Individuals affected by arterial hypertension should not be engaged in any exercise program in the case of: -

stage 2 arterial hypertension systolic blood pressure (SBP) ≥160 mmHg diastolic blood pressure (DBP) ≥ mmHg (22);

No contraindications for exercise prescription are present for individuals affected by dyslipidemia, overweight and obesity. However, caution during pre-exercise evaluation regarding underlying cardiovascular risk factors and other chronic conditions as: hypertension, diabetes, metabolic syndrome. In obese patients the presence of orthopedic and musculoskeletal conditions may require the need for low initial workload and use of arm or leg ergometry. Furthermore, in individuals taking lipid lowering drugs the presences of muscle weakness and myalgia should be detected and monitored during exercise training.

Diabetes mellitus is a chronic endocrine disorder characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both (26). There are two basic types of diabetes, insulin dependent (DM1) and non–insulin dependent (DM2). Symptoms of hyperglycemia include polyuria, polydipsia, weight loss, sometimes polyphagia and blurred vision. The presence of chronic hyperglycemia typical of diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels.

Individuals with severe diabetic retinopathy should avoid aerobic or resistance exercise of vigorous intensity. Hypoglycemia, blunted heart rate response and post- exercise hypotension are concerns in diabetic patients during exercise training. Pre-exercise optimal glycemia level should be 90–250 mg/dL and strict monitoring of glycemia level, heart rate and blood pressure during exercise may be necessary.

Clinical instability, decompensated Heart Failure (HF), worsening of exercise intolerance are conditions that exclude HF patients from exercise prescription (27). Stable and optimal guideline-directed medical therapy patients are eligible for exercise prescription based on recommendations of The American Heart Association (AHA) and American College of Cardiology (ACC) guidelines (28). Stable patients are defined as patients who have not undergone major unplanned cardiovascular hospitalization or procedures in the last 6 weeks, or planned hospitalizations and procedures during the last 6 months.

Post-operative exercise timing should be individualized based on surgical procedure, extent of resection, patient health status, and wound healing. The 2019 ACSM International Multidisciplinary Roundtable emphasizes that cancer survivors should avoid inactivity and return to normal daily activities as quickly as possible after surgery (29).

Surgery-specific timelines guide safe and effective exercise initiation:

Breast cancer surgery: Range of motion exercises begin 1–2 days post-surgery, with evidence from a 2024 JAMA Surgery RCT demonstrating that early exercise implementation significantly improves functional recovery without increasing adverse events. Full upper body exercise typically resumes at 4–6 weeks (30).

Colorectal cancer surgery: Enhanced Recovery After Surgery (ERAS) protocols emphasize enforced mobilization within 24 h post-surgery, with structured exercise programs initiated at 2–4 weeks and full programs at 4–6 weeks for laparoscopic procedures (31).

Lung cancer surgery: Pulmonary rehabilitation begins day of surgery (unless complications occur), with supervised programs continuing during hospitalization and transitioning to outpatient rehabilitation at 2–4 weeks. Recovery timelines vary by surgical approach (VATS vs. open thoracotomy) and extent of resection (32).

Prostate cancer surgery: Exercise begins immediately post-operatively, with progressive resistance training initiated at 2–4 weeks. Pelvic floor exercises start as soon as the catheter is removed (33).

Progression follows a phased approach from immediate post-operative mobilization through early recovery (weeks 1–4), progressive reconditioning (weeks 4–12), and maintenance (week 12+), with modifications for individual patient factors and treatment-related complications

Contraindications to exercise are: hemoglobin concentration <8 g/dL; oxygen saturation on room air <88%, white blood cell number <2,000/mm³; neutropenia <1,500/mm³. Exercise should be avoided if symptoms such as: syncope, wheezing, shortness of breath, claudication are present. The presence of upper extremity lymphedema, bone metastasis, ostomy and neuropathy should be evaluated with caution since resistance training should start with low resistance and progress slowly, loading of muscle that are proximal to metastatic lessons should be avoided, systematic evaluation for falls risk may be necessary. Risk of fractures should be considered in patients with bone metastasis, prostate cancer, diagnosis of osteoporosis, and treatment with hormonal therapy. Swimming and water sports should not be prescribed in cancer patients undergoing radiotherapy, patients with central lines, and ostomies.

Evaluation of physical capacity is closely aligned to cardio-respiratory performance, disease prevention, skills related components and dependency living status. By measuring physical capacity physicians and healthcare providers can: (a)

evaluate baseline health status before exercise prescription

The physiological response to exercise is characterized by the first VT, RCP and VO2max, which allow the identification of three intensity zones. For accurate exercise prescription heart rate and workload to each appropriate zone should be used for exercise prescription. Zone 1 represents light to moderate intensity exercise, zone 2 moderate to high intensity training includes workloads between the first VT and RCP. Zone 3 represents workloads above the CP that result in VO2max at exhaustion and constitute high to sever exercise intensity (43).

