International Journal of Cardiovascular ResearchISSN: 2324-8602

All submissions of the EM system will be redirected to Online Manuscript Submission System. Authors are requested to submit articles directly to Online Manuscript Submission System of respective journal.

Research Article, Int J Cardiovasc Res Vol: 5 Issue: 1

Effect of Phase 2 Cardiac Rehabilitation Program on High Sensitivity C-Reactive Protein Levels in Post-Percutaneous Coronary Intervention Patients

Ahmed Mohamed El Missiri* and Mohamed Awad Taher
Cardiology Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt
Corresponding author : Ahmed El Missiri
Cardiology Department, Ain Shams University, Faculty of Medicine, Abbassia, Cairo, Egypt
Tel: +20-10-016-14-717
E-mail: [email protected]
Received: December 11, 2015 Accepted: January 22, 2016 Published: January 29, 2016
Citation: El Missiri AM, Taher MA (2016) Effect of Phase 2 Cardiac Rehabilitation Program on High-Sensitivity C-Reactive Protein Levels in Post-Percutaneous Coronary Intervention Patients. Int J Cardiovasc Res 5:1. doi:10.4172/2324-8602.1000253

Abstract

Effect of Phase 2 Cardiac Rehabilitation Program on High Sensitivity C-Reactive Protein Levels in Post-Percutaneous Coronary Intervention Patients

Objective: To assess the effects of phase 2 cardiac rehabilitation program on hs-CRP levels in patients revascularized by percutaneous coronary intervention (PCI).

Methods: This study included 80 patients with a history of acute myocardial infarction or acute coronary syndrome for which total coronary revascularization had been performed by PCI. Patients were randomized into 2 equal groups; one enrolled in a cardiac rehabilitation program while the other was not. Risk factors and body mass index were assessed. Hs-CRP was measured at baseline then at the end of cardiac rehabilitation program or after three months for controls.

Results: There was no significant difference between study and control patients regarding baseline characteristics. At baseline, median hs-CRP was higher in the study group 2.36 (0.63-10.6) vs 1.68 (0.57-10.1) mg/L (p=0.012). For the study group, BMI dropped from 29.6 ± 4.5 to 28.9 ± 4.3 kg/m2 (p=0.002) and the number of active smokers was reduced (p<0.0001). Hs-CRP was reduced from 2.36 (0.63-10.6) to 1.63 (0.57-7.91) mg/L (p=0.0006). Significant reductions in hs-CRP levels were found in non-smokers (p=0.018), non-hypertensive (p<0.0001) and non-diabetic patients (p<0.0001). For the control group, there was no change in BMI at 3 months (p=0.422) nor hs-CRP (p=0.145). Comparing study and control groups at follow up, revealed a lower hs-CRP in the study group 1.63 (0.57-7.19) vs 2.4 (0.8-7.85) mg/L (p=0.003).

Conclusion: Participation in phase 2 cardiac rehabilitation program leads to a significant reduction in hs-CRP levels in patients with ischemic heart disease totally revascularized by PCI. Number of active smokers and BMI are also reduced.

Keywords: Cardiac rehabilitation program; Percutaneous coronary intervention; Acute myocardial infarction; Acute coronary syndrome

Keywords

Cardiac rehabilitation program; Percutaneous coronary intervention; Acute myocardial infarction; Acute coronary syndrome

