Coronary Plaque in Athletes.

The relationship between vigorous physical activity (PA) and the development of coronary atherosclerosis has remained less explored for many years. Recently, literature data have focused on coronary atherosclerosis in athletes showing that prevalence is not trivial, that there are differences among various types of sport, and that there are some peculiar features. As a matter of fact, plaque composition in athletes seems to be characterized by calcium rather than soft components. Specific mechanisms through which vigorous PA influences coronary artery disease are not yet fully understood. However, the prevalent calcific nature of coronary plaques in athletes could be related with a trend in a lower cardiovascular event rate.

Change in Peak Oxygen Uptake Predicted by the Moderate 1-km Treadmill Walking Test After Walking Training in Outpatients With Cardiovascular Disease.

PURPOSE: The purpose of this study was to determine the ability of the moderate 1-km treadmill walking test (1km-TWT) to predict changes in peak oxygen uptake (V˙O 2peak ) in patients with stable cardiovascular disease (CVD) during an exercise-based secondary prevention program. METHODS: Sixty-four male outpatients with stable CVD (age 64 [41-85] yr) performed the 1km-TWT before and after an 8-wk walking training program. Patient V˙O 2peak was estimated using a sex-specific equation including age, body mass index, 1km-TWT performance time, and heart rate (V˙O 2peakEST ). Forty-one patients completed a maximal cardiopulmonary treadmill test (CPX) for direct V˙O 2peak determination (V˙O 2peakMEAS ). The training prescription consisted of moderate-to-high intensity supervised walking for 30-40 min/session, and an additional 2-4 times/wk of unsupervised home moderate walking sessions between 20-60 min at the end of the program. The walking intensity was based on the results of the 1km-TWT. RESULTS: Patients participated in an average of 14 of the 16 supervised sessions. An overall significant improvement in V˙O 2peakMEAS and weekly recreational physical activity levels were observed. No differences were observed between V˙O 2peakMEAS and V˙O 2peakEST . Compared with CPX results, the 1km-TWT underestimated the V˙O 2peak increase after the exercise intervention (mean difference -0.3 mL/kg/min, P > .05). CONCLUSIONS: The 1km-TWT provides a reasonably accurate and simple tool to predict changes in V˙O 2peak due to moderate walking training in male outpatients with CVD. These findings contribute to the growing body of evidence supporting the use of the 1km-TWT for exercise testing and training purposes in the context of cardiac rehabilitation/secondary prevention programs.

Attenuation of the increase of heart rate and oxygen consumption during progressive exercise in professional rugby players.

BACKGROUND: The response of oxygen uptake (VO2) and heart rate (HR) to continuous progressive large muscle mass exercise is not always linear. This study aimed to compare the patterns of the Speed/VO2 (S/VO2) and speed/HR (S/HR) relationships during an incremental treadmill-running test in professional rugby players. METHODS: Fourteen professional rugby athletes performed a maximal incremental treadmill-running test, following the Conconi test protocol. Speed, heart rate, and gas exchange parameters were recorded. The slope of the S/VO2 and S/HR relationships were mathematically determined. RESULTS: The S/VO2 and S/HR relationships were linear up to a submaximal speed and curvilinear thereafter. The speed of locomotion at which the slope of the S/VO2 and S/HR relationships start to attenuate (VO2att and HRatt) were coincident (12.3±1.0 and 12.4±0.9 km/h), strongly correlated and in good agreement. VO2 values at VO2att (44.9±8.7 mL/kg/min) were significantly correlated with VO2 values at the ventilatory threshold (43.3±6.0 mL/kg/min) (R2=0.83, P=0.001) and in good agreement. The running speed/VO2 ratio (ΔS/ΔVO2) up to VO2att was significantly lower than that beyond VO2att (2.98±1.1 vs. 5.16±2.31); P<0,001). CONCLUSIONS: The speed/oxygen uptake and S/HR relationships during progressive exercise start to attenuate at a coincident exercise intensity, and at oxygen uptake values strongly correlated with the ventilatory threshold. These findings further support the usefulness of the attenuation of the S/HR relationship as a practical tool for exercise testing and training purposes in professional rugby players.

Association of Stair Use With Risk of Major Chronic Diseases.

