Transcript
International Journal of General Medicine
and Pharmacy (IJGMP)
ISSN(P): 2319-3999; ISSN(E): 2319-4006
Vol. 4, Issue 1, Jan 2015, 61-66
© IASET
A STUDY ON PLASMA 25-HYDROXY VITAMIN D LEVELS AS A RISK FACTOR IN
PRIMARY HYPERTENSION
M. NARAYANASWAMY, NAGAPPA H. HANDARGAL & RAVINANDANAGOWDA
Department of Medicine, Bangalore Medical College and Research Institute, Fort Road, Bangalore, India
ABSTRACT
Aims & Objectives: To determine the serum vitamin D levels in primary hypertensive patients.
Methods: 30 patients who are primary hypertensives will selected and their vitamin D Levels will measured and their
vitamin D levels will be compared to age and sex matched non hypertensive controls.
Results: It is seen from this study that serum vitamin D levels were lower in hypertensive patients when compared to non
hypertensive controls. The levels of vitamin D also inversely correlated to age, duration of hypertension and systolic and
diastolic blood pressure.
Conclusion: 30 hypertensive cases and 30 non hypertensive controls attending to out patient department of hospitals
attached to Bangalore medical college and research center were investigated for evaluation of vitamin D status. Based on
the observations made in them the following conclusions were drawn: The hypertensive patients had lower levels of
vitamin D with vitamin D status of deficiency in 50% of the cases and insufficiency ion 43.3% of the cases and normal
levels in 6.7% of the cases Non hypertensive controls showed vitamin D status of normal in 66.7% of controls and
insufficiency in 33.3% of the controls without deficiency. Age of the cases, duration of hypertension, systolic blood
pressure and diastolic blood pressure inversely correlated to vitamin D levels. Body mass index, diet of the patient, alcohol
consumption, number of anti-hypertensive drugs, drug compliance, family history of Hypertension and fundus status did
not correlate to vitamin D levels. Vitamin D is an independent risk factor that is associated with primary or essential
hypertension.
KEYWORDS: Vitamin D Levels, Hypertensive, Anti-Hypertensive Drugs, Blood Pressure
INTRODUCTION
Vitamin D is a steroid molecule and lipid soluble vitamin, mainly produced by the skin and absorbed from the gut
in diet that regulates the expression of a large number of genes. Its main role is in the control of bone metabolism and
calcium and phosphorus homeostasis. Vitamin D deficiency has been traditionally associated with poor bone growth and
development and development of rickets in children and osteoporosis in adults and in recent years emphasis has been given
to the role of vitamin D in areas beyond those traditionally known. During the last two decades new research and data is
showing that vitamin D could be a risk factor in many chronic diseases like hypertension, diabetes mellitus, dyslipidemia,
cardiovascular disease, some cancers, auto immune disease and tuberculosis. Vitamin D deficiency has been traditionally
associated with poor bone growth and development and development of rickets in children and osteoporosis in adults and
in recent years emphasis has been given to the role of vitamin D in areas beyond those traditionally known. During the last
two decades new research and data is showing that vitamin D could be a risk factor in many chronic diseases like
hypertension, diabetes mellitus, dyslipidemia, cardiovascular disease, some cancers, auto immune disease and tuberculosis.
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M. Narayanaswamy, Nagappa H. Handargal & Ravinandanagowda
Many epidemiological studies have demonstrated an inverses relationship between vitamin D levels and blood pressure.
Studies in India have demonstrated that the level of vitamin D in the population is low and there is high prevalence of
chronic diseases like hypertension, diabetes, cardiovascular disease. To determine the serum 25-hydroxy vitamin D levels
in patients with primary hypertension. This study attempts to demonstrate an inverse co-relation between vitamin D.
MATERIALS AND METHODS
The study was conducted on patients attending the outpatient department (OPD) of hospitals attached to
Bangalore medical college and research Institute (BMC&RI) i.e. Victoria hospital and Bowring and Lady Curzon
hospitals. The study was conducted on 30 hypertensive cases and 30 age and sex matched controls. Informed written
consent was obtained from cases and controls for participation in the study and for conduction of investigations. The study
was conducted between the period of October 2010 and September 2012
Inclusion Criteria
Primary hypertension and age group between 18-65 years were considered
Exclusion Criteria
The Following Exclusion Criteria Were Considered for the Study - Secondary hypertension, Cerebrovascular
disease, Cardiovascular disease, Diabetes mellitus, Dyslipidemia, Chronic kidney disease, Chronic liver disease, Smoker,
Anti epileptic drugs, steroids, Rifampicin, ART, cholestyramine, Antacids, Orlistat and Osteoporosis
Method of Collection of Data
Complete
clinical
history
and
physical
examination
of
60
patients
were
done,
the
following
investigations- Electrocardiogram, Random blood sugar 3) Serum vitamin D2 level, Blood urea, Serum creatinine,
Ultrasound of the abdomen and renal Doppler
STATISTICAL METHODS
Descriptive and inferential statistical analysis has been carried out in the present study. Results on continuous
measurements are presented on Mean ± SD (Min-Max) and results on categorical measurements are presented in Number
(%). Significance is assessed at 5 % level of significance. The following assumptions on data is made, Assumptions:
1. Dependent variables should be normally distributed, 2. Samples drawn from the population should be random,
Institutional ethical clearance obtained as per the norms.