In patients with HF CPET parameters are characterized by reduced VO2max, first VT below 40% of the VO2 max and wide BR, while in patients with COPD, BR is reduced and ventilatory inefficiency is pronounced (38, 39, 41, 45, 46). Table 1 summarizes CPET parameters described above.

Despite its established clinical utility, CPET remains significantly underutilized in contemporary clinical practice. Multiple barriers contribute to this limited adoption, including the technical complexity of the test, insufficient training among healthcare specialists in CPET interpretation, and poor understanding of its parameters among referring physicians. Operational challenges further compound the issue, with equipment costs and limited availability. Addressing these barriers is essential to enhance CPET utilization and optimize patient care. Of interest application of artificial intelligence in CPET interpretation may provide benefits, including improved diagnostic accuracy, reduced interobserver variability, and expedited decision-making (47).

Although CPET represents the only test for multiparametric assessment of functional capability, limitations due to dedicated equipment, personnel qualifications and complex execution have led to the development of simpler functional tests using surrogate parameters to assess functional capacity.

The following paragraphs illustrate such tests.

Also, a graphical flowchart in Figure 1 summarizes exercise intensity evaluation based on CPET and other tests.

In assessing functional capacity, stress testing is used due to its simplicity and cost-effectiveness. The most used ergometric parameters for this purpose are heart rate and exercise tolerance.

In healthy subjects, exercise intensity is defined as the percentage of maximum heart rate using the formula 220-age, or in subjects over 50–60 years of age, the Tanaka formula (208–0.7×age) (48). In cardiac patients, it is preferable to use the real heart rate, that is, the heart rate reached during an exercise test under optimized pharmacological therapy, or the heart rate reserve, which is given by the difference between the maximum heart rate reached during the exercise test and the heart rate at rest. Exercise intensity can also be defined by the workload expressed in watts if using a cycle ergometer or in incline speed if using a treadmill. A parameter associated with good health and a reduced risk of death from cardiovascular events (49) is a rapid decrease in heart rate (30–40 bpm) in the recovery phase of the exercise test (first minute).

In this context is also pivotal to underline the role of metabolic equivalents (METs) in the assessment of activity status of patients. In particular, METs are a measurement of physical activity, defined as the ratio between the energy expended during any given activity compared to the energy at rest, being 1-MET the energy required to sit still (corresponding to 3.5 mL O2 per kg per min of activity) (50).

Age-appropriate exercise time is associated with a favorable prognosis, and a 1-MET increase in exercise tolerance, for males, results in a 12% increase in 6-year survival (51). Furthermore, it has been demonstrated that patients that present a peak exercise capacity inferior to 4.3 METs present higher risk of mortality compared to those reaching 4.3–6.3 or >6.3 METs, with hazard ratios for total mortality declining from 1.0 to 0.66 and 0.45 (52, 53).

Other tests that allow to evaluate exercise capacity and define VO2 Max indirectly are: the Bruce and Balke test, the indirect Mader test, the 6-min walking test and the 12-min Cooper test.

The Bruce and Balke test is performed on a cycle ergometer or treadmill and calculates VO2 max indirectly through specific tables. This test is highly versatile and can be applied to athletes, healthy subjects, and those with heart disease by varying the amount and method of increasing workload. Exercise capacity and intensity can be expressed using the “relative percentage method,” i.e., using the percentage of maximum heart rate (%HR Max) or reserve (%HR Reserve), or the percentage of maximum oxygen consumption (%VO2 Max) or reserve (%VO2 Max Reserve). %VO2 Max and %HR Max exhibit considerable interindividual variation and may not ensure adequate control of exercise intensity, resulting in some individuals who respond well and others who do not respond to chronic exercise training (54).

Cardiac reserve percentage has been adopted in the past as the gold standard for the indirect determination of exercise intensity but, in recent years, the use of heart rate as an index of metabolic intensity has been questioned, since, during prolonged and constant exercise (longer than 10 min) heart rate and oxygen consumption diverge over time as a result of a slow increase in heart rate independent of metabolism (54, 55).

The modified Mader test allows to identify the training load and the target heart rate during training by measuring lactic acid in capillary blood during a stress test.

The 6-min walking test (56) and the 12-min Cooper test (57) are the most widely used clinically to indirectly calculate VO2 max and the perception of physical exertion. In the absence of monitoring systems, exercise intensity can be defined by the sensation of fatigue during exertion using the Borg scale, a 15-point scale ranging from 6 to 20, or by informally applying the Talk Test. Moderate activity can be performed at a pace that allows for fairly comfortable speaking despite increased ventilation, while vigorous activity corresponds to an intensity that makes speaking difficult due to the increased rate and depth of breathing.

