD were included of which 37% participated in CR. Participation significantly increased from 28% in 2013 to 41% in 2016 but remained unchanged thereafter. Participation was highest in the youngest age groups (<50 yrs 52%; 50-65 yrs 50%), men (48%), patients with ST-segment elevation myocardial infarction (73%), non–ST-segment elevation myocardial infarction (59%), and coronary artery bypass grafting (82%). In contrast, it was the lowest in the oldest age group (≥85 yrs 8%), women (30%), and in patients with heart failure (11%). Most participants in CR received referral plus an admission session (97%) and exercise training (82%), whereas complementary services related to dietary (14%) and mental health counseling (10%) had a low utilization. Conclusions: CR participation rates increased to 41% in 2016 but remained unchanged thereafter. Participation modulators included age, sex, CVD diagnosis, and undergoing a cardiothoracic procedure. Education and exercise sessions were frequently adopted, but dietary and mental health counseling had a low utilization rate. These findings suggest the need for reinvigorated referral and novel enrollment strategies in specific CVD subgroups to further promote CR participation and its associated underutilized adjunctive services.