INTRODUCTION: Physical inactivity is associated with a higher risk of chronic diseases. Regular stair use can contribute to increasing physical activity in the population. This study aimed to investigate the association between flights of stairs used daily at home and all-cause mortality and cause-specific incidence and mortality. METHODS: Of the 502,628 UK Biobank participants recruited between 2007 and 2010, 442,027 (mean age, 56±8 years) had available data and were included in the analyses conducted in 2023. Participants were categorized on the basis of flights of stairs climbed daily (1-5, 6-10, 11-15, >15). The disease-specific outcomes were cardiovascular disease, respiratory disease, cancer, type 2 diabetes, and all-cause dementia. Cox proportional hazard models, adjusted for sociodemographic, lifestyle, and health-related confounding factors, were used to analyze the associations between stair use frequency and health outcomes. RESULTS: Participants were followed up for a median of 10.9 years. Climbing stairs >15 times per day was associated with a lower risk of 8 of the 9 outcomes analyzed than not using stairs. The magnitude of association ranged from 3% (95% CI=0.94, 0.99) lower risk for all-cause cancer to 51% (95% CI=0.39, 0.60) lower risk of chronic obstructive pulmonary disease. Findings were similar for mortality outcomes, with the hazard ratios ranging from 0.82 (95% CI=0.77, 0.87) for all-cause cancer to 0.46 (95% CI=0.23, 0.92) for chronic obstructive pulmonary disease mortality. CONCLUSIONS: Stair use was associated with a lower risk of all-cause mortality and cause-specific incidence and mortality independent of confounding factors, including adiposity and multimorbidity.

Effect of physical activity on left ventricular dimensions and function after myocardial infarction: a systematic review.

INTRODUCTION: Coronary artery disease is the major pathophysiological driver of ventricular remodeling. A multimodal intervention is the key strategy to promote a positive left ventricular remodeling with improvement in volumes and ejection fraction, known as "reverse remodeling." The aim of this review was to highlight the effect of physical activity (PA) on echocardiographic and cardiac magnetic resonance parameters of left ventricle in patients with myocardial infarction. EVIDENCE ACQUISITION: We performed a systematic review of the literature to summarize current evidence about the efficacy (in terms of improvement in chamber dimensions, ejection fraction, speckle tracking and diastolic function) of physical activity in patients with myocardial infarction, supported by echocardiographic or magnetic resonance data. Articles were searched in Pubmed, Cochrane Library and Biomed Central. EVIDENCE SYNTHESIS: Only papers published in English and in peer-reviewed journals up to November 2022 were selected. After an initial evaluation, 1029 records were screened; the literature search identified 20 relevant articles. From this data, some PA protocols appeared to favor left ventricular reverse remodeling. CONCLUSIONS: PA provides beneficial effects on left ventricular parameters analyzed by echocardiography and cardiac magnetic resonance.

Treating Binge Eating Disorder With Physical Exercise: A Systematic Review and Meta-analysis.

OBJECTIVE: This review aimed to collect evidence about the effectiveness of exercise programs for managing binge eating disorder (BED) (recurrent binge eating episodes). METHODS: Meta-analysis was developed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Articles were searched in PubMed, Scopus, Web of Science, and Cochrane Library. Randomized controlled trials were eligible for inclusion if they reported the effect of an exercise-based program on BED symptoms in adults. Outcomes were changes in binge eating symptom severity, measured through validated assessment instruments, after an exercise-based intervention. Study results were pooled using the Bayesian model averaging for random and fixed effects meta-analysis. RESULTS: Of 2,757 studies, 5 trials were included, with 264 participants. The mean age was 44.7 ± 8.1 years for the intervention group and 46.6 ± 8.5 years for the control group. All participants were female. A significant improvement was observed between groups (standardized mean difference, 0.94; 95% credibility interval, -1.46 to -0.31). Patients obtained significant improvements either following supervised exercise programs or home-based exercise prescriptions. IMPLICATIONS FOR RESEARCH AND PRACTICE: These findings suggest that physical exercise, within a multidisciplinary clinical and psychotherapeutic approach, may be an effective intervention for managing BED symptoms. Further comparative studies are needed to clarify which exercise modality is associated with greater clinical benefits.

A Moderate Walking Test Predicts Survival in Women With Cardiovascular Disease.

