Scholarly article on topic 'Clinical Characteristics and Course of Patients Entering Cardiac Rehabilitation with Chronic Kidney Disease: Data from the Italian Survey on Cardiac Rehabilitation'

Clinical Characteristics and Course of Patients Entering Cardiac Rehabilitation with Chronic Kidney Disease: Data from the Italian Survey on Cardiac Rehabilitation Academic research paper on "Health sciences"

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Academic research paper on topic "Clinical Characteristics and Course of Patients Entering Cardiac Rehabilitation with Chronic Kidney Disease: Data from the Italian Survey on Cardiac Rehabilitation"

Hindawi Publishing Corporation ISRN Rehabilitation

Volume 2013, Article ID 807546,10 pages http://dx.doi.org/10.1155/2013/807546

Research Article

Clinical Characteristics and Course of Patients

Entering Cardiac Rehabilitation with Chronic Kidney Disease:

Data from the Italian Survey on Cardiac Rehabilitation

Francesco Giallauria,1 Francesco Fattirolli,2 Roberto Tramarin,3 Marco Ambrosetti,4 Raffaele Griffo,5 Carmine Riccio,6 and Carlo Vigorito1

1 Department of Translational Medical Sciences, Cardiac Rehabilitation Unit, University of Naples "Federico II," Via S. Pansini 5, 80131 Naples, Italy

2 Department of Critical Care Medicine and Surgery, Cardiac Rehabilitation Unit, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Via delle Oblate 4, 50141 Florence, Italy

3 Division of Cardiac Rehabilitation, Fondazione Europea di Ricerca Biomedica, Via Uboldo 56, 20063 Cernusco S/N, Italy

4 Clinica "Le Terrazze," Via Foscolo 6/B, 21035 Cunardo, Italy

5 Cardiac Rehabilitation Unit, Department of Cardiology, La Colletta Hospital, Via del Giappone, 16011 Arenzano, Italy

6 Azienda Ospedaliera S. Anna e S. Sebastiano di Caserta, Via Gennaro Tescione 1, 81100 Caserta, Italy

Correspondence should be addressed to Francesco Giallauria; giallauria@libero.it Received 13 May 2013; Accepted 9 June 2013 Academic Editors: Y. Hu, Y. Laufer, and M. Probst

Copyright © 2013 Francesco Giallauria et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

This survey shows the clinical risk profile, resource utilization, pharmacologic treatment, and course of cardiac rehabilitation (CR) programs in patients with chronic kidney disease (CKD). Data from 165 CR units in Italy were collected online from January 28 to February 10, 2008. The study cohort consisted of 2281 patients: 200 CKD patients and 2081 non-CKD patients. CKD patients were older and showed more comorbidity and complications during CR, a more complex clinical course and interventions with less functional evaluation, and a different pattern of drug therapy at hospital discharge. CKD patients had higher mortality during CR programs due to heart failure, respiratory insufficiency, and cognitive impairment. These findings suggest that patients with CKD should not be denied access to CR, provided careful attention to clinical status, possible complications, optimization of drug therapy, and close followup.

1. Introduction

Chronic kidney disease (CKD) is a major public health problem, strongly associated with a high cardiovascular mortality [1]. The high prevalence of established traditional risk factors for atherosclerosis such as diabetes, hypertension, and older age and nontraditional risk factors such as high level of homocysteine, lipoprotein (a), fibrinogen, and C-reactive protein in patients with CKD contributes to an accelerated rate of coronary heart disease (CHD) [2].

The American Heart Association scientific statement on kidney disease and cardiovascular disease has recommended that patients with CKD be placed in the highest-risk group

for prevention, detection, and treatment of CHD risk factors [3]. CKD is prevalent in patients with CHD and is associated with a poor prognosis [4].

Exercise training alone or as core component of cardiac rehabilitation (CR) programs has several beneficial effects reducing long-term morbidity and mortality [5], preventing cardiac remodelling [6, 7], and improving cardiovascular functional capacity, cardiac symptoms, and quality of life [8]. The improvement of endothelial function [9], the antiinflammatory properties [10], the improvement of neurohormonal and autonomic balance [11-14], and the reduction of oxidative stress [15] might be some of the putative mechanisms by which exercise training exerts its beneficial effects.

Table 1: Demographics characteristics of the study population (n, %).

CKD (n = 200) Non-CKD (n = 2081) P value

Age (years) (mean ± SD) 73.6 ± 9.9 66.3 ± 11.7 <0.0001

Gender (male) 141 (70.5) 1536 (73.8) 0.31

Cardiovascular risk factors1

0-2 (low) 57 (28.5) 854 (41.0) 0.0003

3-5 (medium) 113 (56.5) 1046 (50.3)

>5 (high) 30 (15.0) 181 (8.7)

'Smoking, family history of early coronary heart disease, high blood pressure, hypercholesterolemia, body mass index >27, diabetes, sedentary lifestyle, and early menopause.

Of note, some of the 1 beneficial effects of exercise-based CR observed in the general population of CHD patients have also been reported in CKD patients [16, 17]. To our knowledge, there are no data that specifically describe in large population of patients the prevalence of CKD in patients with CHD undergoing CR programs, their clinical characteristics, and course during the CR program.

The present survey aimed at providing an insight in the clinical characteristics and course of a CKD population in the real world of CR in Italy.

