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HTN: Vitamins (2015)

Citation:

Bernini G, Carrara D, Bacca A, Carli V, Virdis A, Rugani I, Duranti E, Ghiadoni L, Bernini M, Taddei S. Effect of acute and chronic vitamin D administration on systemic renin angiotensin system in essential hypertensives and controls. J Endocrinol Invest. 2013; 36: 216-220.

PubMed ID: 23645099
 
Study Design:
Non-Randomized Controlled Trial
Class:
C - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
To investigate systemic renin-angiontensin system (RAS) in essential hypertension and controls after short-term calcitriol administration and in patients with essential hypertension after long-term cholecalciferol therapy.
Inclusion Criteria:
Essential hypertension or normotension.
Exclusion Criteria:
  • Group A (essential hypertensive patients and normotensive controls):
    • Estimated GFR less than 60ml per minute per 1.73m2
    • Hypercalcemia
    • Hepatic insufficiency, chronic granulomatosis
    • BMI higher than 30kg/m2
    • Diabetes
    • Intake of any anti-hypertensive drugs or other drugs affecting calcium-phosphorus metabolism.
  • Group B (essential hypertensive patients):
    • Criteria in Group A
    • Use of angiotensin II receptor antagonists.
Description of Study Protocol:

Recruitment

  • Group A: Ten consecutive essential hypertensive (EH) patients and 10 normotensive controls (NC) recruited from Hypertension Center
  • Group B: A total of 18 consecutive essential hypertensive patients recruited from Hypertension Center.

Design

  • Group A: Non-randomized controlled trial
  • Group B: Non-controlled trial.

Blinding Used

Implied with measurements.

Intervention

  • Group A (non-randomized controlled trial): Provided 1,25-(OH)2D for seven days at 0.25mcg twice daily; EH provided approximately 3g salt diet per day; NC did not restrict salt
  • Group B (non-controlled trial): Provided 300,000 IU 25(OH)D at time zero as single bolus. Received angiotensin II receptor antagonists (telmisartan 80mg once a day) starting from 15 days prior to study and throughout experiment. No salt restriction.

Statistical Analysis

  • Unpaired and paired student's T-test or one-way analysis of variance
  • Linear correlation analysis to assess relationship between individual variables.
Data Collection Summary:

Timing of Measurements

  • Group A:
    • Baseline
    • One week after baseline.
  • Group B:
    • At 15 days before baseline
    • Baseline
    • Four  weeks
    • Eight weeks.

Dependent Variables

  • Blood pressure
  • Plasma creatinine, calcium, phosphorus, magnesium, 25(OH)D, 1,25(OH)2D and PTH
  • PRA, plasma active renin, aldosterone, angiotensin II
  • A 24-hour urinary creatinine, albumin, sodium.

Independent Variables

  • Group A (non-randomized controlled trial): Provided 1,25-(OH)2D for seven days at 0.25mcg twice daily; EH provided approximately 3g salt diet per day; NC did not restrict salt
  • Group B (non-controlled trial): Provided 300,000 IU 25(OH)D at time zero as single bolus. Received angiotensin II receptor antagonists (telmisartan 80mg once a day) starting from 15 days prior to study and throughout experiment. No salt restriction was noted.
Description of Actual Data Sample:

Initial N

  • Group A: N=10 essential hypertensives (EH) (five females, 43.0±11.7 years) and 10 normotensive controls (NC) (six females, 41.2±4.4 years)
  • Group B: N=18 essential hypertensives.

Age

Aged 41 years to 43 years.

Anthropometrics
  • Group A:
    • BMI (kg/m2)
    • EH=26.4±1.0
    • NC=24.4±1.3.
    • SBP:
      • EH=145.0±6.1
      • NC=107.0±5.5
      • P<0.0001.
    • DBP:
      • EH=90.0±4.5
      • NC=65.0±3.5
      • P<0.05.
    • Plasma 25(OH)D (ng/ml):
      • EH=12.6±1.6
      • NC=20.1±2.5
      • P<0.02.
  • Group B:
    • BMI: Not given
    • SBP: 147.2±3.0 at time -15 baseline; 135.0±0.8 at time zero; P<0.01
    • DBP: 93..2±0.9 at time -15 baseline, 85.0±1.1 at time zero, P<0.05
    • Plasma 25(OH)D:14.9±1.4.

Location

Italy.

Summary of Results:

Key Findings

  • Group A:
    • No significant change in plasma 25(OH)D or 1,25(OH)2D in either group after calcitriol administration
    • No suppressive effect of calcitriol administration on PRA and active renin
    • No association between basal plasma 25(OH)D or 1,25(OH)D2 levels and BP levels, RAS components, or PTH values in analysis of the whole group
    • Decrease in SBP from 145.0±6.1mm Hg to 133.0±5.8mm Hg (P<0.05) and in DBP from 90.0±4mm Hg.5 to 81.6±4.5mm Hg (P<0.05) attributed to hospitalization and change in urinary sodium from 131.1±23.7mEq to 87.5±18.6mEq per 24 hours (P<0.02) following a low-salt diet.
  • Group B:
    • Significant increases in plasma 25(OH)D from 14.9±1.4ng per ml to 27.0±2.3ng per ml (P<0.001), and in 1,25(OH)D2 from 27.7±2.4pg per ml to 41.2±3.6pg per ml (P<0.05)
    • Between time -15 and time zero, prior to vitamin D administration, SBP decreased from 147.0±3.0mm Hg to 135.0±0.8mm Hg (P<0.01) and DBP decreased from 93.2±0.9mm Hg to 85.0±1.1mm Hg (P<0.05)
    • Between time zero and eight weeks, changes in SBP to 132.0±1.3mm Hg and in DBP to 79.0±1.4mm Hg were not significant.
Author Conclusion:
Vitamin D receptor activation was unable to influence circulating RAS activity.
Funding Source:
University/Hospital: University of Pisa, Department of Internal Medicine
Reviewer Comments:
Small numbers of subjects in groups. Authors note that they do not rule out that significant effects could be induced if a different type, dose and timing of administration of drugs were adopted, or if a more prolonged study were performed.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? ???
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? ???
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? ???
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? ???
  4.1. Were follow-up methods described and the same for all groups? No
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) ???
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? ???
  4.4. Were reasons for withdrawals similar across groups? ???
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? No
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? ???
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? ???
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? ???
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? ???
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? No
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? No
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes