Table of Contents    
ORIGINAL ARTICLE
Year : 2020  |  Volume : 11  |  Issue : 1  |  Page : 39-44  

High-sensitive C-reactive protein in patients with coronary artery disease


Department of Medicine, Krishna Institute of Medical Sciences Deemed to be University, Karad, Maharashtra, India

Date of Submission10-Jul-2019
Date of Decision26-Aug-2019
Date of Acceptance09-Oct-2019
Date of Web Publication11-Mar-2020

Correspondence Address:
Dr. Virendra C Patil
Department of Medicine, Krishna Institute of Medical Sciences Deemed to be University, Karad, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jnsbm.JNSBM_159_19

Rights and Permissions
   Abstract 


Background: Inflammation plays a key role in the pathogenesis of atherosclerosis and coronary artery disease (CAD). Aim and Objectives: The aim of this study was to assess the relation of serum high-sensitivity C-reactive protein (hs-CRP) with the presence and severity of CAD. Study Design: This was a cross-sectional, observational study done on patients with diagnosis of acute coronary syndrome (ACS) undergoing coronary angiogram (CAG). Materials and Methods: A total of 100 patients were included in this study satisfying the inclusion criteria. The inclusion criteria were patients with the diagnosis of ACS undergoing CAG. All enrolled patients underwent hs-CRP, hemoglobin, serum creatinine, fasting lipid profile, blood sugar level, resting 12-lead electrocardiogram, creatine kinase–myocardial band, troponin -I, and CAG. Statistical Analysis: Data were analyzed for mean, percentage, standard deviation and Chi-square test for quantitative data using SPSS software version 21 (trial version), and P < 0.05 was considered statistically significant. Results: A total of 63% of male and 37% of female patients underwent CAG. The mean level of hs-CRP was 2.73 (±0.73) mg/L. The level of hs-CRP, severity of coronary artery involvement, and CAD risk factors was significantly more with an hs-CRP level of 1–3 mg/L followed by >3 mg/L. The significant number of patients with double-vessel disease (DVD) and triple-vessel disease (TVD) had an hs-CRP level between 1 and 3 mg/L compared to single-vessel disease (SVD) with P < 0.03. About 67.57% of females and 44.44% of males had an hs-CRP level of 1–3 mg/L, respectively (P < 0.02). A total of 53% of population had an hs-CRP level between 1 and 3 mg/L, 23% had <1 mg/L, and 24% had >3 mg/L (P < 0.02). The hs-CRP was positively correlated with severity of CAD by angiogram (+0.21). Conclusions: A significant number of patients had an hs-CRP level of 1–3 mg/L. The severity of CAD was positively correlated with a level of hs-CRP in incremental fashion. Patients with DVD and TVD had a high hs-CRP level compared to SVD. The hs-CRP can be considered as novel CAD risk factors to be screened in the patients with CAD where it cannot be forecasted by traditional risk factors.

Keywords: Coronary angiogram, coronary artery disease, double-vessel disease, high-sensitivity C-reactive protein, single-vessel disease, triple-vessel disease


How to cite this article:
Patil VC, Avhad AB, Kulkarni AR, Pandere KA. High-sensitive C-reactive protein in patients with coronary artery disease. J Nat Sc Biol Med 2020;11:39-44

How to cite this URL:
Patil VC, Avhad AB, Kulkarni AR, Pandere KA. High-sensitive C-reactive protein in patients with coronary artery disease. J Nat Sc Biol Med [serial online] 2020 [cited 2020 Jul 11];11:39-44. Available from: http://www.jnsbm.org/text.asp?2020/11/1/39/280127




   Introduction Top


The involvement of inflammation to atherosclerosis is well established. Atherosclerotic cardiovascular disease (CVD) is estimated to be the foremost cause of death. The incidence of CVD is it keeps on increasing exponentially in the developing nations. Inflammation plays a key role in coronary artery disease (CAD) progression. The Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) results support that the high-sensitivity C-reactive protein (hs-CRP) testing may be useful in intermediate-risk patients to drive statin therapy. Strong evidence indicates that CRP is associated with coronary heart disease (CHD) events. Moderate, consistent evidence suggests that adding CRP to risk prediction models among initially intermediate-risk persons improves risk stratification and reclassification in intermediate-risk persons.[1],[2] Certain coronary events cannot be forecasted only by traditional risk factors. Half of the CADs can be attributed to traditional risk factors and rests are unexplained. The alternate novel risk factor assessment may aid early and accurate identification of individuals at risk of having CAD. This prospective cross-sectional study was conducted to quantify the level of hs-CRP to the severity of CAD assessed by coronary angiography.


