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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 5  |  Issue : 1  |  Page : 7-11

Association of Vitamin D and essential hypertension in a North Indian population cohort


1 Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
2 Department of Cardiology, King George's Medical University, Lucknow, Uttar Pradesh, India

Date of Web Publication8-Mar-2017

Correspondence Address:
Akshyaya Pradhan
Department of Cardiology, King George's Medical University, Lucknow - 226 003, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/heartindia.heartindia_36_16

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  Abstract 

Background: Hypertension (HTN) continues to be a public health menace with substantial morbidity and mortality. The antihypertensive effect of Vitamin D is attributed to its negative regulation of renin–angiotensin–aldosterone system, antioxidant, and antiangiogenic effects. Data regarding Vitamin D deficiency in hypertensive Asian Indian population are scarce.
Materials and Methods: One hundred and two Vitamin D naive essential hypertensive participants were enrolled from the outpatient department. Ninety-nine healthy age- and sex-matched nonhypertensive controls were taken for comparison. Serum Vitamin D level estimation was done in both groups through immunosorbent assay and deficiency defined as values <20 ng/ml.
Results: Vitamin D deficiency was more prevalent among cases vis-à -vis controls (80.4% vs. 67.7%, P = 0.01). The mean 25-hydroxyvitamin D levels among cases were 15.15 ± 12.51 ng/ml versus a value of 33.59 ± 16.69 ng/ml among controls (P = 0.0001). We also observed trends towards an inverse association between Vitamin D levels and systolic blood pressure (BP) (P = 0.02).
Conclusion: Vitamin D deficiency is more prevalent with HTN, and low levels tend to correlate with elevated systolic BP. However, larger studies are needed to confirm this association.

Keywords: Deficiency, hypertension, systolic blood pressure, Vitamin D


How to cite this article:
Priya S, Singh A, Pradhan A, Himanshu D, Agarwal A, Mehrotra S. Association of Vitamin D and essential hypertension in a North Indian population cohort. Heart India 2017;5:7-11

How to cite this URL:
Priya S, Singh A, Pradhan A, Himanshu D, Agarwal A, Mehrotra S. Association of Vitamin D and essential hypertension in a North Indian population cohort. Heart India [serial online] 2017 [cited 2017 Jun 27];5:7-11. Available from: http://www.heartindia.net/text.asp?2017/5/1/7/201740


  Introduction Top


Hypertension (HTN) is the most prevalent primary diagnosis reported in ambulatory care visits and its management accounts for 30% of office visits for individuals aged 45–65 years and more than 40% among those aged 64 and more.[1] According to the seventh report of Joint National Committee on Prevention, Detection, Evaluation, and Management of High Blood Pressure (BP) 7, HTN has been defined as systolic BP more than or equal to140 mmHg and diastolic BP ≥90 mmHg.[2] Vitamin D insufficiency affects almost 50% population worldwide.[3],[4] The pandemic of hypovitaminosis D can mainly be attributed to lifestyle and environmental factors that reduce exposure to sunlight which is required for ultraviolet B radiation-induced Vitamin D production in the skin. The high prevalence of Vitamin D insufficiency is an important public health issue because hypovitaminosis D is an independent risk factor for total mortality in general population.[5] Observational data support the concept that Vitamin D is involved in the pathogenesis of cardiovascular diseases and arterial HTN, but whether this association reflects a causal relationship, remains unclear, and needs further research.[6],[7],[8],[9]

There is a widespread prevalence of varying degrees (50%–90%) of Vitamin D deficiency in Indian population too.[10] There have been a number of studies in Western population directed toward establishment of an association between Vitamin D deficiency and HTN.[11],[12],[13] However, such studies in Indian population are scarce. In the present study, we tried to establish a causal association between Vitamin D deficiency and HTN in a North Indian population cohort.


  Materials and Methods Top


Study design

The present study was conducted in a tertiary care university-based hospital. It was a cross-sectional case–control study for 1-year duration [Figure 1]. The study was approved by the Institutional Ethics Committee and conducted in accordance with Declaration of Helsinki.
Figure 1: Study flowchart

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Patients

Participants aged 18–50 years who were diagnosed with essential HTN and were naive for any form of Vitamin D supplementation were enrolled after informed and written consent to participate. The following groups of patients were excluded from the study:

  • Cases of secondary HTN
  • Participant suffering from any chronic illness such as diabetes mellitus, tuberculosis, chronic kidney disease, or coronary artery disease
  • Participant who had taken Vitamin D supplementation in the last 3 months.


Normotensive individuals of 18–50 years age without any chronic disease and not on any Vitamin D supplementation were enrolled as controls for comparison.

