|Year : 2019 | Volume
| Issue : 3 | Page : 119-122
Effect of ischemic reversal program on high-Sensitivity C-reactive protein in patients of coronary heart disease: An observational study
Rohit Sane1, Gurudatta Amin2, Snehal Dongre3, Rahul Mandole4
1 Department of Research and Development, Madhavbaug Hospital, Khopoli, Maharashtra, India
2 Chief Medical Officer, Clinical Operations, Madhavbaug Hospital, Khopoli, Maharashtra, India
3 Medical Head, Madhavbaug Hospital, Khopoli, Maharashtra, India
4 Senior Research Associate, Madhavbaug Hospital, Khopoli, Maharashtra, India
|Date of Web Publication||3-Dec-2019|
Dr. Rahul Mandole
Senior Research Associate, Madhavbaug Hospital, Khopoli, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Chronic inflammation leads to rupture of atherosclerotic plaque, ultimately causing acute coronary syndromes. High-sensitivity C-reactive protein (hsCRP) is an inflammatory biomarker which is known to predict cardiovascular events in ischemic heart disease (IHD) patients. Ischemic reversal program (IRP) has been found to improve exercise capacity of IHD patients but action on hsCRP is unknown.Methodology: This retrospective study was conducted between July 2018 and December 2018, for evaluating the effect of IRP on hsCRP levels in IHD patients. The data of only those patients were considered who had been given the IRP-based treatment for a minimum of five sittings. The mean serum hsCRP at day 30 of treatment initiation was compared with day 1 values. The association between the comorbidities with decrease in the hsCRP levels was assessed by calculating odds ratio (OR) using regression analysis. Results: Of the 78 enrolled IHD patients, 54 were male with a mean age of 59.94 ± 9.46 years. The mean hsCRP levels at day 30 of the treatment initiation were significantly lower than day 1 values (2.01 ± 2.15 vs. 2.83 ± 3.07 mg/L, P < 0.05). The OR for the decrease in the hsCRP levels in IRP-treated IHD patients having comorbidities such as hypertension and myocardial infarction were insignificant; however, the OR with diabetes was significantly < 1 (OR: 0.35, P < 0.05). Conclusion: IRP treatment leads to a significant decrease in the serum hsCRP levels in majority of the IHD patients, indicating an additional anti-inflammatory action.
Keywords: Coronary heart disease, high-sensitivity C-reactive protein, inflammation, ischemic heart disease, ischemic reversal program
|How to cite this article:|
Sane R, Amin G, Dongre S, Mandole R. Effect of ischemic reversal program on high-Sensitivity C-reactive protein in patients of coronary heart disease: An observational study. J Indian coll cardiol 2019;9:119-22
|How to cite this URL:|
Sane R, Amin G, Dongre S, Mandole R. Effect of ischemic reversal program on high-Sensitivity C-reactive protein in patients of coronary heart disease: An observational study. J Indian coll cardiol [serial online] 2019 [cited 2020 Apr 2];9:119-22. Available from: http://www.joicc.org/text.asp?2019/9/3/119/272171
| Introduction|| |
Cardiovascular disorders are considered now as a global epidemic, with a rising cardiovascular mortality being witnessed worldwide. Even though the general trend has been on the decrease in developed countries, it is on an upturn in developing countries such as India. It is estimated that about 75% of the cardiovascular deaths are seen in developing countries, while a relatively smaller number of deaths is noted in developed countries, perhaps due to better health-care services. The chief cause for cardiovascular mortality is coronary heart disease (CHD), a common cardiovascular disease (CVD) synonymous with ischemic heart disease (IHD). According to the published scientific literature, the IHD prevalence in India has grown from 2% in 1960 to about 14% in 2013. The increase in the prevalence of IHD has been accredited to numerous features which include urbanization and lifestyle modifications. A rising trend in India's cardiovascular mortality is perceived in the past few years, with 20.6% of the deaths occurring in 1990, rising to 29.0% deaths in the year 2013.
