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International Journal of Research and Review Vol.7; Issue: 2; February 2020 Website: www.ijrrjournal.com Original Research Article E-ISSN: 2349-9788; P-ISSN: 2454-2237

Relationship of Serum Retinol and B12 to Essential Hypertension - An Observational Study in Eastern India

Subhramay Chatterjee1, Sandip Chakraborti2

1Associate Professor, Biochemistry Department, Murshidabad Medical College and Hospital, Berhampore, West Bengal, India 2Associate Professor, Biochemistry Department, NRS Medical College and Hospital, Kolkata, West Bengal, India

Corresponding Author: Sandip Chakraborti

ABSTRACT hypertrophy, microalbuminuria, and cognitive dysfunction takes place early Pathophysiology of essential hypertension has in the course of hypertensive cardiovascular been linked to various factors including disease, although catastrophic events such . 139 essential hypertension cases were as stroke, heart attack, renal failure, divided into group 1 (67 younger cases, <50 and dementia usually happen after long years of age) and group 2 (72 older cases, more periods of uncontrolled hypertension only. than 50 years of age. Serum retinol and vitamin (1) B12 levels of the 139 cases and 127 Hypertension is directly responsible for nonhypertensive controls were assayed. There 57% of all stroke deaths and 24% of all was no significant difference between the mean coronary heart disease deaths in India. At an levels of serum vitamin B12levels of cases and underestimate, there are 31.5 million controls, though the levels of serum vitamin hypertensives in rural and 34 million in (2) B12were decreased in cases in comparison to urban populations. controls. But, mean levels of serum retinol were The pathophysiology of essential significantly decreased in cases with respect to hypertension depends on the kidney, central controls, and the decrease was more significant nervous system, endocrine factors, the large in older patients when compared to younger arteries, and the microcirculation, but patients. Levels of serum retinol are decreased in essential hypertension and this decrease is mostly arises as a complex quantitative trait that is affected by varying combinations of more as age advances, but levels of serum (3) are unchanged in essential genetic and environmental factors. There hypertension. Retinol may be used as a marker is still much uncertainty about the for essential hypertension, though further pathophysiology of hypertension. A small studies in this regard are required to validate the number of patients (between 2% and 5%) present observations. have an underlying renal or adrenal disease as the cause for their raised blood pressure. Keywords: Essential hypertension, serum In the remainder i.e. 95%-98%, however, no retinol, vitamin B12 clear single identifiable cause is found and their condition is therefore labelled INTRODUCTION “essential hypertension”. In the past few Essential hypertension can be years, factors other than the traditional or defined as a rise in blood pressure of commonly known factors have been unknown cause that increases risk for evaluated, including endothelial dysfunction cerebral, cardiac, and renal events. Subtle (as manifested by changes in endothelin and target-organ damage such as left-ventricular nitric oxide), low birth weight and

