Age-Dependency of Clinical Characteristics of Patients Participating Cardiovascular Rehabilitation Results from the German Registry of Ambulatory Cardiac Rehabilitation—KARREE

Background: Cardiovascular rehabilitation in Germany traditionally is offered as in-patient service often located far from patient’s residence, and ambulatory rehabilitation still represents a minority. The German Registry of Ambulatory Cardiac Rehabilitation (KARREE) was designed to contribute to rehabilitation quality assurance and to evaluate clinical characteristics of patients participating in ambulatory rehabilitation centers. Methods: In four ambulatory rehabilitation centers 2989 patients were consecutively registered from 2008 to 2011 and evaluated with reCorresponding author. Unfortunately, this author has been deceased.


Introduction
Cardiovascular rehabilitation (CR) in Germany is controlled by a quality assurance program, which has been developed by the German pension funds (Deutsche Rentenversicherung, DRV) in the early nineties primarily concentrating on the structures and processes of the rehabilitation centers.Some years later the quantity and intensity of the multidisciplinary therapeutic interventions during CR were evaluated in addition and included in a benchmarking process [1] [2].Along with the implementation of this quality assurance program CR in Germany increasingly gained scientific interest by evaluating its short-and long-term effects on clinical outcome and secondary prevention measures [3]- [9].However, as a result of the long tradition of rehabilitation clinics in Germany, these studies primarily evaluated inpatient CR.It was not before 1992 when the first model of a German ambulatory CR center was established at the Sporthochschule Köln [10].This was followed by a variety of additional ambulatory CR projects [11]- [13].In the meantime, ambulatory CR in Germany is officially supported by law and included into clinical routine.To guarantee minimal standards in equipment, staff and processes of ambulatory CR centers guidelines have been developed by the "Bundesarbeitsgemeinschaft für Rehabilitation" (BAR) [14].Due to the late development of ambulatory CR in Germany there was an additional need to scientifically evaluate this setting.Several smaller studies investigating a variety of characteristics and outcomes showed non inferiority of ambulatory CR in comparison to inpatients CR [15]- [18].The purpose of the KARREE-registry was to describe patient's characteristics and short-term clinical outcome during ambulatory CR in a large cohort of patients under all day conditions.Moreover, the special aim of this registry was to evaluate potential gender differences, and to characterize different age groups, who may need an individually adjusted rehabilitation care.

Methods
From 2008 until 2011 medical data of 2989 patients participating CR in four German ambulatory cardiovascular rehabilitation centers were consecutively evaluated for quality assurance evaluation.
CR-programs were standardized by following the BAR-guidelines and included 15 ± 2.9 active days of 4 -6 hours each [14].According to the BAR-guidelines the multidisciplinary CR-team consisted of cardiologists, sports scientists and physiotherapists, psychologists, dietary specialists, nurses and social workers.All patients had a basic diagnostic evaluation including laboratory screening, echocardiography, ECG, and a stress test ideally performed at the beginning and at the end of the rehabilitation program.The CR centers furthermore provided an emergency room with full equipment, emergency laboratory tests, 24 hours ECG monitoring, 24 hours blood pressure monitoring, duplex sonography of the vessels and psychological tests for evaluation of anxiety and depression.
The therapeutic program included endurance exercise training (ideally daily), dynamic strength training (twothree times a week), physiotherapy, nursing, relaxation practices, psychological interventions.The rehabilitation program also included regular visits, professional advice and education with respect to physical exercise in daily practice, healthy nutrition, weight loss, stop smoking and reduction of psychological stress.German rehabilitation centers are regularly tested by the German pension funds whether the individual rehabilitation programs in each center meet their standards.
For routine data acquisition an electronic case report form was developed by a rehabilitation expert team in cooperation with the BNK Service GmbH, Munich, Germany, who also was responsible for the online service and data administration.All data have been anonymized.The case report included age, gender, the health care insurance responsible, diagnoses relevant for cardiac rehabilitation, social status, risk factors and risk diseases, body size, weight, body mass index, resting heart rate, blood pressure, laboratory parameters, medication, LV-function, maximal exercise performance.Data relevant for cardiovascular risk estimation were controlled at the end of the rehabilitation program.Furthermore the most important items for social reintegration and re-uptake of work were assessed.
Data evaluation was done by the Stiftung Institut für Herzinfarktforschung Ludwigshafen.The statistical analysis was descriptive focusing on the total population and data variations with respect to the participating rehabilitation centers, gender and age groups.For the statistical analysis continuous variables were expressed as means with standard deviations or medians with 25 th and 75 th percentiles, and were compared by using the Mann-Whitney-Wilcoxon test.Categorical variables are presented as absolute numbers and percentages, and were compared by using the chi-square test.The statistical comparisons were two-tailed, and p-values < 0.05 were considered as statistically significant.All analyses were performed using SAS version 9.1 (SAS Institute Inc., Cary, NC, USA).