Cardiovascular conditions have been found to be associated with inflammation, and there is scientific evidence to support the same. The role of inflammation in atherosclerosis has long being known, and the chronic inflammation usually leads to rupture of the plaque, ultimately causing acute coronary syndromes. High-sensitivity C-reactive protein (hsCRP) is a well-studied inflammatory biomarker which has been known to predict cardiovascular events successfully. Besides, hsCRP has been found to have long-term predictive utility in patients who are suffering from IHD or angina pectoris. A study conducted by Habib and A Al Masri found that CHD patients have significantly greater levels of hsCRP in comparison to that found in healthy individuals, and the biomarker was also important in predicting CHD severity.
Ayurveda is the pillar of Indian traditional medicine, which has been used by numerous alternative physicians for the management of various diseases. Panchakarma and allied therapies are administered by Ayurvedic physicians to deliver relief to patients who are suffering from various diseases. One such integrative method of managing IHD patients is by the administration of the Ischemia Reversal Program (IRP) Kit. This IRP treatment comprises an incorporation of Snehana (Centripetal oleation), Swedana (Thermal vasodilation), as well as Basti (per rectal drug administration), recognized to deliver reprieve to IHD patients. Although it is used in practice by physicians with success, systematic research evidence is lacking.
There is scientific evidence available with regard to the improvement in the exercise capacity in IHD patients treated with IRP. Considering the scientific evidence linking, a higher hsCRP with poor CHD outcomes, it was though by the authors to evaluate the possible impact of IRP on the hsCRP levels in IHD patients, hypothesizing that if IRP was successful in lowering the serum hsCRP, this will indicate a positive effect on the CHD patient outcomes.
| Methodology|| |
This observational study was conducted between July 2018 and December 2018, for evaluating the effect of IRP on the hsCRP levels in IHD patients. Data of patients who had visited the Madhavbaug Clinics and were diagnosed of having positive inducible ischemia by stress test were evaluated for the study. The data of only those patients were considered who had been given the IRP-based treatment with a minimum of five sittings. Cases were screened and identified, and the data were analyzed retrospectively from the database of Madhavbaug Clinic records. The selection was based on the availability of the complete relevant baseline data (day 1 of IRP) and follow-up data (day 30 after IRP initiation) of the IHD patients.
The IRP is a three-step procedure which is a combination of Panchakarma and allied therapies. IRP employs different types of decoctions which are described in [Table 1]. Snehana or external oleation is a 30–35 min procedure which includes oil-based decoction, provided to the IHD patients by the external massage. This massage technique uses various upward or centripetal strokes in the direction of the heart. Swedana or passive heat therapy is a 10–20 min procedure that includes the process of the IHD patients lying down in the supine position in a sudation box, with the head of the patients directed outside the box. Dashmoola (group of ten herbs) temperature steam not ≥40° is passed continuously for about 10–15 min. After the treatment process is over, patients are told to relax for about 3–4 min. Basti is the final process which is the administration of per rectal herbal drugs for about 15 min to the IHD patients, with the extracts of Tribulus terrestris, Curcuma longa, and Emblica officinalis being used for decoction.
On day 1 of the IRP therapy, the patient was asked to come to the clinic after overnight fasting, and the blood sample was collected from all IHD patients by a trained technician. The serum of the samples was separated and then sent to the pathology laboratory for assay and hsCRP assessment. This day 1 values were considered as baseline hsCRP values. After 30 days of IRP completion, the CHD patients were again called after overnight fasting, and blood was again collected for hsCRP assessment.
Data were entered and coded in the Microsoft Excel chart. Graphpad Instat version 3.0 software (San Diego, California, Graphpad Software) was used to analyze the data which was entered. Categorical data were shown in the numerical form, whereas the continuous data were shown as a mean ± standard deviation, paired t-test was utilized to analyze the statistical difference between baseline hsCRP values and the follow-up data. The association between the comorbidities with decrease in the hsCRP levels was assessed using Chi-square analysis as well as regression analysis.
| Results|| |
Seventy-eight IHD patients were found to be appropriate for inclusion in the study after the screening process. The mean age of the IHD patients was found to be 59.94±9.46 years, with a median age of 60 years. Most of the patients enrolled in the study were found to be males (69.23%) [Table 2].
|Table 2: Demographic details of patients with ischemic heart disease (n=78)|
Click here to view
The most common comorbidity in the enrolled IHD patients was hypertension (HTN) (71.79%). The next most common comorbidity which was noted diabetes mellitus (DM) (51.28%) followed bymyocardial infarction (MI) (23.07%) [Table 3].
