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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 16  |  Issue : 1  |  Page : 13-20

High-sensitivity C-reactive protein as a potential marker for hypertension


1 Professor of Clinical Pathology, Faculty of Medicine, Assiut University, Egypt
2 Assistant Professor of Clinical Pathology, Faculty of Medicine, Assiut University, Egypt
3 Assistant Lecturer of Clinical Pathology, Faculty of Medicine, Assiut University, Egypt

Date of Submission07-Feb-2017
Date of Acceptance05-Nov-2017
Date of Web Publication20-Nov-2018

Correspondence Address:
Mohammed Ashraf Mahmoud
Assistant Lecturer at Clinical Pathology Department, Assiut University Hospital, Assiut
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AZMJ.AZMJ_11_17

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  Abstract 


Background Hypertension is a common, asymptomatic, readily detectable, and usually easily treatable disease that leads to lethal complications if left untreated. Hypertension results from the net effect of environmental and genetic factors. These factors include excess dietary salt or alcohol intake, stress, age, genetics, physical inactivity, diet rich in saturated fats, and family history. Evidences indicate that vascular inflammation may be involved in both the initiation and development of hypertension. C-reactive protein is a plasma protein present in trace amounts in healthy patients the concentration of which increases in response to injury, infection or inflammation.
Aim The aim of this article is to evaluate the relationship between serum high-sensitivity C-reactive protein (hs-CRP) levels and various stages of hypertension including prehypertension in the Egyptian people.
Patients and methods This study included 130 patients with hypertension recruited from the cardiology outpatient clinic of the Assiut University Hospital in addition to 50 apparently healthy controls, in the period from September 2014 to April 2016. The patients were classified according to their levels of systolic and diastolic blood pressure into pre-hypertensive group and stages I, II, III hypertensive patients. They were classified according to the duration of hypertension into less than 1-year duration, between 1 and 5 years and more than 5 years. In addition, the patients were classified into two groups according to weather taking treatment or not. hs-CRP assay using the BT-1500 system based on turbidimetric measurement has been performed.
Results The hs-CRP levels were significantly higher in prehypertensive, stages I, II, and III patients compared with controls. In addition, there was significant elevation when comparing prehypertension with both stages II and III; significant increase when comparing stages I with stages II and III and significant increase when comparing stages II with III.
Conclusion Increased serum hs-CRP levels are associated with hypertension, especially in the early stages of the disease.

Keywords: C-reactive protein, hypertension, pre-hypertension


How to cite this article:
Ali EE, Elrhman MA, Mahmoud MA. High-sensitivity C-reactive protein as a potential marker for hypertension. Al-Azhar Assiut Med J 2018;16:13-20

How to cite this URL:
Ali EE, Elrhman MA, Mahmoud MA. High-sensitivity C-reactive protein as a potential marker for hypertension. Al-Azhar Assiut Med J [serial online] 2018 [cited 2018 Dec 18];16:13-20. Available from: http://www.azmj.eg.net/text.asp?2018/16/1/13/244140




  Introduction Top


Hypertension is one of the most common diseases affecting humans throughout the world. Owing to the associated morbidity and mortality and the cost to society, hypertension is an important public health challenge [1].

Hypertension is defined as values greater than or equal to 140 mmHg systolic blood pressure and/or greater than or equal to 90 mmHg diastolic blood pressure. Optimal blood pressure with respect to cardiovascular risk is below 120/80 mmHg [2].

The most recent classification of hypertension according to the European Society of Hypertension are the following [1].

Essential hypertension, or hypertension of unknown cause, accounts for more than 90% of cases of hypertension. It tends to cluster in families and represents a group of genetically based diseases with several resultant inherited biochemical abnormalities [3].

A growing body of evidences indicates that vascular inflammation may be involved in both the initiation and development of hypertension. This is evident from the elevated levels of inflammatory markers such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) found in people with hypertension [4].

