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.
Chronic kidney disease (CKD) is a major public health problem, strongly associated with a high cardiovascular mortality [
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 [
Exercise training alone or as core component of cardiac rehabilitation (CR) programs has several beneficial effects reducing long-term morbidity and mortality [
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.
The multicenter, prospective observational study design of the ISYDE-2008 has been described in detail elsewhere [
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.
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.
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
Table
Demographics characteristics of the study population (
CKD ( |
Non-CKD ( |
|
|
---|---|---|---|
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) |
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/immunological diseases (Table
Previous interventions and comorbidities (
CKD ( |
Non-CKD ( |
|
|
---|---|---|---|
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 |
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
Complications during cardiac rehabilitation programs (
CKD ( |
Non-CKD ( |
|
|
---|---|---|---|
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 |
Differences between CKD and non-CKD patients were also detected in diagnostic or therapeutic procedures during CR (Table
Diagnostic and therapeutic procedures during cardiac rehabilitation programs (
CKD ( |
Non-CKD ( |
|
|
---|---|---|---|
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 |
Echocardiography showed a lower percentage of CKD patients with preserved left ventricular ejection fraction (LVEF > 50%) compared to non-CKD patients (37% versus 61%,
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
Drug therapy at hospital discharge after cardiac rehabilitation programs.
CKD ( |
Non-CKD ( |
|
|
---|---|---|---|
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 |
CKD patients were less likely discharged home (88% versus 91%,
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 postmyocardial 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%) [
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 [
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%,
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%,
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 [
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 [
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 [
The present survey showed higher prevalence of anemia in CKD patients compared to the non-CKD cohort (19% versus 13%,
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 closely monitored and raised to acceptable levels, especially in older and CHF patients [
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 [
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 [
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 [
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 [
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.
On behalf of the ISYDE-2008 Investigators of the Italian Association for Cardiovascular Prevention and Rehabilitation (GICR-IACPR).