Evaluation of Role of Serum Lipoprotein and Lipid Profile in Essential Hypertension Patients in a Tertiary Care Hospital

Hypertension or high blood pressure has emerged as a leading cause of the global burden of disease in both developed as well as developing countries. Data from the National Health And Nutrition Examination Survey (NHANES) have indicated that 50 million or more Americans have high blood pressure warranting some form of treatment [1,2]. Worldwide prevalence estimates for hypertension may be as much as 1 billion individuals, and approximately 7.1 million deaths per year may be attributable to hypertension [3].


Introduction
Hypertension or high blood pressure has emerged as a leading cause of the global burden of disease in both developed as well as developing countries. Data from the National Health And Nutrition Examination Survey (NHANES) have indicated that 50 million or more Americans have high blood pressure warranting some form of treatment [1,2]. Worldwide prevalence estimates for hypertension may be as much as 1 billion individuals, and approximately 7.1 million deaths per year may be attributable to hypertension [3].
Hypertension is classified as either primary/essential hypertension or secondary hypertension. Primary/Essential hypertension is the form of hypertension that by definition has no underlying cause [4]. It is the most common cause of hypertension affecting 90-95% of total hypertensive patients. It is mostly of familial origin. Its prevalence increases with age. Secondary hypertension is caused by an identifiable underlying change. It is much less common than primary hypertension consisting only 5% of hypertensive individuals. It has many different causes including endocrine diseases, kidney diseases, tumours, also due to side effects of certain medications. Essential hypertension remains a major modifiable risk factor for cardiovascular disease (CVD) despite important advances in our understanding of its patho-physiology and the availability of effective treatment strategies. High blood pressure (BP) increases the risk of CVD for millions of people worldwide. Several prospective studies have identified the major risk factors for hypertension like obesity, smoking and alcohol consumption, dyslipidemia apart from dietary patterns [5].
Lp(a) has been of interest in hypertensive patients, since epidemiological studies indicated it to be an independent risk factor for cardiovascular diseases. Lipoprotein (a) is a complex lipoprotein molecule that contains apolipoprotein (a), which shares homology with plasminogen [6,7]. It acts as a competitive inhibitor of tissue type plasminogen activator and there by helps in modulating the fibrinolytic system consistent with an atherogenic role [8,9]. Lp(a) levels are known to exhibit significant inter-individual variation and strictly under genetic control [10,11].
Elevated serum Lp(a) levels are associated with an increasing risk of cardiovascular disease and renal failure in hypertensive patients [12]. As Lp (a) levels are genetically determined, screening for Lp (a) levels in asymptomatic individuals has been suggested to identify the subjects at risk [13].
Elevated Lp (a) could be an independent risk factor for atherosclerosis, and could contribute towards increasing the incidence of cardiovascular disease in people with essential arterial hypertension. There are very limited case-control studies determining association between Lp (a) excess and essential hypertension. Therefore the aim of our present study is to measure the serum concentrations of lipoprotein (a) in a group of hypertensive patients and to find its association with blood pressure and lipid profile.

Materials and Methods
The study was conducted in the Department of Biochemistry, S.C.B. Medical College and Hospital, Cuttack from February 2013 to August 2014. 68 patients of age group 35-74 years, attending OPD and indoor in the Department of Medicine, S.C.B. Medical College and Hospital, Cuttack, were included in the study. Patients with Hypertension were selected and diagnosed based on their history, physical examination, biochemical investigations and according to the JNC 7 (Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) Criteria for the diagnosis of hypertension. 63 age and sex matched healthy adults with normal serum lipid profile, having no symptoms and signs suggestive of hypertension and also with no family history of the disease were selected as controls.
Three ml of blood was collected after overnight fasting of eight hours from all enrolled patients and healthy controls for the assessment of Lipoprotein (a) levels and other biochemical parameters like fasting plasma glucose, serum urea, creatinine, uric acid, lipid profile. Demographic characteristics (name, age, sex), history of risk factors (smoking, family history, medications, alcohol intake etc. ), systolic and diastolic blood pressures, body mass index were recorded in detail ( Table 1).
The inclusion criteria consists of Adults aged 35 years and above diagnosed with hypertension according to JNC 7 (Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure). Age and sex matched healthy adults with systolic blood pressure <120 mmHg and diastolic blood pressure <80 mmHg were taken as controls.
Patient with Diabetes Mellitus, renal disease, endocrinopathy, pregnancy Induced Hypertension, Immunosupression and history of illicit drug use were excluded from the study. In the control group, subjects with family history of hypertension, renal diseases and chronic metabolic diseases were excluded. All the case records were collected in a specified proforma. Written, informed consent was obtained from all subjects. The instruments used were automated Clinical Analyzer Biolis24i Premium (Tokyo Boeki Machinery Ltd.) and Ecolyte (ISE) ( Table 2). Table 2 Depicts the mean age to be 56.11 ± 6.84 yrs in healthy individuals in the control group (n=63); 55.72 ± 6.58 yrs in stage 1 hypertensives (n=39); and 56.9 ± 7.25 in stage 2 hypertensives (n=29). The mean body mass index was 21.67 ± 1.77 kg/m² in control group; 25.06 ± 1.95 kg/m² in stage 1 hypertensives; 25.91 ± 2.11 kg/m² in stage 2 hypertensives. In both stage 1 and 2 hypertensives the BMI values were found to be statistically significant (p<0.001) when compared to control.