CRP, named for its capacity to precipitate the somatic C-polysaccharide of Streptococcus pneumoniae, was the first acute-phase protein to be described and is a sensitive systemic marker of inflammation and tissue damage [5]. Hepatic CRP synthesis is under exquisitely sensitive transcriptional regulation through proinflammatory cytokines including IL-6, IL-1, and TNF-α so that almost any form of tissue injury, infection or inflammation, and indeed also most forms of adverse nonphysiological ‘stress’ are associated with increased circulating CRP values [6].

The term ‘high-sensitivity’ or ‘highly sensitive’ CRP, abbreviated as hs-CRP, has been widely adopted in recent literature. It is very important to recognize that the analyte designated as hs-CRP is just CRP itself, not anything new or different and in particular is not a novel analyte with any special relationship to cardiovascular disease [7].

Hypertension may lead to multiple inflammatory stimuli which promote the production of proinflammatory cytokines such as TNF-α, IL-6, and CRP as a defense against injurious factors. Inflammation, common in hypertensives, decreases endothelium-dependent relaxation, possibly by decreased capacity of the endothelium to generate vasodilator factors, particularly nitric oxide which in turn raises the blood pressure [8].

CRP inhibits the formation of nitric oxide by endothelial cells, which in turn promote vasoconstriction, leukocyte adhesion, platelet activation, oxidation, and thrombosis [9].

There are several other potential mechanisms that may account for the observed relationship between blood pressure and CRP levels. Increased blood pressure may promote vascular inflammation by modulation of mechanical stimuli from pulsatile blood flow. Cyclic strain has been shown to increase the expression of soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by endothelial cells and also upregulate the secretion of monocyte chemoattractant protein-1 that promote monocyte adhesion to endothelium. Furthermore, elevated blood pressure is also known to promote the generation of reactive oxygen species as evident from a study where a significant correlation was observed between the levels of CRP and mononuclear oxidative stress [10].


  Aim Top


This study was carried out to evaluate the relationship between serum hs-CRP levels and various stages of hypertension including prehypertension in the Egyptian people.


  Patients and methods Top


This study included 130 patients with hypertension recruited from the cardiology clinic of Assiut University Hospital in addition to 50 apparently healthy individuals who act as controls, in the period from September 2014 to April 2016. The patients group included 62 (47.7%) male patients and 68 (52.3%) female patients, in the age range from 28 to 66 years. The control group of 50 volunteers consisted of 40 men and 10 women. Their ages ranged from 36 to 58 years. The study was approved by the Ethical Committee of Faculty of Medicine, Assiut University. Written consents were taken from the patients before enrollment in this study.

All patients and controls were subjected to full history taking, including family history, smoking, drug taking, contraceptive pills for women, history of hypertension including duration and treatment, full clinical examination, including general, abdominal and chest examination, with careful measurement of blood pressure, weight, and height. Investigations including radiography and ECG were done. Laboratory investigations included complete blood count, serum glucose (fasting and after 2 h), serum urea and creatinine, lipid profile, and serum hs-CRP level.

Blood pressure was recorded twice at intervals of at least 5 min using mercury sphygmomanometer with the patients in a sitting position and the averaged value was used for the analysis.

Patients with congestive heart failure, chronic kidney disease, diabetes, infective disease, malignancies, and chronic inflammatory disease, history of rheumatoid arthritis or other vasculitis syndrome, inflammatory bowel disease or suffering from other acute inflammatory conditions such as hepatitis, pneumonia, septicemia, meningitis, glomerulonephritis or local pyogenic abscess were excluded from this study.

The patients were classified according to the levels of systolic and diastolic blood pressure into prehypertensive group, and stages I, II, III hypertensive patients. They were classified according to the duration of hypertension into less than 1-year duration, between 1 and 5 years and more than 5 years. In addition, the patients were classified into two groups according to whether taking treatment or not.

hs-CRP assay was tested using the BT-1500 system (Biotecnica Instruments, Roma, Italy); the assay of CRP is based on turbidimetric measurement. Turbidity is caused by the formation of antigen–antibody insoluble complexes. The reaction is nonlinear, endpoint with wavelength at 340 nm, assay temperature between 18 and 37°C and measuring range from 0.0 to 22 mg/dl.