Introduction

Over the past decade, atherosclerotic cardiovascular disease has emerged as the single most important cause of death worldwide. Atherosclerosis, formerly considered a bland lipid storage disease, actually involves an ongoing inflammatory response [1]. An elevated high sensitivity C-reactive protein (hs-CRP) level is now clearly established as an independent risk factor for coronary artery disease (CAD) [2].
Cardiac rehabilitation (CR) services are comprehensive, longterm programs involving medical evaluation, prescribed exercise, cardiac risk factor modification, education, and counselling. These programs are designed to limit the physiologic and psychological effects of cardiac illness, reduce the risk for sudden death or reinfarction, control cardiac symptoms, stabilize or reverse the atherosclerotic process, and enhance the psychosocial and vocational status of selected patients [3].
Cardiac rehabilitation programs are generally divided into 3 main phases: (1) Inpatient CR (also known as Phase 1 CR): a program that delivers preventive and rehabilitative services to hospitalized patients following an index CVD event, such as an MI/acute coronary syndrome; (2) Early outpatient CR (also known as Phase 2 CR): a program that delivers preventive and rehabilitative services to patients in the outpatient setting early after a CVD event, generally within the first 3 to 6 months after the event but continuing for as much as 1 year after the event; (3) Long-term outpatient CR (also known as Phase 3 or Phase 4 CR): a program that provides longer term delivery of preventive and rehabilitative services for patients in the outpatient setting [4].
Exercise training is a core component of the cardiac rehabilitation program which is probably the most effective approach for cardiovascular risk reduction and long-term care of cardiac patients as well as subjects with multiple coronary risk factors. Research indicates that exercise training can reduce coronary end points for patients with documented coronary disease. These data are the result of both observational and randomized, controlled studies. Secondary prevention through enrollment in cardiac rehabilitation programs is now regarded as an essential component of contemporary management of patients with various presentations of coronary disease [5].
Comprehensive cardiac rehabilitation programs have been shown to reduce mortality from coronary heart disease, re-infarction rates and hospital admissions and improve quality of life for the patient and their family. Although cardiac rehabilitation and exercise training is a proven modality for reducing the overall burden of cardiovascular risk, and can be effective in reducing body fat and enhancing exercise capacity in patients following major cardiac events, the effects of this therapy on hs-CRP are not well established [6].
The aim of this study was to assess the effects of phase 2 cardiac rehabilitation program on hs-CRP levels in patients who have been fully revascularized by percutaneous coronary intervention (PCI).

