SciELO - Scientific Electronic Library Online

 
vol.21 número1Asociación entre los factores del proveedor de salud y el número de atenciones prenatales en las usuarias de un hospital del Perú, 2019Diferencias del somatotipo entre niños mapuche y no mapuche de 12 y 13 años de Malleco, Araucanía, Chile índice de autoresíndice de materiabúsqueda de artículos
Home Pagelista alfabética de revistas  

Servicios Personalizados

Revista

Articulo

Indicadores

  • No hay articulos citadosCitado por SciELO

Links relacionados

  • No hay articulos similaresSimilares en SciELO

Compartir


Revista de la Facultad de Medicina Humana

versión impresa ISSN 1814-5469versión On-line ISSN 2308-0531

Rev. Fac. Med. Hum. vol.21 no.1 Lima ene-mar 2021

http://dx.doi.org/10.25176/rfmh.v21i1.3320 

Original article

Association between c-reactive protein and metabolic syndrome in the peruvian population of the peru migrant study

Víctor Juan Vera-Ponce1 

Liliana Cruz-Ausejo1 

Jenny Raquel Torres-Malca2 

1Facultad de Ciencias de la Salud, Universidad Científica del Sur, Lima, Perú

2Universidad Tecnológica del Perú, Lima, Perú.

ABSTRACT

Introduction:

Metabolic syndrome (MetS) is a group of cardiovascular risk factors characterized by the presence of low-grade chronic inflammation. Among all the inflammatory biomarkers associated with MetS, the best characterized and well standardized is C-Reactive protein (CRP).

Objectives:

Evaluate the association between C-Reactive protein and metabolic syndrome in the Peruvian population of the PERU MIGRANT study.

Methods:

An Analytical cross-sectional study. Secondary database analysis of the PERU MIGRANT study. MetS were considered according to the Harmonizing the Metabolic Syndrome criteria. For CRP, a cutoff point of ≥ 3 mg / L was established. Generalized linear Poisson family models were used to find the crude and adjusted prevalence ratio.

Results:

We worked with a total of 958 subjects. The prevalence of MetS was 24.53%. In the simple regression analysis, it was found that people with high CRP levels had a 75% higher frequency of having MetS than those who did not present high CRP levels (PR = 2.21, 95% CI: 1.40 - 2.18). In multiple regression, it was observed that patients with high CRP levels had a 31% greater frequency of having MetS, compared to those with normal CRP levels; adjusting for the rest of the covariates (PR = 1.31, 95% CI: 1.05 - 1.62).

Conclusions:

Plasma CRP was positively associated with MetS. This suggests that a low-grade inflammatory process may be related to the presence of MetS. Against this, physicians should pay attention to glucose, lipid profile, and central obesity in patients with elevated plasma CRP levels.

Key words: Metabolic Syndrome; C-Reactive Protein; Inflammation Mediators (Source: MeSH NLM).

INTRODUCTION

Metabolic syndrome (MetS) is a group of cardiovascular risk factors characterized by abdominal obesity, hypertension, and dyslipidemia1. The prevalence of metabolic syndrome has increased throughout the world and has become a major public health problem recently2. Almost half of the American adults have MetS, and the prevalence increases with age3. In the case of the Peruvian population, according to the criteria used, the prevalence fluctuates between 25 and 45%4.

Although the individual components of MetS contribute independently to the further development of cardiovascular diseases (CVD) and type 2 diabetes mellitus (DM2), overall, the risk increases exponentially5,6. The precise mechanisms for this greater propensity lie in the presence of low-grade chronic inflammation7,8. Among all the inflammatory biomarkers associated with evaluating their value in the prediction of CVD, the best characterized and well standardized is C-Reactive protein (CRP).

CRP is an acute phase reactant produced by hepatocytes, and its production is regulated by interleukin-6 and other inflammatory cytokines9,10. Classically, plasma PCR is used as a test for the detection and activity of inflammatory diseases, such as rheumatological diseases11. However, plasma CRP levels have also been shown to reflect the course of certain chronic diseases, including MetS12-14. Given these observations found, some investigators have suggested that CRP should be added as a clinical criterion for MetS.

Although several countries have studied the relationship between plasma CRP and metabolic syndrome, it has not been thoroughly investigated in the Peruvian population. For this reason, the present study aims to evaluate the association of C-reactive protein in metabolic syndrome in the Peruvian population of the PERU MIGRANT study.