Date entry and data analysis were done using statistical package for the social science (SPSS, version 19; IBM, Chicago, IL, USA). Data were presented as number, percentage, mean, SD. χ2-Test was used to compare between qualitative variables. An independent sample t-test was used to compare quantitative variables between two groups and analysis of variance test was used for more than two groups. The Pearson correlation was done to measure the correlation between quantitative variables. P-value was considered statistically significant when P-value less than 0.05.


  Results Top


The study included 50 apparently healthy individuals and 130 hypertensive patients.

[Table 1],[Table 2],[Table 3],[Table 4] showed that hypertensive patients comprised 62 (47.7%) men and 68 (52.3%) women; their ages ranged from 28 to 66 years, in the control group, the age ranged from −36 to 58 years.
Table 1 Classification of hypertension

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Table 2 Stages of hypertension in the studied patients

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Table 3 Distribution of the studied patients according to the duration of hypertension

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Table 4 Age distribution of the studied groups

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There was statistically significant increase in the mean value of BMI in all studied patient groups compared with the controls (P<0.001, 0.001, 0.001, 0.002, respectively). The mean value of BMI in prehypertensive group showed a significant increase when compared with stages II and III (P=0.014, 0.011, respectively), and insignificant difference when compared with stage I (P=0.144). There was also insignificant difference when comparing stage I with stages II and III, and when comparing stage II with stage III hypertension.

In [Table 5] and [Table 6] total cholesterol showed statistically significant elevation in all patients group compared with the control group (P=0.001, 0.003, 0.004, 0.044, respectively). In addition, there was statistically significant elevation when comparing prehypertensive group with stages II and III (P=0.001, 0.009, respectively), and when comparing stage I group with stages II and III (P=0.048, 0.001, respectively). Otherwise, no significant differences were found.
Table 5 Body mass index of controls and different patient groups

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Table 6 Lipid profile of patients and control groups

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There was statistically significant elevation of serum triglyceride levels when comparing prehypertensive, stages I, II patient groups with controls (P=0.004, 0.006, 0.045, respectively) and when comparing prehypertensive patients with stage III (P=0.05). No other differences were found.

There was statistically significant decrease of high-density lipoprotein cholesterol (HDL-c) levels when comparing prehypertensive, stages I and II with control group (P=0.007, 0.001, 0.004, respectively). There was also significant decrease when comparing prehypertensive group with stages II and III (P=0.046, 0.025, respectively). Significant decrease was found when comparing stages I and II with stage III (P=0.005 and 0.019, respectively).

There was significant increase in the level of low-density lipoprotein cholesterol (LDL-c) in prehypertensive, stages I, II groups compared with the control group (P=0.004, 0.012, 0.032, respectively), and significant increase was found on comparing prehypertensive patient group with stages II and III (P=0.015, 0.006, respectively). In addition, there was significant elevation when comparing stage I with stages II and III (P=0.038, 0.017, respectively).

[Table 7] showed that hs-CRP levels were significantly higher in prehypertensive, stages I, II and III patients compared with controls (P<0.001 for the former three and 0.001 for the latter).
Table 7 High-sensitivity C-reactive protein in different stages of hypertension

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In addition, there was significant elevation when comparing prehypertension with both stages II and III (P=0.032 and 0.003, respectively), significant increase when comparing stage I with stages II and III (P=0.047, 0.011, respectively), and significant increase when comparing stages II with III (P=0.015).

Our study has shown positive correlation between hs-CRP and BMI in the control group, prehypertension and stage I hypertension ([Figure 1],[Figure 2],[Figure 3]).
Figure 1 Correlation between high-sensitivity C-reactive protein (hs-CRP) and BMI in the control group.

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Figure 2 A: Age distribution of the studied groups. B: hsCRP in hypertensive patients and control groups.