International Journal of Research and Review (ijrrjournal.com) 163 Vol.7; Issue: 2; February 2020 Subhramay Chatterjee et.al. Relationship of serum retinol and vitamin B12 to essential hypertension - an observational study in eastern India intrauterine nutrition, and neurovascular After overnight fasting venous blood anomalies. (4) Studies on intake samples were collected from all subjects, and BP have suggested that dietary vitamin serum separated and transferred in ice D may reduce BP or risk of hypertension. blocks. The samples were then stored at (5,6) Other studies have found that disturbed −20°C until the biochemical assay. All and homocysteine metabolism may samples were coded and assayed in a blind play a role in the early stages of fashion by an investigator who was unaware hypertension. (7) Thus, nutrition plays a role of the participant's clinical status. Serum in the pathophysiology of hypertension. retinol and vitamin-B12 levels were assayed These facts prompted the authors to by RP-HPLC. Statistical analysis of data conduct an investigation on the levels of was performed using SPSS software version serum retinol and vitamin B12in adults with 20 (IBM, New York, USA), and inferences essential hypertension. were drawn. A value of p <0.05 was considered to be statistically significant and MATERIALS AND METHODS p<0.001 highly significant. The study was a hospital-based case–control study conducted in a tertiary RESULTS care medical college and hospital in West Table 1. Serum levels (as Mean + SD) of retinol (in mcg/dl) and vitamin B12 (in pg/ml) Bengal, India. The study was approved by retinol vitamin B12 the Institutional Ethical Committee. Before Cases: group 1 287+23 519+43 Cases: group 2 284+31 517+48 enrollment of the subjects, informed consent Controls 293+18 528+32 was obtained from all the participants. The duration of the present study was 10 months Number of subjects: Group 1 – 67, group 2 and included 139 essential hypertension – 72, controls- 127 patients attending the outpatient department during the above mentioned period. These For vitamin B12 levels: patients were further divided into group 1 (67 younger patients, <50 years of age) and 1. Student t test to test for significance group 2 (72older patients, more than 50 between controls and group 1: years of age). 127 age- and sex-matched p value and statistical significance: patients attending outpatient department, The two-tailed p value equals 0.1009 characterized by the absence of By conventional criteria, this difference is hypertension or family history of considered to be not statistically significant. hypertension, served as controls. Confidence interval: Consecutive patients attending the OPD and The mean of group 1 minus controls equals satisfying inclusion criteria were selected -9.00 assuming that the patients attended OPD 95% confidence interval of this difference: randomly. Exclusion criteria included From -19.77 to 1.77 participants who had secondary Intermediate values used in calculations: hypertension from various causes, t = 1.6483 cholestasis, unusual dietary habits, acute or df = 192 chronic infections, fever, malabsorption standard error of difference = 5.460 syndromes, oral supplements or drugs- SEM values are 5.25 and 2.84 for group 1 containing and vitamin B12 and controls during the past 6 months and topical application of vitamin Aduring the 2. Student t test to test for significance preceding 1 month. Complete history and between controls and group 2: physical examination of all cases and p value and statistical significance: controls were undertaken. The two-tailed p value equals 0.0545

International Journal of Research and Review (ijrrjournal.com) 164 Vol.7; Issue: 2; February 2020 Subhramay Chatterjee et.al. Relationship of serum retinol and vitamin B12 to essential hypertension - an observational study in eastern India

By conventional criteria, this difference is standard error of difference = 3.471 considered to be not quite statistically SEM values are 3.65 and 1.60 for group 2 significant. and controls Confidence interval: The mean of group 2 minus controls equals DISCUSSION -11.00 In the present study there was no 95% confidence interval of this difference: significant difference between the mean From -22.21 to 0.21 levels of serum vitamin B12 levels of cases Intermediate values used in calculations: and controls, though the levels of serum t = 1.9347 vitamin B12were decreased in cases in df = 197 comparison to controls. But, mean levels of standard error of difference = 5.685 serum retinol were significantly decreased SEM values are 5.66 and 2.84 for group 2 in cases with respect to controls, and the and controls decrease was more significant in older patients (p = 0.0102 for group 2) when For retinol levels: compared to younger patients (p = 0.0468 for group 1), as depicted in table 1. 1. Student t test to test for significance Hypertension is a major contributor between controls and group 1: to the development of renal failure, p value and statistical significance: cardiovascular disease, and stroke. These The two-tailed p value equals 0.0468 pathologies are associated with vascular By conventional criteria, this difference is functional and structural changes including considered to be statistically significant. endothelial dysfunction, altered Confidence interval: contractility, and vascular remodeling. The mean of group 1 minus controls equals Central to these phenomena is oxidative -6.00 stress. Factors that activate pro-oxidant 95% confidence interval of this difference: enzymes, such as NADPH oxidase, remain From -11.92 to -0.08 poorly defined, but likely involve Intermediate values used in calculations: angiotensin II, mechanical stretch, and t = 2.0007 inflammatory cytokines. Reactive oxygen df = 192 species influence vascular, renal, and standard error of difference = 2.999 cardiac function and structure by SEM values are 2.81 and 1.60 for group 1 modulating cell growth, contraction/ and controls dilatation, and inflammatory responses via redox-dependent signaling pathways. (8) 2. Student t test to test for significance Increased vascular reactive oxygen species between controls and group 2: production, especially superoxide anion, p value and statistical significance: contributes significantly in the functional The two-tailed p value equals 0.0102 and structural alterations present in By conventional criteria, this difference is hypertension. An enhanced superoxide considered to be statistically significant. production causes a diminished NO Confidence interval: by an oxidative reaction that The mean of group 2 minus controls equals inactivates NO. Exaggerated superoxide -9.00 levels and a low NO bioavailability lead to 95% confidence interval of this difference: endothelial dysfunction and hypertrophy of From -15.84 to -2.16 vascular cells. It has been shown that the enzyme NAD(P)H oxidase plays a major Intermediate values used in calculations: role as the most important source of t = 2.5930 superoxide anion in vascular cells. df = 197 (9) Potential sources of excessive ROS in