METHODS

Design and study area

The present study had a cross-sectional analytical observational design. It was a secondary database analysis of the PERU MIGRANT study. This research work was designed to evaluate the magnitude of the differences between rural groups, rural to urban migrants, and urban ones in relation to specific cardiovascular risk factors15.

Population and sample

The PERU MIGRANT study (primary study) considered two different settings. The first was San José de Secce, a village located in Ayacucho, which was selected as the rural study site. The second was the area "Las Pampas de San Juan de Miraflores" in Lima, selected as the urban area for the study. Study groups were defined by a single random sampling of participants aged 30 years or older from the rural site of Ayacucho, the urban site of Lima, and migrants from the countryside to the city of Ayacucho who now reside in Lima.

Ayacucho was chosen for this study because it was one of the most affected areas during the conflict period in Peru, resulting in 50% of the deaths. For the period 1988-1993, 50.7% of the total emigrants from Ayacucho moved to Lima, making Ayacucho the main source of emigrants to Lima.

Additional information on the selection criteria, sample size, and participation rates have been published elsewhere15.

Of the total number of participants recruited in the primary study, 989 people were evaluated. In the present study, all subjects with the variables of interest were included, and all subjects with a diagnosis of DM2 were excluded. Finally, there were a total of 958 subjects.

With a sample size of 958 subjects, with an expected proportion of subjects with high MetS and CRP of 44.5%; and an expected proportion of subjects with MetS without high CRP of 55.5; and with a confidence level of 95%, a statistical power of 92.6% was calculated.

Variables and instruments

The dependent variable was the MetS diagnosis. MetS was considered according to the Harmonizing the Metabolic Syndrome criteria16, presenting three or more of the following alterations: Waist circumference ≥ 80 cm for women or ≥ 94 cm for men; triglycerides ≥ 150 mg / dl; fasting glucose ≥ 100 mg / dl (or if they receive treatment to lower glucose levels); systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85 mmHg (or receive treatment to lower blood pressure levels); HDL-cholesterol <50 mg / dl in women or <40 mg / dl in men.

Our main exposure variable was plasma ultrasensitive CRP levels. In this study, a cut-off point was established where CRP was considered high ≥ 3 mg / L. The American Heart Association and the Center for Disease Control recognized that people with CRP above this value are a high-risk group for CVD17-19.

The other variables of the analysis were age, gender (male or female), group according to migration (urban, rural or migrant), smoker status, alcohol drinker and physical activity. Excessive alcohol consumption was defined as low or high alcohol consumption. Smoking was defined in three categories: if you have not smoked (never), have stopped smoking 6 months ago (old) or if you have smoked in the last 6 months (current). Physical activity levels were defined according to the International Physical Activity Questionnaire (IPAQ) protocol. The categorical physical levels were coded based on the total number of days of physical activity and the metabolic equivalent in minutes/week three categories: high, medium and low.

To collect all the variables of the primary study, a team of community health workers with previous experience in fieldwork was trained in-home visits to enroll the participants and carry out the questionnaires. All laboratory evaluations were performed by trained personnel on venous samples taken in the morning after a minimum of 8 hours of fasting.

Procedures

The database of the primary study is freely accessible, without restrictions. The researchers accessed the scientific information, the variables that were of interest to the study were taken and the present manuscript was prepared.

Statistical analysis

Statistical analysis was performed with STATA v16.0 software. For descriptive analysis, the qualitative variables were summarized in proportions. The quantitative variables were presented as the mean and the standard deviation. For the bivariate analysis, the chi-square test was performed for the categorical variables, and the Student's T test and Wilcoxon were chosen for the numerical variables, according to the normality distribution of the variables.

Subsequently, a generalized linear model of the Poisson family (crude and adjusted) with robust variance was made. The variables included in the adjusted model were age, gender, group (urban, rural or migrant), state of smoker, alcohol drinker and physical activity. The measure of association was the prevalence ratio (PR) with its respective 95% confidence interval (CI).

Ethical considerations

Approval for the primary study was obtained from the Universidad Peruana Cayetano Heredia’s ethics committees in Peru and the London School of Hygiene and Tropical Medicine in the UK. The purpose of the study was explained to each of the study participants and informed consent was obtained, following international standards for ethical research in developing countries.

This is secondary data analysis, so no contact was made with human subjects. In this sense, the possible risks for the subjects of the analysis are minimal. In turn, it is worth clarifying that the database is freely accessible to the general public.

Finally, during the study’s implementation, the ethical principles outlined in the Declaration of Helsinki were respected.

