HTN: Vitamins (2015)
Citation:
Vacek JL, Vanga SR, Good M, Lai SM, Lakkireddy D, Howard PA. Vitamin D deficiency and supplementation and relation to cardovascular health. Am J Cardiol. 2012; 109: 359-363.
PubMed ID: 22071212Study Design:
Retrospective Cohort Study
Class:
B - Click here for explanation of classification scheme.
Quality Rating:

Research Purpose:
To investigate the association of vitamin D deficiency and cardiovascular morbidity and mortality, as well as the effect of supplementation on survival.
Inclusion Criteria:
- Patients followed in cardiovascular practice between January 1, 2004 and October 8, 2009
- Serum vitamin D measurement
Exclusion Criteria:
Less than 18 years of age.
Description of Study Protocol:
Recruitment
Patients seen between January 1, 2004 and October 8, 2009 were identified from patient records of a cardiovascular practice.
Design
Retrospective cohort study.
Blinding used:
Implied with measurements.
Statistical Analysis
- Vitamin D analyzed as both a continuous variable and a dichotomous variable (30ng or more per ml or less than 30ng per ml)
- Descriptive statistics
- Univariate analysis (unpaired T-tests for continuous variables)
- Chi-square analysis
- Multivariate logistic regression analysis for odds ratios
- Survival analysis and Cox proportional hazard modeling
- Interaction between vitamin D deficiency and supplementation studied by development of an interaction variable for retesting the outcomes models, with confirmation using the Wald statistic and likelihood ratio and proportionality testing.
Data Collection Summary:
Timing of Measurements
Not specified, varied for each patient
Dependent Variables
- Survival: Interval between the date of sample collection and the date of death or the end of study period
- Death: All-cause data obtained from the Social Security Death Index
- Cardiovascular events:
- Coronary artery disease
- Atrial fibrillation
- Diabetes mellitus
- Cardiomyopathy
- Hypertension.
Independent Variables
- Vitamin D level (normal vs. deficient): 30ng or more per ml vs. less than 30ng per ml
- Vitamin D supplementation: Active prescription for vitamin D or its analogs or patient-reported use of vitamin D supplements (not all doses reported; usual reported doses ranged from 1,000 IU per day to 50,000 IU weekly; sample mean was 2,254±316 IU; use of multivitamins not included).
Description of Actual Data Sample:
- Initial N: 10,899 patients
- Attrition (final N): 10,899 (71% female)
- Age: 58.3±14.9 years.
BMI of total sample: 29.9±7.7kg/m2.
Variable | Vitamin D (Normal Range) | Vitamin D (Deficient) | P Value |
Age (years) | 60±15 | 58±15 | <0.0001 |
Women (%) | 77 | 69 | <0.0001 |
BMI (kg/m2) | 28±7 | 31±8 | <0.0001 |
Vitamin D (ng per ml) | 40±11 | 17±7 | <0.0001 |
Vitamin D supplement use (%) | 34 | 39 | <0.0001 |
Other significant differences between groups:
- Coronary artery disease (11% vs. 9%)
- Hypertension (defined as higher than 140/90mm Hg) (29% vs. 36%)
- Diabetes mellitus (9% vs. 19%).
Location
Kansas.
Summary of Results:
Key Findings
- Risk of cardiovascular conditions:
- Vitamin D deficiency as a dichotomous variable in univariate analysis was significantly associated with an increased risk of:
- Coronary artery disease (OR 1.16; 95% CI: 1.012 to 1.334)
- Diabetes (OR 2.31; 95% CI: 2.018 to 2.644
- Hypertension (OR 1.4; 95% CI: 1.285 to 1.536)
- All cause death (OR 2.95; 95% CI: 2.135 to 4.073).
- Vitamin D was negatively associated with risk of atrial fibrillation (OR 0.83; 95% CI: 0.693 to 0,984).
- Vitamin D deficiency as a dichotomous variable in univariate analysis was significantly associated with an increased risk of:
- All-cause death:
- In stepwise multivariate logistic regression analysis, vitamin D deficiency was a strong independent predictor of all-cause death (OR 2.64; 95% CI: 1.901 to 3.662, P<0.0001)
- Hazard ratio for reduced survival with vitamin D deficiency (dichotomous) (l=2.48) (P<0.0001).
- Effect of supplementation (risk for death):
- Vitamin D supplementation improved survival overall, but to significant degree only in deficient patients
- Univariate analysis (risk all cause death for subjects taking vitamin D supplements): OR 0.62 (95% CI: 0.469 to 0.806, P=0.0004)
- Stepwise regression analysis for death (OR for vitamin D supplementation): OR 0.44, P<0.0001
- Hazard ratio for death for those taking supplements: 0.40 (95% CI: 0.335 to 0.576), P<0.0001
- OR for death in vitamin D-deficient subjects with supplementation: 1.47; 95% CI: 0.760 to 2.799, NS
- OR for death in vitamin D-deficient subjects without supplementation: 3.07, 95% CI: 2.222 to 4.228, P<0.0001.
Author Conclusion:
Vitamin D deficiency was associated with a significant risk of cardiovascular disease and reduced survival. Vitamin D supplementation was significantly associated with better survival, specifically in patients with documented deficiency.
Funding Source:
University/Hospital: | University of Kansas Medical Center and Hospital |
Reviewer Comments:
Significant differences between groups in terms of age, sex, BMI and presence of coronary artery disease, hypertension and diabetes mellitus. Possible selection bias. Isolated vitamin D measurement might not reflect long-term levels. Dose and duration of vitamin D supplementation are not known for all subjects. Inclusion of vitamin D in multivitamins was not considered.
Quality Criteria Checklist: Primary Research
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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? | No | |
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? | ??? | |
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? | No | |
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? | No | |
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? | No | |
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? | N/A | |
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%.) | N/A | |
4.3. | Were all enrolled subjects/patients (in the original sample) accounted for? | N/A | |
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? | 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? | ??? | |
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? | ??? | |
6.4. | Was the amount of exposure and, if relevant, subject/patient compliance measured? | No | |
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? | 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? | 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? | ??? | |
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? | 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 | |