   Materials and Methods Top


Aim and objectives

The aim of this study was to assess the relationship of serum inflammatory marker, hs-CRP, with the presence and severity of angiographically evaluated CAD.

Study design

This was a cross-sectional, observational study done on patients with diagnosis of acute coronary syndrome (ACS) undergoing CAG.

Study setting

This study was conducted in KIMS Hospital over a period of 1 year (January 2018–December 2018). The Institutional Ethical Committee approval was taken (protocol number: 0639/2018–2019). The informed and written consent was taken from patients before the enrollment for study. A total of 100 patients were included in this study satisfying the inclusion criteria. The inclusion criteria were patients with the diagnosis of ACS undergoing coronary angiogram (CAG). The patients with valvular heart disease, cardiomyopathy, and hepatic and renal dysfunction were excluded from this study. The level of hs-CRP was measured using an automated CRPLX Tina-quant C-reactive protein (Latex) assay (Roche). The hs-CRP assay is based on the principle of particle-enhanced immunological agglutination. The anti-CRP antibodies coupled to latex microparticles react with CRP to form an antigen–antibody complex leading to agglutination causing turbidity of the reaction mixture, which is proportional to the CRP concentration. All enrolled patients underwent hs-CRP, hemoglobin, serum creatinine, fasting lipid profile, blood sugar level, resting 12-lead electrocardiogram, creatine kinase–myocardial band, Trop-I, and CAG.

Statistical analysis

Data collected were entered in Microsoft Excel. The mean, percentage, standard deviation and Chi-square test was calculated for quantitative data using Microsoft Excel spreadsheet. Appropriate statistical tests were applied using SPSS (Statistical Package for the Social Sciences) software version 21 for Windows (SPSS, Chicago, IL) (trial version) for analysis, and P < 0.05 was considered statistically significant.


   Results Top


A total of 100 patients fulfilling the inclusion criteria were included in this cross-sectional observational study, conducted in patients with CAD undergoing CAG. A total of 63 (64%) male and 37 (37%) female patients underwent CAG after informed and written consent as per protocol. The mean age for patients was 55.32 (±9.67) years. The mean level of hs-CRP was 2.73 (±0.73) mg/L. There was no significant statistical difference of mean among the genders [Table 1].
Table 1: Mean and standard deviation of various coronary artery disease risk factors

Click here to view


The present cohort of patients with CAD had predominantly SVD. The level of hs-CRP, severity of coronary artery involvement, and coronary artery disease risk factors was significantly more with an hs-CRP level of 1–3 mg/L followed by >3 mg/L. The significant number of patients with double-vessel disease (DVD) and triple-vessel disease (TVD) had an hs-CRP level between 1 and 3 mg/L compared to single-vessel disease (SVD) with P < 0.03. A total of 67.57% of females and 44.44% of males had an hs-CRP level of 1–3 mg/L, respectively (P< 0.02). A total of 53% of the population had an hs-CRP level between 1 and 3 mg/L, 23% had <1 mg/L, and 24% had >3 mg/L (P< 0.02). A total 37.25% of SVD patients, 11.11% DVD patients, and 4.55% TVD patients had hs-CRP level of <1 mg/L (P< 0.01). The severity of CAD was correlated with a level of hs-CRP in incremental fashion [Table 2] and [Graph 1].
Table 2: Relation of level of high.sensitivity C.reactive protein and relation with coronary artery disease risk factors and artery involved

Click here to view



The TVD involvement was more prevalent in female population compared to males and DVD was more prevalent in males (P< 0.034) [Table 3] and [Graph 2].
Table 3: Demographic distribution of coronary angiographic vessel involved

Click here to view



In multivariate analysis, the hs-CRP level of 1–3 mg/L was significantly associated with angiographically proved severity of CAD independent of age, gender, parameters of lipid profile, and hypertension (P< 0.02).


