Lipid profile but not highly sensitive C-reactive protein helps distinguish prehypertensives from normal subjects.

BACKGROUND: Early identification of the prehypertensive state can greatly improve the disease risk management. Although increased levels of highly sensitive C-reactive protein (hsCRP) and dyslipidemia is reported among patients with hypertension, the correlation of these parameters among prehypertensives in not known. Hence, the present study was designed to compare the levels of serum hsCRP and lipid profile among prehypertensives and normal subjects and correlate it with blood pressure (BP) levels.
MATERIALS AND METHODS: Anthropometric measurements and BP were recorded in 40 prehypertensive and 40 normal subjects. Subjects were assigned to a group based on their BP as per Joint National Committee 7 criteria. Serum hsCRP and lipid profile were measured and correlated with BP levels.
RESULTS: Serum hsCRP showed no significant difference between the two groups. There was no significant correlation of BP with hsCRP in both the groups. Total cholesterol (TC) and low-density lipoprotein (LDL) were significantly increased in prehypertensives as compared to normal subjects. There was no significant association between BP and lipid parameters in prehypertensives.
CONCLUSIONS: Significant increase of TC and LDL but not hsCRP was evident among prehypertensives as compared to normal subjects.

INTRODUCTION

Cardiovascular diseases are the major cause of mortality and morbidity globally,[1] with hypertension often being a common clinical finding[2] that the increasing prevalence of hypertension in developing countries is of significant concern.[34] Hypertension is an independent predictor of cardiovascular disease, cerebrovascular accidents, and death.[5] Seventh report of Joint National Committee (JNC 7) on prevention, detection, evaluation, and treatment of high BP defines hypertension as BP >140/90 mmHg.[6] JNC 7 includes prehypertension as a new category defining people who have BP above optimal levels, but not clinical hypertension. According to JNC 7, prehypertension is defined as systolic blood pressure (SBP) ranging between 120 and 139 mmHg and/or diastolic blood pressure (DBP) ranging between 80 and 89 mmHg.[6] Classifying this range, which was earlier considered as normal BP, as prehypertension has placed many people under this risk category. Incidently, prehypertensives are at higher risk of developing hypertension[7] and in addition, prehypertension itself is a major risk factor for cardiovascular events.[8]

Highly sensitive C-reactive protein is an inflammatory marker; which can induce inflammatory changes in endothelial and smooth muscle cells and is associated with development and progression of atherosclerosis and hypertension.[91011] C-reactive protein is an acute-phase protein found in traces in the blood of healthy subjects, with a concentration of 1 mg/dl.[12] Rate of macrovascular complications is increased by dyslipidemia.[13] Increased levels of serum hsCRP and dyslipidemia are reported in patients with hypertension.[41415] Interestingly, cardiovascular risk groups are classified based on serum levels of hsCRP (low risk: <1.0 mg/L, average risk: 1.0-3.0 mg/L, high risk: above 3.0 mg/L). Nevertheless increased levels of hsCRP and lipid levels signify the increased cardiovascular risk in the patients suffering from prehypertension. Prehypertensives are more likely to progress to hypertension as compared to subjects with normal BP.[7] Hence, early detection of these derangements and early interventions may arrest the progression of prehypertension to hypertension and prevent complications in the individuals suffering from prehypertension. The present study was designed to assess the levels of serum hsCRP and lipid profile in prehypertensives and to compare it with normal subjects and correlate it with BP levels.

MATERIALS AND METHODS

This comparative study consisted of 80 subjects. 40 prehypertensives and 40 age and body mass index (BMI) matched normal subjects. The subjects who satisfied the inclusion criteria, that is, males of the age group 18-40 years, who were non-smokers, had waist circumference <94 cm, BMI between 18.5 kg/m2 and 30 kg/m2, prehypertensives and normal subjects/normotensives as per JNC 7 criteria were included. Subjects with impaired glucose tolerance, diabetes mellitus, history of any drug intake, history of any acute illness, and previous vascular events such as myocardial infarction, vasculitis were excluded from the study.

Study protocol was explained to the subjects, written and informed consent was obtained. Study was approved by the institutional ethics committee. History was taken from all subjects, following recording of BP, subjects were screened for general physical health to rule out any clinical disorder likely to interfere with the study objectives. Based on BP recordings and as per JNC 7 criteria, subjects were assigned to two groups viz Group 1-Prehypertensives, Group 2-Healthy normal individuals; each group consisted of 40 subjects.

Anthropometric measurements (height, weight, waist circumference) were recorded for all subjects. BMI was calculated using Quetelet's index, calculated as weight (kg)/height2 (m2). Blood pressure was measured using a sphygmomanometer from the right arm of the seated participant after 10 min rest and was recorded to the nearest 2 mmHg using 1st and 5th Korotkoff sounds. Three BP measurements were recorded, and the mean of the last two measurements was used for the analysis. 5 ml of the blood sample was collected after 12 hours overnight fast, and serum was isolated and stored at −20°C in Ependorf tubes till the analysis. Fasting serum glucose was determined by glucose oxidase method, using a commercial kit (SPAN diagnostics, India). Lipid profile was estimated using standard enzymatic method, using a commercial kit (AGAPPE diagnostics, India). Blood samples collected in the fasting state were analyzed for total cholesterol (TC), triglycerides (TG) and high-density lipoprotein (HDL) using specific enzymatic methods. Low-density lipoprotein (LDL) was derived by Fredrickson-Friedwald formula (LDL = [TC-HDL]-TG/5).[16] Serum hsCRP levels were measured by turbidimetry method, using a commercial kit (ERBA diagnostics, Germany). All the samples were assayed for hsCRP, lipid parameters and fasting blood glucose using NexGen (SPAN) semiautomated biochemistry analyzer.