RESULTS

Of 958 participants selected for this research, the prevalence of MetS was 24.53%. It was found that the majority were female (52.92%) and belonged to the migrant group (59.71%). The mean age was 47.83 years. Almost half practiced high physical activity (44.84%). 11.17% were current smokers, and 7.31% reported high alcohol consumption. The fourth part (25.47%) presented high levels of CRP.

Patients with high CRP levels had a 15.48% higher frequency of being metabolic syndrome than those with normal CRP levels (56.60% vs. 25.59%; p <0.001). It was found that women had an 18.28% greater frequency of having MetS, compared to men (33.14% vs. 14.86%; p <0.001). Finally, age was significantly associated with having MetS (p = 0.005). Only the smoker state did not show proportional statistical differences in relation to presenting MetS.Table 1.

Table 1.  Important characteristics of the Peruvian population of the PERU MIGRANT study based on metabolic syndrome 

      Metabolic Syndrome p*
Characteristics Total No (n=723) Yes (n=235)
    n (%) n (%) n (%)
Gender       < 0,001
  Female 507 (52,92) 339 (66,86) 168 (33,14)  
  Male 451 (47,08) 384 (85,14) 67 (14,86)  
Age (years) * 47,83 (± 12.05) 47.20 (± 12,58) 49.76 (± 10,02) 0,005¥
Group       < 0,001
  Rural 197 (20,56) 179 (90,86) 18 (9,14)  
  Migrant 572 (59,71) 421 (73,60) 151 (26,40)  
  Urban 189 (19,73) 123 (75,47) 66 (34,92)  
Physical Activity          
  Low 246 (25,89) 176 (71,54) 70 (28,46) 0,002
  Moderate 278 (29,26) 195 (70,14) 83 (29,86)  
  High 426 (44,84) 344 (80,75) 82 (19,25)  
Smoking status       0,265
  Never 789 (82,36) 594 (75,29) 195 (24,71)  
  Old 62 (6,47) 43 (69,35) 19 (30,65)  
  Current 107 (11,17) 86 (80,37) 21 (19,63)  
Alcohol consumption       < 0,001
  Low 888 (92,36) 662 (74,55) 226 (24,45)  
  High 70 (7,31) 61 (87,14) 9 (12,86)  
High CRP       < 0,001
  No 714 (74,53) 567 (79,41) 147 (20,59)  
  Yes 244 (25,47) 156 (63,93) 88 (36,07)  

* Obtained with the Chi square test * Mean ± standard deviation. ¥ Performed with the Student's T test

In the simple regression analysis, it was found that people with high levels of CRP had a 75% higher frequency of having MetS, compared to those who did not present high levels of CRP (PR = 2.21 , 95% CI: 1.40-2.18). Then, in the multiple regression, the observed association in terms of direction and magnitude was preserved. It was observed that patients with high CRP levels had a 31% higher frequency of having MetS, compared to those with normal CRP levels; adjusting for the confounding covariates of gender, age, group, smoking status, alcohol drinker and physical activity (PR = 1.31, 95% CI: 1.05 - 1.62).Table 2.

Table 2.  Crude and adjusted Poisson regression model to evaluate the association between plasma fibrinogen and metabolic syndrome 

Characteristics Crude Analysis Adjusted Analysis*
RP IC 95% p RP IC 95% p
High CRP              
  No Ref     Ref    
  Yes 1,75 1,40 - 2,18 < 0,001 1,31 1,05 - 1,62 0,015

*Adjusted for age, gender, group (urban, rural or migrant), status of smoker, alcohol drinker and physical activity

DISCUSSION

Given the long-term implications of MetS on cardiovascular alterations, and the possible role that the pro-inflammatory state would play in this process, the present work aimed to evaluate the association between CRP and MetS. After performing the analysis adjusted for the most important covariates, we found a close relationship between both variables of interest.

Our results indicate that elevated CRP concentrations are associated with a higher prevalence of MetS. This result is supported by several epidemiological studies. The association between MetS and elevated CRP levels has been demonstrated in non-diabetic Cuban-Americans aged ≥30 years20. A study of 5,728 subjects showed that subjects with three, four, or five MetS features were more likely to increase CRP compared to subjects without any MetS features 21. In Korea, research concluded that people with normal plasma CRP levels are less likely to have MetS, as opposed to those with high levels22.

In a more recent publication, they found that CRP screening could identify a larger group of people who might be at high risk for MetS, regardless of their weight23. Finally, one study observed that CRP was a useful and effective variable in predicting the risk of developing MetS. The connection of this variable and the number of criteria for MetS was also clear because CRP levels increased in the presence of more MetS factors, and CRP levels in normal individuals decreased24.

