EAL

DLM: Homocysteine, Folate, B-12 (2001)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

Outcome measures: Myocardial infarction (MI) or stroke (self-reported).

Inclusion Criteria:

NHANES III, Phase 2 surplus serum project study participants, 40 years of age or older.

Exclusion Criteria:

Diabetes mellitus
Abnormal liver function, as indicated by aspartate aminotransferase or alanine aminotransferase of ? 58 units per Liter
Estrogen replacement therapy
Vitamin and mineral supplements.

Description of Study Protocol:

Evaluation of total Homocysteine (tHcy) concentrations in a more than 40-year-old subgroup of NHANES III, Phase 2 surplus serum project participants and comparison to self-report of previous stroke or heart attack. Outcomes were controlled for potential confounders: Age at examination, sex, race and ethnicity, body mass index, pack-years of cigarette smoking, blood pressure, use of blood pressure medication, menopausal status (women) and serum concentrations of creatinine, total cholesterol and HCL cholesterol.

Data Collection Summary:

Blood was drawn at mobile examintation centers from examined persons across a range of fasting states. Serum samples were stored at –70°C for eight months to three years before tHcy analysis. Interview responses were used to classify subjects as cases (i.e., self-report of one or more previous heart attack or stroke) and non-cases.

Description of Actual Data Sample:

NHANES III subsample: Adults 40 years or more (1,097 males, 1,107 females). Mean tHcy history of MI or stroke. Controls m mol per L: Men (all ages), 12.1, 10.5; less than 60 years, 12.9, 9.9; more than 60 years, 12.3, 11.8. Women (all ages), 11.0, 9.3; less than 60 years, 8.8, 8.4; less than 60 years, 14.0, 10.8

Summary of Results:

After adjustment for age, race and ethnicity, smoking, blood pressure, blood pressure medications, BMI, serum concentrations of creatinine and cholesterol, past stroke or MI were reported 2.4 times (95% CI, 1.0 to 5.5) as often in men with tHcy concentration of more than 12 m mol per L as by men with lower values. The odds ratio for women was 2.6 (95% CI, 1.1 to 6.6) after adjustment for the above factors plus menopausal status. Hyperhomocysteinemic subjects reported having had an MI or stroke at 2.5 times as often as nonhyperhomocysteinemic subjects and the likelihood of having an MI or stroke by approximately 50% per 5m mol per L. tHcy. Age interacted significantly with serum tHcy in relation to MI or stroke only in the men. The results of this study emphasize the need to consider age and sex when interpreting results from studies of the relation between serum tHcy concentration and occlusive vascular events. A stronger relation in men less than 60 years compared with older men may help reconcile conflicting results of earlier studies.

Author Conclusion:

For this analysis, history of MI and stroke was from self-report only, which limits the strength of the study.

Funding Source:

Government:

USDA, NIH, NHLBI

Reviewer Comments:

Given the limitations of this study, the evidence is good that tHcy concentration is positively associated with heart attack or stroke. Additional studies are necessary to prove a causal association between tHcy and vasuclar disease.

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?	N/A
	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)	N/A
	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?	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.)	Yes
	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.)	N/A
	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?		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?	N/A
	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?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	N/A
	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?	N/A
	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?	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?		N/A
	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