Methods

Study design
This prospective study included 80 consecutive patients presenting to the post-PCI clinic at Ain Shams University Hospitals, Cairo, Egypt in the period from August 2014 to March 2015 with a history of acute myocardial infarction (AMI) or acute coronary syndrome (ACS) for which total coronary revascularization had been performed by PCI. These patients were blindly randomized into 2 equal groups (n=40 each); one group was enrolled in the cardiac rehabilitation program (phase 2) offered at the hospital while the other represented a group of patients who chose not to participate in the program at that time.
Patients were excluded if they had not been fully re-vascularized; re-vascularized by coronary artery bypass grafting (CABG); been previously enrolled in a cardiac rehabilitation program; left ventricular ejection fraction (LVEF) <40%; symptoms or signs of ongoing coronary ischemia or decompensation; rhythm other than sinus or significant arrhythmias; significant heart valve disease; a physical disability that prevented participation in exercise training; chronic renal disease; chronic liver diseases; ongoing infections or inflammatory diseases; any form of malignancy; autoimmune or collagen diseases; thrombotic diseases; pregnancy; females receiving contraception or hormonal replacement therapy.
Approval of institutional ethical committee was obtained as well as informed consents from all patients.
Patient interviews
Patients were interviewed thoroughly with detailed history taking and physical examination to assess status of cardiovascular disease, current New York Heart Association (NYHA) [7] and Canadian Cardiovascular Society (CCS) [8] classifications. Presence of any of the exclusion criteria was examined. Physical activity status through an orthopedic and neuromuscular examination; cognitive function and body mass index (BMI) were also assessed.
Risk factors for CAD were examined, including: smoking status according to World Health Organization (WHO) definitions with amount and duration of smoking; diabetes mellitus (DM) regarding type and duration of disease; hypertension; dyslipidemia; and positive family history for premature coronary artery disease. Overweight was defined as a BMI ≥25 kg/m2 and obesity was defined as a BMI ≥30 kg/ m2 according to WHO definitions.
Estimation of high sensitivity C-reactive protein level (hs- CRP)
Hs-CRP was measured at baseline for all patients then at the end of cardiac rehabilitation program for those enrolled in the program and after three months for those not enrolled in the program.
Samples were 3 ml of venous blood that were subjected to centrifugation to separate the serum. Serum was isolated in special tubes which were kept frozen at -70 degrees centigrade. Hs-CRP was then determined using immunoassay method.
Hs-CRP level <1 mg/L was considered normal while levels >1 mg/L were considered elevated, with levels >3 mg/L considered to be high risk according to the AHA/CDC definition [9].
Cardiac rehabilitation program
The cardiac rehabilitation program provided at our institution is a comprehensive one that includes:
Patient education: All patients were subjected to an intensive patient education program about the nature of CAD, risk factor management, alarming symptoms of myocardial infarction, return to physical and sexual activities and work resumption. Education was performed by individual and group counseling and supported by educative videos in Arabic and print-out reminders. Group sessions usually lasted for one hour and were provided at the beginning and end of the program. Individual sessions were arranged every third time and usually lasted from 5 to 15 minutes and included answers to specific patient-tailored questions.
Smoking: Patients were educated about the hazards of smoking on cardiovascular system (CVS) and the need to quit to reduce future risk.
Hypertension: Patients were educated about target values of blood pressure, the importance of exercise, weight modification and invisible sources of dietary salt.
Diabetes: Patients were educated to be alert for signs/symptoms of hypoglycemia or hyperglycemia with emphasis on diet and compliance to medications.
Dyslipidemia: Patients were educated about dietary content of saturated fat, and cholesterol, and encouraged to consume more fruit and vegetable, whole grain, and fish.
Overweight and obese patients: Weight management was performed to overweight and patients which consisted of education, counseling, and dietitian interview. Overweight Patients were interviewed by a dietician and were advised a low caloric diet: 500 calories less than their estimated maintenance energy and educated about sources of dietary carbohydrates in addition to value of exercise in weight loss.
Sedentary patients: Patients were consistently encouraged to accumulate 30-60 minutes per day of moderate-intensity physical activity on at least 5 days of the week.
Diet: All the participants were encouraged to follow a diet low in saturated fat, moderate in proteins (with increased intake of fish) and rich in grains, fruits and vegetables.
Optimization of medical treatment: Drug treatment was added or intensified in those with low-density lipoprotein >100 mg/dL. Anti-hypertensive and anti-anginal medications were up titrated as tolerated by patient so that blood pressure was optimal and anginal episodes were reduced.
Psychosocial management: Smoking cessation was provided by a psychologist. The importance of returning to work for those in the workforce was emphasized regularly.
Medically-supervised exercise program: Patients were prescribed exercise twice weekly for 12 weeks using a treadmill at a low intensity protocol with intensity starting from 1.6 km/h. and gradually rising to 5 km/h. Symptom-limited exercise testing was performed at baseline using the modified Bruce protocol to identify the patient’s maximal heart rate after which the target heart rate was calculated using the Karvonen formula [10] with an intensity of 65- 85%. Exercise was monitored by Borg scale of perceived exertion, ECG, heart rate, blood pressure as well as signs or symptoms of ischemia. Sessions ranged from 15 minutes at the beginning of the program to 40 minutes near the end.
For diabetic patients blood sugar levels were tested pre- and postexercise at each session: if blood sugar value was <100 mg/dL, exercise was delayed and patient was provided 15 g of carbohydrate; retested in 15 minutes; proceeded if blood sugar value was >100 mg/dL; if blood sugar value was >300 mg/dL, patient may exercise if he or she felt well, was adequately hydrated, and blood and/or urine ketones were negative; otherwise, patient’s exercise session was postponed till blood sugar was controlled.
Exercise session was terminated if the patient developed: hypotension >10 mmHg, arrhythmias, severe dyspnea or chest pain on a low workload, or if clinical examination showed de novo congestion [11].
Statistics
Data were coded, tabulated, and statistically analyzed using Graph Pad Prism software. Continuous variables that passed normality test were expressed as mean ± standard deviation and analyzed using twotailed Student t-test. Those which were not normally distributed were expressed as median (range) and analyzed using the non-parametric tests Mann-Whitney U-test for unpaired values and Wilcoxon matched pairs for paired values. Categorical variables were expressed as number and percentage and analyzed using Chi squared test. The level of significance was taken at p value less than 0.05, otherwise was considered non-significant.