The pathophysiological role of CRP in MetS is through its participation in the process of atherosclerosis, through several potential mechanisms: 1) CRP can bind to oxidized LDL; 2) CRP can decrease nitric oxide production and inhibit angiogenesis; 3) the synergy between CRP and inflammatory mediators could play a role in the pathogenesis of atherosclerosis; and 4) PCR can also activate complement10,25,26.

Several limitations of this study are worth mentioning. The present analysis was based on a primary study where a single measurement of the CRP level was performed without repeating the tests; however, a first shot already brings us closer to the state of the subject under study. The population of this study was only carried out in two cities of the country and not nationally, so it is possible that this population does not represent the entire Peruvian population; however, given the characteristics that they may have in common, a certain inference could finally be made.

CONCLUSION

Plasma CRP was positively associated with MetS in the Peruvian population of the PERU MIGRANT study. The results of this study suggest that a low-grade inflammatory process may be related to the presence of MetS. Against this, physicians should pay attention to glucose, lipid profile, and central obesity in patients with elevated plasma CRP levels.

REFERENCES

1. Engin A. The Definition and Prevalence of Obesity and Metabolic Syndrome. Adv Exp Med Biol. 2017;960:1-17. DOI: 10.1007/978-3-319-48382-5_1 [ Links ]

2. Saklayen MG. The Global Epidemic of the Metabolic Syndrome. Curr Hypertens Rep. 2018;20(2):12. DOI: 10.1007/s11906-018-0812-z [ Links ]

3. Moore JX, Chaudhary N, Akinyemiju T. Metabolic Syndrome Prevalence by Race/Ethnicity and Sex in the United States, National Health and Nutrition Examination Survey, 1988-2012. Prev Chronic Dis. 2017;14:E24. DOI: 10.5888/pcd14.160287 [ Links ]

4. Chávez V, E J. Prevalencia de sobrepeso y obesidad en el Perú. Rev Peru Ginecol Obstet. octubre de 2017;63(4):593-8. ISSN 2304-5132. Disponible en: http://www.scielo.org.pe/scielo.php?script=sci_arttext&pid=S2304-51322017000400012Links ]

5. Mendrick DL, Diehl AM, Topor LS, Dietert RR, Will Y, La Merrill MA, et al. Metabolic Syndrome and Associated Diseases: From the Bench to the Clinic. Toxicol Sci Off J Soc Toxicol. 2018;162(1):36-42. DOI: 10.1093/toxsci/kfx233 [ Links ]

6. McCracken E, Monaghan M, Sreenivasan S. Pathophysiology of the metabolic syndrome. Clin Dermatol. 2018;36(1):14-20. DOI: 10.1016/j.clindermatol.2017.09.004 [ Links ]

7. Grandl G, Wolfrum C. Hemostasis, endothelial stress, inflammation, and the metabolic syndrome. Semin Immunopathol. 2018;40(2):215-24. DOI: 10.1007/s00281-017-0666-5 [ Links ]

8. Catrysse L, van Loo G. Inflammation and the Metabolic Syndrome: The Tissue-Specific Functions of NF-?B. Trends Cell Biol. 2017;27(6):417-29. DOI: 10.1016/j.tcb.2017.01.006 [ Links ]

9. Yao Z, Zhang Y, Wu H. Regulation of C-reactive protein conformation in inflammation. Inflamm Res Off J Eur Histamine Res Soc Al. 2019;68(10):815-23. DOI: 10.1007/s00011-019-01269-1 [ Links ]

10. Del Giudice M, Gangestad SW. Rethinking IL-6 and CRP: Why they are more than inflammatory biomarkers, and why it matters. Brain Behav Immun. 2018;70:61-75. DOI: 10.1016/j.bbi.2018.02.013 [ Links ]

11. Rhodes B, Fürnrohr BG, Vyse TJ. C-reactive protein in rheumatology: biology and genetics. Nat Rev Rheumatol. 2011;7(5):282-9. DOI: 10.1038/nrrheum.2011.37 [ Links ]

12. Kazemi-Bajestani SM, Tayefi M, Ebrahimi M, Heidari-Bakavoli AR, Moohebati M, Parizadeh SM, et al. The prevalence of metabolic syndrome increases with serum high sensitivity C-reactive protein concentration in individuals without a history of cardiovascular disease: a report from a large Persian cohort. Ann Clin Biochem. 2017;54(6):644-8. DOI: 10.1177/0004563216676842 [ Links ]