Methods

Blood pressure measurement

Diagnosis of essential HTN was based on office BP recordings with 2 or more values of systolic BP more than or equal to 140 mmHg and/or diastolic BP more than or equal to 90 mmHg. Ambulatory BP monitoring (ABPM) was also performed to exclude the white coat HTN and conclude upon a more reliable association between Vitamin D levels and true hypertensive. BP was measured by a trained physician after 5 min of rest in the right arm in sitting position with a mercury sphygmomanometer. It was ensured that the patient must not have taken either tea or coffee within a period of 30 min before measurement.

Collection of blood sample

The samples were taken between 06:00 am and 10:00 am after a 12-h fasting. The serum or plasma was separated within 3–60 min of collection, and the aliquots were subjected to the analyzer.

Method of estimation of serum 25-hydroxyvitamin D

Concentrations of 25-hydroxyvitamin D (25(OH) D) were measured in serum samples using a Diasorin Liaison analyzer. The method that this machine uses is chemiluminescence immunosorbent assay. Vitamin D levels were categorized according to Hollick's classification [4] [Table 1].
Table 1: Classification of Vitamin D levels

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Statistical tools employed

The statistical analysis was done using SPSS (SPSS Inc., Chicago, IL, USA) version 16.0 statistical analysis software. The values were represented in number (%) and mean ± standard deviation. Chi-square test was used to see the association between two groups. ANOVA test was used to compare the within group and between group variances among the study groups. Student's t-test was used to test the significance of two means. For all cases, in which a statistical test was conducted, a P < 0.05 was considered to indicate a significant difference.


  Results Top


Our study comprised of 102 participants of essential HTN and 99 age-matched controls as previously described. The mean age of study population was 40.69 ± 8.28 years, with maximum patients being in the age group of >40 years. Among cases, 52.9% were male and 47% were female. There was no statistically significant between the case and control group in relation to age and gender distribution (P = 0.06 and P = 0.07). The mean level of 25(OH) D among cases was 15.15 ± 12.51 ng/ml, while among controls, the corresponding value was 33.59 ± 16.69 ng/ml [Table 2] and [Figure 2]. The difference was statistically significant (P = 0.0001).
Table 2: Comparison of 25-OH Vitamin D level between cases and controls

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Figure 2: Comparison of mean 25-hydroxyvitamin D level between cases and controls (in ng/ml)

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We further stratified patients according to their levels of Vitamin D. Among cases, 80.4% were Vitamin D deficient and 9.8% had insufficient levels of Vitamin D. Among controls, 16.2% each had Vitamin D deficiency and insufficiency [Table 3]. Association of Vitamin D levels was found to be significant with systolic BP (P = 0.02) but same was not true for diastolic BP [Table 4] and [Figure 3]. However, the receiver operating characteristic curve revealed a low predictive value of 25(OH) D levels for predicting HTN with low sensitivity and specificity [Figure 4].
Table 3: Distribution of Vitamin D deficiency

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Table 4: Association of Vitamin D deficiency with blood pressure

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Figure 3: Association of Vitamin D deficiency with blood pressure levels

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Figure 4: Receiver operating characteristics curve showing predictive value of 25-hydroxyvitamin D levels for hypertension (cases). Diagonal segments are produced by ties

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  Discussion Top


Vitamin D deficiency is an emerging risk factor for multiple comorbidities worldwide, despite abundant sunshine. So far, various studies have been done to prove an association between Vitamin D deficiency and HTN. This relationship has already been established in the Western population but needs further validation in the Indian scenario.[14],[15],[16]

Our study population consisted of 102 cases of HTN and 99 healthy controls. There were no significant differences between the groups and both were comparable regarding age and sex distribution. The mean 25(OH) D levels in hypertensive participants were significantly lower than their normal counterparts. Low Vitamin D levels were present in 56% males and 41% females among cases while in 41% males and 59% females among controls. In our total study population, overall 61.69% had deficiency or insufficiency of Vitamin D. A prior study in Indian participants had also revealed high prevalence (80%) of Vitamin D deficiency.[17] In this study, however, the mean 25(OH) D levels for hypertensive were found to be 17.07 ± 9.72 ng/ml, while in the normotensive controls, it was 22 ± 10 ng/ml (P = 0.027). The lower level of Vitamin D in controls may be because of inclusion of older age groups as no limits were set for age criteria. There are few studies which did not find any significant association between 25(OH) D and BP because of higher Vitamin D levels in the general population.[16]

In our study, the levels of Vitamin D were compared with both systolic and diastolic BP. The association with systolic BP was found to be statistically significant while the same turned out to be inconclusive with diastolic BP (P = 0.49). The mean systolic BP associated with Vitamin D deficiency (<20 ng/ml) was 154.1 ± 12.55 mmHg while that with Vitamin D insufficiency (20–30 ng/ml) was 145.6 ± 7.82 mmHg. Thus, an approximate linear relation can be concluded from this observation; however, owing to a low sample size, this observation is only hypothesis generating.

