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ORIGINAL ARTICLE
Year : 2019  |  Volume : 32  |  Issue : 1  |  Page : 187-193

A comparative analysis of the level of high-sensitivity C-reactive protein in individuals with and without hypertension


1 Department of Cardiology, Menoufia University, Menoufia, Egypt
2 Department of Medical Biochemistry, Menoufia University, Menoufia, Egypt

Date of Submission13-May-2015
Date of Acceptance15-Jun-2015
Date of Web Publication17-Apr-2019

Correspondence Address:
Reda M El-brol
Kalib-Ebiar, Kafr-Elzayat, Gharbia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_210_15

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  Abstract 


Objective
The objective of this study was to compare the level of serum high-sensitivity C-reactive protein (hs-CRP) in hypertensive and normotensive individuals.
Background
Hs-CRP production is part of the nonspecific acute-phase response to most forms of inflammation, infection, and tissue damage. The association between hs-CRP and hypertension (HTN) could be related in part as follows: correlation between elevated CRP and arterial stiffness; association between CRP and metabolic syndrome, one of whose criteria is HTN and the possibility that CRP may directly contribute to reduced nitric oxide synthesis in endothelial cells, leading to increased vascular resistance.
Patients and methods
Our study comprised 80 patients, divided into two groups: the first group consisted of 55 patients with blood pressure more than140/90 mmHg recorded in at least two separate clinic-based measurements after ruling out secondary causes. The second group consisted of 25 normotensive individuals with a blood pressure of 100–120/60–80 mmHg as a control group. All individuals were subjected to full history taking, complete medical examination, 12-lead ECG, conventional echocardiography, routine laboratory investigations, and measurement of hs-CRP by CRP HS enzyme-linked immunosorbent assay.
Results
The study showed that the mean age of the studied group was 43.9 years; 58.8% were male individuals. Mean systolic and diastolic blood pressure was 146.4 and 91.5 mmHg, respectively. There were highly significant differences between the patient and control groups with regard to age, blood pressure, left ventricular mass, left ventricular mass index, lipid profile, and hs-CRP (higher in the patient group). The study showed also highly significant positive correlations between hs-CRP and age, blood pressure, left ventricular mass and left ventricular mass index. There was a significant positive correlation between hs-CRP and total cholesterol.
Conclusion
The levels of hs-CRP were elevated in hypertensive individuals, which suggests the possibility of an inflammatory pathogenesis in HTN.

Keywords: High-sensitivity C-reactive protein, normotensive, hypertension


How to cite this article:
Abd El Aziz WF, Abou Elnour ES, Mena MB, El-brol RM. A comparative analysis of the level of high-sensitivity C-reactive protein in individuals with and without hypertension. Menoufia Med J 2019;32:187-93

How to cite this URL:
Abd El Aziz WF, Abou Elnour ES, Mena MB, El-brol RM. A comparative analysis of the level of high-sensitivity C-reactive protein in individuals with and without hypertension. Menoufia Med J [serial online] 2019 [cited 2019 May 27];32:187-93. Available from: http://www.mmj.eg.net/text.asp?2019/32/1/187/256090




  Introduction Top


Hypertension (HTN) is a health concern because it is a major risk factor for a number of cardiovascular diseases including stroke, atherosclerosis, type II diabetes, coronary heart disease, and renal disease. It affects 26% of adults worldwide, and its prevalence is predicted to increase to 29% by 2025 [1].

Data from more than 30 epidemiologic studies have shown a significant association between elevated serum concentrations of C-reactive protein (CRP) and the prevalence of underlying atherosclerosis, the incidence of first cardiovascular event in individuals at risk for atherosclerosis, and the risk of recurrent cardiovascular events among patients with established diseases [2].

In recent years, the role of the inflammatory process in the pathogenesis of HTN has been suggested. Consequently, the relationship between CRP and HTN can be evaluated [3].

In recent years, the term 'high-sensitivity CRP (hs-CRP)' has been used widely. One common misunderstanding has been the incorrect belief that hs-CRP is different in some way from CRP. The fact is that hs-CRP only denotes the utilization of an assay designed to measure very low levels of CRP, that is, the so-called low-grade inflammation [4].

Low-grade and acute inflammation states differ from each other in several ways. For instance, the latter occurs in response to infection and tissue injury and the former is induced in response to metabolic stress [5].