Flexibility is the intrinsic property of muscles and connective tissue to determine the range of motion (ROM), achievable without injury at a group of joints or a single joint (67). Shoulder stretch, trunk lift, sit and reach test, bilateral sit-and reach test and back-saver sit and reach tests are field tests applied in the evaluation of flexibility (67). Passive straight leg test raise test and passive knee extension in the isokinetic dynamometer are also methods applied in ROM assessment (68).

Balance impairment is common among older adult adults and in patients with multiple comorbidities. Therefore, before the prescription of therapeutic exercise evaluation of balance and risk of falls is essential in special populations. Visual, vestibular, audiologic and symptoms stimulation tests are applied in the ambulatory settings for the clinical assessment of balance (69). Functional performance tests evaluate the movements and postural activities which occur in the occur during everyday life. The timed up-and-go evaluates dynamic balance and measures the time taken by the seated individual to stand up from a standard armchair, walk a distance of 3 meters, turn, walk back to the chair and sit down. Community dwelling is considered unsafe for persons who take >20 s to complete the test (70).

Another validated method for balance assessment in older adult is the Performance-Oriented Mobility Assessment (POMA) which consists of balance and gait subscales. The POMA takes only about 10 min to complete and can fit into most clinical contexts (71).

Body composition describes and qualifies various elements within human body such as fat mass, total body water, muscle mass and bone mass. Anthropometry measures such as: simple measurement of subcutaneous fat body weight, height, calculation of body mass index (BMI) and waist circumference are important not only for the detection of overweight and obesity, but also to monitor the health-related changes in body composition associated to ageing process. Other simple measures which have demonstrated a valuable role in the identification of cardio-vascular risk and physical capacity as well are waist to hip ratio and a body shape index (72–74). Dual-energy x-ray absorptiometry (DXA), magnetic resonance, and computer tomography are methods characterized by high accuracy, reliable and repeatable for the evaluation of both muscle mass, fat mass regional and total evaluation as well (75). However, these methods are characterized by high costs and radiation exposure. Bioelectrical Impedance Analysis (BIA) is a quick and not invasive method, which measures the impedance (Z) to the flow of an alternating current, which is directly related to body's fluid content and its distribution among intra and extracellular spaces, allowing to estimate hydration status, nutritional status (via bioelectrical impedance vector analysis, BIVA), and prognosis (76, 77).

The SPPB is a three-part physical function test with excellent reliability, validity, and clinical applicability for the physical capacity of older adult, risk of falls and overall survival (78, 79). SPPB consists of 3 components: (1) 4-m usual walk (2) five-repetition chair stand without using one's arms, and (3) progressive test of standing balance. Study personnel demonstrated each component ahead of participant testing. Total SPPB scores ranges between 4 and −12, with 4–6 representing low, 7–9 middle, and 10–12 best performances (78). Table 2 summarizes use of functional capacity evaluation methods.

Frailty is a clinical condition characterized by vulnerability, associated with loss of physiological reserves and declining function of multiple physiological systems (80–82). Frailty has tremendous effects on dependence, disability, hospitalizations, mortality, hospitalization, and significant healthcare cost (83). Two main models are used to define frailty: (a)

the physical phenotype of frailty which considers muscle strength, gait speed, physical inactivity, weight loss and exhaustion (84);

Physical inactivity increases the risk of developing high blood pressure by 5%–13% (90). After a single session of aerobic activity, systolic blood pressure decreases by 6–12 mmHg, this is post-exercise hypotension. A systematic review and Meta-analysis have demonstrated blood pressure reduction with aerobic and resistance exercises in both normotensive and hypertensive patients (91, 92). Blood pressure reductions after dynamic resistance training were largest for prehypertensive participants −4.0 mmHg Confidence Interval (CI): −7.4 to −0.5 and −3.8 mmHg CI −5.7 to −1.9 mm Hg compared with patients with normal blood pressure or hypertension (90). The benefits of exercise in reducing blood pressure occur at any age and are independent of gender and race (93, 94).

The regulation of blood pressure is multifactorial including hemodynamic and neurohormonal mechanisms. Resting heart rate results reduced following regular exercise training and increased stroke volume have been described (95). Prior research has demonstrated that arterial stiffness is significant reduced after regular exercise training programs (96) in part explained by beneficial vessel adaptations, vascular homeostasis, synthesis and bioavailability of nitric oxide (NO) (97). Different exercise modalities including aerobic, resistance and combined exercise training produce similar effect on endothelial function in individuals with prehypertension or hypertension (98). In response to exercise, endothelial cells release vascular endothelia growth factor, angiopoietins and metalloproteinases which promote chemotaxis, endothelial cells migration, increase of vessel network and angiogenesis (99).

