Vitamin D and High Blood Pressure

: Introduction: Cardiovascular diseases are the main cause of death in the world, and some of these diseases can be controlled or avoided with a healthier lifestyle. These diseases are often associated with the emergence of other diseases such as diabetes mellitus, obesity, high cholesterol levels and high blood pressure. Research has shown that vitamin D deficiency can be a factor that also helps in the appearance of these diseases, since if the serum levels of vitamin D are adequate, it can help in the control and prevention of these diseases. Objectives: To evaluate the relationship between vitamin D and cardiovascular diseases, specifically systemic arterial hypertension and its effects. Methods: A systematic review was carried out by searching for original articles in scientific databases: Pubmed, Science Direct, Lilacs and Scielo in English and Portuguese. Results: No conclusive data were found for the indication of vitamin D supplementation in the treatment of systemic arterial hypertension, due to its lack of efficiency so far, requiring further research to better clarify the subject. Conclusion: The results obtained do not present conclusive data for the indication of vitamin D supplementation in the treatment of systemic arterial hypertension, due to its lack of efficiency up to the present moment, more research is necessary for a better clarification on the subject.


Introduction
Cardiovascular diseases are the main causes of death in the Brazilian population 1,2 , and are responsible for at least 20% of deaths in our population over 30 years of age³.Recent studies have shown an association between vitamin D deficiency and an increased risk of cardiovascular complications 4 , especially hypertension 5,6 .Hypertension is an important risk factor for other cardiovascular diseases and is a popular health problem worldwide [7][8][9][10] where some research confirms how vitamin D supplementation is associated with the reduction of important markers of cardiovascular risk in inflammation and hypertrophy left ventricular 11 , as well as associated with several other biological processes, including blood pressure modulation.Among the proposed mechanistic pathways for the development of high blood pressure, studies show the relationship between vitamin D and the inhibition of the renin-angiotensin-aldosterone system 12 .According to several studies that evaluated the effects of vitamin D supplementation on blood pressure results, what was observed is the inconsistency in relation to their results, since there are studies that aim to evaluate the potential causal relevance of vitamin deficiency D and high blood pressure, updating the evidence on the effect of vitamin D supplementation on circulating 25(OH)D levels, as well as its impact on systolic and diastolic blood pressure.In addition, some researchers also present evidence of a genetic association of 25(OH)D and blood pressure levels 13 .Currently, trials of vitamin D supplementation and heart rate have shown mixed results.A meta-analysis of 11 studies concluded that vitamin D was beneficial in people with a high heart rate (defined as >140/90 mm Hg), but not in people whose arterial compression was normal 14 .However, another metaanalysis of 10 trials found that vitamin D supplementation caused a non-significant reduction in systolic blood pressure (-1.9 mm; 95% confidence interval, -4.2 to 0.4), although had no effect on diastolic pressure 15 .Given this, strategies aimed at improving the management of people already affected by cardiovascular disease should be an integral component of a comprehensive approach to the prevention and control of cardiovascular disease.Hypertension is a health problem worldwide due to increased longevity and the prevalence of contributing factors such as obesity, physical inactivity and unhealthy diet 16,17 .Its current prevalence in many developing countries, particularly in urban societies, is already as high as that observed in developed countries 18 , where data estimate that hypertension is responsible for 7.1 million www.cmhrj.compremature deaths and 4.5% of the disease burden.(64 million disability-adjusted life years) worldwide 19 .With this, this study aimed to evaluate the relationship of vitamin D in relation to the treatment of cardiovascular diseases, supplementation and the consequence of deficiency.

Methodology
To carry out this systematic review, a search was carried out in the databases: LILACS, MEDLINE and SCIENCE DIRECT using Boolean operators in the keywords in English: Vitamin D OR Cholecalciferol AND Arterial hypertension.As inclusion criteria, only original articles were used, which used vitamin D supplementation for the treatment of hypertension, while the exclusion criteria were articles with animal studies, as well as articles prior to the year 2013, setting the maximum period to be studied for 10 years and articles that did not present data on supplementation dosage and/or sample number.For the inclusion of the articles, all the articles in the databases that contained the keywords were chosen.After initial analysis, the most suitable works were separated, which were used for this review.Applied the inclusion and exclusion criteria, articles in the English language were selected for review.The analysis of the results was tabulated in an Excel spreadsheet and the following variables were compared: Country/population studied, N value, Author-year, blood pressure, BMI and age range of the sample, study objectives.