2. Methods

2.1. Study Design. The multicenter, prospective observational study design of the ISYDE-2008 has been described in detail elsewhere [18,19]. In summary, the primary purpose of this study was to take a snapshot on current organization, settings, and provision of CR in Italy and to describe the patient population referred to CR, giving a comprehensive and detailed description of clinical characteristics, risk profile, diagnostic procedures, exercise and educational program, discharge modalities, treatment at discharge, and follow-up schedules. The enrolment period lasted from January 28 to February 10 2008. Data were collected on a web-based case report form, which reported data on clinical characteristics, diagnostic procedures, exercise and educational programs, treatment, and follow-up plans of all the consecutive patients discharged from CR programs in the 2-week study period. The present study focused on CKD patients. As suggested by the National Kidney Foundation Kidney Disease Outcome Quality Initiative, CKD was prospectively defined and considered present if the estimated glomerular filtration rate (eGFR) was <60 mL/ min/1.73m for 3 months at study entry [20]. The eGFR was calculated using the abbreviated Modification of Diet in Renal Disease Study Equation [21]: eGFR (mL/min/1.73 m of body surface area) = 186 x (serum creatinine in mg/dL) -1.154 x (age in years) - 0.203 x 0.742 in female subjects. As a part of geriatric multidimensional evaluation, performed in about one-fourth of our population, cognitive function was evaluated by MMSE [22], and cognitive impairment was assigned when corrected MMSE value was <21.

2.2. Participating Centers. The survey was designed to be carried out in all Italian residential and outpatient CR centers. Centers were invited to participate in the survey on a purely

voluntary basis by the executive board of the study and by the regional GICR-IACPR coordinator, who was responsible for interfacing with the investigators in each of the participating centers and overlooked the implementation of the survey protocol. Data collected in the study refer to 165 CR units (87% of all invited facilities). These CR units, representative of national CR organization, were subdivided in 103 (62.4%) residential units, 18 (10.9%) facilities with day-hospital care, and 33 (20%) facilities with outpatient CR (information not available in 11 CR units (6.7%)). The complete list of ISYDE-2008 investigators and participating centers with names of the directors or contact physicians is reported in the Acknowledgments.

2.3. Role of the Funding Source. No funding sources had any role in the study design, conduct, data collection, analysis, data interpretation, or writing of this paper. The GICR-IACPR coordinated the study, managed the data, and undertook all analyses. All members of the scientific board and writing committees had full access to the database and assumed final responsibility for the results submitted for publication.

2.4. Statistical Analysis. The main analysis was performed subdividing the study cohort into two groups, according to the diagnosis of CKD. Data are expressed as means ± standard deviation (SD) or proportions. Comparisons between groups were performed by unpaired i-test, or Fisher exact test as required. Correlations between variables were assessed with Pearson's correlation coefficient. Predictors of death were evaluated with multivariate logistic regression analysis. All analyses were performed using SAS (version 9.1, Cary, NC) with significance set at P < 0.05.

3. Results

Table 1 summarizes the demographic characteristics of the study population. The study cohort consisted of 2281 patients (66.9± 11.8 yrs): 200 (71.3± 12.2 yrs, 66% male) CKD patients and 2081 (66.3 ±11.6 yrs, 74% male) non-CKD patients. CKD patients showed a significantly higher cardiovascular risk factors score (including smoking, history, hypertension, dys-lipidemia, obesity, diabetes, sedentary lifestyle, and early menopause) compared to the non-CKD cohort (P = 0.0003).

Table 2: Previous interventions and comorbidities («, %).

CKD (« = 200) Non-CKD (« = 2081) P value

Previous myocardial infarction 77 (38.5) 426 (20.5) <0.0001

Previous percutaneous transluminal coronary angioplasty 37 (18.5) 188 (9.0) <0.0001

Previous cardiac surgery 33 (16.5) 217 (10.4) 0.008

Heart failure 69 (24.2) 131 (6.6) <0.0001

Carotid arteries atherosclerosis1 20 (10.0) 140 (6.7) 0.08

Peripheral artery disease2 25 (12.5) 126 (6.0) 0.0005

Chronic obstructive pulmonary disease 52 (26.0) 246 (11.8) <0.0001

Respiratory insufficiency 19 (9.5) 93 (4.5) 0.002

Hepatic disease 11 (5.5) 52 (2.5) 0.01

Stroke 12 (6.0) 71 (3.4) 0.06

Cognitive impairment 21 (10.5) 43 (2.1) <0.0001

Diabetes 97 (48.5) 378 (18.2) <0.0001

Orthopedic/joints/immune-related disease 29 (14.5) 178 (8.5) 0.005

'Stenosis >70% or previous revascularization; 2Fontaine stage >1 or previous revascularization.

Table 3: Complications during cardiac rehabilitation programs («, %).

CKD (« = 200) Non-CKD (« = 2081) P value

Atrial fibrillation 49 (24.5) 403 (19.4) 0.08

Severe ventricular arrhythmias1 11 (5.5) 79 (3.8) 0.23

Permanent pacemaker implantation 13 (6.5) 57 (2.7) 0.003

Acute myocardial infarction 4 (2.0) 31 (1.5) 0.57

Cerebrovascular events2 5 (2.5) 36 (1.7) 0.43

Cognitive impairment' 7 (2.5) 31 (1.5) 0.03

Anemia3 38 (19.0) 275 (13.2) 0.02

Worsening of CKD or new onset of renal failure4 63 (31.5) 56 (2.7) <0.0001

Hepatic insufficiency 4 (2.0) 14 (0.7) 0.04

Sternal revision 7 (3.5) 27 (1.3) 0.01

Massive pleural effusion needing thoracenthesis 6 (3.0) 51 (2.5) 0.63

Inotropic support/mechanical assistance 24 (12.0) 88 (4.2) <0.0001

Respiratory assistance5 17 (8.5) 78 (3.7) 0.0001

Systemic infections 16 (8.0) 62 (3.0) 0.0002

Death 4(2) 11 (0.5) 0.02

1 >30 sec or symptomatic ventricular tachycardia; 2stroke, transient ischemic attack; 3Hb <10g/dL or >3g/dL reduction with respect to the preindex event value; 4creatinine increase >1 mg/dL; 5including oxygen therapy, mechanical ventilation, continuous positive airway pressure (cPAP), bilevel positive airway pressure (biPAP) >96 h. 'Worsening of cognitive impairment or new onset of cognitive impairment.