Arterial hypertension is defined as use of antihypertensive medication for blood pressure control or having repeated office values for resting systolic and or diastolic blood pressure of ≥140/90 mmHg, and primary arterial hypertension accounts for 95% of cases (100). The current prevalence of arterial hypertension is estimated to be 30%–45%. About 70% of adults of age 65 years or above are affected by hypertension. As population ages by 2025, the number of the hypertensive population, globally is expected to increase up to 60%.

In patients with arterial hypertension aerobic exercise is expected to reduce SBP in a range of −4.9 to −12 mmHg and −3.2 to −5.8 DBP (101). A recent meta-analysis study revealed that the optimum duration of moderate- intensity aerobic exercise such as walking, jogging and running for reducing blood pressure is 150 min/week (102). Indeed, each 30 min/week of aerobic exercise reduced SBP by 1.78 mmHg 95% CI: −2.22 to −1.33. Furthermore, a 100 min/ week of moderate-intensity aerobic exercise reduced resting heart rate by −5.77 bpm, 95% CI: −7.79 to −3.75. Beyond the traditional moderate intensity continuous training, a recent study concluded that the effects of high intensity interval training on SBP and DBP are not different (103), high intensity interval training is more effective in reducing SBP during daytime monitoring: weighted mean difference −4.14, 95% CI −6.98 to −1.30 mmHg and no significant adverse events are reported (104). Another study reported that SBP and DBP significantly decreased following isometric exercise training of 9.35 mmHg 95% CI −7.80 to −10.89 and 4.30 mmHg 95% CI = −3.01 to −5.60 respectively. Compared to leg extension and isometric handgrip exercise wall squat resulted the most effective isometric exercise training mode intervention in blood pressure control (95).

An 8-week stretching program was superior to walking in patients with stage 1 arterial hypertension or high normal blood pressure (99). A randomized clinical trial also found that multicomponent training associated with flexibility training improved blood pressure control in older inactive woman (105). A systematic umbrella review provided convincing and strong evidence of the importance of exercise in the prevention of hypertension and its protective effects in the treatment of hypertension by attenuation of CV risk factors (106). For the above indicated changes in blood pressure, it is important to reevaluate constantly hypertensive patients, since therapy might be excessive by the increase in physical activity, and a reduction in dosage and number of active principles might be required.

People with hypertension should choose exercises that help reduce blood pressure without reaching very high values during training (107). For instance, systolic blood pressure ≤220 mmHg and/or diastolic blood pressure values ≤105 mmHg are considered safe (108).

Table 3 summarizes the fundamental components of exercise prescription in patients with hypertension and evidence-based recommendations (17).

Dyslipidemia is a well-established cardiovascular risk factor, which refers to lipid abnormalities consisting of either one or any combination of the following: elevated total cholesterol, low high-density lipoprotein cholesterol, elevated low-density lipoprotein cholesterol (LDL-c), and elevated triglycerides. The prevalence of dyslipidemia has been estimated to reach up to 53.7% in Europe (109). Previous meta-analyze study have reported reduced total cholesterol, reduced triglycerides and increased high density lipoprotein cholesterol level associated to exercise training (3) and exercise is essential for weight loss. Despite the high heterogeneity, weighted mean difference resulted 5.31 mg/ dL (95% CI 10.63–0.89) for triglycerides, 2.32 mg/dL (95% CI 1.16–3.87) for HDL-C, and 0.03 g/L (95% CI 0.02–0.04) for apolipoprotein A1 (3).

Prolonged aerobic exercise promotes upregulation of lipoprotein lipase activity, which enhances triglyceride hydrolysis (110). ATP-binding cassette transporter A-1 (ABCA1) in macrophages plays a crucial role in plasma high-density lipoprotein cholesterol (HDL-C) synthesis, and exercise increases ABCA1 mRNA expression (111). Additionally, PCSK9 activity is important in regulating low-density lipoprotein cholesterol (LDL-C) receptor levels, and regular daily exercise is independently associated with decreased PCSK9 levels over time (112).

In general, aerobic exercise tends to increase HDL-C and decrease triglycerides. Regular exercise consistently raises HDL cholesterol levels while helping to maintain or counterbalance increases in LDL cholesterol and triglycerides and higher activity levels correspond with greater improvements in HDL cholesterol. On the contrary aerobic exercise has little or no beneficial effect on low-density lipoprotein cholesterol (LDL-C) (113, 114). However, reducing LDL cholesterol and triglycerides requires more vigorous exercise intensity. High-intensity aerobic exercise proves particularly effective for improving overall lipid profiles, producing benefits that exceed those of moderate physical activity (114).

Table 4 summarizes the evidence-based recommendations for exercise prescription in patients with dyslipidemia (17, 114).