Statistical analysis

Descriptive statistical analysis has been carried out in the present study. Results on continuous measurements are presented as mean ± standard deviation (min-max) and results on categorical measurements are presented in number (%). Significance is assessed at 5% level of significance. Student's t-test (two-tailed, independent) was used to find the significance of study parameters on continuous scale between two groups on metric parameters, Chi-square/fisher exact test was used to find the significance of study parameters on categorical scale between two or more groups. Pearson correlation was used to find a correlation between BP and study variables. The statistical software namely SPSS 15.0, by SPSS Inc. was used for the analysis of the data and Microsoft Word and Excel have been used to generate graphs, tables.

RESULTS

The two groups were matched and were similar in terms of the basic characteristics [Table 1]. Comparison of BP values between two groups showed a significant difference (P < 0.001) [Table 2]. Fasting blood sugar levels was similar in both the groups. hsCRP levels were not significantly (P = 0.348) different between two groups, even though the levels were marginally increased in prehypertensives [Table 3]. TC (P < 0.001) and LDL (P < 0.001) values were significantly increased in prehypertensives as compared to normal subjects; there was no significant difference between the groups with respect to parameters like TG (P = 0.886), HDL (P = 0.553) and very low density lipoprotein (P = 0.886) [Table 4].

Table 1

Comparison of baseline variables between prehypertensives and normal subjects

Table 2

Comparison of BP values between prehypertensives and normal subjects

Table 3

Comparison of hsCRP values between prehypertensives and normal subjects

Table 4

Comparison of lipid parameters between prehypertensives and normal subjects

The findings did not show significant correlation between SBP and serum hsCRP (r-0.037, P = 0.819) in prehypertensives and (r - 0.045, P = 0.781) in normal subjects and also there was no significant correlation between DBP and serum hsCRP in prehypertensives (r - 0.139, P = 0.391) and normal subjects (r - 0.011, P = 0.085) [Table 5]. Correlation between SBP and lipid parameters in preypertensives was non-significant. There was moderately significant negative association between SBP and HDL in normal subjects (r - 0.377, P = 0.016). There was no significant correlation between DBP and lipid parameters in prehypertensives. In normal subjects, there was strongly significant negative association between DBP and HDL (r - 0.429, P = 0.006) [Table 6].

Table 5

Correlation between hsCRP levels and BP

Table 6

Correlation of BP with lipid parameters

DISCUSSION

We aimed to compare the levels of serum hsCRP and serum lipid profile among prehypertensives and normal subjects and correlated these parameters with BP levels. Although a marginal increase of hsCRP levels was observed in prehypertensives, there was no significant difference observed between prehypertensives and normal subjects, which is consistent with previous reports.[15] Few studies have reported significant increase in hsCRP levels in prehypertensives as compared to normal subjects.[1417] However, in our study, there was no significant difference in hsCRP levels between the two groups. The probable reason for such result in the present study could be because of the mean age group of the study subjects, which was 26.15 ± 5.57 years for prehypertensives and 27.40 ± 5.89 years for normal subjects. This age group is younger as compared to the age group of the subjects in the studies which have reported significant increase in hsCRP levels in prehypertensives as compared to normal subjects. Thus suggesting that inflammation and raise in hsCRP levels could be an age-related[1819] phenomenon and is not independently associated with prehypertensive status. It is also possible that raised hsCRP and therefore inflammation is just a sequelae of prehypertension and not the cause of prehypertension.

Prehypertension was associated with significantly higher TC levels and LDL levels when compared to normal subjects. Suggesting that prehypertensives are at increased risk of cardiovascular events as compared to normal subjects, which is consistent with previous epidemiological studies.[2021] This significant increase in lipid parameters in prehypertensives as compared to normal subjects and insignificant difference of hsCRP among prehypertensives and normal subjects suggests that lipid parameters could be elevated in prehypertensives much earlier, even before the inflammation sets in.

Association of prehypertension with risk factors such as hypercholesterolemia, diabetes mellitus and overweight/obesity are previously reported.[72022] Our results further support the point that elevated levels of TC and LDL is evident in prehypertensives. This clustering of cardiovascular disease risk factors among persons with prehypertension suggests that prehypertensives should be screened for other cardiovascular disease risk factors, regardless of age. Our study further necessitates the need for intervention either in the form of lifestyle modifications or pharmacological interventions[2324] to arrest the progression of prehypertension to hypertension and to prevent complications in prehypertensives.

Limitations of the study

The present study was a cross-sectional study, so causal relationship among BP, hsCRP, and lipid profile could not be found out.