Compared to non-CKD, CKD patients showed a greater frequency of previous interventions and comorbidities such as myocardial infarction, percutaneous coronary intervention (PCI), cardiac surgery, heart failure, diabetes, peripheral artery disease (PAD), chronic obstructive pulmonary disease (COPD), cognitive impairment, and orthopedic/immuno-logical diseases (Table 2).

During CR programs, CKD patients underwent more permanent pacemaker implantation or developed more complications such as anemia, systemic infections, and worsening of CKD and required more frequently inotropic support or respiratory assistance compared to non-CKD patients (Table 3).

Differences between CKD and non-CKD patients were also detected in diagnostic or therapeutic procedures during

CR (Table 4). Compared to non-CKD, CKD patients less likely underwent diagnostic procedures such as exercise stress testing on admission or at discharge, whereas no significant differences were found among groups in six-minute walking test (6MWT) on admission or at discharge and cardiopulmonary exercise stress tests at discharge (Table 4). As many as 77 CKD patients (38%) received no physical performance test (nor 6MWT, exercise stress testing, or cardiopulmonary exercise testing); this proportion was significantly greater than that in non-CKD patients (20%, P < 0.0001). Compared to non-CKD not performing any physical performance testing, CKD patients not performing any physical performance testing showed a higher percentage of comorbidities such as myocardial infarction (36% versus 16%, P < 0.0001), percutaneous coronary intervention (PCI) (16% versus 5%,

Table 4: Diagnostic and therapeutic procedures during cardiac rehabilitation programs («, %).

CKD (« = 200) Non-CKD (« = 2081) P value

6-minute walking test on admission 79 (39.5) 904 (43.4) 0.28

6-minute walking test at discharge 83 (41.5) 864 (41.5) 0.99

Exercise stress testing on admission 9 (4.5) 437 (21.0) <0.0001

Exercise stress testing at discharge 27 (13.5) 678 (32.6) <0.0001

Cardiopulmonary exercise stress testing on admission 4(2.0) 118 (5.7) 0.02

Cardiopulmonary exercise stress testing at discharge 16 (8.0) 141 (6.8) 0.51

Holter electrocardiogram 88 (44.0) 832 (40.0) 0.27

Venous infusions 68 (23.9) 171 (8.6) <0.0001

Thoracentesis 6 (3.0) 26 (1.2) 0.04

Blood transfusions 9 (4.5) 13 (0.6) <0.0001

Geriatric multidimensional evaluation 58 (29.0) 396 (19.0) 0.0007

Computed tomography 16 (8.0) 73 (3.5) 0.002

Ultrasounds 44 (22.0) 330 (15.6) 0.02

Individual exercise sessions 92 (46.0) 495 (23.8) <0.0001

Table 5: Drug therapy at hospital discharge after cardiac rehabilitation programs.

CKD (« = 200) Non-CKD (« = 2081) P value

Inhibitors of angiotensin-converting enzyme 86 (43.0) 1171 (56.3) 0.0003

Angiotensin II receptor blockers 46 (23.0) 341 (16.4) 0.02

Beta-blockers 133 (66.5) 1433 (68.9) 0.49

Nitrates 68 (34.0) 372 (17.9) <0.0001

Diuretics 156 (78.0) 1012 (48.6) <0.0001

Statins 119 (59.5) 1391 (66.8) 0.03

Omega-3 fatty acids 26 (13.0) 352 (16.9) 0.15

Oral anticoagulant therapy 72 (36.0) 532 (25.6) 0.001

Aspirin 100 (50.0) 1408 (67.7) <0.0001

Digitalis 23 (11.5) 101 (4.8) <0.0001

Amiodarone 25 (12.5) 107 (5.1) <0.0001

Calcium channel blockers 51 (25.5) 385 (18.5) 0.01

Antidepressant 21 (10.5) 120 (5.8) 0.008

P = 0.0008), carotid arteries atherosclerosis (13% versus 6%, P = 0.02), peripheral artery disease (PAD) (14% versus 6%, P = 0.006), heart failure (32% versus 12%, P < 0.0001), chronic obstructive pulmonary disease (COPD) (31% versus 13%, P < 0.0001), diabetes (54% versus 16%, P < 0.0001), hepatic disease (6% versus 2%, P = 0.02), cognitive impairment (16% versus 5%, P = 0.0005), and orthopedic disease (26% versus 14%, P = 0.007) and a higher percentage of complications during the CR program such as anemia (21% versus 9%, P = 0.003), worsening of CKD (30% versus 3%, P < 0.0001), need of inotropic support (5% versus 1%, P = 0.007) or respiratory assistance (8% versus 3%, P = 0.02), infections (12% versus 4%, P = 0.007), and blood transfusions (8% versus 2%, P = 0.005), respectively.

Echocardiography showed a lower percentage of CKD patients with preserved left ventricular ejection fraction (LVEF > 50%) compared to non-CKD patients (37% versus 61%, P < 0.0001, resp.) and a higher percentage of moderate (LVEF = 30-49%, 37% versus 26%, P < 0.0001, resp.) and

severe (LVEF < 30%, 17% versus 5%, P < 0.0001, resp.) compromise of LVEF compared to the non-CKD cohort.

Patients with CKD also underwent more frequent geriatric multidimensional evaluation, and CT or ultrasound diagnosis, venous infusion, blood transfusion, or thoracentesis. They also performed preferentially more individually tailored rather than group exercise training session.