International Journal of Research and Review (ijrrjournal.com) 165 Vol.7; Issue: 2; February 2020 Subhramay Chatterjee et.al. Relationship of serum retinol and vitamin B12 to essential hypertension - an observational study in eastern India hypertension include RA levels in the embryo are affected by dinucleotide phosphate (NADPH) oxidase, several factors, such as maternal vitamin A mitochondria, xanthine oxidase, nutrition and disturbances in retinol endothelium‐derived NO synthase, metabolism. Maternal vitamin A deficiency cyclooxygenase 1 and 2, cytochrome P450 during is widespread in epoxygenase, and transition metals. developing countries and segments of these including A, C and populations may be exposed to low , L‐arginine, flavanoids, and A during fetal life when nephron number is mitochondria‐targeted agents (Coenzyme determined. Infants are likely to be born Q10, acetyl L carnitine, and alpha lipoic with suboptimal nephrons and may develop ‐ ‐ ‐ (14) acid) have been used to decrease primary hypertension later in life. hypertension or its risk. (10) In whole blood Whether this data is relevant to the present and in mononuclear cells from hypertensive work can be determined only by further subjects, Redon et al found an increase in research. oxidative stress and a reduction in the This study has limitations that must activity of mechanisms that be considered. To assess retinol and vitamin appeared to be independent of the blood B12, RP-HPLC was used. Retinol and pressure values. (11) Engelhard et al found vitamin B12 can be estimated by various that treatment with antioxidant-rich tomato methods, but the present method was extract can reduce blood pressure in patients employed as it is the most commonly used, with grade-1 HT, naive to drug therapy. time tested and standard method. Also, (12) Interest in vitamin A‐related compounds number of patients in the study groups was focus primarily on beta‐, given not large. Thus, care must be taken in promising epidemiological data with respect extrapolating the present findings to other to its cardioprotective effects and a populations. Patients were taking a number correlation of higher plasma levels to lower of medications to control hypertension. blood pressure in men. (13) Thus, the authors However, these treatments are characteristic think that the decreased levels of retinol in of patients with hypertension and do not the present study are probably a result of affect serum retinol and vitamin B12 levels. relative exhaustion of antioxidant capacity Despite these limitations, we believe that in hypertension due to excess free radicals, our study points towards using retinol as an and this exhaustion is more pronounced as important, promising antioxidant marker for the process of hypertension progresses with hypertension. As our findings point to a age. This is apparent by the levels of retinol, decrease in the antioxidant retinol, the which are decreased further in the older problem of oxidative stress in hypertension subset of patients (group 2) when compared should also be further investigated in a to the younger patients (group 1). larger number of patients, and other markers Vitamin A (retinol) and its analogs of oxidative stress and antioxidants should () are important regulators of cell be assessed. proliferation, differentiation, immune function, and apoptosis. (RA), CONCLUSION a vitamin A metabolite, is involved in Levels of serum retinol are embryonic kidney patterning through the decreased in essential hypertension and this control of receptor tyrosine kinase decrease is more as age advances, but levels expression, which modulates ureteric bud of serum vitamin B12 are unchanged in branching morphogenesis. Humans at the essential hypertension. Retinol may be used low end of nephron number are predisposed as a marker for essential hypertension, to primary hypertension. Because RA though further studies in this regard are regulates nephron mass, its optimal required to validate the present availability during nephrogenesis is critical. observations.

International Journal of Research and Review (ijrrjournal.com) 166 Vol.7; Issue: 2; February 2020 Subhramay Chatterjee et.al. Relationship of serum retinol and vitamin B12 to essential hypertension - an observational study in eastern India

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International Journal of Research and Review (ijrrjournal.com) 167 Vol.7; Issue: 2; February 2020