   Discussion Top


The published studies from India have reported an association between hs-CRP and metabolic syndrome, impaired glucose tolerance, diabetes mellitus (DM), CAD, and stroke. Previous studies on the relationship between hs-CRP and severity of coronary atherosclerosis have revealed inconsistent results. The JUPITER results support that hs-CRP testing may be useful in intermediate-risk patients to drive statin therapy. Strong evidence indicates that CRP is associated with CHD events. Moderate, consistent evidence suggests that adding CRP to risk prediction models among initially intermediate-risk persons improves risk stratification and risk reclassification in intermediate-risk persons. Hs-CRP (≥2 mg/L) was associated with risk, and its use resulted in some reclassification in intermediate-risk persons. For myocardial infarction (MI) and cardiovascular (CV) mortality, adding hs-CRP to traditional risk factors improves risk prediction. If, after quantitative risk assessment, a risk-based treatment decision is uncertain, assessment of ≥1, family history, hs-CRP, coronary artery calcium score, or ankle-brachial index may be considered to inform treatment decision-making (Class of Recommendation-IIb and Level of evidence-B).[1],[2] The inflammatory biomarker hs-CRP adds prognostic information on CV risk comparable to blood pressure or cholesterol. Values <1, 1–3, and >3 mg/L indicate lower, intermediate, and high relative CV risk, respectively.[3] The inflammation in the propagation of atherosclerosis and susceptibility to CV events is well established. Of the wide array of inflammatory biomarkers that have been studied, hs-CRP was used in screening and risk reclassification and as a predictor of clinical response to statin therapy.[4] In the present study, 63% of males and 37% of females underwent CAG, predominated by male gender. Majority of the patients with angiographically insignificant CAG had an hs-CRP level of <1 mg/L, and majority of the patients with SVD, DVD, and TVD had an hs-CRP level of 1–3 mg/L. There was a statistically significant positive correlation between the level of hs-CRP and the severity of CAD on CAG. Similarly, Tan et al. in their study of 128 patients undergoing percutaneous coronary intervention (PCI) found that. the hs-CRP level in the PCI treatment group was significantly higher.[5] Mokhtar et al. in their study of 45 patients who underwent diagnostic CAG stated that the serum levels of hs-CRP were significantly increased in CAD, MVD, and SVD patients when compared with non-CAD patients.[6] Similarly, in the present study, the significant number of patients with DVD and TVD had an hs-CRP level between 1 and 3 mg/L compared to SVD with P < 0.03. Hs-CRP has emerged as one of the most important novel inflammatory markers. The hs-CRP assay has made screening this marker simple, reliable, and reproducible and can be used as a clinical guide to the diagnosis, management, and prognosis of CAD.[7] Lee et al. studied 418 diabetic patients who had undergone coronary angiography, and they found that patients with CAD had a longer duration of diabetes (8.2 ± 21.8 vs. 10.2 ± 29.8 years, P = 0.027), high titers of hs-CRP (P = 0.015), and increased hemoglobin A1c levels (P = 0.007). They concluded that the hs-CRP levels were significantly correlated with multivessel involvement; similarly, in present study, the severity of CAD had a linear relation with a level of hs-CRP.[8] The hs-CRP has been accepted to provide additional value to the Framingham Risk Scoring System devised for future 10-year CAD risk prediction, even in the presence of conventional CAD risk factors.[9] Similar to the present study, 774 CAD members from the Indian Atherosclerosis Research Study demonstrated high levels of hs-CRP among participants with repeat coronary event in Asian Indian population.[9] Mitra and Panja mild elevation of baseline levels of hs-CRP among apparently healthy individuals is associated with higher risk for future CV events. This predictive capacity of hs-CRP is independent of traditional CV risk factors and offers a prognostic advantage over measurement of lipid alone. Similarly, in the present study in multivariate analysis, hs-CRP level of 1–3 mg/L was significantly associated with angiographically proved severity of CAD independent of age, gender, parameters of lipid profile, and hypertension (P< 0.02). Increased hs-CRP levels in patients with high-risk CAD without documented CAD warrant treatment with statin even if low-density lipoprotein-cholesterol (LDL-C) levels are within target range.[10] Habib and Al Masri studied 87 patients and found that the CAD patients presented with significantly higher hs-CRP levels than controls. Linear regression analysis between hs-CRP and CAD severity with a significant positive correlation (r = 0.423, P = 0.018). TVD patients had significantly higher hs-CRP levels than one-vessel and two-vessel disease.[11] Similarly, in the present cohort of patients with CAD, the severity of CAD was correlated with a level of hs-CRP in incremental fashion. Kazemi-Bajestani et al. studied 110 participants undergoing CAG. Serum hs-CRP is an independent predictor of angiographically defined CAD in an Iranian population, and these findings are comparable with the present study.[12] Nyandak et al. studied 73 patients with the diagnosis of ACS and found that the hs-CRP level were significantly elevated in angiographically confirmed CAD patients (P = 0.004). Similarly, in the present study, a significant correlation was observed between the extent of CAD and hs-CRP levels.[13] Global risk algorithms that include hs-CRP outperform those solely using Framingham covariates. Although diet, exercise, and smoking cessation are the first steps for patients with a proinflammatory response, JUPITER trial data demonstrate that statins reduce by 47% the rate of first MI, stroke, or confirmed CV death when given to patients with LDL-C levels of <130 mg/L and hs-CRP of >2 mg/L. In the current U. S. guidelines, hs-CRP carries a Cass IIb assessment and is most appropriate in primary prevention decision for initiating statin therapy.[3] Mild CRP elevation hs-CRP has shown to be associated with future major CV risk (hs-CRP: <1 mg/L – low risk, 1–3 mg/L – intermediate risk, and 3–10 mg/L – high risk). The American Heart Association recommended that patients at intermediate or high risk of coronary heart disease may benefit from measurement of hs-CRP. Elevation of hs-CRP is associated with increased risk of type 2 diabetes development in patients with all levels of metabolic syndrome.[14] The current evidence supports that inflammation is a major driving force underlying the initiation of coronary plaques, and the mild elevation of hs-CRP among apparently healthy individuals is associated with higher risk for CV events. The predictive value of hs-CRP is found to be independent of traditional CV risk factors.[15] Soinio et al. with study population consisting of 1059 patients with type 2 DM stated that hs-CRP was an independent risk factor for CHD deaths, and these findings are comparable with the present study.[16] The role of low-grade systemic inflammation as evidenced by elevated hs-CRP levels in the pathogenesis of atherosclerotic vascular disease has been intensely investigated through observational studies and clinical trials in the past two decades. On the basis of evidence that has accrued, hs-CRP measurement has been integrated into the Reynolds Risk Scoring System to predict CV risk. The JUPITER trial proved the benefit of statins in CV risk reduction in patients with low grades of systemic inflammation and “normal” cholesterol levels.[17] Similar to the present study, Hiregoudar et al. studied 68 patients presenting with acute segment elevation myocardial infarction (STEMI) and observed that the patients with TVD had higher hs-CRP and LDL-C compared to SVD.[18] Geluk et al. in their study of Prevention of Renal and Vascular End-Stage Disease of 8139 participants without previous documented CAD and quoted that the hs-CRP significantly contributes to coronary atherogenesis.[19] Ongoing multinational trials are pursuing whether reducing inflammation will decrease vascular event rates [Table 4].[3]
Table 4: Comparison of interpretation of various studies