At discharge, compared to non-CKD, CKD patients were less frequently prescribed angiotensin-converting enzyme inhibitors, statins, and aspirin. Conversely, CKD patients were more frequently prescribed angiotensin II receptor blockers, nitrates, diuretics, oral anticoagulant therapy, digitalis, amiodarone, insulin, oral hypoglycemic drugs, and calcium channel blockers (Table 5). No significant differences were observed in beta-blockers or omega-3 fatty acids discharge prescription among the 2 groups (Table 5).

CKD patients were less likely discharged home (88% versus 91%, P = 0.05) and more likely transferred to intensive care units (8% versus 4%, P = 0.005). CKD patients

had higher death rate during CR programs (2.0% versus 0.5%, P = 0.02). After adjusting for age, ejection fraction, comorbidities (acute myocardial infarction, percutaneous coronary intervention, cardiac surgery, carotid artery critical lesions, peripheral artery disease, respiratory insufficiency, heart failure, diabetes, stroke, and cognitive impairment), and complications during CR program (atrial fibrillation and severe ventricular arrhythmias), multivariate logistic analysis showed that heart failure (OR 1.6, 95% CI, 1.1 to 2.4, P = 0.04), respiratory insufficiency (OR 2.4, 95% CI, 1.4 to 4.0, P = 0.0007), and cognitive impairment (OR 4.5, 95% CI, 2.5 to 8.1, P < 0.0001) were significant predictors of death in CKD patients.

4. Discussion

To the best of our knowledge, the present study is the first to explore the characteristics of the "real world" CKD patients admitted to CR programs in Italy. The principal findings of this study were the higher burden of cardiovascular risk factors and comorbidities associated with a worse clinical course during CR in patients with CKD compared to patients without CKD.

This survey revealed that only about 9% of patients admitted to CR had diagnosed CKD, a number significantly lower than that reported in a cohort of patients with post-myocardial infarction followed at the Mayo Clinic (29.6%), among patients enrolled in the Valiant Trial (33.6%), among a national cohort of elderly patients with myocardial infarction (37%), and in a other cohorts of patients referred for CR (25.6%) [4, 23-25]. The lower percentage of CKD patients found in our study, compared to previous reports in CR environment [25], may reflect indication bias, with a the tendency of deny referral to CR programs of patients with CKD in Italy. In addition, in agreement with previously reported studies, our patients with CKD had a greater burden of comorbidities and cardiovascular risk factors than their non-CKD counterparts.

This survey showed the higher prevalence of CKD patients participating to CR programs with previous PCI or coronary artery bypass graft (CABG). Patients with CKD undergoing myocardial revascularization have worse survival than other CAD patients [26, 27]. Several studies have reported that PCI in patients with CKD may be associated with poor long-term results [28, 29]. In a large retrospective analysis of patients undergoing elective PCI with balloon angioplasty or/and bare-metal stent implantation, CKD was found to have a negative prognostic impact, similar to that of diabetes, on cardiovascular morbidity and mortality [30]. Recently, Ashrith et al. [31] showed that in patients with CKD and multivessel CAD, CABG led to better survival than PCI with drug-eluting stents, but CABG patients had a greater short-term risk of requiring permanent hemodialysis. In our study, despite the worsening of CKD observed in many patients, no patient required hemodialysis. This might be a consequence of a selection bias, since our observational study likely represents a selected population of patients with CKD after an acute cardiac event, where the worst patients

requiring hemodialysis immediately after coronary revascularization were not addressed to CR. Future prospective studies are needed in order to evaluate the effect of CR in CKD patients undergoing PCI or CABG in terms of post-procedure hemodialysis dependence and mortality.

Compared to non-CKD patients, we found a roughly doubled prevalence of symptomatic PAD in CKD patients enrolled to CR programs (12.5% versus 6%, P = 0.0005). Selvin and Erlinger [32] reported that low kidney function (OR 2.00, 95% CI 1.08 to 3.70) was positively associated with prevalent PAD. In patients with CAD, the prevalence of previously unrecognized PAD is 15% [33]. In this survey, 7% of CKD patients had coexisting diabetes and PAD, thus representing a very high-risk patient population referred to CR programs.

This survey also highlighted the higher prevalence of diabetes in CKD patients participating to CR programs compared to the non-CKD cohort (48% versus 18%, P < 0.0001, resp.). This high prevalence of diabetes in our CKD patients is not surprising, since diabetes is one of the major risk factor for CKD and for CHD [34].

Despite the fact that geriatric multidimensional evaluation was performed in less than one-third of the patients, the present survey showed that cognitive impairment prevalence (10 versus 2%) and worsening of cognitive impairment during CR (2.5 versus 1.5%) were significantly higher in CKD patients compared to the non-CKD cohort. In fact, CKD is known to independently affect cognitive status: recent studies have shown impaired kidney function to be associated with greater prevalence of cognitive impairment [35], a more-rapid rate of cognitive decline [36], and incident cognitive impairment [37, 38].

A previous study showed that in patients with mild cognitive impairment of heterogeneous etiology including vascular, metabolic, or endocrine factors, CKD was an independent risk factor for cognitive impairment [39], and it showed that CKD in older adults with mild cognitive impairment was a potentially modifiable risk factor.

An additional cause of mental deterioration in our CKD patients was the frequent association with CHF. In our survey, 24.2% of CKD patients had CHF. It is well recognized that CHF is an independent factor affecting cognitive impairment [40], and cognitive dysfunction and heart failure are common conditions in the elderly [41]. Mild cognitive impairment, a subtle but measurable deficit usually involving the memory domain, is the most commonly reported dysfunction in elderly patients with heart failure, being detectable in more than half of the patients [40]. Potential underlying mechanisms for cognitive dysfunction in heart failure may involve low cardiac output status with consequent cerebral hypoperfusion as well as increased risk of cerebrovascular ischemic events [40]. Therefore, these findings suggest that an initial evaluation of cognitive performance should be implemented in CKD patients, especially in older patients and those with CHF.

