European Journal of Cardiovascular Medicine

Cardiovascular disease is one of the leading cause of mortality and morbidity worldwide. Epidemiological investigations pointed out that Hypertension is a powerful cardiovascular risk factor. Elevated blood pressure levels have been found to be highly predictive of cardiovascular events including Coronary Artery Disease, stroke and peripheral Arterial Disease. Relationship between elevated blood pressure and risk of cardiovascular events is continuous, consistent and independent of other risk factors^(1-6).    

The Cardiovascular events have a predominant vascular origin resulting from Atherosclerosis. Factors contributing to Atherosclerosis are multiple and complex. Multiple theories including role of dyslipidemia, hypercoaguability, oxidative stress, inflammation, and endothelial dysfunction are reported. Manifestations of Coronary Artery Disease (CAD) vary from Angina, Myocardial Infarction (MI), Arrythmia to sudden death.

Uric Acid plays a role in Endothelial function and Vascular Remodeling. It acts as a pro-oxidant inside the cell and as Antioxidant outside the cell ^{(7), (8)}. 

Hence in this study 3 groups of subjects namely 1. Hypertensive Patients with Myocardial infarction, 2. Hypertensive Patients without Myocardial infarction, 3.Healthy controls are taken.

AIM OF STUDY:

1. To evaluate risk of Coronary Artery Disease in Hypertensive Patients by estimating Uric Acid levels and Lipid Profile.
2. To evaluate relationship between Hypertension and Uric Acid.

Hypertension is considered as a state of Oxidative Stress⁽⁸⁾.   Excessive production  of ROS (Reactive Oxygen Species), outstripping antioxidant mechanism, decreased bioavailability of NO (Nitric Oxide) in the vasculature and kidneys and ROS mediated cardiovascular remodeling plays an important pathophysiological role in development of hypertension. Biomarkers of systemic oxidative stress such as isoprostanes, malondialdehyde and nitrotyrosine are elevated in hypertension.

Increased ROS bioactivity leads to endothelial dysfunction, increased contractility, vascular smooth muscle cell growth, monocyte invasion, lipid peroxidation, inflammation and increased deposition of extracellular matrix proteins⁽⁹⁾, important factors in hypertension mediated vascular damage.

An excessive activity of rennin-angiotensin-aldosterone system leads to the production of ROS and also contributes to endothelial dysfunction, vascular inflammation and thrombosis^(10,11).  

 Nitric Oxide (NO) and Hypertension:

Impaired endothelium –mediated vasodilatation in hypertension has been linked to decreased NO bioavailability. This may be secondary to decreased NO synthesis or to increased NO degradation because of its interaction with superoxide anion (O₂^-) to form peroxynitrite (ONOO^-). 

 Dyslipidemia and Hypertension:

Recent experimental data suggests marked similarities between the effects of hypertension and hypercholesterolemia on the arterial intima. Both conditions exert proinflammatory effects on the artery, resulting in the recruitment of monocytes into the intima. These effects may be due to the production of free radicals, which in turn stimulate the genes involved in the recruitment of inflammatory cells into the arterial wall ⁽¹²⁾. 

Endothelial dysfunction is in cross road between hypertension and dyslipidemia. The key feature in this disorder is the reduced availability of Nitric Oxide (NO) due to both decrease in synthesis as well as enhanced degradation. Hypercholesterolemia plays an important role, as oxidized LDL diminishes the expression of endothelial NO synthase ⁽¹³⁾.

90 subjects were selected for the study. They were divided into 3 groups.

• Group A: 30 Hypertensive patients
• Group B: 30 Hypertensive patients who had Myocardial Infarction recently ( < 7 days duration)
• Group C: 30 age and sex matched healthy controls. 

INCLUSION CRITERIA:

Group A:

• Hypertensive patients of age 30 years and above
• Out patients attending Government General Hospital, Guntur.
• Hypertension was considered to be present if an individual had a history of Hypertension and was on antihypertensive agents or if the systolic blood pleasure exceeding 140 mm Hg or the diastolic pressure exceeded 90 mm Hg.

Group B:

• Hypertensive patients who had Myocardial infarction recently (< 7 days)
• Age 30 years and above
• Inpatients admitted in the Cardiology Department in Government General Hospital, Guntur in between the period 01.03.2021 to 31.12.2021.

Group C:

• Age and Sex matched healthy controls.