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Figure 3 A: hsCRP in different stages of hypertension. B: hsCRP in treated and untreated patients.

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[Table 8] showed that there were positive correlations between hs-CRP and cholesterol, triglycerides and LDL levels in the control group, and there were positive correlations between hs-CRP and cholesterol, LDL levels in stage I patients, but there were no significant correlations between hs-CRP and lipid profile in prehypertensive, stages II and III groups.
Table 8 Correlation between high-sensitivity C-reactive protein and lipid profile in control and hypertensive stages

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[Table 9] showed that there was significant increase in the levels of hs-CRP in prehypertensive group compared with patients with more than 5 years duration of hypertension (P=0.037), and significant increase in hs-CRP in patients with a history of hypertension for less than 1 year compared with patients with more than 5 years (P=0.043).
Table 9 Relation between high-sensitivity C-reactive protein and duration of hypertension

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[Table 10] showed that there were significant decreases in hs-CRP levels when comparing the patients under regular treatment with those without treatment in each group (P=0.011, 0.018, 0.014, and 0.046, respectively).
Table 10 High-sensitivity C-reactive protein according to regular treatment in each stage of hypertension

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  Discussion Top


This study has shown that the hs-CRP levels were significantly higher in the patient group compared with control. This is in accordance with many other studies [10],[11],[12],[13],[14].

In our study serum hs-CRP levels were higher in prehypertensive patients as compared with stages I, II, and III. The difference in values was not significant between prehypertension and stage I, but it was significant between prehypertension and stages II and III. It was also significantly higher when comparing stage I with stages II and III, and also when comparing stage II with stage III.

Other studies also found a positive association between increasing hs-CRP and prehypertensive condition [15], and some hypothesized that the prehypertensive condition is associated with a proinflammatory condition that can be linked to a significant increase in the levels of hs-CRP in plasma [4].

There are several other potential mechanisms that may account for the observed relationship between blood pressure and CRP levels. Increased blood pressure may promote vascular inflammation by modulation of mechanical stimuli from pulsatile blood flow. Cyclic strain has been shown to increase the expression of soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by endothelial cells and also upregulate the secretion of monocyte chemoattractant protein-1 that promotes monocyte adhesion to the endothelium. Furthermore, elevated blood pressure is also known to promote the generation of the reactive oxygen species as evident from a study where a significant correlation was observed between levels of CRP and mononuclear oxidative stress [10].

Another research studied the cardiometabolic predictors of progression of prehypertensives to hypertensives and found that those prehypertensives that developed hypertension had higher levels of inflammatory markers, higher triglycerides and lower HDL-c [16]. CRP increases the expression of endothelin-1, plasminogen activator inhibitor-1 to promote vasoconstriction, platelet activation and thrombosis. CRP has also shown to upregulate angiotensin receptor-1 thus enhancing angiotensin-II-induced rise in blood pressure [17]. Some researchers hypothesized that the prehypertensive condition is associated with a proinflammatory condition that can be linked to a significant increase in the levels of hs-CRP in plasma but he also reported that few studies have explored interrelations between the levels of CRP and hypertensive risk factors and data from these reports were also inconsistent [4].

This study shows that, in patient groups the hs-CRP levels were also found to vary with the duration of hypertensive history. Significantly higher levels of hs-CRP were found in patients with less than 1 year duration of hypertensive history compared with those with 1–5 years of hypertension and those with more than 5 years of hypertension, but it was not significant between those with 1–5 years duration and those with more than 5 years.

This is similar to a study conducted in Kashmir, where it was shown that a significant difference in hs-CRP levels was found in patients with shorter duration of hypertensive history (<1 year) when compared with those with more than 5 years of hypertensive history although the difference between patients with less than 1 year duration of hypertensive history compared with those with 1–5 years of hypertensive history was not significant in that study [10]. Some studies have stated that many hypotheses suggest that in the early stage of hypertension, grade of inflammation determines the level of hypertension. Many studies show that the difference in the elevation levels of hs-CRP was also found to be duration dependent as patients with shorter duration of hypertensive history (<1 year) were found to have significantly elevated levels of hs-CRP compared with those with longer duration of hypertensive history (>5 years) [4].

This could be also attributed to the fact that the more the duration of the disease, the more likely that the patient is under medical treatment, which was stated before that it could have an impact on hs-CRP by lowering the inflammatory status in vascular wall.

In our study, BMI was notably increased in hypertensive patients compared with controls. This is similar to the results of multiple studies [13],[14]. Environmental, physiological, and genetic factors influence the impact of obesity on arterial pressure, and the most important factors are increased sympathetic nervous system activity, renal sodium retention and impaired pressure natriuresis, activation of the renin–angiotensin system, impaired endothelial function, and increased plasma leptin concentrations. He also suggested that plasma aldosterone is associated with blood pressure and BMI, and that the mineralocorticoid action of aldosterone contributes to obesity-related hypertension [18].

The hs-CRP values were found to be directly proportional to BMI in both patients and control groups. This data was similar to other studies [13],[14].

In this study, lipid profile shows an increase of the mean values of cholesterol, triglycerides, and LDL in the patient group with decrease in HDL; all have significant differences when compared with the control group and this is similar to other studies. [11],[14]. Other studies have shown increased triglyceride levels in the control group [13].

The study also showed higher levels of cholesterol and LDL in prehypertensive patients compared with controls, which is similar to other studies [19].

Some studies found higher triglycerides and cholesterol levels in patients who are hypertensive. While others found higher levels of LDL-c and lower levels of HDL-c in prehypertensive groups than in the normotensive groups. High triglyceride levels represent the most significant risk factor associated with cardiovascular diseases [20]. An increase in total cholesterol and LDL-c is associated with unfavorable effects on endothelial function and the development of atherosclerosis, and also with the clinical importance of HDL-c in counteracting atherosclerosis [21].

Our study also shows that in both patient and control groups, it was noted that hs-CRP has a positive correlation with cholesterol, triglycerides and LDL, while there is a negative correlation with HDL. This was very similar to the data obtained from other studies [11],[19]. There is relation between some acute-phase reactants as sialic acid and LDL metabolism inducing vascular smooth muscle damage, and the damaged muscle can promote the development of hypertension [4].

Our study also shows that hs-CRP levels are significantly higher in patients who are not under treatment, than in patients who are under it. No data could be found from other studies to confirm this result, although some studies suggested that some antihypertensive drugs exert a favorable effect on vascular inflammation, which is a feature of endothelial dysfunction and promotes the development of atherosclerosis [22].


  Conclusion Top


Increased serum hs-CRP levels are associated with hypertension, especially in the early stages of the disease. Atherosclerosis is increasingly being recognized as a chronic inflammatory disease. Hypertension is a well-established risk factor for atherosclerosis. An increased level of hs-CRP in hypertension implies a role of inflammation in hypertension; but whether inflammation is a cause or effect of hypertension is not clear.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Al-Kirwi ENS, Abed BA. Hypertension and obesity in relation to high sensitivity c-reactive protein and lipid profile in Iraqi patients. J Al-Nahrain Univ 2009; 12:145–150.  Back to cited text no. 14
    
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Sesso HDBJ, Rifai N, Blake GJ, Gaziano JM, Ridker PM. C-reactive protein and the risk of developing hypertension. JAMA 2003; 290:2945–2951.  Back to cited text no. 15
    
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De Marco M, de Simone G, Roman MJ, Chinali M, Lee ET, Russell M et al. Cardiovascular and metabolic predictors of progression of prehypertension into hypertension: the Strong Heart Study. Hypertension 2009; 54:974–980.  Back to cited text no. 16
    
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Kotchen TA. Obesity-related hypertension: epidemiology, pathophysiology, and clinical management. Am J Hypertens 2010; 23:1170–1178.  Back to cited text no. 18
    
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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10]



 

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