Pakistan Journal of Medical Sciences


ISSN 1681-715X



Short Communication


Volume 24

April - June 2008 (Part-I)

Number 2


PDF of this Article

Does plasma fibrinogens and c-reactive protein predicts
the incidence of myocardial infraction in
patients with normal lipids profile?

Arun Kumar1, Ramiah Sivakanesan2


Objectives: To evaluate plasma fibrinogen and C-reactive proteins in patients with acute myocardial infarction (AMI) and compare it with normal lipid profile in healthy controls.

Methodology: Plasma fibrinogen and C-reactive proteins were determined in 165 patients and 165 age –sex matched control. The plasma fibrinogen was determined using kit, which was obtained from TECO GmbH, Dieselstr. 1, 84088 Neufahrn NB. The C-reactive protein were determined using high sensitivity enzyme Immunoassay kit manufactured by Life Diagnostics, inc. Also lipid profile was analysed enzymatically in these subjects. The values were expressed as means ± standard deviation (SD) and data from patients and controls was compared using student "t" test.

Results: Serum CRP and Plasma Fibrinogen were increased significantly (p<0.001) in AMI subjects compared to controls. High fibrinogen concentration and C-Reactive proteins seem to be important contributory risk factor in Indian CAD patients.

Conclusions: Thrombotic and inflammatory markers in combination may contribute to AMI with increased severity of the disease. Further larger studies on a nationwide basis recruiting a large number of AMI patients should be done to substantiate these findings. 

KEY WORDS: Normal lipid profile, Plasma Fibrinogen, C-Reactive proteins and AMI.

Pak J Med Sci    April - June 2008 (Part-I)    Vol. 24 No. 2    336-339

1. Dr. Arun Kumar,
Dept. of Biochemistey,
Muzaffarnagar Medical College,
Muzaffarnagar, Uttar Pardesh,India.
2. Prof. Ramiah Sivakanesan,
Dept. of Biochemistry, Faculty of Medicine,
University of Peradeniya, Kandy, Srilanka.


Dr. Arun Kumar

* Received for Publication: September 25, 2007
* Accepted: January 26, 2008


Although studies have demonstrated the role of fibrinogen and C-reactive protein as a coronary risk factor, there are controversial data on the correlation between plasma fibrinogen and c-reactive proteins and the ischemia process. Data regarding the role of fibrinogen and C-reactive proteins in patients of acute myocardial infarction with normal lipid profile is scanty. With the current understanding of the role of fibrinogen and C-reactive protein the present study was undertaken in normolipaedemic patients of acute myocardial infarction. Coronary Heart Disease (CHD) is associated with the greatest morbidity and mortality in industrialized countries.1 The cost of management of CHD is a significant economic burden and so early detection and management is crucial. In the last decades a number of studies showed effective cost-benefit ratio of interventional approaches on the so-called "traditional" risk factors for coronary artery disease, with significant reductions in both cardiovascular morbidity and mortality.2,3 The advancement in the understanding of pathophysiology of atherosclerotic vascular disease has given new insights regarding potential indicators of underlying atherosclerosis and cardiovascular risk. Thus, it has been recently tried world-wide to identify "new" possible atherosclerosis risk factors, including biochemical factors and genetic polymorphisms.4 Several studies have suggested that high concentrations of fibrinogen may represent a strong risk factor for cardiovascular diseases5-7 particularly Acute Myocardial Infarction.8-10 Some of the newly emerged risk factors are called ‘novel risk factors’ which includes Lp(a), homocysteine, and hs CRP. Therefore, the aim of the present study was to evaluate, in a group of patients of AMI with normal lipid profile, the possible predictive role of plasma fibrinogen and C - reactive protein levels compared to normal healthy control. This study was undertaken due to lacunae of data on plasma fibrinogen and C-Reactive proteins in AMI patients with normal lipid profile.


Setting Design and patients: The study consisted of 165 patients (123 men and 42 women) with AMI, admitted to the Intensive Cardiac Care Unit, Faculty of Medicine, University of Peradeniya, Sri Lanka. The diagnosis of AMI was established according to diagnostic criteria: chest pain, which lasted for up to three hours, ECG changes (ST elevation of 2mm or more in at least two leads) and elevation of serum creatine phosphokinase (CPK-MB) and aspartate aminotransferase enzyme elevation. The study was conducted for a period of four and half years from April 2002 to September 2006. Informed consent was taken.

Inclusion criteria: Patients with diagnosis of AMI with normal lipid profile.

Exclusion criteria: Patients with diabetes mellitus, renal insufficiency, current and past smokers, hepatic disease or taking lipid lowering drugs or antioxidant vitamin supplements.

Selection of Controls: Age-, sex-matched subjects healthy volunteers consisting of 165 subjects, 123 men and 42 women were studied as control.

Collection of Samples: Blood collection and biochemical methods used: 10ml of blood was collected after overnight fasting in different containers.

1. EDTA vial: 5.0ml of blood was taken which was used for Plasma Fibrinogen assay.

2. Plain vial: Remaining blood was taken and serum was separated. Serum was used for determination of lipid profile, C-reactive proteins.

Lipid profile: Total cholesterol, triglycerides, and HDL-cholesterol) were analyzed enzymatically using kit obtained from (Randox Laboratories Limited, Crumlin, UK). Plasma LDL-cholesterol was determined from the values of total cholesterol and HDL-cholesterol using the following formulae:

LDL-cholesterol = Total cholesterol -

Triglycerides – HDL-cholesterol (mg/dl)


C-reactive protein: The C-reactive protein were determined using high sensitivity enzyme Immunoassay kit11 manufactured by Life Diagnostics,inc., Catalog Number: 2210. The principle of the assay was based on a solid phase enzyme-linked immunosorbent assay.

Plasma Fibrinogen: The plasma fibrinogen was determined using kit12 which was obtained from TEClot Fib Kit 10 Catalog No: 050-500, manufactured by TECO GmbH, Dieselstr. 1, 84088 Neufahrn NB Germany.

Statistical Analysis: The data from patients and controls were compared using Student’s ‘t’-test. Values were expressed as mean ± standard deviation (SD). Microft excel for windows 2000 was used for statistical analysis. ‘P’ value of less than 0.05 was considered to indicate statistical significance.


Baseline variable of control and AMI patients are shown in Table-I. The differences in age, height and body mass index (BMI) in control and AMI patient are insignificant. The weight, waist circumference, mid arm circumference, biceps and triceps skin fold thickness were higher in AMI subjects as compared to control (p<0.001) (Table-I) and (Table-II). Systolic and diastolic blood pressure was significantly higher in AMI patient compared with controls (p<0.05) (Table-I).

The lipid profile are shown in Table-II. Total cholesterol, TC: HDL-C ratio, triglycerides, LDL-cholesterol, LDL: HDL-C ratio were higher in AMI subjects as compared to control (Table-II) (p<0.001). Also, significant differences were seen in HDL-C levels between AMI and controls (p<0.001). LDL-cholesterol, LDL: HDL-C ratio were higher in male AMI subjects compared to control (Table-IV) (p<0.001).

The C-reactive protein and plasma fibrinogen concentrations are shown in Table-II. Both parameters were significantly increased (p<0.001) in AMI patients compared to controls.


The present study investigated fibrinogen and C-reactive protein in acute myocardial infarct patients since there is a paucity of data in Indian patients. There have also been reports which show that cardiovascular disease has reached alarming proportions in India and it cannot be neglected.13,14 The present study found higher levels of plasma fibrinogen and C-reactive protein (CRP) in patients with AMI compared to control (p<0.001). Fibrinogen levels were significantly elevated in MI patients in agreement with previous Indian studies.15-17

Various studies have18 suggested that the genesis of atherosclerotic plaque is dependent on the interplay of cellular components of the immune system like cytokines, adhesion molecules, lipids, platelets and endothelial cells, and the role of inflammatory markers like C-reactive protein cannot be ignored.19 It is an acute phase reactant considered as a classical marker for inflammation. Acute inflammation, infection, or tissue injury induces a marked increase in CRP. As atherosclerosis involves inflammation of the vascular endothelium, CRP levels tend to be raised.20 The notion that fibrinogen is strongly, consistently, and independently related to coronary risk has been widely accepted. The evidence is based on numerous prospective epidemiological studies and clinical observations. However, the reasons why fibrinogen is elevated in coronary disease and in atherosclerosis are not fully understood. All cells involved in the atherogenetic process are able to produce cytokines which induce an acute phase reaction. The potential pathophysiologic mechanisms by which elevated fibrinogen levels mediate coronary risk are manifold: It forms the substrate for thrombin and represents the final step in the coagulation cascade; it is essential for platelet aggregation; it modulates endothelial function; it promotes smooth muscle cell proliferation and migration; it interacts with the binding of plasminogen with its receptor; and finally it represents a major acute phase protein. Whether or not fibrinogen is causally involved in atherothro-mbogenesis still remains to be determined and even though other unsolved issues await conclusive answers, fibrinogen has emerged as an important additional marker of coronary risk.


High fibrinogen concentration and C-Reactive proteins seem to be important in Indian CAD patients. Thus, it can be said that thrombotic and inflammatory markers in combination may contribute to AMI with increased severity of the disease. Further larger studies on a nationwide basis recruiting a large number of AMI patients should be done to substantiate these findings. 


1. Mendis S, Wissler R. A Nutritional experiment to study short term effects of coconut in diet on serum cholesterol and platelet factor 4 in man. Scientific Proceedings of the International Congress on Coronary Heart Disease Conference; 1988;18-21; Bombay, India.

2. Neaton JD, Wentworth D. Multiple Risk Factor Intervention Trial Research Group.Serum cholesterol, blood pressure, cigarette smoking, and Death from coronary heart disease. Overall findings and differences by age for 316099 white men. Arch Intern Med 1992;152:56-64.

3. Gould AL, Roussouw JE, Santanello NC, Heyse JF, Furberg CD. Cholesterol reduction yields clinical benefit. Impact of statin trials. Circulation 1998;97:946-52.

4. Ridker PM. Evaluating novel cardiovascular risk cfactors: Can we better predict heart attack? Ann Intern Med 1999;130:933-7.

5. Gil M, Zarebinski M, Adamus J. Plasma fibrinogen and troponin I in acute coronary syndrome and stable angina. Int J Cardiol 2002;83:43-6.

6. Ridker PM, Stamper MJ, Rifai N. Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a) and standard cholesterol screening predictors of peripheral arterial disease. JAMA 2001;285:2481-5.

7. Smith EB, Crospbie L. Fibrinogen and fibrin in atherogenesis. In: Ernst E, Koeing W, Lowe GD, Meade TW, eds, Fibrinogen: a new cardiovascular risk factor. Wein: Blackwell, 1992;4-10.

8. Seifried E, Oethinger M, Tansewell P, Hoegee-de Nobel E, Nieuwenhuizen W. Influence of acute myocardial infarction and rt-PA therapy on circulating fibrinogen. Thromb Haemost 1993;69:321-7.

9. Wilhelmsen L, Svardsudd K, Korsan-Bengsten K, Larson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984;311:501-5.

10. Tataru MC, Schulte H, von Eckardstein A, Heinrich J, Assmann G, Koehler E. Plasma fibrinogen inrelation to the severity of arteriosclerosis in patients with stable angina pectoris after myocardial infarction. Coron Artery Dis 2001;12:157-65.

11. Kindmark CO. The concentration of C-reactive protein in Sera from Healthy Individuals. Scand J Clin Lab Invest 1972;29:407-11.

12. Stefan Wagener. National Committee for Clinical Laboratory Standards: Guidelines for the Standardized Collection, Transport and Preparation of Blood Specimens for Coagulation Testing and Performance of Coagulation Assays. American Biological Safety Association (April 5, 2004),

13. Reddy KS. Neglecting cardiovascular disease is unaffordable. Bulletin of WHO 2001;79:984-5. 

14. Reddy KS. Cardiovascular diseases in the developing countries: dimensions, determinants, dynamics and directions for public health. Public Health Nutr 2002;51:231-7. 

15. Gheye S, Lakshmi AV, Krishna TP, Krishnaswamy K. Fibrinogen and Homocysteine levels in coronary artery disease. Ind Heart J 1999;51:499-502.

16. Deepa R, Velmurugan K, Saravanan G, Dwarkanath V, Agarwal S, Mohan V. Relationship of tissue plasminogen activator, plasminogen activator inhibitor-1 and fibrinogen with coronary artery disease in South Indian male subjects. J Assoc Physicians Ind 2002;50:901-6. 

17. Chambers JC, Obeid OA, Refsum H, Ueland P, Hackett D, Hooper J, et al. EORTC Breast cancer group and EORTC radiotherapy group. Plasma homocysteine concentrations and risk of coronary heart disease in UK Indian Asian and European men. Lancet 2000;355:523-7.

18. Ridker PM. High-sensitivity C-reactive protein: Potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation 2001;103:1813-18.

19. Berton G, Cordiano R, Palmieri R, Pianca S, Pagliara V, Palatini P. C-Reactive Protein in Acute Myocardial Infarction: Association with Heart Failure. Am Heart J 2003;145:1094-1101.

20. Rosenson RS, Koenig W. Utility of inflammatory markers in the management of coronary artery disease. Am J Cardiol 2003;92(Suppl):10i-18i.


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