Results
Table 1 shows the distribution of the patients between the four participating rehabilitation centers.Almost all patients had a post-acute CR (98.7%), with acute coronary syndrome or cardiovascular surgery as main reasons for CR admission.The population of the centers differed with respect to age and consequently with respect to the social status (e.g.employed or retired).
In Table 2 the clinical characteristics of the KARREE population are outlined.In addition to the total population three age groups (age < 50 years, 50 -70 years, above 70 years) as well as gender differences were evaluated.Several clinical characteristics strongly depend on the particular age group including the CR initiating diagnosis.Although the majority of patients participated in CR after acute coronary syndrome, this diagnosis as the basis for CR-referral decreased significantly with age, whereas the number of patients after bypass surgery or aortic valve surgery increased.Also the cardiovascular risk factors in the patient's history varied with age.Whereas risk factors likephysical inactivity, overweight, psychosocial stress as well as cigarette smoking declined with age, diabetes and hypertension significantly increased (Table 2, Figure 1).At CR start major cardiovascular risk factors already were medically treated or positively influenced by individual behavior changes along the preceding in-hospital treatment.Thereby average LDL-cholesterol was measured only slightly above the target value of 100 mg/dl, and triglycerides were fairly adjusted (Table 2).The average resting blood pressure also was within the expected target values.
Depression and anxiety only could be verified in a minority of the total population.However, both, depression and anxiety strongly depended on age, being highest in the young age group below 50 years.Furthermore, female patients were more prone to psychological stress (Table 2).These anamnestic reports could be confirmed by data from the HADS-tests showing the highest number of patients with pathological depression and anxiety scores in the young age group and in female gender (Table 2).
The majority of patients exhibited a normal or only slightly reduced left ventricular function.The stress test at the beginning of the rehabilitation showed a reasonable performance declining with age and being significantly lower in female patients.However, only 50.1% of all patients had a stress test at the CR start (Table 2).
Medical treatment of the patients reflected guideline recommendations already at CR start, and there were only slight changes in medication during the rehabilitation process (Table 3).In accordance with the prevalent risk diseases like diabetes and hypertension, drug prescription varied between the age groups.Especially the use of ARBs, vitamin-K antagonists, calcium channel blockers, diuretics and anti-diabetics increased with age.
During the course of the rehabilitation program there was a significant increase of exercise performance in all age groups independent of gender.In addition there was a further adjustment of other risk factors like a reduction of LDL-cholesterol and triglycerides.Also resting heart rate and blood pressure at rest were significantly reduced (Table 4).
From the patients supported by the German pension (DRV) funds 43.5% directly returned to work after rehabilitation.In addition 16.7% of the CR patients still working got support by organizing a stepwise reintegration into their previous working place.Almost all patients supported by the German pension funds were integrated into a special DRV aftercare program, whereas 65.5% of the retired patients were integrated into ambulatory heart groups.