Overweight and obesity have reached epidemic proportions and more than half of adults in almost all European Regions live with overweight or obesity. The highest levels of obesity and overweight are found in Eastern Europe and Mediterranean countries (115).

Exercise promotes thermogenesis, fat mass reduction, increases the browning of adipose tissue and increase of muscle mass, enhances glucose uptake in muscles and regulates lipid homeostasis in liver (116). The final results are characterized by modulation of neuro-hormonal axes, regulation of appetite, increased energy expender, and prevention of overweight and obesity. The effects of exercise on obesity are characterized by multiple interactive pathways which include up-regulation of the expression of thermogenic genes, release of myokines, modulation of adiponectin, ghrelin, leptin and insulin sensitivity (117).

A dose dependent relationship between exercise and weight loss has been described. Individuals who initially reported 60 min/ week of physical activity and increased to 134 min/week had a change in BMI of 0.4 kg/m2 across long term follow-up period (118), while, in a randomized controlled trial, aerobic exercise of 370 min/week in men and 295 min/week in women resulted in significant reduction of BMI (119). Moderate intensity exercise 150–250 min/week improves weight loss in combination with moderate diet restriction. A meta-analysis study which compared six randomized clinical trials ranging from 10 to 52 week found a 20% greater weight loss in diet plus exercise programs compared to diet-only programs and a 20% greater sustained weight loss after 1 year follow up (120). Resistance training does not affect weight loss but significantly impacts the modification in body composition related to increase in fat free mass and reduction of fat mass (84, 121). Table 5 summarized the evidence-based recommendations for exercise prescription in patients overweight or obese (17, 121).

Over 64 million patients worldwide are affected by Heart failure (HF), which is associated with extremely negative prognosis (122). Due to ageing process, the burden of chronic HF is expected to rise. The subtypes of HF includes HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF).

The therapeutic goals of exercise prescription in patients with chronic and stable HF are related to the improvement of exercise tolerance and to ameliorate the clinical features of HF (123). It should be mentioned that several mechanisms contribute to the beneficial effects of exercise training in patients with HF, including: restoration of balance between sympathetic and parasympathetic activity, and endothelial function improvement. Exercise training has been associated to reduced norepinephrine levels (124) and improved heart rate variability in older patients with HF (125). Chronic exercise training leads to increase of NO synthase production (126).

It should be mentioned that peak VO2 changes in response to supervised moderate intensity endurance exercise training in older patients with HF varies by HF subtype, with greater peak VO2 improvement in HFpEF compared to HFrEF: The proportion of patients with >5% and >10% improvement in peak VO2 resulted significantly higher in HFpEF vs. HFrEF patients (75% vs. 33.3%, p-value = 0.004 for >5% improvement and 66.7% vs. 29.2%, p-value = 0.009 for >10% improvement (127). In addition, patients with low baseline inflammatory biomarkers such as IL-6 and TNF-α showed significant improvements in peak VO2 with exercise training: 3.5 mL/kg/min improvement, while those with high inflammatory biomarkers showed no significant changes (128).

Currently, the population of HF patients with Cardiac Implantable Devices (CIDs) such as cardioverter-defibrillators (ICDs), cardiac resynchronization therapy-/defibrillators (CRT/CRT-D), permanent pacemakers (PM), leadless pacemakers and left ventricular assist devices (LVADs), has increased drastically. In this population exercise can partially reverse ventricular remodeling, restore endothelial function, and improve skeletal muscle abnormalities (129). CIDs patients should be carefully evaluated, and titration of exercise should be monitored by trained professionals. Adverse effects including shocks, anti-tachycardia pacing), device complications, arrhythmias, and deaths are low during exercise training of moderate to high intensity indicating safety and improvement of cardiopulmonary outcome (130, 131). Aerobic exercise training demonstrated an average increase in peak oxygen uptake of 2.61 mL/kg/min, ICD = 2.43, CRT = 3.2 mL/kg/min and LVADs = 2.2 mL/kg/min (107). It should be mentioned that compared to end stage HF VO2 peak was lower 14 ± 4.2 mL/kg/min vs. 11.2 ± 4.2 mL/kg/min, while ventilatory efficiency presented higher VE/VCO2 slope: 36 ± 8.3 vs. 42 ± 7.1 (131). Exercise intensity prescription in HF should ideally be anchored to CPET-derived VT rather than percentage-based methods, as VT1 and VT2 occur at highly variable percentages of peak HR (and HRR (39.0% ± 13% and 78.0% ± 13%), with percentage-based methods misclassifying intensity in up to one-third of patients (132). Training targets should be: moderate-intensity continuous training at VT1 HR + 5–10 bpm progressing toward VT2 HR; HIIT work intervals at VT2 HR + 5–10 bpm (85%–95% peak HR) with recovery below VT1 HR. When CPET is unavailable, approximate VT1 at 69% peak HR or 40% HRR and VT2 at 89% peak HR or 78% HRR, though individual variation is substantial (27).