In one study, it was suggested that low-grade inflammation causes endothelial dysfunction and impaired nitric oxide availability, leading to an increased production of oxidative stress [6].

Moreover, the relationship between this form of inflammation and obesity, a major risk factor of HTN, has been evaluated before [7].

The aim of our work was to compare the level of serum hs-CRP in hypertensive and normotensive individuals.


  Patients and Methods Top


This is a preliminary cross-sectional study carried out in the Cardiology and Medical Biochemistry Departments in Faculty of Medicine, Menoufia University, Egypt. Written consent was taken from every subject and this study was approved by the ethical committee of faculty of Medicine, Menoufia University.

Eighty patients were divided into two groups on the basis of their blood pressure as follows:

  1. Group 1 comprised 55 patients with blood pressure more than 140/90 mmHg recorded in at least two separate clinic-based measurements after ruling out secondary causes
  2. Group 2 comprised 25 normotensive individuals with blood pressure of 100–120/60–80 mmHg.


Patient selection

The study was carried out on patients who presented to the Cardiology Department in Faculty of Medicine, Menoufia University.

Exclusion criteria

  1. Conditions causing elevation of CRP, for example, inflammation, infection, and tissue damage
  2. Systemic disease, for example, chronic kidney disease (Cr>2), liver failure, and diabetes mellitus
  3. Patients with structural heart diseases (valvular heart diseases, congenital cardiac anomalies, and prosthetic valves)
  4. Patients with heart failure.


Methods

All individuals were subjected to the following:

Full history taking

Demographic and clinical parameters were recorded, for example, age, sex, and history of acute and chronic medical diseases.

Complete clinical examination

In all individuals, blood pressure was measured in the seated position with manual mercury sphygmomanometers after a 5–10 min relaxation period.

12-lead ECG

Left ventricular hypertrophy was measured using the following (and they are):

  1. Sokolow–Lyon index, SV1 + RV5 or V6 more than 3.5 mv, RaVL more than 1.1 mV
  2. Cornell method, Sv3 + Ravl more than or equal to 2.8 mv (men) or more than or equal to 2.0 mv (women) [8].


Conventional echocardiography

Estimation of the following was carried out:

  1. Left ventricular end-systolic volume
  2. Left ventricular end-diastolic volume
  3. Ejection fraction
  4. Left ventricular posterior wall and interventricular septum
  5. E/A wave ratio
  6. Left ventricular mass, using Penn or American Society of Echocardiography formulas[9], and then left ventricular mass normalized according to body surface to obtain left ventricular mass index.


Laboratory investigations

  1. Fasting and 2 h postprandial plasma glucose using glucose oxidase method (Spinreact, Spain)
  2. Blood urea using Berthelot enzymatic colorimetric reaction (Diamond, Egypt)
  3. Serum creatinine using Jaffé Kinetic reaction
  4. Lipid profile total cholesterol, high-density lipoprotein cholesterol and triglycerides using Spinreact Kit and low-density lipoprotein cholesterol was calculated
  5. Hs-CRP was measured by CRP HS enzyme-linked immunosorbent assay [10] using Kit Chemux Bio Science Inc. (South San Francisco, USA), carried out by infinite F50 TECAN device.


Normal values of hs-CRP [11]: adult serum: 0.068–8.2 mg/l.


  Results Top


[Table 1] shows that the mean age of the studied group was 43.9 years. An overall 58.8% were male individuals. Mean systolic and diastolic blood pressure was 146.4 and 91.5 mmHg, respectively.
Table 1: Characteristics of the studied group (n=80)

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[Table 2] shows that there was a highly significant difference between the patient and control groups with regard to their age and blood pressure, P value less than 0.001.
Table 2: Statistical comparison between the studied groups with regard to age, BMI, and blood pressure

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[Table 3] shows that there was a highly significant difference between the patient and control groups with regard to their left ventricular mass and left ventricular mass index (higher in patient group), P value less than 0.001.
Table 3: Statistical comparison between the studied groups with regard to echo findings

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[Table 4] shows that there was a highly significant difference between the patient and control groups with regard to their lipid profiles and hs-CRP (higher in patient group), P value less than 0.05.
Table 4: Statistical comparison between the studied groups with regard to lipid profile and high-sensitivity C-reactive protein (n=80)

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[Table 5] shows that there was a highly significant positive correlation between hs-CRP and each of age and blood pressure in the patient group, P value less than 0.001 [Figure 1], [Figure 2], [Figure 3].
Table 5: Pearson's correlation of high-sensitivity C-reactive protein with age, BMI, and blood pressure in the patient group (n=55)

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Figure 1: Correlation between hs-CRP and age of patient group. Hs-CRP, high-sensitivity C-reactive protein.

