DLM: Homocysteine, Folate, B6 or B12 (2007-2011)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To compare serum homocysteine concentrations in Hispanics and non-Hispanic whites (NHWs), examine their associations with serum folate and vitamin B12 concentrations, and correlate this with the prevalence of CHD

Inclusion Criteria:

--age 65 years or older

--in Healthcare Financing Administration (HCFA) (Medicare) registrant list for Bernalillo County (Albuquerque), New Mexico

--Hispanic or NHW (self-identification and ¾ grandparents identified as Hispanic or NHW)
Exclusion Criteria:

--those that died, moved from the county, or could not be located (no known street address or no response from notes mailed to homes)

--did not meet criteria to qualify as Hispanic or NHW
Description of Study Protocol:

--GLM (general linear model): made group comparisons based upon gender by ethnicity to compare serum Hcyt concentrations using serum folate and B12 as predictors and age as covariate

--4 groups: Hispanic males, NHW males, Hispanic females, NHW females and all 4 groups were each broken down by 3 age groups

--2 main visits:

1.        paid for a home interview

2.        paid interview/exam covering health and health-related issues

 

Data Collection Summary:

--blood samples for serum tHcy concentrations, total tHcy, vitamin B12, folate, serum creatinine

--participants had CHD if they met ¼ criteria:

1.        self report of MD dx of MI or angina

2.        hx CABG

3.        presence of definite MI by ECG read by cardiologist

4.        hx of chest pain in past 6 months with at least 2/5 qualifiers suggesting CHD (pain in certain areas of body, SOB, N/V, etc)

--known CHD risk factors (age, diabetes, HTN, smoking, dyslipidemia, adiposity/BMI) were accounted for and adjusted

 

Description of Actual Data Sample:

--1666 were eligible from the random 2200 people selected from HCFA

--1130 (67.8%) agreed to participate in home interviews

--29 interviews eliminated from study b/c did not meet ethnicity standards, died, or moved prior to completion of the exam

--883 (80.2%) participated in 4-hour interview/exam

Summary of Results:

--791 samples of serum tHcy available

--men had significantly higher mean tHcy concentrations than women (by 0.14; p=0.0001)

--Hispanic men and women had significantly higher unadjusted mean fasting serum tHcy concentrations compared to NHW (by 0.09, p=0.004 form men; by 0.06, p=0.48 for women)

--testing main effects of gender and ethnicity separately—gender significant (p=0.0001) but not ethnicity (p=0.7).

--looking at folate alone, effects of gender and ethnicity are additive; rate of change in log (tHcyt) given log (folate) were same for 4 groups

--log (tHcyt) concentrations were significantly different between males and females (p=0.0001) regardless of ethnicity, therefore, differences in Hcyt concentrations between 2 ethnicities are probably due to differences in serum folate

--significant association between fasting serum Hcyt and prevalence of CHD found after adjusting for CHD risk factors (DM, current smoking history, systolic and diastolic blood pressure, total chol, HDL-C, BMI, age, gender, ethnicity)

--all participants included—OR 1.59 (0.94-2.69 (95%CI)) for association between log Hcyt and prevalence of CHD is marginally significant (p=0.087)

--analysis of gender separately—association for males not significant, but OR for females is (p=0.008) OR=3.52 (1.16-7.22 (95% CI))

--analysis of women separated by ethnicity—Hispanic women Hcyt associated with prevalence of CHD (OR= 4.61 (1.16-18.4 (95% CI)); p=0.03)

Author Conclusion:

--results suggest that differences in Hcyt is probably due to differences in age, gender, folate and B12 concentrations, but after adjusting for these variables, there is no difference by ethnicity (R 28%), indicating that important predictors may not have been included in this model

--low folate does not necessarily equal high Hcyt—especially with folate fortification. Must also consider renal insufficiency, vitamin B12 deficiency, poor B6 nutrition, poor riboflavin nutrition
Funding Source:
Not-for-profit
0
Foundation associated with industry:
Reviewer Comments:

--what about RBC folate vs serum: which is the best marker?

--what was the time frame for the lab draw?

--what was the time frame between the 2 interviews?
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? 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? 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? 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? 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? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? Yes
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? ???
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? ???
  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? Yes
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? N/A
  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? No
  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? 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