INTRODUCTION: Cardiovascular disease (CVD) is the principal cause of death in U.S. women. Peak oxygen uptake is strongly related to mortality and CVD. This study aimed to investigate the association between estimated peak oxygen uptake, determined using a moderate 1-km walking test, and all-cause mortality in female patients with stable CVD. METHODS: Of the 482 women in our registry between 1997 and 2020, we included 430 participants in the analysis (aged 67 [34-88] years). A Cox proportional hazard model was used to determine the variables significantly associated with mortality. On the basis of the peak oxygen uptake estimated using the 1-km walking test, the sample was subdivided into tertiles, and mortality risk was calculated. The discriminatory accuracy of peak oxygen uptake in estimating survival was assessed by receiver operating characteristic curves. All results were adjusted for demographic and clinical covariates. RESULTS: A total of 135 deaths from any cause occurred over a median of 10.4 years (IQR=4.4-16.4), with an average annual mortality of 4.2%. Estimated peak oxygen uptake was a stronger predictor of all-cause mortality than demographic and clinical variables (c-statistic-0.767; 95% CI=0.72, 0.81; p<0.0001). The survival rate decreased from the highest tertile of fitness to the lowest. Compared with the lowest group, hazard ratios (95% CIs) for the second and third tertiles were 0.55 (0.37, 0.83) and 0.29 (0.16, 0.51), respectively (p for trend <0.0001). CONCLUSIONS: Higher peak oxygen uptake levels were associated with a lower risk of all-cause mortality. The indirect estimation of peak oxygen uptake using the 1-km walking test is feasible and can be applied for risk stratification among female patients undergoing secondary prevention programs.

Multi-domain lifestyle intervention in older adults after myocardial infarction: rationale and design of the PIpELINe randomized clinical trial.

BACKGROUND: Traditional cardiac rehabilitation (CR) is effective in improving physical performance and prognosis after myocardial infarction (MI). Anyway, it is not consistently recommended to older adults, and its attendance rate is low. Previous studies suggested that alternative, early and tailored exercise interventions are feasible and effective in improving physical performance in older MI patients. Anyway, the demonstration that they are associated also with a significant reduction of hard endpoints is lacking. AIM: To describe rationale and design of the "Physical activity Intervention in Elderly patients with myocardial Infarction" (PIpELINe) trial. METHODS: The PIpELINe trial is a prospective, randomized, multicentre study with a blinded adjudicated evaluation of the outcomes. Patients aged ≥ 65 years, admitted to hospital for MI and with a low physical performance one month after discharge, as defined as short physical performance battery (SPPB) value between 4 and 9, will be randomized to a multi-domain lifestyle intervention (including dietary counselling, strict management of cardiovascular and metabolic risk factors, and exercise training) or health education. The primary endpoint is the one-year occurrence of the composite of cardiovascular death or re-hospitalization for cardiovascular causes. RESULTS: The recruitment started in March 2020. The estimated sample size is 456 patients. The conclusion of the enrolment is planned for mid-2023. The primary endpoint analysis will be available for the end of 2024. CONCLUSIONS: The PIpELINe trial will show if a multi-domain lifestyle intervention is able to reduce adverse events in older patients with reduced physical performance after hospitalization for MI. TRIAL REGISTRATION: ClinicalTrials.gov NCT04183465.

Association between walking pace and incident type 2 diabetes by adiposity level: A prospective cohort study from the UK Biobank.

AIMS: To investigate the combined association of adiposity and walking pace with incident type 2 diabetes. METHODS: We undertook a prospective cohort study in 194 304 White-European participants (mean age 56.5 years, 55.9% women). Participants' walking pace was self-reported as brisk, average or slow. Adiposity measures included body mass index (BMI), waist circumference (WC) and body fat percentage (BF%). Associations were investigated using Cox proportional hazard models, with a 2-year landmark analysis. A four-way decomposition analysis was used for mediation and additive interaction. RESULTS: The median (interquartile range) follow-up was 5.4 (4.8-6.3) years. During the follow-up period, 4564 participants developed type 2 diabetes. Compared to brisk-walking participants with normal BMI, those with obesity who walked briskly were at an approximately 10- to 12-fold higher risk of type 2 diabetes (hazard ratio [HR] 9.64, 95% confidence interval [CI] 7.24-12.84, in women; HR 11.91, 95% CI 8.80-16.12, in men), whereas those with obesity and walked slowly had an approximately 12- to 15-fold higher risk (HR 12.68, 95% CI 9.62-16.71, in women; HR 15.41, 95% CI 11.27-21.06, in men). There was evidence of an additive interaction between WC and BF% and walking pace among women, explaining 17.8% and 47.9% excess risk respectively. Obesity mediated the association in women and men, accounting for 60.1% and 44.9%, respectively. CONCLUSIONS: Slow walking pace is a risk factor for type 2 diabetes independent of adiposity. Promoting brisk walking as well as weight management might be an effective type 2 diabetes prevention strategy given their synergistic effects.