13. Szmitko PE, Verma S. C-reactive protein and the metabolic syndrome: useful addition to the cardiovascular risk profile? J Cardiometab Syndr. 2006;1(1):66-9; quiz 70-1. DOI: 10.1111/j.0197-3118.2006.05340.x [ Links ]

14. Mazidi M, Toth PP, Banach M. C-reactive Protein Is Associated With Prevalence of the Metabolic Syndrome, Hypertension, and Diabetes Mellitus in US Adults. Angiology. 2018;69(5):438-42. DOI: 10.1177/0003319717729288 [ Links ]

15. Miranda JJ, Gilman RH, García HH, Smeeth L. The effect on cardiovascular risk factors of migration from rural to urban areas in Peru: PERU MIGRANT Study. BMC Cardiovasc Disord. 2009;9:23. DOI: 10.1186/1471-2261-9-23 [ Links ]

16. Alberti KGMM, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640-5. DOI: 10.1161/CIRCULATIONAHA.109.192644 [ Links ]

17. Yeh ETH, Willerson JT. Coming of age of C-reactive protein: using inflammation markers in cardiology. Circulation. 2003;107(3):370-1. DOI: 10.1161/01.cir.0000053731.05365.5a [ Links ]

18. Bustos P, Rosas B, Román P, Villagrán J, Amigo H. Síndrome metabólico e inflamación en adultos: Un estudio poblacional. Rev Médica Chile. 2016;144(10):1239-46. DOI: 10.4067/S0034-98872016001000001 [ Links ]

19. Myers GL, Rifai N, Tracy RP, Roberts WL, Alexander RW, Biasucci LM, et al. CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: report from the laboratory science discussion group. Circulation. el 21 de diciembre de 2004;110(25):e545-549. DOI: 10.1161/01.CIR.0000148980.87579.5E [ Links ]

20. Oda E, Kawai R. Tentative cut point of high-sensitivity C-reactive protein for a component of metabolic syndrome in Japanese. Circ J Off J Jpn Circ Soc. 2009;73(4):755-9. DOI: 10.1253/circj.cj-08-0848 [ Links ]

21. Voils SA, Cooper-DeHoff RM. Association between high sensitivity C-reactive protein and metabolic syndrome in subjects completing the National Health and Nutrition Examination Survey (NHANES) 2009-10. Diabetes Metab Syndr. 2014;8(2):88-90. DOI: 10.1016/j.dsx.2014.04.021 [ Links ]

22. Jeong H, Baek S-Y, Kim SW, Park E-J, Lee J, Kim H, et al. C reactive protein level as a marker for dyslipidaemia, diabetes and metabolic syndrome: results from the Korea National Health and Nutrition Examination Survey. BMJ Open. 2019;9(8):e029861. DOI: 10.1136/bmjopen-2019-029861 [ Links ]

23. Song Y, Yang SK, Kim J, Lee D-C. Association between C-Reactive Protein and Metabolic Syndrome in Korean Adults. Korean J Fam Med. 2019;40(2):116-23. OI: 10.4082/kjfm.17.0075 [ Links ]

24. Cattafesta M, Bissoli NS, Salaroli LB. Metabolic syndrome and C-reactive protein in bank employees. Diabetes Metab Syndr Obes Targets Ther. 2016;9:137-44. DOI: 10.2147/DMSO.S101283 [ Links ]

25. Ndumele CE, Pradhan AD, Ridker PM. Interrelationships between inflammation, C-reactive protein, and insulin resistance. J Cardiometab Syndr. 2006;1(3):190-6. DOI: 10.1111/j.1559-4564.2006.05538.x [ Links ]

26. Ridker PM. High-sensitivity C-reactive protein, inflammation, and cardiovascular risk: from concept to clinical practice to clinical benefit. Am Heart J. 2004;148(1 Suppl):S19-26. DOI: 10.1016/j.ahj.2004.04.028 [ Links ]

Financing: Self-financed.

Received: October 09, 2020; Accepted: December 21, 2020

Correspondence: Víctor Juan Vera Ponce Address: Calle Cantuarias 398, Miraflores 15074 Phone: + 51 940072431 Email:victor_jvp@hotmail.com

Authorship contributions: The authors participated in the genesis of the idea, project design, data collection and interpretation, analysis of results and preparation of the manuscript of this research work.

Conflict of interest: The authors declare no conflict of interest.

Creative Commons License Este es un artículo publicado en acceso abierto bajo una licencia Creative Commons