On evaluating the change in the mean hsCRP after day 30 of treatment initiation, there was a significant reduction found after IRP therapy. On assessing the number of patients with a decrease in the hsCRP, majority (74.35%) of the IHD patients showed a reduction [Table 4].
|Table 4: Change in the mean high-sensitivity C-reactive protein in the ischemic heart disease patients (n=78)|
Click here to view
The odds ratio (OR) for the decrease in the hsCRP levels in IRP-treated patients having comorbidities such as HTN, DM, and MI were calculated. It was found that the OR for IRP-treated IHD patients with all these comorbidities was <1. Patients suffering from both IHD and DM had an OR which was 0.35, and this was a significant finding (P< 0.05). The other OR values were statistically insignificant (P > 0.05). [Table 5] gives a tabular representation of these OR findings.
|Table 5: Odds ratio for decrease in the high-sensitivity C-reactive protein based on the presence of common comorbidities|
Click here to view
| Discussion|| |
Inflammation has been found to be an important factor which initiates as well as leads to progress of atherosclerosis, ultimately causing cardiovascular events such as CHD. Multiple inflammatory biomarkers have emerged in the recent past for the identification of risk as well asprognosis of CVDs such as IHD., C-reactive protein (CRP) is an acute-phase reactant which is produced mainly by the liver and is driven most crucially by interleukin-6 (IL-6). CRP has been found to bind to the low-density lipoproteins-cholesterol -, found in the lipid-rich plaques, and exerts a pro-atherogenic action which plays a crucial role in atherosclerosis development. There are several advantages in measuring serum hsCRP in IHD patients. Besides, its proven efficiency in measuring risk as well as progress of CHD, hsCRP can be measured at any time of the day, irrespective of the fasting status of the patient. Studies have shown the association between a higher level of serum hsCRP and the IHD severity. IRP has shown promising results when assessed with respect to its impact on exercise capacity in IHD patients, but the anti-inflammatory aspect had not been explored earlier.
On evaluating the effect of IRP on the serum hsCRP levels after 30 days of IRP treatment, a significant decrease was seen, and the decrease was found in 74.35% cases. This shows that IRP probably has an effect on the inflammatory factor of atherosclerotic plaque, which will not only help in the prevention of plaque expansion but also aids in improving the CVD outcomes in the IHD patients. The common comorbidities were noted down in this study included HTN, DM as well as MI, and the OR of IRP decreasing the serum hsCRP in these patients was calculated. It was found that IHD patients with concomitant DM had a significantly lower OR, indicating that IRP was not possible that effective in decreasing hsCRP in this set of patients. However, as the sample size of this study is small, future studies with larger sample size can help in evaluating this finding more robustly.
The sympathetic activity has been linked with the inflammatory activities in the body by various scientific publications. According to a study, the sympathetic tone had a positive correlation with the plasma IL-6 levels, the force which drives the release of hsCRP. IRP is made up of three main components, namely Snehana, Swedana, and Basti.Snehana has been assumed to reduce the sympathetic activity of the body, which will probably affect the IL-6 levels in the body, thereby affecting the hsCRP levels and ultimately having an anti-inflammatory effect. Similarly, Swedana has a probable vasodilatory effect which leads to peripheral vasodilation. Endothelial dysfunction is an early sign of atherosclerosis and can lead to impaired vasodilation in the IHD. The peripheral vasodilation leads to normalized tissue blood supply, which may otherwise be compromised in IHD. Inflammation plays a part in not only causing IHD but also leading to cardiac dysfunction and ultimately, decreased the left ventricular function. There is evidence to propose that Basti has a part in regulating the pro-inflammatory cytokine release, as well as inhibition of the inflammatory response. Besides the effect on hs-CRP, this effect may also have a contributory effect in improving the cardiac response to physical activity, due to IRP.