Discussion
KARREE is the first registry evaluating ambulatory cardiovascular rehabilitation in Germany under the conditions of all day care and in alignment with the BAR-guidelines in a large cohort of patients treated in four rehabilitation centers.Although this registry only is an observational study there are several results of importance: 1) In the KARREE registry post-acute CR (AHB, Anschlussheilverfahren; AR, Anschlussrehabilitation) represented 98.7% of all patients (Table 1), whereas in the population of patients supported by the German pension funds (DRV) the proportion of post-acute CR only was 68% in 2012 [19].Therefore it may be suggested, that patients with chronic cardiovascular disease primarily are admitted to rehabilitation clinics.This potentially indicates a conflict of interest with respect to the distribution of the patients, as many rehabilitation clinics still are owned by the German pension funds, which may have influence on patients' allocation to various CR settings.
2) The proportion of patients with peripheral arterial disease (PAD) in this cohort is low.This potentially indicates a severe shortage of special care of this group of patients at least in some areas of Germany, and therefore deserves further investigation.As PAD patients especially benefit from cardiovascular rehabilitation by supervised implementation of systematic walking and support in smoking cessation, their admission and participation to CR should be clinical routine.
3) The baseline characteristics of the patients admitted to CR were similar as reported recently with an average age of 65 years in KARREE and 62 years of age in the OMEGA population (mostly in-patient rehabilitation) [7].This clearly contradicts previous assumptions that ambulatory cardiovascular rehabilitation may be preferred by young patients [20].Still, the proportion of female patients remains to be low raising the question of the attractiveness of ambulatory services for women.4) All patients participating in KARREE reported a combination of several cardiovascular risks and risk diseases indicating a high risk population.However, depending on age a remarkable variation of the risk pattern could be observed.Whereas diabetes and hypertension were significantly increasing with age, smoking and psychosocial stress were decreasing.Although these data only have an observational basis, this age dependent risk pattern strongly indicates the necessity of an individual counselling and treatment of the patients during CR and thereafter.Especially in the young group of patients additional psychological support should be guaranteed in every rehabilitation center.5) At least as far as cardiovascular risk factors can be treated by medication, this already has been consequently started during the patients' hospital stay.Therefore guideline adjusted medication primarily was continued during CR and changed only to a small extend.Moreover many recent smokers at least provisionally had stopped smoking already at rehabilitation start.Although during the rehabilitation program of three weeks the cardiovascular risk pattern still could be improved (Table 4) a major task of modern cardiovascular rehabilitation therefore is to further inform and educate the patients with respect to the individual relevance of cardiovascular prevention and to stimulate the individual motivation on compliance and adherence to preventive medication and life style.To improve sustainability of secondary prevention in the individual participation in after-care programs have been shown to be important [8] [21] [22].It has to be noted that participation in such after-care programs could be achieved in the vast majority of these patients participating in ambulatory rehabilitation, and this is far above the numbers reported from inpatient cardiac rehabilitation [5].6) Apart from long term implementation of cardiovascular prevention reintegration into normal life and especially into working ability is a major task of cardiovascular rehabilitation.Of the employed patients 43.5% could start working again directly after cardiac rehabilitation.In addition 16.75 were supported by stepwise reintegration into work.Unfortunately the register does not provide information on the remaining patients.This is a limitation of the registry, as especially blue color workers may keep serious limitations being a barrier against subsequent reintegration into work.This urgently needs to be investigated in more detail in future.

Limitations of the Study
This is an observational study reflecting patients characteristics and actual all day care in ambulatory CR in Germany.The data do not allow any suggestions on the clinical long-term effect of this intervention neither in comparison to inpatient CR nor in comparison to cardiac patients not participating CR.Moreover, for purposes of quality assurance the presented program of data acquisition and registration was too intensive and time consuming to be continuously integrated into all day care.Still, a simple and effective routine evaluation of the clinical short and long-term results by testing independent samples of patients participating and not participating CR are urgently needed for further development and improvement of this therapeutic instrument.

Conclusion
The KARREE registry reflects the actual clinical practice of ambulatory cardiac rehabilitation in Germany.Almost all patients consecutively enrolled in KARREE had an acute coronary syndrome or cardiovascular surgery before rehabilitation.This underscores the importance of a close networking between heart centers and cardiac rehabilitation facilities.Moreover, the majority of the patients were at high cardiovascular risk, and the marked differences of risk factor patterns between the age groups under investigation underscore the imperative necessity of an individualized therapeutic approach during cardiac rehabilitation.

Figure 1 .
Figure 1.Age dependent distribution of various cardiovascular risk factors.Depending on the age group the prevalence of each of the selected risk factors varied significantly (p < 0.0001).

Table 1 .
Basic characteristics of participating ambulatory rehabilitation centers.

Table 2 .
Distribution of key characteristics between age groups and gender.

Table 3 .
Medication at start and at the end of the CR-program.

Table 4 .
Changes of risk parameters during rehabilitation.
* no significant difference between the age groups.