RESULTS
A cross sectional study done on 30 hypertensive cases and 30nonhypertensive controls is undertaken to know the
vitamin D status in them. The baseline characteristics of the study population were similar, out 30 of cases 22 were males
and 8 were females and out of 30 controls 23 were males and 7 females. The majority of the cases were from the 41 to 50
age group followed by the 51 to 60 age group and the control group majority of the population were from 31 to 40 age
group followed by 51 to 60 age group. There no patients of less than 30 years in both the groups and there were 2 patients
above 60 in case group Among the hypertensives 11 of them were diagnosed to be hypertensive less than or equal to year
from the time of study, 14 were diagnosed between 2 to 5 years, 4 of them were diagnosed between 5 to 10 years and only
1 had long standing hypertension of greater than 10 years. All of them were on anti-hypertensive medications with 25 of
Impact Factor (JCC): 2.9545
Index Copernicus Value (ICV): 3.0
A Study on Plasma 25-Hydroxy Vitamin D Levels as a Risk Factor in Primary Hypertension
63
them on single drug regimen and 5 of them on combination regimen Most of the patients were on calcium channel blockers
followed by almost equal number of patients on angiotensin converting enzyme inhibitors, angiotensin receptor blockers
and beta blockers. Out of the 30 hypertensive who were on treatment 16 of them were having good compliance and were
not missing any of their doses and 10 of them were missing 1 dose a week and 4 of them were missing more than 1 dose
per week Among the 30 cases 11 of them had family history of hypertension in their parents or siblings and among the 30
controls 15 of them had family history of hypertension. Majority of cases and controls were of mixed diet at 27 and
26respectively and only 3 and 4 respectively were vegetarians. In both the groups 20 of them did not consume alcohol and
8 in case group and 6 control group were occasional alcohol consumers and 2 in case group and 4 in control group were
regular alcohol consumers taking alcohol daily The body mass index (BMI) of case group were predominantly in the 21
to25.9 range and in the control group also were in the same range. 2 each in case group and control group were overweight,
there were no obese subjects in both the groups and there were 2 underweight subjects in the control group. All patients
had normal cardiovascular examination. All subjects had a normal abdominal ultrasound and normal renal Doppler study.
All patients had normal range of random blood sugar, blood urea and serum creatinine The systolic blood pressure most of
the patients were between 121 to 130 mmof Hg, there were no patients with SBP more than 160 or less than 120 mm ofHg.
The Diastolic blood pressure of most of the patients was between 81to 90 mm of Hg, there were no patients with DBP
more than 100 mm of Hg. The fundus of most of the patients were normal with 5 patients had grade 1fundus, 4 had grade 2
fundus, 2 patients had grade 3 fundus and none of the patients had grade 4 fundus. The ECG of 8 hypertensives showed left
ventricular hypertrophy and rest of them had a normal ECG. The mean vitamin D in cases was 19.91 and the median
vitamin D in cases was 20. The mean Vitamin D in controls was 32.22 and the median vitamin D in controls was 31.6. The
highest vitamin D level in cases was 37.56 and the lowest vitamin D level in cases was 3.94. The highest vitamin D level in
controls was 39.41 and the lowest level in controls was 24.54 Vitamin D deficiency was seen in 15(50%) of the cases and
in 0 of controls, Vitamin D insufficiency was seen in 13(43.3%) of the cases and in 10(33.3%) of controls and normal
levels was seen in 2(6.7%) of cases and in 20(66.7%) of controls. There was significant inverse correlation between
vitamin D and hypertension (p < 0.001). Vitamin D deficiency and insufficiency was seen in most of the hypertensive
cases. Among the controls none of the subjects showed deficiency most of the subjects had normal levels of vitamin Age
showed an inverse correlation with Vitamin D (p – 0.023), with increasing age there was tendency towards lower levels of
vitamin D in both the case and control groups. Systolic blood pressure increased with lower levels of vitamin D(p – 0.045).
Diastolic blood pressure also increased with lower levels of vitamin D (p– 0.026). Vitamin D levels tended to be lower in
hypertensive cases with longer duration of hypertension (p – 0.032). BMI did not show any significant correlation with
hypertension (p – 0.347). Other characteristics and parameters like diet, alcohol consumption, and number of drugs in
anti-hypertensive therapy, compliance to therapy, family history of hypertension, fundus status, ECG and random blood
sugar levels did not any significant correlation with the levels of vitamin D.
DISCUSSIONS
Essential or primary hypertension is a major and significant risk factor for cardiovascular disease. The incidence
of hypertension is increasing and there is large hypertensive population at risk for cardiovascular morbidity and mortality.