Results

Comparing patient groups at baseline
Baseline characteristics: There was no significant difference between study and control patients regarding baseline clinical and echocardiographic characteristics as detailed in Table 1.
Table 1: Baseline characteristics.
Type of myocardial infarction: In the study group, a larger number of patients had a history of developing ST-segment elevation MI (STEMI) 37 (92.5%) vs 30 (75%) while in the control group a larger number of patients had a history of non-STEMI 10 (25%) vs 3(7.5%) (p=0.034) (Table 1).
High sensitivity C-reactive protein level (hs-CRP): At baseline, the median (range) hs-CRP of the study group was higher than the control group 2.36 (0.63-10.6) vs 1.68 (0.57-10.1) mg/L. This was statistically significant using Mann-Whitney U-test (p=0.012) (Figure 1).
Figure 1: Comparing median hs-CRP at baseline and at the end of the program/follow-up.
Study group
Clinical characteristics: There were significant reductions in patients’ BMI at the end of the cardiac rehabilitation program compared to baseline. Mean BMI dropped from 29.6 ± 4.5 to 28.9 ± 4.3 kg/m2 (p=0.002).
The number of active smokers was significantly reduced from 22 (55%) to 7 (17.5%) at the end of the program (p<0.0001)
Hs-CRP levels: The median (range) hs-CRP was reduced from 2.36 (0.63-10.6) to 1.63 (0.57-7.91) mg/L at the end of the program. This was statistically significant using Wilcoxon matched-pairs test (p=0.0006) as illustrated in Figure 2.
Figure 2: Median hs-CRP at baseline and at the end of the program/follow-up in each group.
On further dividing patients into those with hs-CRP levels <1, 1 to <2; 2 to <3; ≥3 mg/L it was obvious that there was a trend towards reduction of hs-CRP levels at the end of the cardiac rehabilitation program even if they hadn’t dropped below the normal value of <1 mg/L (p for trend=0.006) (Figure 3).
Figure 3: Trends of hs-CRP levels in both groups at baseline and follow-up.
Comparing changes in hs-CRP level with clinical characteristics
There was a significant reduction in hs-CRP levels in patients who were originally non-smokers from 2.8 ± 1.68 to 1.83 ± 0.89 mg/L at the end of the program (p=0.018). This was also the case in those who were non-hypertensive from 3.27 ± 1.86 to 1.68 ± 0.74 mg/L (p<0.0001), as well as, non-diabetics from 2.99 ± 1.58 to 1.46 ± 0.55 mg/L (p<0.0001).
For male patients, the median was reduced from 2.36 (0.68-10.6) to 1.59 (0.57-7.9) mg/L (p=0.0009). For patients with a BMI <30 kg/ m2, mean hs-CRP dropped from 2.81 ± 2.1 to 1.96 ± 1.2 mg/L but this did not reach statistical significance (p=0.057) (Table 2).
Table 2: hs-CRP before and after cardiac rehabilitation.
Control group
Clinical characteristics: There was no change in patients’ mean BMI at 3 months compared to baseline. Mean BMI changed from 29.5 ± 4.7 to 29.1 ± 3.4 kg/m2 (p=0.422).
The number of active smokers was significantly reduced from 26 (65%) at baseline to 6 (15%) after 3 months (p<0.0001).
Hs-CRP levels: The median (range) hs-CRP changed from 1.68 (0.57-10.06) to 2.4 (0.8-7.85) mg/L at the end of the program. However, this was not statistically significant using Wilcoxon matched-pairs test (p=0.145) as illustrated in Figure 2.
On dividing patients into those with hs-CRP levels <1, 1 to <2; 2 to <3; ≥3 mg/L there was a trend towards increase of hs-CRP levels at follow up (Figure 3).
Comparing changes in hs-CRP level with clinical characteristics: There were no significant changes in hs-CRP levels in control patients on further dividing patients according to gender, BMI, presence of hypertension or diabetes mellitus (Table 3).
Table 3: hs-CRP in the study group.
Comparison between study and control groups at follow up
Smoking status: The number of patients who were active smokers was significantly reduced at the end of the program in each group compared to its baseline. However, there was no difference in the number of active smokers on comparing both groups at follow up (p=0.762).
BMI: There was no significant difference in BMI at follow-up between both groups: 29 ± 4.3 kg/m2 in the study group vs 29.1 ± 3. 4 kg/m2 (p=0.866).
The number of obese patients (BMI≥30 kg/m2) was more reduced in the study group from 16 (40%) to 9 (22.5%) vs from 16 (40%) to 17 (42.5%) in the control group. However, this did not reach statistical significance p=0.056.
High sensitivity C-reactive protein level: The median (range) hs-CRP of the study group at 3 months was lower than the control group 1.63 (0.57-7.19) vs 2.4 (0.8-7.85) mg/L. This was statistically significant using Mann-Whitney U-test (p=0.003) (Figure 1).