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Figure 2: Correlation between hs-CRP and SBP of patient group. Hs-CRP, high-sensitivity C-reactive protein; SBP, systolic blood pressure.

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Figure 3: Correlation between hs-CRP protein and DBP of patient group. DBP, diastolic blood pressure; Hs-CRP, high-sensitivity C-reactive protein.

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[Table 6] shows that there was a highly significant positive correlation between hs-CRP and each of left ventricular mass and left ventricular mass index in the patient group, P value less than 0.001 [Figure 4] and [Figure 5].
Table 6: Pearson's correlation of high-sensitivity C-reactive protein with echo finding in the patient group (n=55)

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Figure 4: Correlation between hs-CRP and left ventricular mass of patient group. Hs-CRP, high-sensitivity C-reactive protein.

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Figure 5: Correlation between hs-CRP and left ventricular mass index of patient group. Hs-CRP, high-sensitivity C-reactive protein.

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[Table 7] shows that there was a significant positive correlation between hs-CRP and total cholesterol in patient group, P value less than 0.05 [Figure 6].
Table 7: Pearson's correlation of high-sensitivity C-reactive protein with lipid profile in the patient group (n=55)

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Figure 6: Correlation between hs-CRP and total cholesterol of patient group. Hs-CRP, high-sensitivity C-reactive protein.

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  Discussion Top


Increase in the concentration of acute-phase reactants comprises a major pathophysiologic phenomenon accompanied by inflammation and tissue injury. Changes in the levels of acute-phase reactants largely result from the effects of the inflammatory process [12].

Cytokines are primarily produced by macrophages and monocytes. Some of the major cytokines relevant to acute-phase response are interlukin-6 (IL-6), IL-1, tumor necrosis factor-alpha (TNF-α), and interferon gamma. These proteins influence acute-phase protein production in hepatocytes. One of these acute-phase reactants is CRP, which is produced predominantly by hepatocytes under the influence of IL-6 and TNF-α [13].

The possible predictive value of serum CRP for the development of HTN was evaluated in an analysis from the women's health study in the United States with a baseline blood pressure below 140/90 mmHg and no history of HTN. Serum CRP was measured at baseline, and the women were followed-up for a median of 7 years: HTN developed in 11.5%, and there was a progressive increase in the rate of developing HTN with increasing value of serum CRP [14].

The association between serum CRP and HTN could be related in part as follows: correlation between elevated CRP and arterial stiffness; association between serum CRP and metabolic syndrome, one of whose criteria is HTN and the possibility that CRP may directly contribute to reduced nitric oxide synthesis in endothelial cells, leading to increased vascular resistance [15].

Because of the influence of race and environmental factors such as diet and smoking in the development of HTN and their different prevalence in numerous countries depending on the prevalent lifestyle, the association between hs-CRP and cardiovascular events has been separately evaluated in different populations such as Nigerians, Kashmiris, and Indians [16].

Hence, in this Egyptian study, our aim was to compare the level of serum hs-CRP in hypertensive and normotensive individuals. The study comprised 80 patients, divided into two groups, each of which are as follows: the first group consisted of 55 patients with blood pressure more than140/90 mmHg recorded in at least two separate clinic-based measurements after ruling out secondary causes. The second group consisted of 25 normotensive individuals with blood pressure of 100–120/60–80 mmHg as a control group.

The diagnosis of the patients was based on full history taking, complete medical examination, 12-lead ECG, conventional echocardiography, fasting and postprandial blood sugar, blood urea, serum creatinine, lipid profile and measurement of CRP by enzyme-linked immunosorbent assay.

Our study showed that there was a highly significant difference between patients and the control group with regard to their age, blood pressure, left ventricular mass, left ventricular mass index, lipid profile, and hs-CRP (higher in patient group).