The present survey showed higher prevalence of anemia in CKD patients compared to the non-CKD cohort (19% versus 13%, P = 0.02). It is well known that anemia is a very common feature of CKD patients [42], and it is not

surprising that in patients with CKD undergoing CABG surgery or other invasive procedures anemia may be even more frequent. Reduced hemoglobin levels and CKD are common and interrelated factors in CHF [43, 44].

Chronic kidney disease can contribute to the development and exacerbation of heart failure and progressive heart failure contributes to renal hypoperfusion and activation of inflammatory factors, which can lead to the development or worsening of kidney dysfunction. These findings suggest that in CKD patients during CR hemoglobin level should be closelymonitored and raised to acceptable levels, especiallyin older and CHF patients [43]. It is also recommended that in CHF patients with CKD the hemoglobin values should not be raised beyond 12 mg/dL, in order to avoid risk of thrombosis [45].

The present survey also highlighted that larger proportion of CKD patients did not perform any type of physical performance test compared to the non-CKD cohort. This might have prognostic relevance, since the lack of referral to exercise stress testing is by itself a negative prognostic indicator [46].

The present survey revealed also interesting differences relatively to drugs use. The rather low discharge indication to statin in the total populations is a consequence of the difficulties of adopting in the real clinical world the recommendations of international guidelines regarding secondary prevention [47] or of the presence of many patients after noncoronary surgery not requiring statins (59.5% (CKD) versus 66.8% (non-CKD patients), P = 0.03). Moreover, CKD patients showed a higher use of diuretics that might have precipitated in some patient in the worsening of CKD [48].

Finally, complications (particularly arrhythmias, pump failure requiring inotropic support, respiratory insufficiency, worsening of CKF, or infections) and mortality during CR were higher in CKD patients compared to the non-CKD cohort, reflecting the higher clinical risk profile of these patients after an acute cardiac event. In patients with CHD or CHF, CKD has been identified as an important predictor of adverse outcome and increased morbidity [4, 23, 24]. Anavekar et al. [4] reported a 10% increase in the hazard of death and nonfatal cardiovascular outcomes after myocardial infarction for every 10-unit decrease in GFRbelow 81 mL/min per 1.73 m2. Wright et al. [23] reported a 3-fold increase in inhospital mortality after myocardial infarction in individuals with mild renal failure (GFR = 51-75 mL/min per 1.73 m2), a 7-fold increase among those with moderate renal failure (GFR = 35-50 mL/min per 1.73 m2), and a >10-fold increase among patients with severe renal failure. Bruch et al. [49] reported a 3-fold increase of cardiac events in CHF patients with CKD; and outcome was significantly worse in CKD patients than in patients without CKD (event-free survival rate 51% versus 87% in those without CKD, P = 0.001). Therefore, more attention to the clinical stabilization of these patients is required during CR.

Our study has several limitations. The observational nature of the study cannot rule out that the more severely compromised patients with CKD were not addressed to CR

and, therefore, those described in our study may represent a selected relatively healthy minority. The number of patients with CKD reported in the present survey is very small (about 9% of the overall population). This makes the study underpowered for a deepened interpretation. This probably depends on the very small time of the enrolment period (only two weeks). The combination of data from CR centers offering very different cardiac rehabilitation regimens (e.g., residential versus outpatients) is another confounder. The observational nature of the study cannot rule out that the more severely compromised patients with CKD were not addressed to CR and, therefore, those described in our study may represent a selected more relatively healthy minority. Moreover, according to recent evidence [50-52], the present survey did not collect data regarding modality of exercise training regimen (interval versus continuous) or the dose of exercise (in terms of volume and intensity) that can greatly affect the functional and clinical parameters (together with outcome) of CKD patients. Another major limitation of the present study was the lack of reporting some important functional and clinical parameters of possible interest; this was due to the short-term survey type of study, which collected the essential data in order to characterize the demographic and clinical course of the patients. Despite these limitations, the survey successfully highlighted crucial differences in the clinical characteristics, risk profile, management, and short term outcome in CKD patient population entering CR programs in Italy, compared to non-CKD patients.

In conclusion, this survey shows in a large population the clinical risk profile, resource utilization, pharmacologic treatment, and course of CR programs in CKD patients, compared to non CKD patients. In the future, prospective studies are needed in order to identify the best strategies for expanding referral to CR in more compromise patients, fostering the application of tailored functional evaluation, optimization of pharmacological and nonpharmacological treatment, and adherence to secondary prevention guidelines, with the aim of reducing in-hospital complications and improving functional recovery, long-term mortality, morbidity, and quality of life in CKD patients. Therefore, patients with CKD should not be denied access to CR, provided careful attention to clinical status, possible complications, optimization of drug therapy, and close followup.

