| Abstract|| |
Context: Coronary atherosclerosis still presents one of the main causes of death. Efficacious prevention should focus on the early control of cardiovascular risk factors, including lipid profiles, which are unable early detect in subclinical cases. High-sensitive C-reactive protein (hs-CRP) can prove to be an early cardiac risk predictor. Aims: 1) To compare hs-CRP levels between healthy volunteer with normal blood pressure and those with prehypertension, and 2) to use hs-CRP levels along with other risks to be a cardiac risk predictor. Setting and Design: This was a cross-sectional study for 6 months' duration from January to June 2013 at Kudjab Hospital located in Udon Thani province, Thailand. Materials and Methods: Forty (40) healthy volunteers with prehypertension and 40 volunteers with normal blood pressure were included in the study. Both groups were similar in age range and sex. Twelve-hour (12-h) fasting blood samples were collected from all the participants. Serum was assayed for hs-CRP and lipid profile. Results: All of parameters were statistically significant difference (P < 000.1). The hs-CRP level (6.27 ± 7.8 mg/L) was elevated in the prehypertension group. The relative risk of hs-CRP for prehypertension was 6.3 with the odds ratio of 15.48, whereas the relative risk of lipid profiles for prehypertension prediction was only 1.28, with the odds ratio of 1.67. Statistical Analysis: SPSS version 11.0 using the unpaired t-test for comparing demographic data and blood parameters and risk prediction of hs-CRP and lipid profiles were calculated by relative risk with odds ratio [95% confidence interval (CI)]. Conclusions: Hs-CRP is an early cardiac risk predictor even with normal lipid profile, and can help measure additional risk especially subclinical people such as prehypertension.
Keywords: Hs-CRP, prehypertension, lipid profile, prediabetes, fasting blood glucose
|How to cite this article:|
Sudjaroen Y. High sensitive C-reactive protein (hs-CRP) level and biochemical parameters for prehypertension and prediabetes diagnosis. Ann Trop Med Public Health 2015;8:177-81
|How to cite this URL:|
Sudjaroen Y. High sensitive C-reactive protein (hs-CRP) level and biochemical parameters for prehypertension and prediabetes diagnosis. Ann Trop Med Public Health [serial online] 2015 [cited 2019 Nov 18];8:177-81. Available from: http://www.atmph.org/text.asp?2015/8/5/177/162639
| Introduction|| |
Heart disease and coronary artery disease are important health problems in the world population, especially in the countries influenced by Western fast food culture. The study in Thailand showed that the death rate from the two diseases mentioned above is in the top three of fatal diseases. The study showed that in 2003, 16.7 million people or 29.2% of the world population died from these diseases. The number increased to 17.5 million people in 2005. Moreover, there are about 20 million people who are subclinical FOR heart disease and coronary artery and need permanent treatment with high costs. This includes coronary artery disease, heart failure, and stroke. In 2002, there were 77,323 people subclinical with coronary artery disease, and 32,903 who died. In 2003, the number of patients increased to 92,733, and 40,092 died.  In addition, the cardiovascular patients will trend to younger, which may due to the change in life activities, food consumption, and low physical activity. Urban societies is also a factor for the risk of heart disease, involving lack of exercise, less movement, excessive food consumption but with inadequate amounts of fruits and vegetables. There have been studies on risk factors for coronary artery disease including blood checks to find substances that indicate risks.
In general, the pathological lesion of coronary artery disease is the accumulation of cholesterol in the artery walls, causing atherosclerosis. This gradual process starts from the teenage years and becomes more serious in adults in the form of atherosclerotic plaque, which finally blocks the artery. Atherosclerosis occurs when the artery becomes narrow. This disease with other complications requires high-cost treatment and leads to a high fatality rate. The behavior of the Thai population tends to imitate that of many Western people especially in food consumption. Thus, efficacious prevention should focus on the treatment of the most important cardiovascular risk factors, such as cigarette smoking, hypertension, hypercholesterolemia, diabetes, and obesity. However, the traditional risk factors, such as lipid profiles, cannot detect the disease accurately, especially in cases without serious symptoms. High-sensitive C-reactive protein (hs-CRP), an acute-phase reactant protein, is a proinflammatory atherogenic circulating marker which may to be an early cardiac risk predictor.  According to epidemiology data, hs-CRP can predict coronary artery diseases. The Adult Treatment Panel III Guidelines of the National Cholesterol Education Program suggest that the level of hs-CRP and fibrinogen together with a general biochemical substance check can be used as a risk indicator. 
