HTN: Vitamins (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To examine the effect of acute (two grams po) and chronic (500mg per day for one month) ascorbic acid supplementation on conduit vessel endothelial dysfunction in patients with hypertension.
Inclusion Criteria:
  • Healthy persons with hypertension; HTN defined as a history of antihypertensive tx or untreated diastolic BP>90mm Hg on at least three occasions
  • Non-hypertensive healthy persons for controls.
Exclusion Criteria:
Hx of CAD, diabetes mellitus, uncontrolled HTN defined as diastolic BP>110mm Hg, congestive cardiac failure or use of antioxidant vitamins or estrogen replacement tx within one month.
Description of Study Protocol:

Recruitment

Subjects were recruited by advertisement.

Design

  • At baseline all subjects were fasted overnight, did not smoke for 24 hours, antihyperstensive medications were maintained before and during the study
  • Subjects were randomized to tx with one treatment of two grams of vitamin C or placebo followed by a blood sample and assessment of flow mediated brachial artery dilation, subjects were then treated with daily 500mg vitamin C or placebo for one month, treatment was doubly blinded
  • Compliance was measured by tablet count and plasma ascorbic acid levels
  • Non-hypertensive subjects were included as controls, thus there was a non-hypertensive and a hypertensive group receiving placebo and a non-hypertensive and a hypertensive group receiving vitamin C.

Blinding Used

Double-blind treatment.

Intervention

One-time dose of two grams vitamin C at baseline, followed by daily dose of 500mg vitamin C for one month.

Statistical Analysis
  • Baseline characteristics were compared using unpaired Sudent's T-test, chi-square test or Fisher's exact test
  • Effect of tx was compared by two-way repeated-measures ANOVA with post-hoc Student-Newman-Keuls
  • P< 0.05 was used to determine significance.
Data Collection Summary:

Timing of Measurements

At baseline, two hours after single dose of two grams vitamin C and one month later following intervention of daily placebo or 500mg vitamin C.

Dependent Variables

  • SBP and DBP measured after 10 minutes of rest in a semirecumbent position, the average of three meaures was used 
  • Resting arterial diameter
  • Reactive hyperemic flow 
  • Serum total and HDL-cholesterol, triglycerides and glucose measured using automated analyzer
  • LDL-cholesterol calculated using Friedewald formula
  • Plasma ascorbic acid concentrations.

Independent Variables

  • 500mg vitamin C per day for one month
  • Two grams vitamin C 
  • Compliance was measured by tablet count and plasma ascorbic acid levels.
Description of Actual Data Sample:
  • Initial N: 127 (82 healthy, 45 hypertensive)
  • Attrition (final N): 121 (82 healthy, 39 hypertensive; 40 and 20 females, respectively).

Age

  • 46±4 years (mean±SD) for healthy controls
  • 48±12 for hypertensive subjects
  • 49±13 for placebo groups
  • 48±11 for treatment groups.
Ethnicity
  • 33 African-Americans were healthy controls, 20 were hypertensive
  • 13 African-Americans were in placebo groups, seven were in treatment groups.

Other Relevant Demographics

None discussed.

Anthropometrics

  • BMI of 27.8±6.6 for healthy controls
  • 30.2±6.0 for hypertensives
  • 31.1±5.6 for placebo groups, 29.1±6.5 for treated groups
  • There was no difference between groups at baseline.

Location

Boston, MA.

Summary of Results:

Effect of Treatment on Brachial Artery, Hemodynamic Parameters and Blood Pressure

  Placebo
Baseline
Placebo
2 hour
Placebo
1 month
Vitamin C
Baseline
Vitamin C
2 hour
Vitamin C
1 month
Systolic BP mmHg 156±21 154±23 153±19 155±22 156±23 142±16*
Diastolic BP mmHg 88±14 86±13 84±14 87±9 84±12 79±8
Mean BPmmHg 110±15 109±15 107±13 110±12 108±13 100±8*
Resting arterial diam., mm 4.0±0.7 4.0±0.7 4.0±0.7 4.1±0.8 4.2±0.7 4.2±0.8
Reactive hyperemic flow, % change 568±295 593±319 455±259 591±256 581±224 696±354

*P<0.001 vs. baseline

Other Findings

No effect of vitamin C on measures of bioavailability of endothelium derived vasodilators (cGMP) or on urinary protaglandin F (a meaure of lipid peroxidation), or on serum total cholesterol, LDL-C, HDL-C, Tgs, or glucose was seen.

Author Conclusion:
  • A significant reduction in systolic and mean blood pressure was seen following one month of treatment with 500mg vitamin C
  • Conduit vessel endothelial dysfunction secondary to hypertension is not reversed by acute or chronic treatment with oral ascorbic acid.
Funding Source:
Government: NHLBI
University/Hospital: Boston University School of Medicine
Reviewer Comments:
  • BP data previously published in 1999
  • Results discussed in this publication focused on endothelial dysfunction and effect on brachial artery response
  • Current paper did not differentiate between changes in BP between controls and hypertensive subjects
  • No discussion of dietary control, exercise, or weight change during study
  • Only one month treatment period considered chronic.
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? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) No
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  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? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  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%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? N/A
  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? Yes
  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? Yes
  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? No
  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? No
  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? No
  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? ???
  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)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? No
  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