International Journal of Advances in Medicine

Ramdas J et al. Int J Adv Med. 2016 May;3(2):162-165

http://www.ijmedicine.com

pISSN 2349-3925 | eISSN 2349-3933

Elevated C reactive protein levels in obese individuals with metabolic syndromes

Jella Ramdas*, Vasantha Jella


Department of General Medicine, Bhaskara Medical College, Rangareddy, Telangana, India

Received: 15 February 2016

Revised: 21 March 2016

Accepted: 23 March 2016

*Correspondence:

Dr. Jella Ramdas,

E-mail: Jrdas2000@yahoo.co.in

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background: C reactive protein (CRP) is a sensitive marker of inflammation. Apart from CRP, obesity is also one of the established risk factor for CVD in adults and children. This study was therefore conducted to assess the association between elevated levels of CRP and obesity.

Methods: 1432 patients, >35 years of age who had come to our hospital for the assessment of risk factors for Cardiovascular disease were included into study. A detailed medical and clinical history was taken from all the patients and BMI was calculated based on the height and weight. Phlebotomy was performed on all patients and blood was collected to test the samples for CRP, LDL cholesterol, HDL cholesterol, triglycerides, fasting blood glucose, uric acid.

Results: The mean age for 1432 patients was 55.3 years. Males had a mean age of 57.2 years and females were 52.9 years. The levels of CRP were within the normal ranges till class I obese individuals. Among the class II and III patients there was an elevated level of CRP. Only about 4.5% of the patients with CRP levels more than 10 mg/l had normal BMI while 42.8% of the patients were under the class III obese BMI.

Conclusions: It was shown in our studies that higher BMI is associated with higher CRP concentrations especially in patients with metabolic syndromes.

Keywords: C reactive protein, Obesity, Metabolic syndromes

INTRODUCTION

The acute phase protein, the C reactive protein (CRP) is a sensitive marker of inflammation. Plasma CRP levels are low in healthy patients without acute illness. But through the use of high sensitivity tests, it has been possible to investigate the relation between plasma CRP levels and cardiovascular disease and inflammation.1,2 These tests have shown that CRP is independently associated with the risk of cardiovascular disease causing severe morbidity and mortality along with acute coronary events in both men and women.3-7

Apart from CRP, obesity is also one of the established risk factor for CVD in adults and children.8,9 Obesity has double worldwide since 1980. In 2014, it has been estimated that more than 1.9 billion adults who were 18 years or older were overweight, and of these 600 were obese. 39% of the adults aged 18 years and over were overweight in 2014 and 13% were obese.10

Adipose tissue has always been considered a passive storage depot for fat, but it is also known to play an active role in metabolism by producing the proinflammatory cytokine, interleukin-6 (IL 6).11-14 As IL-6 has inflammatory properties, as well as stimulation of acute phase protein production in liver, the release of IL-6 from adipose tissue may induce low-grade systemic inflammation in persons with excess body.15,16

This study was therefore conducted to assess the association between elevated levels of CRP and obesity in patients with metabolic syndromes.

METHODS

1432 patients >35 years who had come to the Department of Medicine were included into the study. This study was conducted over a period of two years at Bhaskara Medical College. All these patients had come to our hospital for the assessment of risk factors for cardiovascular disease.

All these patients were included into the study after obtaining an informed consent. Patients who refused the informed consent or those with an overt inflammatory disease were excluded from the study.

A detailed medical and clinical history was taken from all the patients. Demographic details such as age, gender, height, weight etc. were taken. History of cigarette smoking was noted as ‘never’, ‘occasional’ or ‘regular’. Amount of physical activity was also categorized as never, rare or regular, depending the amount of physical activity done by the patient. BMI was calculated based on Weight (kg) and height (m) of the patient using the formula weight/height.2 Patients were categorized as normal with BMI <25 kg/m2, overweight BMI 25.0-29.9 kg/m2, Class I obese BMI 30.0-34.9 kg/m2; Class II obese BMI 35.0-39.9 kg/m2; and class III obese BMI 40.0 kg/m2. This categorization was according to the classification proposed by World Health Organizational expert committee.17

The categorization of metabolic syndrome in patients was based on the third report of national cholesterol educational program expert panel on detection, Evaluation and treatment of high blood cholesterol in adults’ criteria.18 The following cutoff limits were as per this criteria; 1. Blood pressure ≥135/85 mmHg, (2) triglyceride 150 mg/dl, (3) low HDL cholesterol 40 mg/dl for men and 50 mg/dl for women, (4) fasting glucose 110 mg/dl (5) a BMI cut point of 30 kg/m2 for obesity.19 Patients with 3 or more of the above criteria were considered to have a metabolic syndrome.

Phlebotomy was performed on all patients and blood was collected to test the samples for CRP, LDL cholesterol, HDL cholesterol, triglycerides, fasting blood glucose, uric acid.

All statistical analysis was performed using SPSS statistical software (version 10.1).

RESULTS

The mean age for 1432 patients was 55.3 years. Males had a mean age of 57.2 years and females were 52.9 years. Of the patients around 40% had a family history of diabetes.

Table 1: Demographic details of the patients.
Table reproduced from source PDF page 2

The average blood pressure of the patients were in the normal range but the lipid profile of the patients and the fasting blood sugars were on the higher side showing that many of the patients were diabetic.

Table 2: Blood pressure and lipid profile in patients.
Table reproduced from source PDF page 2

The levels of CRP were within the normal ranges till class I obese individuals. Among the class II and III patients there was an elevated level of CRP (Figure 1).

Figure 1: Levels of CRP in Different categories of BMI. | 0 2 4 6 8 10 12 14 16 3.6 6.2 8.9 12.1 14.7
Figure 1: Levels of CRP in Different categories of BMI.

Only about 4.5% of the patients with CRP levels more than 10 mg/l had normal BMI while 42.8% of the patients were under the class III obese BMI (Figure 2).

Figure 2: Percentage of patients with >10 mg/l CRP levels. | 4.5 6.4 12.1 34.2 42.8 0 10 20 30 40 50
Figure 2: Percentage of patients with >10 mg/l CRP levels.

DISCUSSION

One of the factors which pose a considerable health risk especially for cardiovascular diseases is obesity and overweight and elevated levels of CRP.20-22 CRP levels above 10 mg/l have been associated with increased risk of myocardial infarction, ischemic stroke and peripheral arterial disease.23,24 Raised CRP levels release IL6, which is observed in patients with angina.25,26 These levels are also expected to predict the incidence of cardiovascular disease in patients.5,27

Our results showed that in patients above the age of 35 years, CRP is strongly associated with obesity and Body Mass Index and to components of metabolic syndrome. This was independent of other factors which are known to influence CRP levels, such as smoking, HRT and physical activity. Levels of CRP were found to increase with the increasing number of metabolic syndromes, although BMI was found to be the predominant contributor.28

This association of metabolic syndrome with elevation of acute phase proteins was shown in many other studies. Festa et al found a linear increase of CRP levels with increase in metabolic disorders and that body mass index, systolic blood pressure and insulin sensitivity were related to CRP levels.29 Frohlich et al also observed that there was a statistically significant correlation between CRP and BMI, triglycerides, glucose and uric acid and a negative correlation with HDL cholesterol.30 Similar results were observed in other studies also.31-33 It was found that subjects with metabolic syndrome had high CRP levels if they were obese that those who were not obese. Also regardless of the presence of metabolic syndrome, obese persons had high CRP levels the normal weight persons.28,29,34

Around 25% of the circulating IL6 is estimated to be released by human subcutaneous adipose tissues and stimulates the production of acute phase proteins in the liver. This might explain the relation between CRP and obesity.15,16

In our study the levels of IL6 were not available. As a result, the hypothesis that increase in IL6 levels increases the CRP levels could not be verified. Thus future studies should be performed to gather this association.

CONCLUSION

It was shown in our studies that higher BMI is associated with higher CRP concentrations especially in patients with metabolic syndromes. >10 mg/l levels of CRP suggest a source of infection or inflammation which is more common in obese individuals.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the institutional ethics committee

REFERENCES

  1. 1. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340:448-54.
  2. 2. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340:115-26.
  3. 3. Koenig W, Sund M, Fröhlich M, Fischer HG, Löwel H, Döring a et al. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation. 1999;99:237-42.
  4. 4. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342:836-43.
  5. 5. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336:973-9.
  6. 6. Ridker PM, Glynn RJ, Hennekens CH. C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation. 1998;97:2007-11.
  7. 7. Thompson SG, Kienast J, Pyke SD, , Haverkate F, van de Loo JC. Haemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med. 2000;332:635-41.
  8. 8. Jager A, van Hinsbergh VW, Kostense PJ, Emeis JJ, Yudkin JS, Nijpels G, Dekker JM, Heine RJ, Bouter LM, Stehouwer CD. Von Willebrand factor, C-reactive protein, and 5-year mortality in diabetic and nondiabetic subjects: the Hoorn study. Arterioscler Thromb Vasc Biol. 1999;19:3071-8.
  9. 9. Ridker PM. Inflammation, infection, and cardiovascular risk: how good is the clinical evidence? Circulation. 1998;97:1671-4.
  10. 10. WHO Fact Sheet. Updated in Feb 2015. Available at, http://www.who.int/mediacentre/factsheets/fs311/en/. Accessed on 20 February, 2016.
  11. 11. Flier JS. The adipocyte: storage depot or node on the energy information superhighway? Cell.1995;80:15-8.
  12. 12. Mohamed-Ali V, Pinkney JH, Coppack SW. Adipose tissue as an endocrine and paracrine organ. Int J Obes Relat Metab Disord.1998;22:1145-58.
  13. 13. Purohit A, Ghilchik MW, Duncan L, Wang DY, Singh A, Walker MM et al. Aromatase activity and interleukin-6 production by normal and malignant breast tissues. J Clin Endocrinol Metab. 1995;80:3052-8.
  14. 14. Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin J S et al. Subcutaneous adipose tissue releases interleukin-6, but not tumour necrosis factor-α, in vivo. J Clin Endocrinol Metab. 1997;82:4196-200.
  15. 15. Banks RE, Forbes MA, Storr M, Higginson JE, Thompson D, Raynes JG. The acute phase response in patients receiving subcutaneous IL-6. Clin Exp Immunol. 1995;102:217-23.
  16. 16. Papanicolaou DA, Wilder RL, Manolagas SC, Chrousos GP, Chrousos GP. The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med. 1998;128:127-37.
  17. 17. World Health Organization Expert Committee. Physical status: the use and interpretation of anthropometry. WHO technical report series No 854 1995. World Health Organization: Geneva.
  18. 18. Executive summary of the third report of the National Cholesterol Education Program (NCEP). expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285:2486-97.
  19. 19. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998;15:539-53.
  20. 20. Pi-Sunyer FX. Health implications of obesity. Am J Clin Nutr.1991;53:1595S-1603S.
  21. 21. Rexrode KM, Carey VJ, Hennekens CH, Walters EE, Colditz GA, Stampfer MJ et al. Abdominal adiposity and coronary heart disease in women. JAMA.1998;280:1843-8.
  22. 22. Folsom AR, Stevens J, Schreiner PJ, McGovern PG. Body mass index, waist/hip ratio, and coronary heart disease incidence in African-Americans and whites. Am J Epidemiol. 1998;148:1187-94.
  23. 23. Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation. 1998;98:731-3.
  24. 24. Koenig W, Sund M, Frohlich M, Fischer H, Lo¨wel H, Do¨ring A et al. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men. Circulation. 1999;99:237-42.
  25. 25. Maseri A, Biasucci LM, Liuzzo G. Inflammation in ischaemic heart disease. BMJ. 1996;312:1049-50.
  26. 26. Haverkate F, Thompson SG, Pyke SDM, Gallimore JR, Pepys MB. Production of C-reactive protein and risk of coronary events in stable and unstable angina. Lancet. 1997;349:462-6.
  27. 27. Mendall MA, Patel P, Ballam L, Strachan D, Northfield TC. C-reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study. BMJ. 1996;312:1061-5.
  28. 28. Aronson D, Bartha P, Zinder O, Kerner A, Markiewicz W, Avizohar O et al. Obesity is the major determinant of elevated C-reactive protein in subjects with the metabolic syndrome. Intern J Obes. 2004;28:674-9.
  29. 29. Festa A, D'Agostino Jr R, Howard G, Mykkanen L, Tracy RP, Haffner SM. Chronic subclinical inflammation as part of the insulin resistance syndrome: the insulin resistance atherosclerosis study. Circulation. 2000;102:42-7.
  30. 30. Frohlich M, Imhof A, Berg G, Hutchinson WL, Pepys MB, Boeing H et al. Association between C-reactive protein and features of the metabolic syndrome: a population-based study. Diabet Care. 2000;23:1835-9.
  31. 31. Hak AE, Stehouwer CD, Bots ML, Polderman KH, Schalkwijk CG, Westendorp IC, Hofman A, Witteman JC. Associations of C-reactive protein with measures of obesity, insulin resistance, and subclinical atherosclerosis in healthy, middle-aged women. Arterioscler Thromb Vasc Biol. 1999;19:1986-91.
  32. 32. Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol. 1999;19:972-8.
  33. 33. Lemieux I, Pascot A, Prud'homme D, Almeras N, Bogaty P, Nadeau A et al. Elevated C-reactive protein: another component of the atherothrombotic profile of abdominal obesity. Arterioscler Thromb Vasc Biol. 2001;21:961-7. |
  34. 34. Visser M, Bouter LM, McQuillan M, WeneMH, Harris TB. Elevated C-reactive protein levels in overweight and obese adults. JAMA. 1999;282(22):2131-5.