Exercise training program should be considered in stable patients with optimal therapy. Early mobilization should be initiated from the bedside, however in ICDs patients some reports suggest a waiting period of six months before starting exercise programs (131, 133). During the initial phase of exercise training, low-intensity endurance training may be considered with gradual increase of intensity to moderate and high in low risk and stable patients. The prescription for CRT continuous aerobic training may be similar to that used in HF patients, up to 60 min using various modalities 2–3 times per week at 60%–80% max HR based on pre-exercise tests (134). For ICD patients, target HR must remain ≥10–20 bpm below device detection threshold (typically 160–180 bpm) to prevent inappropriate shocks; a 6-month post-implantation waiting period is suggested though supervised earlier mobilization is generally safe CRT patients follow standard HF prescription targeting 60%–80% max HR for 20–60 min, 2–3 times weekly (134). All device patients require supervised initiation with ECG monitoring for 6–12 sessions to assess device function and hemodynamic response.

Nevertheless, considering the diverse risk profiles underlying heart failure pathophysiology, exercise training should be integrated and tailored alongside optimal antihypertensive therapy, heart rate control in atrial fibrillation, and metabolic and renal management strategies (135). Regarding training modalities in HFpEF patients, no significant difference in peak VO2 at 3 months was observed between high-intensity interval training and moderate continuous training (136).

HIIT is safe in supervised cardiac rehabilitation settings (137). Key safety limits include: (1) reserve HIIT for stable patients demonstrating 2–4 weeks MICT tolerance; (2) maximum work interval intensity 90%–95% peak HR (VT2 + 10 bpm limit); (3) exclude patients with LVEF <25%, recent decompensation (<6 weeks), significant arrhythmias, or unstable angina; (4) begin with conservative work: rest ratios (1:2 or 1:3, e.g., 1 min work/2–3 min recovery) before progressing to 1:1; (5) include 10–15 min warm-up/cool-down; and (6) use low-impact modalities (cycling preferred) in older or frail patients. Common protocols alternate 3–4 min intervals at 90%–95% peak HR with 3–4 min recovery at 50%–70% peak HR, or 1-min work/1-min recovery intervals (138). Of note that 51% of HFrEF patients exercised below prescribed 90%–95% targets, indicating individual tolerance varies substantially and theoretical prescriptions may exceed achieved intensities (139).

Table 6 summarizes the evidence based (17) recommendation of exercise prescription in patients with HF.

Diabetes is one of the most common chronic conditions, affecting almost 10% of the population, and remains a major public health concern (140). Thus, international guidelines recommend lifestyle modification and physical activity for the improvement of diabetes care. Indeed, exercise has shown to improve the glycemic control, reduce the risk for disabilities and ameliorate the overall survival.

The immediate effects of exercise on glucose homeostasis are characterized by increased expression of glucose transporter isoform 4 (GLUT4) and its translocation from an intracellular pool to the plasma membrane, which results in increased glucose transportation to muscle (140). In addition, exercise increases the expression of insulin receptor substrates-1and-2 and actives a variety of molecular pathways including Ca2+/calmodulin signaling, AMP-activated protein kinase and restores mitochondrial content and biogenesis (138, 141).

A recent meta-analysis study evaluated that about 36 min/week of brisk walking are necessary for an optimal control of control glycosylated hemoglobin (142). The minimal dose of physical activity needed to move from uncontrolled to controlled diabetes resulted 330 MET min/week, and the optimal dose of physical training was achieved at 1,100 MET min/week in all diabetes categories, resulting in HbA1c change ranging from −1.02% to −0.66% for severe uncontrolled diabetes, −0.64% to −0.49% for uncontrolled diabetes, −0.47% to −0.40% for controlled diabetes, and −0.38% to −0.24% for prediabetes (124). Despite the best protocol for exercise intervention in diabetic population is still not clear, high intensity interval training and resistance activity have been shown to improve the cardiorespiratory fitness and glycemic control (143, 144). Compared to controls, high intensity interval training showed significantly favorable effects on HbA1C: standardized mean difference (SMD) = − 0.74, 95% CI = − 1.35 to−0.14 (107). Resistance training significantly reduced HbA1c compared with controls weighted mean difference = –0.39, 95% CI −0.60 to −0.18 (143).

Furthermore, it seems that exercise has some anti-inflammatory and metabolism-improving effects (143).

Table 7 summarizes the evidence based (17) recommendation of exercise prescription in patients with type 2 diabetes.