Experience and Perceptions among Older Outpatients after Myocardial Infarction following an Exercise Intervention: A Qualitative Analysis from the PIpELINe Trial.

Traditional cardiac rehabilitation (CR) programs effectively improve physical performance and outcomes after myocardial infarction (MI). However, older patients are less likely to participate in such programs. The aim of this qualitative analysis was to investigate experiences and perceptions of cardiac outpatients enrolled in an innovative and exercise-based CR program and to identify possible barriers to improving adherence and quality of life. Semi-structured interviews were conducted on a sample of 31 patients (84% male; age 76 ± 6 years) from the Physical Activity Intervention in Elderly after Myocardial Infarction (PIpELINe) trial, after about six months of the event. Three main themes were identified: Personal feelings after the event; lifestyle change and perception of barriers; and relationships with familiars. Participants perceived sensations of fear at the time of their diagnosis and showed awareness of the importance of following specific health suggestions. They reported a significative change in previous habits and highlighted the need for periodic controls. Few of them felt insecure in carrying out daily activities or practicing exercise and reported an unnecessary protection from the family members. These findings will provide valuable insights for the development of a more feasible patient-centered CR model of intervention.

Exercise program for the management of anxiety and depression in adults and elderly subjects: Is it applicable to patients with post-covid-19 condition? A systematic review and meta-analysis.

The Coronavirus Disease 2019 (Covid-19) pandemic had dramatic effect on mental health, causing long-term psychiatricmorbidity. At present, there are no randomized trials reporting the effect of physical exercise on individuals with post- Covid-19 condition are available. The aim of this review was to summarize the evidence regarding the evidence on exercise as a treatment for anxiety and depression symptoms secondary to chronic diseases, which may be generalized to individuals suffering from the post- Covid-19 condition. Trials were included if they reported the effects of physical exercise programs on anxiety or depression symptoms in adults, either healthy or affected by chronic diseases. Outcomes were changes of anxiety or depression severity after an exercise-based intervention. Of the 2161 RCTs identified, eight out of 15 studies were included. Exercise was associated with greater improvements of depressive (SMD = -0.169; 95 % CI -0.302 at -0.003; p = 0.013) and anxiety symptoms (SMD = -0.263, 95 % CI -0.418 at -0.109; p = 0.001), compared with control interventions. Supervised exercise programs were effective against symptoms of anxiety or depression among individuals with chronich illnesses. Pending specific clinical trials, exercise may be considered for adoption among patients with the post Covid-19 condition.

Moderate walking speed and survival association across 23-years follow-up in female patients with cardiovascular disease.

AIMS: To estimate the association between average walking speed (WS), determined using a moderate 1-km treadmill-walking test (1 k-TWT), and all-cause mortality in female patients with stable cardiovascular disease (CVD). METHODS: A sample of 431 patients (age 67 [34-88] years), performed a 1 k-TWT and were followed for all-cause mortality for up to 23 years. Variables significantly associated with mortality were determined by Cox proportional hazard models. Based on average WS during the 1k_TWT the sample was subdivided into tertiles, and mortality risk was calculated. Receiver-operating-characteristic curves were constructed to assess the discriminatory accuracy of WS for estimating survival. RESULTS: During a median follow-up of 10.4 years, a total of 135 deaths from any cause occurred, with an average mortality rate of 4.2%. The strongest predictor of mortality was WS (c-statistic for all-cause mortality 0.801, 95% confidence intervals: 0.51-1.11, p < 0.0001). Survival rate decreased from the fastest to the lowest tertile. Compared to the group with the lowest WS, the hazard ratios (95% confidence intervals) for the second and third tertiles were 0.73 (0.48-1.12) and 0.47 (0.25-0.91), respectively (p for trend <0.0001). CONCLUSION: Average WS maintained during a moderate treadmill-walk is inversely related to survival in female patients with CVD. The 1 k-TWT is a simple and useful tool for assessing progress and stratifying risk in women undergoing secondary prevention programs.

The Effect of Active Stretching Training in Patients with Chronic Venous Insufficiency Monitored by Raster-Stereography.

