HTN: Vitamins (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To examine the relation of serum antioxidant vitamins, including vitamins A, C and E, alpha-carotene and beta-carotene to blood pressure.
Inclusion Criteria:
  • Civilian noninstitutionalized US population participating in NHANES III
  • At least 20 years old.

 

Exclusion Criteria:
  • Not non-Hispanic white, non-Hispanic black or Mexican
  • Lack of blood pressure data
  • Lack of serum antioxidant vitamin levels
  • Those on antihypertensive medications were included however their data was excluded from the linear regression analysis for association of serum antioxidants with blood pressure.
Description of Study Protocol:

Recruitment

Those enrolled in the NHANES III between 1988 and 1994.

Design

  • A stratified multistage probability design used to obtain a respresentative sample of general US population
  • Oversampling of the very young, the elderly, non-Hispanic blacks and Mexican-Americans
  • Standardized home interview followed by detailed physical examination in a mobile exam center
  • Blood pressure (BP) was measured three times during the home interview and during mobile center exam; mean of all systolic and of all systolic readings was used for each individual
  • Hypertension was defined as systolic BP at least 140 or diastolic BP at least 90mm Hg
  • Blood samples were collected at second visit.

Blinding Used

Not discussed.

Intervention

None.

Statistical Analysis 

  • Statistical signicance of differences was analyzed by Student's T-test (continuous variables) and chi-squared test (categoric variables)
  • Analysis of association of serum level of vitamins and supplement use or dietary intake was assessed by Pearson correlation coefficients (R)
  • Linear regression analysis was used to assess the association between serum antioxidant vitamin levels and BP
  • Logistic regression analysis was used to assess the relation between serum antioxidant vitamin levels and odds of hypertension
  • Regression coeffeicients or odds ratios are reported as the difference in BB (mm Hg) or odds of hypertension associated with a one-SD increment in serum antioxidant vitamin levels
  • Two models were used for analysis: one adjusted for age, gender and race; one adjusted for age, gender, race, education, alcohol consumption, BMI, dietary intake of sodium, potasium, saturated fat and energy.
Data Collection Summary:

Timing of Measurements

Cross-sectional between 1988 and 1994.

Dependent Variables

  • Variable One: Systolic BP (mean of six measures using standard protocol)
  • Variable Two: Diastolic BP (mean of six measures using standard protocol)
  • Variable Three: Hypertension (defined as systolic BP at least 140 or diastolic BP at least 90mm Hg).

Independent Variables

Serum levels of vitamin A, alpha-carotene, beta-carotene, vitamn C, vitamin E (measured using isocratic HPLC).

Control Variables

  • One analysis model adjusted for age, gender and race
  • One analysis model adjusted for age, gender, race, education, alcohol consumption, BMI, dietary intake of sodium, potassium, saturated fat and energy.
Description of Actual Data Sample:

 

  • Initial N: 18,825 persons at least 20 years old, who participated in NHANES III.
  • Attrition (final N): 15,317 (N=10,457 normotensives, 4,860 hypertensives; 48% normotensive males, 47.7% hypertensive males).
  • Age: At least 20 years old; 40.1±0.38 years (mean±SE) for normotensives, 60.3±0.50 years for hypertensives (P<0.001)
  • Ethnicity: Non-Hispanic blacks, non-Hispanic whites, Mexican-American
  • Other relevant demographics: 79.8% high school graduates for normotensives, 65.4% high school graduates for hypertensives (P<0.001)
  • Location: United States.
Summary of Results:

Descriptive Results

  • Normotensives were 20 years younger than hypertensives, P<0.001
  • Normotensives had a lower proportion of non-Hispanic blacks, P<0.001
  • Normotensives had a higher proportion of high school graduates, P<0.001
  • Diabetes was higher in hyperensives, P<0.001
  • Normotensives had a lower BMI than hypertensives, P<0.001
  • Mean serum levels of vitamin A, C, E and bta-carotene were lower in normotensives, P≤0.008.
Odds Ratio of Hypertension Associated with Serum Vitamin C and E

Serum Vitamins, 1 SD

Multivariate-Adjusted
OR (95% CI)

P

Vitamin C, 0.47 mg/dL

0.98 (0.91-1.07)

0.7

Vitamin E, 496 microgrm/dL

1.18 (1.09-1.27)

<0.001

  • Adjusted for age, gender, race and ethnicity, education, alcohol consumption, BMI, hx of diabetes, dietary intake of sodium, potassium, saturated fat and total energy
  • A one-SD difference in the level of serum vitamin E (496micrograms per dL) is positively associated with 18% increased odds of having hypertension
  • After adjusting for all confounding factors, serum vitamin C was not significantly associated with odds for hypertension, P=0.7.

Effect of Serum Vitamins C and E on SBP and DBP: Multiple Linear Regression Analysis

Serum Vitamin, 1 SD

SBP, mm Hg

Effect (95% CI)

P

DBP, mm Hg

Effect (95% CI)

P

Vitamin C, 0.47 mg/dL

-0.10 (-0.52, 0.32)

0.6

-0.37 (-0.62, -0.13)

0.003

Vitamin E, 496 microgrm/dL

0.66 (0.22, 1.11)

0.004

0.84 (0.59, 1.08)

<0.001

  • Participants on antihypertensive medications were excluded. N=12, 102 for multivariate analysis adjusted for age, gender, education, alcohol consumption, BMI, hx of diabetes, dietary intake of sodium, potassium, saturated fat and total energy
  • Vitamin E was positively associated with both systolic and diastolic BP, whereas vitamin C was inversely assoicated with both systolic and diastolic BP
  • Vitamin A was positively associated with both systolic and diastolic BP and the carotenoids were inversely associated with both systolic and diastolic BP (data not shown here).

Other Findings

  • A one-SD difference in serum vitamin A was positively associated with a 43% increased odds of having hypertension, P<0.001
  • Multivariate-adjusted differences in systolic and diastolic BP associated with a one-SD in level of serum vitamin among specified subgroups by age, gender, race and ethnicity and hypertension were analyzed
  • Serum vitmain C was inversely associated with diastolic BP in those who were younger than 60 years, in men and women and in hypertensives and normotensives
  • Serum vitamin C was inversely associated with both systolic and diastolic BP among blacks, P<0.05.
  • Serum vitamin E was positively associated with both systolic and diastolic BP among most of the subgroups (age, gender, race, hypertension status) as analyzed by multivariate-adjusted differences, P<0.05 overall.
Author Conclusion:
  • A significant and postive relation between serum levels of vitamin A and E and risk of hypertension independent of age, gender, race and other risk factors was found
  • A significant inverse relation between serum vitamin C and diastolic BP only was identified
  • Apha- and beta-carotene levels were also inversely associated with BP. These relationships were stronger in normotensive and younger participants.
  • The cross-sectional study design does not allow inferences to be made regarding causality between antioxidant vitamins and BP.
  • Authors suggest that antioxidant vitamins may play an important role in the underlying cause and prevention of hypertension.
Funding Source:
Government: NHLBI, NIH
Reviewer Comments:
Physical activity not included as a confounding variable.
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) N/A
 
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? Yes
  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? Yes
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) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  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? Yes
  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? N/A
  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? Yes
  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? N/A
  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? Yes
  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? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? Yes
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  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? N/A
  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? Yes
  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)? N/A
  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? No
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
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