Lee et al. [17] showed that serum hs-CRP level was not a risk factor in the rural population over 50 years of age. Nevertheless, because of different lifestyles, daily activity, and diet between rural and urban populations, this study cannot be generalized.

Boos and Lip [18] reported that serum hs-CRP was a strong predictor of HTN occurrence in normal or prehypertensive people in comparison with other inflammatory markers such as IL-6, TNF-α, and angiotensin II.

Positive association of CRP levels with HTN is shown by Fernandez-Real et al. [19]; Sung et al. [20]; King et al. [21], and Bautista et al. [22].

Abramson et al. [23] also found positive CRP association with pulse pressure (PP). Elevated PP was associated with impaired acetylcholine-induced endothelial-dependent relaxation, and impaired relaxation was prevented by administration of antioxidant superoxide dismutase. PP is also positively associated with increased production of reactive oxygen species and increased reactive oxygen species could stimulate 28 inflammatory signaling pathways.

Cottane et al. [24] observed direct association of mean arterial pressure with CRP and other inflammatory markers and showed that oxidant stress is increased. Therefore, increased oxidant stress and inflammatory process might possibly be explained by high mean arterial pressure in the higher CRP group.

Given the role of serum hs-CRP in HTN, Ridker et al. [25] have studied the effect of hypertensive medications on the serum hs-CRP level, prevention of HTN, and its complications. Valsartan is known to decrease blood pressure and hs-CRP levels. Aspirin and statins have the same effects on the serum hs-CRP level and could prevent HTN.

In our study, there was a highly significant positive correlation between hs-CRP and age, blood pressure, left ventricular mass, and left ventricular mass index, and there was a significant positive correlation between hs-CRP and total cholesterol in the patient group.

King et al. [26] investigated the relationship between dietary fiber and inflammatory markers in people with diabetes, HTN, and obesity. They found a significant association between dietary fiber intake and levels of inflammatory markers in individuals with diabetes, HTN, or obesity and an even stronger relationship among people with two or more of these conditions.

Quarck et al. [27] investigated a potential role of CRP as a predictor of pulmonary HTN severity and outcome. They showed that circulating CRP may predict the severity and the outcome in pulmonary HTN and that its sensitivity to disease-specific medication may orientate therapeutic options.

Shafi Dar et al. [28] evaluated the relationship of serum CRP levels and blood pressure across the range of blood pressure categories including pre-HTN in the Kashmiri people. A total of 104 patients and 63 controls were included in the present study. The level of CRP in the serum samples was estimated by a high-sensitivity immunoturbidometric assay. The mean serum hs-CRP level in hypertensive patients was 3.26 mg/l compared with 1.36 mg/l among normotensive controls. On comparison with normotensive controls, the hs-CRP levels vary significantly both with grades and duration of HTN, with the most significant difference found in patients with pre-HTN, followed by stage-I and stage-II hypertensive patients. Significant difference in hs-CRP levels was also found in patients with shorter duration of hypertensive history when compared with those with 5 years of hypertensive history.

Shafi Dar et al. [28] suggested that increased serum CRP levels are associated with HTN, more significantly with pre-HTN and in new onset patients with HTN, in Kashmiri people. Thus, serum CRP estimation can be a potential tool for early identification of individuals at the risk for development of HTN and eventually cardiovascular diseases.

Rajesh et al. [29] concluded that the higher CRP levels are significantly correlated with higher grade of HTN. The raised levels of CRP in HTN suggest the possibility of inflammatory pathogenesis.

Although the existing literature contains only a small number of studies that have demonstrated the direct effect of serum hs-CRP lowering on the improvement of cardiovascular diseases, other interventions such as body weight reduction, cigarette smoking cessation, and aspirin (and statins) consumption are believed to be associated with reduced cardiovascular events and serum hs-CRP level, indicating an indirect role of hs-CRP lowering.

It should be emphasized that interference on a wide range of physiologic and pathologic conditions and lifestyle may be associated with increased preinflammatory markers such as the serum hs-CRP level. It is, therefore, advisable that confounding factors be taken into consideration.


  Conclusion Top


We showed that the level of hs-CRP was elevated in hypertensive patients, which may reflect the role of the inflammatory process in the pathogenesis of HTN.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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