This study had a few limitations. This was a retrospective study which looked at the serum hsCRP levels after 30 days of the IRP initiation, and hence, the long-term effects on the inflammatory biomarker were not assessed. Future studies with larger sample size, diverse population, and longer duration can aid in creating robust evidence with regard to the effect of IRP on the hsCRP.
| Conclusion|| |
IRP treatment leads to a significant decrease in the serum hsCRP levels in the majority of IHD patients. This indicates that along with the already known positive effect on the exercise capacity of the IHD patients, an additional anti-inflammatory role will probably aid in improving the prognosis of these patients
The authors would like to acknowledge the study participants and their families, without whom this study would not have been possible.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Fuster V, Kelly BB. Board for Global Health. Promoting Cardiovascular Health in Developing World: A Critical Challenge to Achieve Global Health. Washington, DC: Institutes of Medicine; 2010.
Prabhakaran D, Jeemon P, Roy A. Cardiovascular diseases in India: Current epidemiology and future directions. Circulation 2016;133:1605-20.
Gaziano TA, Gaziano JM. Epidemiology of cardiovascular disease. In: Harrison's Principles of Internal Medicine. 19th
ed.. New York: McGraw Hill; 2016. p. 266.e1-5.
Osman R, L'Allier PL, Elgharib N, Tardif JC. Critical appraisal of C-reactive protein throughout the spectrum of cardiovascular disease. Vasc Health Risk Manag 2006;2:221-37.
Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002;105:1135-43.
Hamer M, Chida Y, Stamatakis E. Association of very highly elevated C-reactive protein concentration with cardiovascular events and all-cause mortality. Clin Chem 2010;56:132-5.
Habib SS, A Al Masri A. Relationship of high sensitivity C-reactive protein with presence and severity of coronary artery disease. Pak J Med Sci 2013;29:1425-9.
Sane R, Sugwekar V, Nadapude A, Hande A, Depe G, Mandole R. Study of efficacy of ischemia reversal program (IRP) in ischemic heart disease (IHD) patients with VO2 max and Duke's treadmill score. Int J Basic Clin Pharmacol 2018;7:1642-7.
Pepys MB, Hirschfield GM. C-reactive protein: A critical update. J Clin Invest 2003;111:1805-12.
Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: Meta-analyses of prospective studies. JAMA 1998;279:1477-82.
Pai JK, Pischon T, Ma J, Manson JE, Hankinson SE, Joshipura K, et al.
Inflammatory markers and the risk of coronary heart disease in men and women. N
Engl J Med 2004;351:2599-610.
Libby P. Inflammation in atherosclerosis. Nature 2002;420:868-74.
Zhang YX, Cliff WJ, Schoefl GI, Higgins G. Coronary C-reactive protein distribution: Its relation to development of atherosclerosis. Atherosclerosis 1999;145:375-9.
Ockene IS, Matthews CE, Rifai N, Ridker PM, Reed G, Stanek E. Variability and classification accuracy of serial high-sensitivity C-reactive protein measurements in healthy adults. Clin Chem 2001;47:444-50.
Bernstein IM, Damron D, Schonberg AL, Sallam RM, Shapiro R. The relationship of plasma volume, sympathetic tone, and proinflammatory cytokines in young healthy nonpregnant women. Reprod Sci 2009;16:980-5.
Li Y, Ge S, Peng Y, Chen X. Inflammation and cardiac dysfunction during sepsis, muscular dystrophy, and myocarditis. Burns Trauma 2013;1:109-21.
Thatte U, Chiplunkar S, Bhalerao S, Kulkarni A, Ghungralkar R, Panchal F, et al.
Immunological & metabolic responses to a therapeutic course of Basti in obesity. Indian J Med Res 2015;142:53-62.
] [Full text]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]