Acknowledgments

On behalf of the ISYDE-2008 Investigators of the Italian Association for Cardiovascular Prevention and Rehabilitation (GICR-IACPR). ISYDE-2008 Study Investigators. Scientific Board. R. Tramarin (Cernusco S/N-MI), R. Griffo (Aren-zano, GE), C. Riccio (Caserta), R. Carlon (Cittadella, PD), A. Castello (Palermo), M. Ferratini (Milano), C. Schweiger (Milano), C. Chieffo (Napoli), C. Vigorito (Napoli). Writing Committee. R. Tramarin (Cernusco S/N-MI), C. Vigorito (Napoli); M. Ambrosetti (Cunardo, VA), S. De Feo (Peschiera del Garda, VR), R. Griffo (Arenzano, GE), M. Piepoli (Piacenza), C. Riccio (Caserta). Executive Committe. M. Ambrosetti (Cunardo, VA), S. De Feo (Peschiera del Garda, VR), T. Diaco (Rivolta d'Adda, CR). Delegati Regionali del

Gruppo Italiano di Cardiologia Riabilitativa e Preventiva: Abruzzo: C. Ciglia (Chieti), Basilicata: A. Lapolla (Policoro, MT), Calabria: F. Pietropaolo (Soriano Calabro, VV), Campania: G. Furgi (Telese Terme, BN), Friuli Venezia Giulia: G. Martin (Sacile, PN), Emilia Romagna: P. Semprini (Rimini), Lazio: A. Avallone (Roma), Liguria: D. Bertoli (Sarzana, SP), Lombardia: T. Diaco (Rivolta d'Adda, CR), Marche: R. Belardinelli (Ancona), Piemonte: F. Soffiantino (Lanzo Torinese, TO), Puglia: D. Scrutinio (Cassano Murge, BA), Sardegna: P. Maxia (Cagliari), Sicilia: R. Coco (Catania), Toscana: C. Giustarini (Volterra, PI), Umbria: P. Anniboletti (Perugia), Veneto: G. Favretto (Motta di Livenza, TV). Technical Support. P. Vaghi (Saronno), P. Calisi (Arenzano, GE), C. Chiavetta (Genova), Aristea S.p.A. (Genova), Segno & Forma S.p.A. (Milano). ISYDE-2008 Investigators (Italian Regions in Italic). Abruzzo: Leonello Guarracini, Presidio Ospsaledaliero Tagliacozzo, Tagliacozzo; Carlo Ciglia, Casa di Cura Villa Pini DAbruzzo, Chieti; Giorgio, Marcellini, Presidio Ospedaliero S. Omero, S. Omero. Calabria: M. Iannopollo, Presidio Ospedaliero Siderno, USL 9 Locri (RC), Siderno; Gennarino Borrello, Azienda Ospedaliera Mater Domini, Catanzaro; Milena Matta, Presidio Ospedaliero di Cetraro, Cetraro; N. Peccerillo, Ospedale di Mormanno, ASL 2 Castrovillari, Mor-manno; Franco Boncompagni, Ospedale dell'Annunziata, Cosenza; Achille Amici, Casa di Cura "San Francesco", Mendicino (CS), Mendicino; Francesco Pietropaolo, Presidio Ospedaliero, Soriano Calabro; Emidio Feraco, IRCCS INRCA, Cosenza; G. Pulitano, Presidio Ospedaliero Policlin-ico Madonna della Consolazione, Reggio Calabria; Ermete Tripodi, ASP 5 Regione Calabria, Scilla. Campania: Giuseppe Furgi, IRCCS Fondazione Salvatore Maugeri, Telese Terme; Carmelo Chieffo, Casa di Cura Clinical Center, Napoli; Soc-corso Capomolla, Presidio Ospedaliero Polispecialistico Don Gnocchi Onlus, SantAngelo dei Lombardi; Paolo Golino, Azienda Ospedaliera di Caserta, Dipartimento di Cardiologia, Caserta; Gennaro Parrilli, Campolongo Hospital S.p.A. Casa di Cura, Eboli; Antonio Di Patria, Casa di Cura Villa delle Magnolie, Castel Morrone; Claudio Di Gioia, Casa di Cura Privata Villa Margherita, Istituto S. Giuseppe Moscati, Benevento; Domenico Micieli, Azienda Ospedaliera V. Monaldi, Napoli; Carlo Vigorito, Azienda Universitaria Policlinico, Universita di Napoli Federico II, Napoli; Silvio Perrotta, ASL Napoli 1, Napoli; Alessandro Rubino, Azienda S. G. Moscati, Avellino; Vincenzo Aulitto, Centro Serapide S.p.A., Pozzuoli; Gerardo Riccio, Ospedale di Nocera, Nocera Inferiore. Emilia Romagna: Luciano Codec, Azienda Universitaria Ospedale S. Anna, Ferrara; Paolo Coruzzi, Fondazione Don Carlo Gnocchi, Onlus, Parma; Enrico Violi, Azienda Ospedaliera di Reggio Emilia, Castelnovo Monti; Massimo Nardini, Ospedale Regina Margherita, Castelfranco Emilia; Stefano Urbinati, Azienda USL di Bologna, Bologna; Sylvia Dcruz, Casa di Cura Privata ad Indirizzo Riabilitativo San Giacomo srl, Ponte dell'Olio; Pierluigi Semprini, Ospedale Infermi Rimini, Rimini; Massimo Piepoli, Azienda Unita Sanitaria Locale di Piacenza, Piacenza; Alessandro Fucili, Ospedale Sant'Anna, Ferrara; Massimo Cerulli, Ospedale Privato Accreditato Villa Pineta, Gaiato di Pavullo N/F; Bini Roberto, Azienda USL Cesena, Cesenatico; Guido Balestra, Villa Maria Cecilia Hospital, Cotignola. Friuli Venezia