Recent studies show that vitamin D plays a key role in influencing various parameters that regulate high blood pressure via
various pathways including endothelial cell function, proliferation of vascular smooth muscle cells, regulation of
renin-angiotensin pathway and in regulation of blood pressure via increased intracellular calcium leading to decreased
renin activity[13] Vitamin D is a proximal inhibitor of RAS and inhibition of 1,25(OH)vitamin D synthesis results in an
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M. Narayanaswamy, Nagappa H. Handargal & Ravinandanagowda
increase in renin expression and increase in 1,25(OH)vitamin synthesis results in renin suppression[9]. More recently a
study [53] showed that both25 (OH)D and 1,25(OH)D were inversely associated with plasma renin and angiotensin II
concentrations. Vitamin D plays a role in regulating vascular tone by influencing the concentration of calcium in vascular
smooth muscle cells. Intracellular calcium accumulation results in an inhibition of renin secretion in juxta glomerular cells.
In addition to potential effects on the RAS and regulation of vascular smooth muscle contractility, vitamin D has also been
hypothesized have other effects on vascular endothelium and smooth muscle. It is a vascular protective agent, it reduces
the deleterious effect of advanced glycation end products on the endothelium, improves activity of the NO system, and
reduces inflammatory and atherosclerotic parameters. 1,25 (OH)vitamin D has also been implicated in the growth of
vascularmyocytes and has been shown to enhance prostacyclin production in vascular smooth muscle cells. In this study
there was a significant correlation between low levels of vitamin D and hypertension. There was also a significant
correlation between age, systolic blood pressure and diastolic blood pressure and duration of hypertension.
Epidemiological observations have shown incidence of hypertension increases with higher latitude, and winter months
blood pressure recordings show higher recording of blood pressure and for each 100 north or south shift of the equator BP
increases by 2.5mm of Hg and prevalence of hypertension increases by 2.5%. Initial retrospective observational studies
have shown a significant inverse correlation between vitamin D and and systolic blood pressure[14,15,16]. Duprez et
al[14]in a study conducted on 25 hypertensive patients demonstrated that vitamin D levels inversely correlated with
systolic blood pressure. In a study conducted by Kristal-Boneh E et al on normotensive men showed a similar correlation
between vitamin Dlevels and systolic blood pressure .The third national health and nutrition examination survey
(NHANES 3) study [17] was a large cross-sectional study involving non-institutionalized population aged more 20 years in
a total population of 12644 patients and was used to evaluate the relationship between serum 25(OH)vitamin D and
hypertension. The mean blood pressure varied inversely with serum 25(OH) vitamin D levels, with the association
remaining significant after adjustment for age, gender, race, ethnicity and physical activity. A study involving 613 men
from health professionals follow up study [10] and 1198women from nurses health study [35] found that lower serum
25(OH)vitamin D levels of15/ng/mL (<37nmol/L) increased the relative risk for hypertension by 6.13 in men and 2.67 in
women when compared to vitamin D sufficient population (>75nmol/L). Another prospective study in 1448 women
demonstrated a 2.21 fold increase in incident hypertension in hypovitaminosis D group versus control groups [18]. A
crosssectionalstudy [19] conducted on 4125 subjects showed a significant association between hypovitaminosis D and
hypertension. In a randomized controlled trial on 148 elderly women demonstrated that a modest amounts of vitamin D
(400IU) with calcium given over 8 week period significantly reduced systolic blood pressure (SBP) by 9% [11].
The largest trial to date the women`s health initiative (WHI)[20] done on a population of non hypertensive at baseline
failed to show any significant impact of a small dose of vitamin D (400IU)with calcium 1000mg/day on systolic blood
pressure or diastolic blood pressure after mean follow up of 7 years in post menopausal women. These studies demonstrate
that vitamin D supplementation may play a key role in controlling high blood pressure however the current evidence is
weak and further randomized trials with larger populations may be required
CONCLUSIONS
30 hypertensive cases and 30 non hypertensive controls attending to outpatient department of hospitals attached to
Bangalore medical college and research center were investigated for evaluation of vitamin D status. Based on the
observations made in them the following conclusions were drawn: 30 hypertensive cases and 30 non hypertensive controls
attending to outpatient department of hospitals attached to Bangalore medical college and research center were investigated
Impact Factor (JCC): 2.9545
Index Copernicus Value (ICV): 3.0
65
A Study on Plasma 25-Hydroxy Vitamin D Levels as a Risk Factor in Primary Hypertension
for evaluation of vitamin D status. Based on the observations made in them the following conclusions were drawn: on
hypertensive controls showed vitamin D status of normal in 66.7% of controls and insufficiency in 33.3% of the controls
without deficiency
Age of the cases, duration of hypertension, systolic blood pressure and diastolic blood pressure inversely
correlated to vitamin D levels. Body mass index, diet of the patient, alcohol consumption, number of antihypertensive
drugs, drug compliance, family history of hypertension and fundus status did not correlate to vitamin D levels. Vitamin D
is an independent risk factor that is associated with primary or essential hypertension.
ACKNOWLEDGEMENTS
The author acknowledge the Professor and Head, Department of Medicine, Dean cum Director, BMCRI,
Bangalore
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