The inverse association of systolic BP with 25(OH) D levels has not been studied in Indian population before but has been proven in Western studies.[18],[19] In our study, hypertensive patients were mainly diagnosed on the basis of office BP recordings. However, ABPM of few cases was done to conclude on any association, if existing, between Vitamin D levels and diurnal variation in BPs and comment upon any relation between Vitamin D deficiency and loss of normal nocturnal dipping phenomenon. Unfortunately, only 35 cases turned up for ABPM, out of which 15 cases were found to be white coat HTN. Among remaining 20 cases, all had a Vitamin D levels <30 ng/ml with no loss of normal dipping with exception of one. The inclusion of ABPM added to the strength of association between Vitamin D deficiency and HTN.

Limitations

The study being a case–control cross-sectional study is ineffective to establish causation. An interventional prospective study on this subject would be more appropriate. Furthermore, we need a larger sample size to obtain results which can be extrapolated to general population.


  Conclusion Top


Vitamin D deficiency is significantly more prevalent in hypertensive population compared to their age- and sex-matched control population. The low Vitamin D levels show a trend toward correlation with higher systolic BP values. However, larger randomized studies are needed to confirm these potential findings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Cohen JD. Hypertension epidemiology and economic burden: Refining risk assessment to lower costs. Manag Care 2009;18:51-8.  Back to cited text no. 1
    
2.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr., et al. 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.  Back to cited text no. 2
    
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Holick MF. The Vitamin D epidemic and its health consequences. J Nutr 2005;135:2739S-48S.  Back to cited text no. 3
    
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Holick MF. High prevalence of Vitamin D inadequacy and implications for health. Mayo Clin Proc 2006;81:353-73.  Back to cited text no. 4
    
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Melamed ML, Michos ED, Post W, Astor B. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med 2008;168:1629-37.  Back to cited text no. 5
    
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Li YC. Molecular mechanism of Vitamin D in the cardiovascular system. J Investig Med 2011;59:868-71.  Back to cited text no. 6
    
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Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: Lessons from Vitamin D receptor null mice. Endocr Rev 2008;29:726-76.  Back to cited text no. 7
    
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Pilz S, Tomaschitz A, Drechsler C, Dekker JM, März W. Vitamin D deficiency and myocardial diseases. Mol Nutr Food Res 2010;54:1103-13.  Back to cited text no. 8
    
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Valdivielso JM, Fernandez E. Vitamin D receptor polymorphisms and diseases. Clin Chim Acta 2006;371:1-12.  Back to cited text no. 9
    
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Harinarayan CV, Joshi SR. Vitamin D status in India – Its implications and remedial measures. J Assoc Physicians India 2009;57:40-8.  Back to cited text no. 10
    
11.
Forman JP, Curhan GC, Taylor EN. Plasma 25-hydroxyvitamin D levels and risk of incident hypertension among young women. Hypertension 2008;52:828-32.  Back to cited text no. 11
    
12.
Martins D, Wolf M, Pan D, Zadshir A, Tareen N, Thadhani R, et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: Data from the Third National Health and Nutrition Examination Survey. Arch Intern Med 2007;167:1159-65.  Back to cited text no. 12
    
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Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, ethnicity, and blood pressure in the Third National Health and Nutrition Examination Survey. Am J Hypertens 2007;20:713-9.  Back to cited text no. 13
    
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Burgaz A, Orsini N, Larsson SC, Wolk A. Blood 25-hydroxyvitamin D concentration and hypertension: A meta-analysis. J Hypertens 2011;29:636-45.  Back to cited text no. 14
    
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Vimaleswaran KS, Cavadino A, Berry DJ; LifeLines Cohort Study investigators, Jorde R, Dieffenbach AK, Lu C, et al. Association of Vitamin D status with arterial blood pressure and hypertension risk: A mendelian randomisation study. Lancet Diabetes Endocrinol 2014;2:719-29.  Back to cited text no. 15
    
16.
Scragg R, Wishart J, Stewart A, Ofanoa M, Kerse N, Dyall L, et al. No effect of ultraviolet radiation on blood pressure and other cardiovascular risk factors. J Hypertens 2011;29:1749-56.  Back to cited text no. 16
    
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Velayudhan G, Sasidharan PK. Vitamin D status in hypertension. Am Int J Res Form Appl Nat Sci 2014;8:28-30.  Back to cited text no. 17
    
18.
Smotkin-Tangorra M, Purushothaman R, Gupta A, Nejati G, Anhalt H, Ten S. Prevalence of Vitamin D insufficiency in obese children and adolescents. J Pediatr Endocrinol Metab 2007;20:817-23.  Back to cited text no. 18
    
19.
Gannagé-Yared MH, Chedid R, Khalife S, Azzi E, Zoghbi F, Halaby G. Vitamin D in relation to metabolic risk factors, insulin sensitivity and adiponectin in a young Middle-Eastern population. Eur J Endocrinol 2009;160:965-71.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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