Discussion

Cardiac rehabilitation is defined by the WHO as “the sum of activities required to influence favorably the underlying cause of the disease, as well as to ensure the patient the best possible physical, mental and social conditions, so that they may, by their own efforts, preserve or resume when lost, as normal a place as possible in the life of the community” [12]. The expected outcomes after enrollment in a cardiac rehabilitation program include improved exercise tolerance regardless of age and sex, symptom control, an improvement in lipid levels, a reduction of body weight, reduction of smoking, reduction of blood pressure, improved psycho-social wellbeing, enhanced social adjustment and a reduction in mortality [13-19].
Hs-CRP has been linked to coronary artery disease in a magnitude of studies [20] and current practice guidelines support its use in intermediate risk patients for risk stratification [21-23]. This is because considerable evidence supports the role of inflammation in the pathogenesis and progression of major cardiovascular diseases and events with most of this evidence involving hs-CRP. Epidemiological and cohort studies showed an inverse relationship between physical activity/fitness and hs-CRP. In addition, cardiac rehabilitation has been shown to significantly reduce levels of hs-CRP, especially in the overweight/obese patients [24].
The present study examined changes in hs-CRP and other clinical characteristics in coronary artery disease patients fully revascularized by PCI after being enrolled in a 12 week exercise-based phase 2 cardiac rehabilitation program compared to a similar group of patient who chose not to participate in the program.
Smoking status
There was a significant decrease in the number of active smokers in both the study and control groups at follow-up, indicating that smoking cessation was probably due to the impact of the patients’ developing an acute MI rather than the interventions performed during the cardiac rehabilitation program. This was demonstrated by a significant reduction in each group compared to its own baseline (p<0.0001 for each). However, no difference was found on comparing the magnitude of change in both groups to each other (p=0.762).
Similar conclusions were reached in the Framingham Study that stated that recent hospitalization and development of acute coronary artery disease were strong predictors of smoking cessation [25]. Another study performed on 87 patients after coronary artery bypass grafting (CABG) found that nearly one half of smokers quit for 5 years after CABG even without specific interventions [26]. It was also found that patients who had unstable angina were more likely to quit smoking than those who had stable angina after percutaneous coronary revascularization [27].
Body mass index
Our results showed a significant reduction in BMI for the study group (p=0.002). This was not seen in the control group (p=0.422). On comparing both groups together at baseline and follow up, there was no significant change in BMI, however, the percentage of obese patients was reduced in the cardiac rehabilitation group although it did not reach statistical significance (p=0.056).
Significant reductions in BMI have been noted in several cardiac rehabilitation studies even in the elderly [28,29].
High sensitivity C-reactive protein
The current study demonstrated a significant reduction in hs- CRP levels in the study group (p=0.0006) this did not occur in the control group (p=0.145). On comparing both groups together, hs- CRP started up as significantly higher in the study group at baseline (p=0.012) and ended up to be significantly lower at follow up (p=0.003) indicating a marked reduction in the study group.
Similar results have been reported in other studies: a study performed on 172 patients with CAD concluded that participation in a cardiac rehabilitation program was associated with a marked improvement of cardiac risk factors and appears to independently decrease the level of CRP regardless of gender, age, or presence of metabolic syndrome [30]. Another study performed on 29 patients with CAD who underwent PCI before and after phase 2 cardiac rehabilitation and 10 similar control patients who did not attend cardiac rehabilitation concluded that cardiac rehabilitation in CAD patients after PCI induces significant reduction in hs-CRP and inflammatory cytokines [31].
Other investigators studied 277 patients with CAD (235 patients before and after phase 2 cardiac rehabilitation and 42 control patients who did not attend cardiac rehabilitation) and found that a three month cardiac rehabilitation program significantly improved numerous cardiac risk factors with significant reductions in hs-CRP levels. They concluded that reducing hs-CRP can be achieved by another modality beyond statin drugs and suggested it to be formal phase 2 cardiac rehabilitation and exercise training programs [32].
Change in hs-CRP in relation to patient characteristics
Several studies have pointed to the fact that certain patient characteristics are associated with elevated hs-CRP. Smoking has been shown to have a positive interaction with hs-CRP in CAD patients. Smokers are thought to develop coronary events at a lower hs-CRP level compared with non-smokers [33]. Reports have also pointed to a role of an inflammatory processes marked by hs-CRP in the development of hypertension [34]. Evidence also strongly shows a significant correlation between the presence of diabetes mellitus, elevated levels of glycosylated hemoglobin and elevation of hs-CRP [35,36].
On relating those clinical characteristics and others to hs-CRP levels in patients from the cardiac rehabilitation group in the current study, significant reductions were noted among those patients who were originally non-smokers, non-diabetic, non-hypertensive and male patients compared to their counterparts. This seems to imply that these groups would benefit more from cardiac rehabilitation programs.

Study Limitations

The limitations of the current study are that it comes from single center with a relatively small number of patients. Long term follow up to assess sustained benefits of cardiac rehabilitation beyond the first 3 months was not performed.

Conclusion

Participation in phase 2 cardiac rehabilitation program leads to a significant reduction in hs-CRP levels in patients with ischemic heart disease who have been totally revascularized by PCI. The number of active smokers and body mass index are reduced after participation in cardiac rehabilitation programs.

References





































Track Your Manuscript

Scheduled supplementary issues

View More »

Media Partners