Giulia: Dulio Tuniz, IMFR Udine, ASS N. 4, Udine; Giovanni Martin, Azienda Ospedaliera Santa Maria degli Angeli Pordenone, Sacile; Pierpaolo Gori, Casa di Cura Pineta del Carso, Aurisina; Roberto Marini, ASS N. 2 Isontina, Gorizia; Tullio Morgera, Ospedale San Polo, Monfalcone. Lazio: Franco Di Mario, Istituto Clinico Riabilitativo Villa delle Querce, Nemi; Maurizio Volterrani, IRCCS San Raf-faele Pisana, Roma; Alfonso Galati, Presidio Ospedaliero Santo Spirito, Presidio Villa Betania, ASL Roma E, Roma; Alessandro Salustri, Policlinico Luigi Di Liegro, Roma; Anna Patrizia Jesi, Presidio Ospedaliero Salus Infirmorum, Roma; Augusto Lacch, Azienda Ospedaliera San Camillo, Forlanini, Roma; Francesco Loperfido, Complesso Integrato Columbus. Universita Cattolica del Sacro Cuore, Roma. Liguria: Luca Corsiglia, Istituto Cardiovascolare Camogli, Ruta di Camogli; Raffaele Griffo, ASL 3 Genovese, Aren-zano; Paolo Pantaleo, Struttura Ospedaliera Privata Accred-itata Villa Azzurra, Rapallo; Guido Gigli, Regione Liguria ASL 4, Centro Regionale di Riabilitazione Cardiologica, Sestri Levante; Daniele Bertoli, ASL 5 Spezzino, Sarzana. Lombardia: Diego Marchesi, Clinica Domus Salutis Ancelle della Carita, Brescia; Oreste Febo, IRCCS Fondazione Sal-vatore Maugeri, Montescano; Franco Cobelli, IRCCS Fon-dazione Salvatore Maugeri Pavia, Pavia; Claudio Malinverni, Azienda Ospedaliera "Bolognini", Seriate; Maurizio Ferratini, Fondazione Don Gnocchi Onlus, Milano; Norman Jones, Ospedale Trabattoni Ronzoni, Seregno; Claudio Anza, Multi-medica Holding, Presidio Ospedaliero di Castellanza, Castel-lanza; R. Frizzelli, Azienda Ospedaliera C. Poma di Man-tova, Bozzolo; Paolo Gei, Spedali Civili di Brescia, Gardone Riviera; Flavio Acquistapace, Policlinico di Monza, Monza; Roberto Pedretti, IRCCS Fondazione Salvatore Maugeri, Tradate; Roberto Tramarin, Fondazione Europea di Ricerca Biomedica, Onlus, Cernusco S/N, Milano; Stefano Carugo, Centro di Cardiologia Riabilitativa, Pio Albergo Trivulzio, Milano; Gabriella Malfatto, Istituto Auxologico Italiano IRCCS, Milano; Tommaso Diaco, Azienda Ospedale Mag-giore di Crema, Rivolta DAdda; Marco Ambrosetti, Clinica Le Terrazze, Cunardo; Carlo, Meloni, Ospedale San Raffaele IRCCS U.O. Riabilitazione Cardiaca, Milano; Amerigo Giordano, IRCCS Fondazione Salvatore Maugeri, Lumezzane; Alberto Schizzarotto, Azienda Ospedaliera S. Antonio Abate di Gallarate, Somma Lombardo; Renzo Zanettini, Azienda Ospedaliera Istituti Clinici di Perfezionamento, Milano; Roberto Bosco, Ospedale Romano di Lombardia, Romano di Lombardia; Giuseppe Occhi, Azienda Ospedaliera della Valtellina e Valchiavenna, Sondalo; Stefano Aglieri, Istituto Clinico Humanitas, Rozzano; Giuseppe Caprioli, Humanitas, Cliniche Gavazzeni S.p.A., Bergamo; Nicola Cuocina, Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo; Luciano Lazzaroni, Aurelio Lorenzi, Centro di Cardiologia Riabilitativa di Cesano Boscone, Casa di Cura Ambrosiana, Cesano Boscone; Cinzia Savonelli, Cof Lanzo Hospital S.p.A. Clinica Ortopedica e Fisiatrica., Lanzo D'Intelvi; Marco Veni-ani, Azienda G. Salvini Garbagnate Milanese, Rho; Giovanni Corda, Azienda Ospedaliera ed Universitaria: Ospedale di Circolo ed Universita dell'Insubria, Varese, Cuasso al Monte; Claudia Meinecke, Azienda Istituti Ospitalieri di Cremona, Cremona; Giuseppe Castiglioni, ASL Prov. Milano, Presidio

