Structured Abstract
Please note: In 2003, the CTF updated its Grades of
Recommendations to include an "I Recommendation" for situations where
insufficient evidence exists to allow a recommendation to be made.
(Formerly, these situations were captured under a "C
Recommendation".) This change is not retroactive, and all
"C Recommendations" made prior to 2003 have not been
reevaluated in light of the new "I" recommendation grade. For a
discussion of these recommendation grades, please link to the 2003 article in
the Canadian Medical Association Journal here.
Preventive Health Care, 2000 Update: Screening and Management of Hyperhomocysteinemia
for the Prevention of Coronary Artery Disease Events
Prepared by Gillian L. Booth, MD, Departments of Medicine, Clinical
Epidemiology and Health Care Research Program, University of Toronto, Elaine
E. L. Wang, MD, Departments of Pediatrics, Clinical Epidemiology and Health
Care Research Program, University of Toronto
These recommendations were finalized by the Task
Force in July 1999
Contents
Objective
To evaluate the quality of evidence pertaining to
homocysteine and coronary artery disease (CAD) and make recommendations
regarding screening and treatment of hyperhomocysteinemia.
Burden
of Suffering
Cardiovascular disease is the leading cause of death
in Canada, accounting for almost 40% of all deaths. While mortality rates
for ischemic heart disease are declining, the costs to society remain high.
Since a number of cardiovascular deaths may be preventable, the search
for novel risk factors continues. Homocysteine is an intermediate that
is generated in the metabolism of methionine. Therefore, altered homocysteine
metabolism has become the focus of increasing attention based on its potential
role in the pathogenesis of atherosclerosis and other conditions, such
as venous thrombosis and neural tube defects.
The prevalence of hyperhomocysteinemia in the
general population is between 5 and 10%, based on a threshold set at the
90th or 95th percentile (approximately 15 mmol/L).
However, rates may be as high as 30 to 40% in the elderly. If population-based
studies are correct, then up to 10% of coronary events may be attributable
to plasma homocysteine. Thus, homocysteine may represent an important and
potentially modifiable risk factor for cardiovascular disease.
Options
Screening of serum homocysteine in patients who have
either no symptoms of CAD at baseline (primary prevention) or those with
known CAD (secondary prevention); treatment of patients with high homocysteine
levels to prevent CAD
Outcomes
Cardiovascular death and overall mortality in patients with established
coronary artery disease.
Evidence
MEDLINE was searched from 1966 to June 1999 using
the MeSH headings homocysteine; hyperhomocysteinemia; methionine; coronary
disease; arteriosclerosis; myocardial ischemia; folic acid; vitamin B12;
vitamin B6; and pyridoxine. Relevant articles were also identified
through a manual review of references.
Recommendations were graded as:
|
A
|
Good evidence to support the recommendation that the condition
be specifically considered in a PHE. |
|
B
|
Fair evidence to support the recommendation that the condition
be specifically considered in a PHE. |
|
C
|
Poor evidence regarding inclusion or exclusion of the condition
in a PHE, but recommendations may be made on other grounds. |
|
D
|
Fair evidence to support the recommendation that the condition
be specifically excluded from consideration in a PHE. |
|
E
|
Good evidence to support the recommendation that the condition
be specifically excluded from consideration in a PHE. |
Quality of evidence was rated according to 5 levels:
|
I
|
Evidence from at least 1 properly randomized controlled
trial (RCT). |
|
II-1
|
Evidence from well-designed controlled trials without randomization. |
|
II-2
|
Evidence from well-designed cohort or case-control analytic
studies, preferably from more than 1 centre or research group. |
|
II-3
|
Evidence from comparisons between times or places with
or without the intervention. Dramatic results in uncontrolled experiments
could also be included here. |
|
III
|
Opinions of respected authorities, based on clinical experience,
descriptive studies or reports of expert committees. |
Values
The 10-member Task Force of experts in family medicine, geriatric medicine,
pediatrics, psychiatry and epidemiology used an evidence-based method for
evaluating the effectiveness of preventive health care interventions. Recommendations
were not based on cost-effectiveness of options. Patient preferences were
not discussed.
Background papers providing critical appraisal
of the evidence and tentative recommendations prepared by the chapter author
were pre-circulated to the members. Evidence for this topic was presented
and deliberated upon in a 2-day meeting in May 1998. Consensus was reached
on final recommendations.
Benefits,
Harms, and Costs
High-pressure liquid chromatography (HPLC), the most common method used
to measure total homocysteine (tHcy), has a coefficient of variation of
3 to 11%. tHcy levels may be falsely lowered in the acute phase of
illness, such as myocardial infarction, while factors that may elevate
tHcy include genetic predisposition, increasing age, male gender, serum
creatinine, as well as delays in placing samples on ice. Medications
such as anti-epileptic drugs, methotrexate, nitrous oxide, and certain
disease states, such as psoriasis, acute lymphoblastic leukemia, breast
cancer, and hypothyroidism also increase levels, likely through effects
on vitamin status. Homocysteine is inversely correlated with serum
vitamin B6, B12, and folate. Thus, in populations with a higher prevalence
of B12 deficiency (such as the elderly), the specificity of plasma tHcy
as a cardiac risk factor may be reduced.
Current costs range between $30 and $50. However, newer, less
costly techniques for measuring tHcy have been developed and should become
more readily available.
Recommendations
Recommendation grade [A, B, C, D, E] and level of evidence
[I, II-1, II-2, II-3, III] are indicated after each recommendation. Citations
in support of individual recommendations are identified in the guideline
text.
-
There is insufficient evidence to recommend for or
against screening for hyperhomo-cysteinemia in the general population [C,
II-2]
-
There is insufficient evidence to recommend for or
against screening for hyperhomo-cysteinemia in high-risk populations [C,
II-2], however, screening may identify individuals
at higher risk of developing coronary artery disease, leading to aggressive
risk factor modification.
-
There is insufficient evidence to recommend for or
against treatment of hyperhomo-cysteinemia with vitamin therapy [C,
II-1, II-2, II-3]
Validation
This report was externally peer reviewed. The American Heart Association
state that it may be reasonable to screen individuals who are at risk for
hyperhomocysteinemia (such as patients with renal failure) or those who
have a personal or family history for premature atherosclerosis.
Several experts in the area concur.
Sponsors
The Canadian Task Force on Preventive Health
Care developed this guideline with funding from
the Provincial and Territorial Ministries of Health and Health Canada.
Link to Full Text of this
review
Link to Summary Table of Recommendations of this review
Link to Selected References list of this review
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