C-reactive protein (CRP) is the protein produced by the liver to react with the innate immune response by stimulating cytokines, interleukin-6, and tumor necrosis factor alpha. During infection or tissue damage, there is a high increase of CRP by up to 1,000 times, making it difficult to define the normal range. Hs-CRP is a more accurate value because its normal range gives better interpretation, especially for the prediction of atherosclerosis and artery disease. As hs-CRP can measure CRP values as low as 0.3 mg/L, it is useful to evaluate and indicate the risk of atherosclerosis. The Centers for Disease Control and Prevention/American Heart Association (CDC/AHA) statement suggested that when CRP < 1 mg/L, there is low cardiovascular risk; when it is 1-3 mg/L, intermediate (average) cardiovascular risk; when it is >3 mg/L, high cardiovascular risk; and when >10 mg/L, the infected part or the acute coronary syndrome should be detected. 
The data to distinguish the categories given above were from a study of more than 15 groups of people, with over 40,000 cases. In the high cardiovascular risk group, the risk is doubled compared to the low cardiovascular risk group. Individuals with high hs-CRP at the highest point of a normal range will have a higher risk by up to 1.5-4 times of having a heart attack compared with those with lower hs-CRP at the lowest point of a normal range. Hs-CRP can stimulate the building of adhesion molecules such as vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM1), and elastin in endothelial cells. Moreover, hs-CRP can stimulate monocytes to build tissue factor, causing blood clots in the extrinsic pathway process. ,
In overweight people with obesity, there is an increase of adipose tissue and abnormal protein with hormone characteristics, causing infection of the systemic inflammation type and affecting the metabolic pathway in several processes, such as dysglycemia (clinically called prediabetes), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and abnormal blood pressure control (i.e., prehypertension). ,,, Moreover, the increase of systemic inflammation can cause abnormal circadian blood pressure and result in endothelial dysfunction. If the disorder remains for a long time, it results in heart disease and coronary artery disease. 
For prehypertension, the blood pressure measurement will be done after 5 min resting 2 times (resting clinic blood pressure). The values of 120 < systolic blood pressure (SBP) < 139 mmHg and 80 < diastolic blood pressure (DBP) < 89 mmHg will be averaged according to the Prehypertension: Joint National Commission 7 criteria.  For the prediabetes, the measurement will be done during fasting to get 110 mg/dL < fasting blood glucose, FBG < 126 mg/dL, and/or glycosylated haemoglobin (HbA1C) level 5.7-6.4%. This can be used to indicate prediabetes, according to the American Diabetes Association diagnostic criteria. 
It can be said that hs-CRP (normal value = 0.0-0.3 mg/L) in blood can indicate systemic inflammation and the risk of heart disease and coronary artery disease. When using hs-CRP to diagnose with other biochemical substances, such as glucose, HbA1C, lipid profile, it will be useful for greater sensitivity of diagnosis, especially for subclinical groups such as prehypertension and prediabetes. The researchers were interested in: 1) comparing hs-CRP levels between healthy volunteers with normal blood pressure and those with prehypertension, and 2) using hs-CRP levels, along with other risk factors including body mass index (BMI) and lipid profiles, to act as a cardiac risk predictor.
| Materials and Methods|| |
This was a cross-sectional study of 6 months' duration spanning January-June 2013, at Kudjab Hospital located in Udon Thani province, Thailand. Eighty (80) individuals were recruited for this study including 40 healthy volunteers with prehypertension and 40 other volunteers with normal blood pressure. The two groups were similar in age range and sex.
- The healthy volunteers (20 males, 20 females) signed the letter of consent.  They were aged 20-40 years with normal vital signs and normal physical examination. The exclusion criteria included drug use, recent surgery, pregnancy, smoking, drinking, exercise before blood penetration, and presence of a bloodborne infection such as hepatitis B or C, AIDS, and syphilis.
- Healthy volunteers with prehypertension (20 males, 20 females) required the same criteria as the first group, but they were prehypertension. Their blood pressure measurement was done after 5 min resting 2 times (resting clinic blood pressure). The values of 120 < SBP <139 mmHg and 80 < DBP < 89 mmHg will be averaged according to the Joint National Commission 7 criteria for prehypertension. 
This research project was approved by Ethical Human Research Committee of Kudjab Hospital, Thailand. The specimens must be clearly labeled with name, surname, age, sex, height, weight, and collection date on the blood collecting tubes.