Ospedaliero Cassano D'Adda, Cassano DAdda; Ravizza Pier-franco, Azienda Ospedaliera Ospedale di Lecco, Merate; Paolo Giani, Fondazione Europea di Ricerca Biomedica Onlus, Trescore Balneario; Fabio Robustelli della Cuna-Ospedale di Morbegno, ASL Provincia di Sondrio, Mor-begno; Giuseppe Gullace, Azienda Provinciale Ospedale di Lecco, Lecco; Federico Passoni, Azienda Ospedaliera di Leg-nano, Cuggiono; Maria Vittoria Barelli, Centro Fisioterapico Riabilitativo Club Francesco Conti, Milano; Italo Richichi, Ospedale San Matteo U.O. di Riabilitazione, Belgioioso; Angelo Rossi, Casa di Cura Villa Esperia, Salice Terme; Alessandro Politi, Ospedale Generale di Zona, Gravedona. Marche: Romualdo Belardinelli, Azienda Ospedaliero, Universitaria Umberto I, Ancona; Casa di Cura Villa Serena, Jesi; Mauro Persico, ASUR Marche Zona Territoriale 12, San Benedetto del Tronto, Area Vasta N. 5, San Benedetto del Tronto. Piemonte e Valle d'Aosta: Pantaleo Giannuzzi, IRCCS Fondazione Salvatore Maugeri, Clinica del Lavoro e della Riabilitazione, Veruno; Gianmauro Mazzucco, Casa di Cura Villa Serena, Centro Medico di Riabilitazione Cardiologica e Pneumologica, Piossasco; Enzo Bosimini, Casa di Cura Major, Sede Distaccata IRCCS Fondazione Maugeri Veruno, Torino; Giuseppe Riva, Casa di Cura Riabilitativa Stella del Mattino, Boves; Francesco Soffiantino, Presidio Ospedaliero di Lanzo, Lanzo Torinese; Nicola Massobrio, Ospedale Evangelico Valdese di Torino, Torino; Luca Gon-doni, Unita Operativa ad indirizzo Cardiologico, IRCCS Istituto Auxologico Italiano, Piancavallo di Oggebbio; Franco Aina, Azienda Ospedaliero-Universitaria Ospedale Maggiore della Carita di Novara, Novara; Biagio Ingignoli, Ospedale Ss Trinita, Fossano; Maria Vincenza Cal, Ospedale di Acqui Terme, Acqui Terme; Aillon Costante, Azienda USL Valle DAosta, Ospedale Regionale "Umberto Parini", Aosta. Puglie: Domenico Scrutinio, IRCCS Fondazione Salvatore Maugeri, Cassano Murge; Massimo Villella, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo; Concetta La Rosa, Casa di Cura Villa Verde snc, Taranto. Sardegna: Luigi Sannia, ASL Sassari, Sassari. Sicilia: Paolo Barbanto, Presidio Ospedaliero M. Ascoli, S. Tommaselli, Azienda Ospedaliera, Catania; Antonio Castello, Ospedale Buccheri La Ferla Fatebene-fratelli, Palermo; Rosario Coco, Azienda Ospedaliera Canniz-zaro, Dipartimento Cardiovascolare, Catania; Renato Ram-etta, Azienda Ospedaliera "San Giovanni di Dio", Agri-gento; Daniele Albanese, Unitaa di Valutazione Funzionale e Riabilitazione del Cardiopatico, Ospedale Civico A.R.N.A.S., Palermo; Antonio Circo, Casa di Cura Carmide Villa l'Ulivo, Catania; Rosaria Raciti, Centro Cuore Morgagni, Pedara; Luigi Scarnato, Casa di Cura Regina Pacis, San Cataldo; Flavia Dispensa, Fondazione Istituto San Raffaele Giglio, Cefalu; Leondardo La Spina, Centro Ionico di Cardiologia, Riposto; Alfio Stuto, Star For Life c/o Poliambulatorio di Cardiologia Dr. Armaro Biagio s.a.s., Siracusa; Calogero Vasco, Azienda Ospedaliera Umberto I, Enna; Salvatore Gibiino, Diagnostica Cardiovascolare del Dr. S. Gibiino & C. snc., Catania; Michele Gabriele, Ospedale di Mazara Del Vallo, Mazara Del Vallo; Claudio Dispensieri, Azienda Ospedaliera Piemonte, Messina; Vittorio Carini, Casa di Cura Riabilitativa "Villa Sofia", Acireale. Toscana: Michele Provvidenza, ASL 12 Versilia, Presidio Ospedaliero di Viareggio, Lido di Camaiore;

Alessandro Scalzini, ASL 6 Livorno, Presidio Ospedaliero di Cecina, Cecina; Carlo Giustarini, Auxilium Vitae Volterra S.p.A., Volterra; Claudio Macchi, Fondazione Don Gnocchi Onlus, IRCCS, Impruneta; Francesco Fattirolli, Azienda Ospedaliero Universitaria Careggi, Firenze; Mauro Vannucci, IFCA Villa Ulivella e Glicini, Firenze; Luciana Iacopetti, ASL 3 Pistoia, Presidio Ospedaliero Pescia, Pescia; Mario Cordoni, ASL 6 Livorno, Presidio Ospedaliero di Piombino, Piombino. Trentino e Alto Adige: Ferrario Gabriele, Casa di Cura Eremo, Arco; Renato Santoni, Ospedale Classificato San Pancrazio, Arco; Walter Pitscheider, Centro di Riabilitazione del Cardiopatico, Salus Center, Bolzano; Roberto Bettini, Ospedale di Trento, Mezzolombardo; Daniela Girardini, S. Maria del Carmine, Rovereto, Centro di Riabilitazione Cardiologica Ospedale di Ala, Ala. Umbria: Sara Mandorla, ASL 1, Gualdo Tadino, Gualdo Tadino; Fabrizio Anniboletti, ASL 2 Servizio di Cardiologia Ex Ospedale Grocco Perugia, Perugia; Federico Patriarchi, UO Cardiologia Ospedale di Foligno, Nocera Umbra. Veneto: Giuseppe Favretto, Ospedale Riabilitativo di Alta Specializzazione S.p.A., Motta di Livenza; Pier Luigi Baroni, Casa di Cura Villa Garda, Garda; Fede Bordin, ASL N. 4, Presidio Ospedaliero di Thiene, Thiene; Pietro Biondi, ULSS 8, Montebelluna; Fabio Bellotto, Istituto Riabilitativo, Cortina D'Ampezzo; Albino Zanocco, Azienda Ospedaliera, Mirano; Andrea Ponchia, ULSS 16, Padova; Enzo Mantovani, Azienda ULSS 15, Camposampiero; Ennio Li Greci, Ospedale Don L. Chiarenzi, AALSS 21 Legnago (Verona), Zevio; Roberto Carlon, Azienda ALSS 15 Presidio Ospedaliero di Cittadella, Cittadella; Leopoldo Celegon, UO di Cardiologia, Riabilitazione Cardiologica, Castelfranco Veneto; Stefano Baracchi, Ospedale al Mare Lido di Venezia, Lido di Venezia; Grazia Pizzolato, AUSSL N. 10, San Dona di Piave; Lorenzo Peroni, Policlinico San Marco, Mestre; Enzo Apolloni, Ospedale di Asiago, Asiago; Gianmarco Mosele, Casa di Cura Privata Villa Margherita S.r.l., Arcugnano; Mario Guarnerio, Ospedale di Feltre, Feltre; Loris Roncon, Ospedale di Rovigo, Rovigo.

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