About 10 million deaths occurred in 2020 due to cancer. Cancers arise from a complex and multiple etiology including genetic, environmental and life-style factors. It has been reported that physical activity reduces the risk of cancers of breast, stomach colon, kidney, bladder, and endometrium. Limited evidence exists regarding the association between hematologic, prostate, pancreas and ovary cancers (145, 146). Furthermore, patients which exercised following a diagnosis of cancer were observed to have a lower risk of cancer mortality and experienced fewer severe adverse effects (147).

Exercise training in cancer patients modulates the inflammatory response by reducing pro-inflammatory cytokines (TNF-α and IL-6) while significantly increasing anti-inflammatory cytokines (IL-10), thereby lowering systemic inflammation and modulating oxidative stress (148). Exercise enhances synergistic antitumor activity between natural killer (NK) cells and CD8+ T cells in various cancers through multiple molecular pathways. These include CD8+ T cell recognition via the CXCL9/11-CXCR3 pathway, enhanced T cell receptor response to tumor-associated antigens, and increased CCL5 and CXCL10 levels mediated by elevated epinephrine levels. This epinephrine-driven mechanism accelerates CD8+ T cell recruitment, contributes to antitumor effects and ultimately limits tumor growth (149).

Additionally, exercise interventions including: walking, cycling, strength training, resistance training, yoga, or Tai Chi have a positive effect on health-related quality of life among cancer survivors (150). Among cancer survivors, exercise improved the quality of life and social functioning compared to controls SMD 0.99; 95% CI 0.41–1.57 SMD 0.49; 95% CI 0.11–0.87 after 6 months follow-up (150).

Despite, only 8% of cancer survivors engaged in 150 min/week of moderate to vigorous intensity exercise and about 66% of breast cancer patients were sedentary, cancer survivors should avoid inactivity. 150–300 min/week of moderate intensity or if possible 75–150 min/week of aerobic exercise is recommended. Resistance exercise should be performed on at least 2 days/week in combination with flexibility and balance training if no contraindications are present. Indeed, balance and muscle strengthening exercise had a positive multidimensional effect on patients receiving chemotherapy (151).

A pilot randomized controlled trial revealed that supervised continuous aerobic training and interval aerobic training significantly increased the cardiorespiratory fitness by 11.5% and 13% of breast cancer survivors and aerobic interval training had a greater influence on body weight and lower extremity strength (152). In patients undergoing chemotherapy exercise protocols resulted in a significant improvement in postural control (153). Recent studies support the combination of aerobic exercise and inspiratory muscle training in lung cancer (154), breast cancer (155), head and neck cancer (156) and patients undergoing hematopoietic stem cell transplantation (157). Indeed, combination of aerobic and high intensity training in patients with non- small cells lung cancer was associated with significant improvement in VO2 peak: 2.13 mL/Kg/min, 95%CI 0.06–4.20 (138). Three months of exercise training improved both respiratory muscle endurance +472 s; 95% CI, 217–728 and cycling endurance +428 s; 95% CI, 223–633 (155). These studies confirm that inspiratory muscle training is feasible and safe in patients affected by cancers.

Exercise has been demonstrated to be able to reduce same negative effect due to chemotherapy such as fatigue, lymphoedema, pulmonary disfunction and toxicity for the heart (158).

Furthermore, a meta-analysis has shown that exercise reduces fatigue and improves quality of life after radiation therapy (159).

In patients with prostate cancer two sessions per week of moderate-high intensity aerobic and resistance exercise reduced fatigue and psychological distress and improving social functioning and mental health (160).

Table 8 summarizes the evidence-based recommendations for exercise prescription in cancer patients (29, 161, 162).

Age-dependent cumulative decline in multiple physiological systems promotes the development of frailty, while physical activity and exercise improve the physical functioning.

Higher levels of physical activity were associated with 37% decreased odds of physical frailty and 49% for multidimensional frailty (163). Furthermore, exercise was shown to improve gait speed in frail individuals and significant increased SPPB score was also revealed (164).

Exercise addresses frailty through multiple systemic function improvements and effects on ageing related comorbidities. Key mechanisms include modulation of oxidative stress pathways, reduction of chronic inflammation, modification of immune response and restoration of mitochondrial function. It has been reported that trained individuals have fewer senescent CD4 + as well as CD8+ CD28−CD57 + cells, and a higher proportion of naive T cells (165), which are important in the development of atherosclerosis. Additionally, exercise induces an increased signaling of the transcription factor peroxisome proliferator-activated receptor γ coactivator-1α which improves mitochondrial function and reduces inflammation (166). Protein synthesis via activation of IGF-1 pathway is also modulated by exercise these molecular adaptations collectively improve muscle strength, physical function, and overall resilience in frail individuals.