Specimen preparation and laboratory assay
Twelve-hour fasting 6 mL blood samples were collected from each of the participants. Serum was assayed for hs-CRP and lipid profile by COBAS INTEGRA ® 400 plus (Roche-diagnostics, Rotkreuz, Switzerland). Each 3 mL blood sample was separated for serum preparation to be analyzed for hs-CRP, total cholesterol, triglyceride, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol. The experimental serum centrifugation (3,000 rpm/5 min) was done by analyzing the separated sample with COBAS INTEGRA ® 400 plus. The measurement of hs-CRP was based on immunonephelometry or turbidimetry by using monoclonal antibody specified to CRP binding with the CRP in serum, creating agglutination and the sediment of the solution. The sediment of the solution was directly related to the CRP amount compared with standard samples in mg/L. The test of total cholesterol, triglyceride, LDL-cholesterol, and HDL-cholesterol by using the principle of absorbance photometry shown with COBAS INTEGRA ® 400 plus was analyzed together with controlled materials according to low or high level following the manufacturer's method.
Data were analyzed through SPSS computer program version 11.0 (SPSS, Chicago, IL, USA) by analyzing the level of hs-CRP and lipid profile. Age, gender, BMI, and blood pressure were reported in mean and standard deviation, followed by descriptive statistics. The comparison between the healthy group and the prehypertension group was done with the hs-CRP level together with the lipid profile with a t-test at the statistic significant level of 0.05. Moreover, the calculation of odds ratio and relative risk was based on hs-CRP ≥3 mg/L and hs-CRP <3 mg/L to find the risk of hypertension.
| Results|| |
The study of risk factors of prehypertension group with 120 < SBP < 139 mmHg and 80 < DBP < 89 mmHg in comparison with the healthy group showed that there was a significant difference (P < 0.0001) as shown in [Table 1]. The group with prehypertension had an hs-CRP average value higher than the normal range (CRP >3 mg/L) while the healthy group had hs-CRP in the normal range (0.00-3.00 mg/L).
|Table 1: The comparison of risk factors between the prehypertension group and the normal group|
Click here to view
When separating the prehypertension group from the normal group, hs-CRP value in the normal range (hs-CRP ≤ 3 mg/L) and the abnormal (hs-CRP >3 mg/L), it was found that hs-CRP could be used to indicate the risk of heart disease and coronary artery disease by calculating relative risk and odds ratio at 6.30 and 15.48 respectively [Table 2].
|Table 2: Hs-CRP (>3 mg/l) to indicate risk prediction for prehypertension**|
Click here to view
However, when separating the prehypertension group from the normal group by using the lipid profile with the normal range of cholesterol < 200 mg/dL, triglyceride < 150 mg/dL, HDL-cholesterol >40.0 mg/dL, LDL-cholesterol 0.0-130.0 mg/dL, and dyslipidemia, it was found that some healthy people had abnormal lipid profiles due to lower HDL-cholesterol. When using the lipid profile value to indicate the risk of heart disease and coronary artery disease in the prehypertension group, the result was not so accurate, due to the relative risk and odds ratio being 1.28 and 1.67, respectively [Table 3].
|Table 3: Lipid profi le to indicate risk prediction for prehypertension***|
Click here to view
| Discussion|| |
The researchers investigated the hs-CRP levels of the two groups to compare the level of hs-CRP, lipid profile, and other risk factors such as age and BMI, and found that every risk factor showed a statistically significant difference (P < 0.0001) but was still in its respective reference range, except that the hs-CRP level of the prehypertension group was higher than the normal range. It can be concluded that lipid profile could not accurately detect the risk of heart disease and coronary artery disease in the prehypertension group. However, hs-CRP level could be accurately used to detect the risk of both diseases in the prehypertension group due to the very high relative risk and odds ratio (6.30 and 15.48 respectively).