Discussion
The present study was carried out in the Department of In this study the mean age of stage 1 hypertensives was 55.72 ± 6.58 years, stage 2 hypertensives was 56.9 ± 7.25 years and of healthy individuals was 56.11 ± 6.84 years ( Table 2). The age distribution was in consistent with that of Catalano et al. [14].
A significantly higher level of BMI was found in stage 1 and 2 hypertensives when compared to healthy controls ( Table 2). This finding was in accordance to that of Charles U Osuji et al. [15] Gowda et al. [16] and Gupta et al. [17]. It is due to the fact that increased BMI is associated with an increase in plasma volume and cardiac output. Thus obesity is a risk factor for hypertension. Table 3   and diastolic blood pressure (SBP and DBP) in control and cases. Mean SBP and DBP in stage 1 and stage 2 hypertensives was significantly raised when compared to SBP and DBP of control. Table 3 shows the systolic and diastolic blood pressure in control and study group. The mean SBP was 126. 38 ± 4.87 mmHg in control group; 151.08 ± 6.03 mmHg in stage 1 hypertensives; 169.86 ± 9.23 mmHg in stage 2 hypertensives. The mean diastolic blood pressure was 80.38 ± 3.17 mmHg in control group; 92.26 ± 3.82 mmHg in stage 1 hypertensives; 103.93 ± 5.46 mmHg in stage 2 hypertensives.
The systolic and diastolic blood pressures were found to be significantly higher (p<0.001) in both stage 1 and 2 hypertensives as compared to control group.
This finding was in accordance with the studies of, Bhavani BA, et al. [5], Charles U. Osuji, et al. [15], Kashem et al. [18] and Pooja et al. [19]. Blood pressure has a continuous and consistent relationship with the risk of cardiovascular events; the higher the BP, the higher the chance of CVD. The presence of each additional risk factor multiplies the risk for hypertension (Tables 4-6).
Elevated SBP confers significantly higher risk of coronary heart disease mortality than elevated DBP or combined systolic/ diastolic hypertension [20,21] especially with advancing age. As age increases, mean blood pressure levels tend to rise and the prevalence of hypertension increases. After age 60, however, mean diastolic pressures tend to plateau or fall, whereas systolic pressures continue to increase [22]. Because the majority of coronary heart disease events and cardiovascular morbidity occur in older individuals, the result is that there is also a greater attributable risk conferred by SBP elevation than by DBP elevation. The rise in systolic blood pressure with ageing is mainly caused by an increase in vascular stiffness of the great arteries in combination with atherosclerotic changes in the vessel wall.
Of the lipid parameters in hypertensive cases and control, a significantly higher level of total cholesterol, triglycerides and LDL was found in stage 1 and 2 hypertensives when compared to controls. While serum HDL was significantly reduced.
Hypertension and dyslipidemia are two of the main risk factors for vascular diseases and are often associated. The co-existence of the two risk factors has more than an additive adverse impact on the vascular  The exact mechanism by which a low HDL-C increases CVD risk has however not been fully elucidated, though experimental studies suggest a direct role for HDL-C in promoting reverse cholesterol transport from foam cells in the atherosclerotic plaque depots in blood vessels to the liver for excretion. HDL-C also exhibits potent anti-inflammatory and antioxidant effects that inhibit the atherogenic process [23,24]. It has additionally been shown that a low HDL-C level correlates with the presence of other atherogenic risk factor.
In the present study, 70.6% of hypertensive patients had Lp(a) levels ≥ 30 mg/dL when compared to 9.5% in controls, which, in general, is considered as a high-risk level for atherogenesis (Table 7). Bhavani et al. [5] found that in Indians 40.5% of hypertensive patients had Lp(a) >30 mg/dl when compared to 10% in controls. Catalano et al. [14] in their study found that in Caucasians only 13% of hypertensive patients had Lp(a) >30 mg/dL when compared to 8% in controls.
Elevated serum Lp (a) values could play an important role in essential hypertension pathogenesis and can be considered as an individual risk factor in hypertensive patients. Lp (a) could be an independent risk factor for atherosclerosis and can contribute towards increasing the risk for cardiovascular disease in persons with essential hypertension.
The correlation study between serum lipoprotein (a) concentrations and BMI in stage 1 and 2 hypertensives (Table 8) showed a positive correlation (r=0.024) in stage 1 hypertensives but it was not statistically significant (p=0.88). Similarly a positive correlation (r=0.035) was obtained between Lp(a) and BMI in stage 2 hypertensives but was not statistically significant (p=0.86).
The correlation between serum Lp(a) and lipid profile in stage 1 and 2 hypertensives showed that Total cholesterol, triglycerides, VLDLc were positively correlated while HDLc was negatively correlated with Lp(a) in both stage 1 and 2 hypertensives but were not found to be statistically significant (Table 13).
However, a significant positive correlation (r=0.321, p<0.05) was found in stage 1 hypertensives and in stage 2 hypertensives (r=0.379, p<0.05) between Lp(a) and LDLc (          Serum total cholesterol, triglyceride, VLDL cholesterol were positively correlated with lipoprotein (a) which were not statistically significant. Serum HDL cholesterol was negatively correlated with lipoprotein (a) and was not statistically significant.

Conclusion
The above findings suggest that in addition to conventional lipid profile parameters, estimation of Lp(a) can prove to be a valuable tool in risk assessment of population with hypertension and their progression to cardiovascular disease. Further, long term studies in a large group of population are needed to establish the role of Lp(a) in assessing the risk of cardiovascular disease in hypertensive patients.