Click here to view


The hs-CRP find its role in pathogenesis, prognosis, and prevention of CVD, which is one of the foremost causes of death worldwide.[19] It is worthwhile to remember that hs-CRP testing has role in heart failure, atrial fibrillation, hypertension, valve disease, and prognosis of coronary stent thrombosis. Multiple studies and guidelines have recommended hs-CRP testing for stratifying CVD risk groups, selecting patients for statin therapy and prognosis of CVD. Measurement of the serum hs-CRP level may improve risk stratification among patients suspected of having CAD. Patients with documented CAD and high hs-CRP levels should be managed aggressively. Drugs reducing hs-CRP concentration are being investigated.[20]


   Conclusions Top


The hs-CRP levels were higher in patients with high degree of angiographic stenosis (DVD and TVD) and have correlation with the disease burden in the present cohort of CAD patients. Significant CAD on CAG was appreciable in patients with what is considered an average hs-CRP of 1–3 mg/L. An elevated hs-CRP was associated with other conventional CAD risk factors. These findings suggest that among patients with CAD, hs-CRP levels can be used to gain essential insight into which patients can have significant CAD and subsequently requiring intervention. Currently, there is no directive to measure CRP in all patients with CAD because statins gives an equal benefit in reduction of hs-CRP. We concluded that the elevated hs-CRP was a forecaster of CAD. Hs-CRP improves risk stratification and identifies patient groups who might benefit from particular treatment strategies. Ongoing trials will clarify whether targeting drug therapy based on CRP levels and even targeting CRP itself will be of benefit to patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Goff DC Jr., Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB, Gibbons R, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: A report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation 2014;129:S49-73.  Back to cited text no. 1
    
2.
Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: Executive summary: A report of the American College of Cardiology/American Heart Association task Force on Clinical practice guidelines. J Am Coll Cardiol 2019;74:1376-414.  Back to cited text no. 2
    
3.
Ridker PM. A test in context: High-sensitivity C-reactive protein. J Am Coll Cardiol 2016;67:712-23.  Back to cited text no. 3
    