Multimodal physical activity including a combination of aerobic, strengthening, balance, and flexibility significantly reduced the risk of falls related injuries by about 32%–40%. Nevertheless, the benefits of exercise programs in reducing the risk of falls were similar between older adults identified as being at high risk of falling compared to those who were at an unspecified risk (167). In addition, exercise significantly reduced the occurrence of falls in community dwelling older adults rate ratios = 0.63 (95% confidence interval 0.51–0.77. Exercise programs designed to prevent falls in older adults also seem to reduce the rate of falls leading to medical care and to prevent injuries caused by falls. A randomized controlled trial studying the effect of a 12-month intervention of walking, resistance exercise, and flexibility, found similar rates of serious and non-serious adverse events for both the intervention and control subjects (168), and other studies underly that life-threatening adverse events after exercise prescription are rare among frail individuals (169). Resistance training alone or in a multimodal training program may induce increases of maximal strength and improvement of functional capacity (170, 171). Although uncertainty exists regarding the principles of exercise prescription in frail individuals (172) a three-month home-based resistance exercise regimen in combination with protein intake resulted successful in reversing frailty: absolute risk reduction was 11.9% (CI: 0.8%–22.9%) (173). It should be emphasized that barriers to exercise prescription in frail patients are multidimensional. Frail individuals face physical and cognitive limitations, depression, inadequate socioeconomic support, and transportation constraints. In community settings, exercise should be prescribed with the same specificity as pharmacological interventions, clearly defining frequency, intensity, volume and progression based on evidence-based programs. Tailored interventions must also address social and behavioral factors to enhance motivation and adherence. Furthermore, since frail individuals often require assistance with healthcare management and activities of daily living, engaging caregivers and volunteers is essential for program success and sustainability (172).

Table 9 summarizes the evidence-based recommendations for exercise prescription in patients with frailty.

Supplementary Tables 1, 2, summarize the main mechanisms related to exercise induced benefits and literature evidence regarding the effects of exercise in cardiovascular risk factors, chronic coronary disease, heart failure and cancers.

Non-adherence to exercise therapy remains a significant challenge, with rates ranging from 40% to 50% among patients with chronic conditions (174). Across cancer, cardiovascular disease, and diabetes populations, the average adherence rate to physical activity interventions was 77%, with an overall dropout rate of 7.0% (16). However, structured interventions can substantially improve outcomes: supervised exercise therapy in patients with intermittent claudication increased adherence by 22% compared to unsupervised programs, resulting in measurable healthcare cost reductions (175). Patient-level factors significantly influence adherence rates, with prior physical activity history, fewer comorbidities, and higher educational attainment associated with improved compliance (176, 177). Program design features are equally critical—individualized prescriptions regarding frequency, intensity, and duration enhance participation, while single weekly sessions were associated with poor adherence even among physically active individuals (178). Furthermore, compared to patients with cognitive decline, individuals with preserved cognitive status more frequently dropped from exercise programs (179). Cognitive frail patients, incontinent or even institutionalized older adult may respond with a certain level of adherence in the case of a tailored and personalized exercise prescription (180). These findings may indicate that exercise prescription should be adjusted to the functional level and a gradual increase in frequency and intensity may motivate the adherence to physical activity.

While ventilatory thresholds provide physiologically grounded demarcations between exercise intensity domains, evidence supporting their use to guide training prescription remains predominantly confined to healthy populations, in the absence of adequately powered RCTs. Indeed, exercise intensity domains influence the biological response to VO2 max in healthy adults (181). In a population of sedentary adults, exercise training based on individual ventilatory thresholds resulted superior to standardized methods based on heart rate reserve (182). The use of thresholds for intensity markers accounts for individual metabolic characteristics and should be considered in the prescription of exercise intensity. Future research should prioritize large-scale RCTs comparing individualized, threshold-based exercise prescription against conventional intensity recommendations in diverse clinical populations, examining not only physiological adaptations but also patient-centered outcomes including functional capacity, symptom burden, quality of life, and long-term adherence.

Multidisciplinary team involvement, including physicians, nurses, and psychologists, positively impacts adherence rates, with more than 70% of studies emphasizing the necessity of comprehensive baseline participant assessment before program design (183). In part this finding may be explained by the supervision of the health status, and support, which may reduce the potential risks and increase self-efficacy (183, 184). Regular communication, social interaction may increase the adherence to exercise (183), and social support was reported as a significant prognostic factor of adherence to home-based physiotherapy (184). Regular and continuous use of technology, as ICTs (Information and Communication Technology), may be helpful to monitor the exercise program and also to provide instructions and feedback. A meta-analysis study of randomized controlled trials revealed that the adherence of patients using mobile applications for completion of cardiac rehabilitation programs was 1.4 times higher than the control group: relative risk = 1.38; CI 1.16–1.65 (185). Therefore, applications have a great potential to improve the adherence to exercise prescription the implementation of applications with intelligent wearable needs to be further explored in the terms of improvement of healthcare surveillance.