Rogowski et al.  reported that the average hs-CRP level of healthy people (n = 6,588) was low (0.16 mg/L), and also that other risk factors, such as lipid profile, systemic inflammation (by using the erythrocyte sedimentation rate, ESR), white blood cell count, and fibrinogen level, were decreased. Celik et al.  studied the aorta (impaired aortic elasticity) of prehypertension with the same age group (33-35 years) and revealed that the hs-CRP levels in the prehypertension subjects with impaired arterial stiffness were higher, which was similar to this study. It can be concluded that people with prehypertension tend to have less aortic elasticity but higher hs-CRP values. The children and teenagers group (6-18 years old) with obesity status defined by decreased HDL-cholesterol, increased triglyceride, hypertension, and impaired glucose metabolism (prediabetes) or at least two of the mentioned aspects showed that the average hs-CRP was higher than normal (average normal = 3.8 mg/L, 95% CI: 2.8-4.8) as well.  Moreover, hs-CRP can be used to follow up the treatment and self-care of diabetes type 2 (insulin-independent diabetic mellitus, IIDM) patients, who tend to suffer from complications of heart disease and coronary artery disease with a normal lipid profile. 
The hs-CRP check together with lipid profile can be useful to detect heart disease and coronary artery disease with more accuracy especially for subclinical group. hs-CRP will be also useful in impaired glucose tolerance group when detect with FBG and/or HbA1C. hs-CRP detection can be done in large population in the community to give the suggestion on self caring such as weight control, diet control, and exercise.
| Acknowledgment|| |
We are grateful to Suan Sunandha Rajabhat University, Bangkok, Thailand for the grant support. We would like to sincerely thank all the staff of the Clinical Chemistry Laboratory Section, Division of Pathology, Kudjab Hospital located in Udon Thani province, Thailand for use of a research facility, and all the volunteers for providing useful data and helping with this research.
| References|| |
Nakapong R, Meerit S. Cardiovascular diseases report in 2006. Department of Disease Control. Ministry of Public Health, Thailand. 2006.
Corrado E, Novo S. Role of inflammation and infection in vascular disease. Acta Chir Belg 2005;105:567-79.
Pearson TA, Mensah GA, Alexander, RW Anderson JL, Cannon RO 3 rd
, Criqui M, et al
.; Centers for Disease Control and Prevention; American Heart Association. Markers of inflammation and cardiovascular disease: Application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003;107:499-511.
Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 2003;107:363-9.
Ridker PM. Inflammation, infection, and cardiovascular risk: How good is the clinical evidence? Circulation 1998;97:1671-4.
Moreno-Aliaga MJ, Campion J, Milagro FI, Berjon A, Martinez JA. Adiposity and proinflammatory state: The chicken or the egg. Adipocytes 2005;1:1-16.
Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 2005;115:911-20.
Vettor R, Milan G, Rossato M, Federspil G. Review article: Adipocytokines and insulin resistance. Aliment Pharmacol Ther 2005;22(Suppl 2):3-10.
Xu H, Barnes GT, Yang Q, Tang G, Yang D, Chou CJ, et al
. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003;112:1821-30.
Kougias P, Chai H, Lin PH, Yao Q, Lumsden AB, Chen C. Effects of adipocyte-derived cytokines on endothelial functions: Implication of vascular disease. J Surg Res 2005;126:121-9.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al
.; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, National High Blood Pressure Education Program Coordinating Committee. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: The JNC 7 report. JAMA 2003;289:2560-72.
American Diabetes Association. Standards of medical care in diabetes-2007. Diabetes Care 2007;30(Suppl 1):S4-41.
Horowitz LG. Reference intervals: Practical aspects. Electronic J Int Fed Clin Chem Lab Med 2008;19:1-11.
Rogowski O, Shapira I, Toker S, Melamed S, Shirom A, Zeltser D, et al
. Very low C-reactive protein in apparently healthy individuals: Physiological status or just a reflection of an improved health profile. Biomarkers 2007;12:645-56.
Celik T, Yuksel UC, Demirkol S, Bugan B, Iyisoy A, Kabul HK, et al
. Relationship between increased systemic inflammation and impaired aortic elasticity in young patients with prehypertension. Blood Press Monit 2011;16:55-61.
Soriano-Guillén L, Hernández-García B, Pita J, Domínguez-Garrido N, Del Río-Camacho G, Rovira A. High-sensitivity C-reactive protein is a good marker of cardiovascular risk in obese children and adolescents. Eur J Endocrinol 2008;159:R1-4.
Asegaonkar SB, Marathe A, Tekade ML, Cherekar L, Bavikar J, Bardapurkar J, et al
. High-sensitivity C-reactive protein: A novel cardiovascular risk predictor in type 2 diabetics with normal lipid profile. J Diabetes Complications 2011;25:368-70.
Faculty of Science and Technology, Suan Sunandha Rajabhat University, Bangkok - 10300
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3]