(1) Background: Musculoskeletal disorders can be associated with advanced clinical stages of chronic venous insufficiency (CVI). The aim of the study is to investigate the effect of active stretching (AS) training on lower limb venous function and quality of life in patients affected by CVI. (2) Methods: A prospective two-armed pilot randomized controlled was conducted. Twenty (20) CVI patients were randomly assigned to an AS training or to a control group (C) who did not receive any exercise indication. At baseline and after three months all the participants were tested for leg volumetry (LV), air plethysmography (APG), and quality of life (QoL) measured by a disease specific validated questionnaire (VVSymQ), ankle range of motion (ROM), and postural deformities using an optoelectronic body posture machine. (3) Results: At the end of the training in the AS group a significant leg volume reduction was detected (from 2340 ± 239 mL to 2239 ± 237 mL (4.3%); p < 0.0001), whereas in the C group no significant volume changes were found. The ejection fraction rate (EF%) increased significantly from 49.3 ± 9.3 to 61.1 ± 14.5, p < 0.005. A moderate-strong linear correlation with EF% and ankle ROM variation was found (R2 = 0.6790; p < 0.0034). Several postural outcomes such as pelvic tilt, pelvic torsion, and lordotic angle significantly improved in the AS group (p < 0.01, p < 0.04, p < 0.01 respectively). (4) Conclusion: The AS training impacts on the APG parameters related to the musculoskeletal pump efficiency, opening a further possibility in the management of CVI patients by means of an appropriate adapted physical exercise program.

The Effect of Submaximal Exercise on Jugular Venous Pulse Assessed by a Wearable Cervical Plethysmography System.

The jugular venous pulse (JVP) is a one of the crucial parameters of efficient cardiovascular function. Nowadays, limited data are available regarding the response of JVP to exercise because of its complex and/or invasive assessment procedure. The aim of the present work is to test the feasibility of a non-invasive JVP plethysmography system to monitor different submaximal exercise condition. Twenty (20) healthy subjects (13M/7F mean age 25 ± 3, BMI 21 ± 2) underwent cervical strain-gauge plethysmography, acquired synchronously with the electrocardiogram, while they were carrying out different activities: stand supine, upright, and during the execution of aerobic exercise (2 km walking test) and leg-press machine exercise (submaximal 6 RM test). Peaks a and x of the JVP waveform were investigated since they reflect the volume of cardiac filling. To this aim, the Δax parameter was introduced, representing the amplitude differences between a and x peaks. Significant differences in the values of a, x, and Δax were found between static and exercise conditions (p < 0.0001, p < 0.0001, p < 0.0001), respectively. Particularly, the Δax value for the leg press was approximately three times higher than the supine, and during walking was even nine times higher. The exercise monitoring by means of the novel JVP plethysmography system is feasible during submaximal exercise, and it provides additional parameters on cardiac filling and cerebral venous drainage to the widely used heartbeat rate value.

Maintenance of Exercise Habit and Its Impact on Cardiovascular Risk Factors in Previously Sedentary People: A 7-Year Follow-Up.

The aim of the study was to assess whether the level of physical activity in daily life in previously sedentary adults had been sustained 7 years beyond a 1-year supervised walking program. One hundred ten participants (63 females, 57.5 ± 8.4 years; 47 males, 66.4 ± 7.9 years) were recalled and assessed for physical activity in daily life, weight, body mass index, blood pressure, and walking speed. Fifty-nine percentage of the participants measured met and exceeded the World Health Organization physical activity guidelines (Group 1), while 41% did not (Group 2). In both groups, we observed a significant decrease of weight (72.0 ± 14.0 kg vs. 69.7 ± 14.0 kg in Group 1; 77.4 ± 19.5 kg vs. 75.4 ± 18.6 kg in Group 2) and body mass index (25.9 ± 3.7 vs. 25.1 ± 3.9 in Group 1; 27.9 ± 5.6 vs. 27.2 ± 5.4 in Group 2). Group 1 showed a significant increase in walking speed (5.8 ± 0.7 km/hr vs. 6.2 ± 0.8 km/hr), while systolic pressure did not change from the baseline. In Group 2, systolic pressure significantly increased (131.3 ± 13.5 mmHg vs. 138.0 ± 15.5 mmHg), while walking speed did not change. A guided walking program seems to have been effective in educating sedentary people to remain physically active over time.

Promotion and maintenance of physically active lifestyle in older outpatients 2 years after acute coronary syndrome.