Results
After defining the inclusion and exclusion criteria, 10 articles were eligible, involving 6 countries, with 1 Asian, 4 American, 3 European and 2 Oceania studies.
In total, 2,461 individuals were involved as samples in the studies and received vitamin D supplementation, with tests to measure blood pressure.The largest sample group was the study by Arora et al. 20 with 534 people, carried out in the United States, and the smallest group was the article by Chai et al. 21ith 92 people, also carried out in the United States.All studies used a randomized double-blind, placebo-controlled trial, with two studies using 4 sample groups, while the 22,23 other 8 using a test group and a placebo group.The studies did not use the same treatment group: (a) four studies used patients with some type of hypertension 20,[24][25][26] ; (b) three studies were performed with healthy people 23,27,28 and; (c) the other three studies used patients with diabetes 22 or with colorectal adenoma 21 and postmenopausal women 29 .In all studies, it was observed that the people who participated were mostly elderly, although there were also adults, with an average age ranging from 38 years to 77 years.Study time ranged from 8 weeks to 1.5 years and could have occurred continuously or with time intervals.The dosage used in the studies varied from 400IU to 200,000IU of vitamin D to verify which dosage could have an effect.Some studies presented the body mass index to help with the study parameters, although four did not do so 20,23,24,26 .
For the study to be carried out on the efficiency of vitamin D, measurements of the blood pressure of the participants were carried out before the start of supplementation and after supplementation.In addition, some studies carried out measurements between the testing period, but the results shown in Table 1 only show the results acquired after the treatment was completed, with blood pressure measurements ranging from 122.1 mmHg to 137.7 mmHg for systolic and, 78.4 mmHg to 81.8 mmHg for the diastolic after supplementation

Discussion
Analyzing the data, we observed that the groups used for sampling are very heterogeneous, with no classification of the groups by specific diseases, having been used from patients with type 2 diabetes, patients with colorectal adenoma and postmenopausal women, with the possibility of a nonconformity of the final data.Another factor analyzed was the age of the patients.In this regard, we observed that the vast majority were elderly, with a mean age of 77 years, although adults were also used in the studies.In view of this, these data may also contribute to an inconsistency in the results, due to the fact that the elderly are more prone to nutritional deficiency due to difficulty in ingestion, chewing and digestion, altering the absorption of the vitamin.
When analyzing the duration of the studies, we observed that they ranged from 8 weeks to 1.5 years.According to studies by Forman et al. 25 , this is necessary to prevent exposure to sunlight from influencing the results, since the main way of absorbing vitamin D is through skin production during exposure to the sun, which is why the study was carried out in two winters of consecutive years.On the other hand, other studies considered that since in winter in North American countries the sun appears with less intensity, this factor should not be taken into account, to the point of triggering interference in the results 23,24 .
Of the analyzed studies, six of them presented the BMI of the participants to make it possible to analyze the influence of having arterial hypertension, and thus, to help in the analysis of the results.Therefore, when analyzing these data, we found that all participants had an average BMI greater than 27.1 kg/m², making it possible to classify them as obese and overweight, which according to Forman et al. 25 makes it possible to state that these patients have risk factors for cardiovascular disease, such as hypertension.
Another data analyzed was in relation to the dosage of Vitamin D used in the studies, where we observed a dosage ranging from 400UI to 200,000UI per day.According to Henry et al. 9 , the daily recommendation for vitamin D is 600UI per day for adults and 800UI for the elderly.In the analyzed studies, we observed that most of them used a higher dosage than the recommended one, since the intention was to verify the efficiency of the higher dosage of the vitamin, and if in higher doses the effect would be different.This factor was not confirmed even with the large variation in the value of the doses.When analyzing the results, we observed that when comparing the values obtained by measuring blood pressure at the beginning of the treatment with the values obtained at the end of the treatment, it was verified that the study that presented the  23 , who were able to prove that the administration of doses of Vitamin D act in such a way as to favor blood pressure, and thus, reduce the probability of cardiovascular diseases.According to Sluyter et al. 23 , their results showed a reduction in systolic blood pressure from 137.7mmHg to 125.5mmHg (-12.2mmHg) after treatment, with diastolic blood pressure falling from 78.4 to 72.8 (-5.6mmHg).However, other studies did not present such significant data, showing reductions in systolic blood pressure of 0.8 mmHg and diastolic blood pressure of 1.1 mmHg.In addition, some studies have even shown the opposite, with results showing an increase in systolic blood pressure of up to 1.9 mmHg and diastolic blood pressure of up to 1.6mmHg.And there were also studies by Witham et al 25 and Chai et al. 21that showed no change in diastolic pressure.
All studies used the same randomized, double-blind, placebocontrolled study method, with two studies using four study groups to administer vitamin D with calcium 22 or to administer more than one dose of vitamin D 23 .The studies did not take into account the patients' diet and the practice of physical activities, factors that can positively or negatively influence the results, since patients who use a lot of sodium in their diet can blood pressure values even with medication use.In addition, we also observed that not all studies showed whether the patients were using medication to control blood pressure directly with antihypertensive drugs or with the use of medication that helped in the treatment, such as diuretics.
From the general balance analyzed in all the studies observed, we verified that the alterations are more visible in the systolic arterial pressure, presenting a small decrease, while in the diastolic arterial pressure, what was observed was a very low or null alteration.These results may have been obtained by differences in the studies or by the inefficiency in the treatment of vitamin D supplementation in relation to arterial hypertension.
If there is a relationship between vitamin D and arterial hypertension, it is still necessary to establish the mechanism that makes the relationship through more randomized clinical studies with larger sample groups and with longer carefully planned follow-up periods.Therefore, we can say that the results did not reach the specific objectives of this review, as we did not find a dose capable of providing some relationship between vitamin D and arterial hypertension.

Conclusion
The results obtained from this systematic review do not present conclusive data for the indication of vitamin D supplementation in the treatment of systemic arterial hypertension, due to its lack of efficiency up to the present moment, more research is necessary for a better clarification on the subject.