4.
Yousuf O, Mohanty BD, Martin SS, Joshi PH, Blaha MJ, Nasir K, et al. High-sensitivity C-reactive protein and cardiovascular disease: A resolute belief or an elusive link? J Am Coll Cardiol 2013;62:397-408.  Back to cited text no. 4
    
5.
Tan Z, Li L, Ma Y, Geng X. Clinical significance of cys-C and hs-CRP in coronary heart disease patients undergoing percutaneous coronary intervention. Braz J Cardiovasc Surg 2019;34:17-21.  Back to cited text no. 5
    
6.
Mokhtar ER, Saleh BI, Aboualia AM, Nageb HM. Relationship between monocyte subsets, IL-6 and hs-CRP with the severity of coronary artery disease in stable angina pectoris patients. Am J Biochem 2017;7:114-26.  Back to cited text no. 6
    
7.
Shrivastava AM, Singh HV, Raizada A, Singh SK. C-reactive protein, inflammation and coronary heart disease. Egypt Heart J 2015;67:89-97.  Back to cited text no. 7
    
8.
Lee HJ, Her SH, Im YS, Won KY, Yoo SH, Kim DB, et al. Significance of inflammatory markers in diabetic patients with stable coronary artery disease. Korean J Intern Med 2009;24:212-9.  Back to cited text no. 8
    
9.
Rao VS, Kadarinarasimhiah NB, John S, Hebbagodi S, Shanker J, Kakkar VV. Usefulness of C-reactive protein as a marker for prediction of future coronary events in the Asian Indian population: Indian atherosclerosis research study. Int J Vasc Med 2010;Article ID 389235:8. https://doi.org/10.1155/2010/389235.  Back to cited text no. 9
    
10.
Mitra B, Panja M. High sensitive C-reactive protein: A novel biochemical markers and its role in coronary artery disease. J Assoc Physicians India 2005;53:25-32.  Back to cited text no. 10
    
11.
Habib SS, 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.  Back to cited text no. 11
    
12.
Kazemi-Bajestani SM, Ghayour-Mobarhan M, Ebrahimi M, Moohebati M, Esmaeili HA, Ferns GA. C-reactive protein associated with coronary artery disease in Iranian patients with angiographically defined coronary artery disease. Clin Lab 2007;53:49-56.  Back to cited text no. 12
    
13.
Nyandak T, Gogna A, Bansal S, Deb M. High sensitive C-reactive protein (hs-CRP) and its correlation with angiographic severity of coronary artery disease (CAD). J Indian Acad Clin Med 2007;8:217-1.  Back to cited text no. 13
    
14.
Pfützner A, Forst T. High-sensitivity C-reactive protein as cardiovascular risk marker in patients with diabetes mellitus. Diabetes Technol Ther 2006;8:28-36.  Back to cited text no. 14
    
15.
Zakynthinos E, Pappa N. Inflammatory biomarkers in coronary artery disease. J Cardiol 2009;53:317-33.  Back to cited text no. 15
    
16.
Soinio M, Marniemi J, Laakso M, Lehto S, Rönnemaa T. High-sensitivity C-reactive protein and coronary heart disease mortality in patients with type 2 diabetes: A 7-year follow-up study. Diabetes Care 2006;29:329-33.  Back to cited text no. 16
    
17.
Kamath DY, Xavier D, Sigamani A, Pais P. High sensitivity C-reactive protein (hsCRP) & cardiovascular disease: An Indian perspective. Indian J Med Res 2015;142:261-8.  Back to cited text no. 17
[PUBMED]  [Full text]  
18.
Hiregoudar NS, Baligar BD, Renukappa VB, Rathod VR. Correlation between serum HsCRP and coronary artery disease severity in patients with acute STEMI. J Evid Based Med Healthc 2018;5.  Back to cited text no. 18
    
19.
Geluk CA, Post WJ, Hillege HL, Tio RA, Tijssen JG, van Dijk RB, et al. C-reactive protein and angiographic characteristics of stable and unstable coronary artery disease: Data from the prospective prevend cohort. Atherosclerosis 2008;196:372-82.  Back to cited text no. 19
    
20.
Adukauskienė D, Čiginskienė A, Adukauskaitė A, Pentiokinienė D, Šlapikas R, Čeponienė I. Clinical relevance of high sensitivity C-reactive protein in cardiology. Medicina (Kaunas) 2016;52:1-10.  Back to cited text no. 20
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

Top
  
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Conclusions
    References
    Article Tables

 Article Access Statistics
    Viewed348    
    Printed14    
    Emailed0    
    PDF Downloaded75    
    Comments [Add]    

Recommend this journal