 EXCLUSION CRITERIA:

• Patients with Diabetes Mellitus
• Patients with Renal Disorders
• Patients with Liver Diseases
• Chronic smokers and Alcoholics.
• Other Endocrinological Disorders.

BLOOD COLLECTION:

5 ml of Blood sample was collected from all subjects after overnight fasting and transferred to serum tubes. The blood was allowed to clot and the serum was separated after centrifugation at 300 RPM for 15 minutes. The serum levels of Uric Acid, Total cholesterol, Triglycerides, HDL-Cholesterol were measured immediately. Uric Acid is estimated by Uricase Method. Total serum cholesterol was estimated by ZLATKS, ZAK and BOYLE method. High density lipoprotein cholesterol was assessed by phosphotungstate – Magnesium chloride precipitation method. (ref BURSTEIN, M. SCHOLNICK, H.R. AND MORFIN 1970). Serum triglycerides were estimated by Acetyl acetone method. VLDL Cholesterol was calculated by using Friedewalds formula.   

              VLDL Cholesterol =

              LDL Cholesterol = Total Cholesterol –(HDL Cholesterol + VLDL Cholesterol)mg%

Table 1. Comparison of Uric Acid levels in HTN with MI, HTN and Controls

S-Significant;  NS – Non significant

Fig 4. Levels of Uric Acid

Table 2. Comparison of Lipid Profile in HTN with MI, HTN and Controls

S-Significant;  NS – Non significant

Fig 5. Total Cholesterol

Fig 6. HDL Cholesterol

Fig 7. Triglycerides

Fig 8. LDL Cholesterol

Hypertension is an independent risk factor for cardiovascular disease. Coronary Artery Disease is a leading cause of morbidity and mortality in hypertensive patients. About 47% of Ischemic Heart Disease are attributable to high blood pressure ⁽¹⁴⁾. 

In our study the Mean Uric Acid level was elevated in hypertensive patients when compared with controls and Uric Acid level in hypertensive patients with Myocardial Infarction was statistically significantly increased (p Value 0.002) when compared with Mean of control group.  

Francisco Rodrigues et al. noted that serum Uric Acid levels higher in patients with acute myocardial infraction⁽²⁾. Uric Acid plays a role in endothelial function & vascular remodeling. It act as a pro oxidant inside the cell and as an anti oxidant outside the cell⁽¹⁵⁾.  

As an anti-oxidant Uric Acid protects the LDL from Cu²⁺ mediated oxidation and shows protection against cardiovascular disease, ageing and cancer ⁽¹⁶⁾.

In ischemic conditions, Xanthine dehydrogenase is converted into Xanthine oxidase. Here it uses O² instead of NAD⁺ as an electron acceptor resulting in the formation of Uric Acid, hydrogen peroxide, & Superoxide anion. The inflammation & arterial wall damage are related to the free radicals produced during the reaction or by Uric Acid itself ⁽⁰³⁾.

The Mean Total Cholesterol, Triglycerides and LDL –Cholesterol in Hypertensive patients and Hypertensive patients with MI were elevated when compared with Mean of Control group.

The Mean Triglyceride levels were statistically significantly increased in Hypertensive patients with Myocardial Infarction (p Value 0.01) when compared with Mean of control group. ZhangY, et.al ⁽¹⁷⁾ in their study observed association of Hypertriglyceridemia  with Hyperuricemia, as the increase of Triglycerides  causes increased free fatty Acids production which accelerates decomposition of Adenosine Triphosphate, causing increase Uric Acid production.

Mean HDL Cholesterol was lowered in Hypertensive patients when compared with controls. The Mean HDL Cholesterol levels were statistically significantly lowered in hypertensive patients with Myocardial Infarction (p Value 0.004) when compared with Mean of control group. A decreased HDL Cholesterol can result in endothelial damage and trigger an increasing BP. HDL also exhibits potent anti-inflammatory and anti-oxidant effects that inhibit the atherogenic process.          

In our study, it is noticed that in Hypertensive patients increased Uric Acid levels and Dyslipidemia were observed. Once the causal role of increased levels of Uric Acid in Hypertension is established, it could create a milestone in management of Hypertension, which is a public health challenge all over the world and hence management of Uric Acid levels and Dyslipidemia in Hypertensive patients will help to control risk of developing Myocardial Infarction and also to avoid further complications. 

Conflict of Interest: None

Funding Support: Nil

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