AIMS: To examine long-term changes in lifestyle and exercise capacity of older patients hospitalized for acute coronary syndrome (ACS) involved in an innovative centre- and home-based exercise-based secondary prevention program. METHODS: A sample of 118 patients with ACS (age 76 [72-80] years) was analysed. Long-term changes in self-reported weekly leisure-time physical activity (wLTPA), walking speed (WS), and estimated cardiorespiratory fitness (eCRF, VO2peak, mL/kg/min) were the outcome variables. The program consisted of seven individual on-site sessions including motivational interviewing to reach exercise goals. Exercise prescription was based on the results of a standardized moderate and perceptually regulated treadmill walk to estimate VO2peak. wLTPA, WS, and eCRF were assessed at 1 (baseline), 2, 3, 4, 6, 12, and 24 months after discharge. RESULTS: 87, 76, and 70 patients completed follow-up at 6, 12, and 24 months, respectively. wLTPA significantly increased during the follow-up period (median METs/H/week 2.5, 11.2, 12.0, and 13.4 at baseline, 6, 12, and 24 months, respectively; P < 0.0001). At baseline, 18% of the sample met the current international guidelines for physical activity, while 75%, 70%, and 76% of them met the recommended values at 6-, 12-, and 24-month follow-up sessions, respectively. These results were associated with increasing median WS (2.9 ± 1.0, 4.3 ± 1.2, 4.5 ± 1.1, 4.5 ± 1.2 km/h, respectively, P < 0.0001), and VO2peak (16.5, 21.4, 21.1, 21.3 mL/kg/min, respectively, P < 0.0001). CONCLUSIONS: This early, individualized exercise intervention improved long-term adherence to a physically active lifestyle, walking capacity, and eCRF in older patients after ACS. Larger studies are needed to confirm short- and long-term clinical benefits of this intervention.

Relationship between exercise capacity and grip strength in a cohort of older cardiac outpatients.

BACKGROUND: Progressive ageing of the population has highlighted the importance of the relationship between physical function and frailty in patients with chronic disease. The aim of this study was to assess the association between exercise capacity and grip strength (GS) in a cohort of older patients involved in an exercise-based secondary prevention program. METHODS: Sixty-five outpatients (aged 75±6 years) were included. Exercise capacity was assessed through the estimation of maximal oxygen consumption (V̇O2peak) and the measurement of walking speed (WS). GS was evaluated in the dominant arm using a hand-held dynamometer. RESULTS: Patients with higher V̇O2peak and WS values exhibited significantly higher GS (P<0.01). GS was significantly related to WS (P<0.01) and V̇O2peak (P<0.01), and inversely associated with age (P<0.01). Results from linear multiple regression analysis (P<0.01) demonstrate that GS was strongly associated with WS (P<0.01) and age (P=0.01), while BMI, weekly LTPA, cardiovascular diagnosis, V̇O2peak and education were not. CONCLUSIONS: The evaluation of WS, V̇O2peak and GS was feasible and well tolerated. These preliminary results suggest that prescribing regular walking activity, educating subjects to perform it at higher average WS, can help to maintain physical function in older patients with cardiovascular disease.

Improving walking speed reduces hospitalization costs in outpatients with cardiovascular disease. An analysis based on a multistrata non-parametric test.

BACKGROUND: To assess the association between walking speed (WS) and its improvement on hospitalization rates and costs in outpatients with cardiovascular disease. METHODS: Six hundred forty-nine patients participating in an exercise-based secondary prevention program were studied. Patients were divided at baseline into two groups characterized by low and high WS based on the average WS maintained during a moderate 1-km treadmill-walking test. WS and other covariates were grouped into three domains (demographic factors, medical history and risk factors), and used to estimate a propensity score, in order to create homogeneous groups of patients. All-cause hospitalization was assessed 3 years after baseline as a function of WS. Hospitalization and related costs were also assessed during the fourth-to-sixth years after enrollment. To test whether the hospitalization costs were related to changes in WS after 36 months, a multistrata permutation test was performed by combining within strata partial tests. RESULTS: The results support the hypothesis that hospitalization costs are significantly reduced in accordance with an improvement in WS. This effect is most evident among older patients, overweight or obese, smokers, and those without a history of coronary artery bypass surgery. CONCLUSIONS: The present study supports growing evidence of an inverse association between WS, risk of hospitalization and consequent health-care costs. The joint use of propensity score and multistrata permutation approaches represent a flexible and robust testing method which avoids the possible effects of several confounding factors typical of these studies.