Transcript Moseley Woods

The Meta-analysis: A noon
conference presentation
Kendall Moseley, MD
Kevin Woods, MD
With commentary by Hunter Young, MD MHS
Alcohol Dosing and Total
Mortality in Men and
Women
An Updated Meta-analysis of 34 Prospective Studies
Augusto Di Castelnuovo, ScD; Simona Costanzo, ScD; Vincenzo Bagnardi, ScD;
Maria Benedetta Donati, MD, PhD; Licia Iacoviello, MD, PhD; Giovanni de
Gaetano, MD, PhD
How much alcohol is healthy for
you?
Background
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Previous studies have shown that moderate
amounts of alcohol have helped prevent
coronary artery disease (CAD).
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Alcohol abuse can be harmful.
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Some studies indicate that alcohol may have
different effects in men and women.
How is ETOH good for you?
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Increased HDL cholesterol
Increased fibrinolysis
Decreased platelet aggregation and coagulation
factors
Possible beneficial effects on endothelial
function and inflammation
Clinical Questions
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What is the relationship between alcohol
dosing and all-cause mortality?
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Is there a statistical difference between men
and women?
Methods
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Pubmed search
Limits: Human
Dates: (all studies – 12/2005)
Searched titles and abstracts containing:
alcohol, beer, wine, spirits AND mortality or
death
Exclusion Criteria
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only 1 category of risk (n=4)
did not report mortality separately for the
sexes (n=5)
considered mortality for specific causes (n=3)
comprised multiple reports (n=9)
reference category was not the one with the
lowest alcohol intake (n=4)
relative risks or numbers of cases and personyears were not available (n=14)
Data Extraction
73 studies identified
Exclusion criteria applied
34 studies
56 studies total**
** 14 reported results separately for the
sexes; 1 study reported data for 2 age
groups; 1 study for wine and beer. (These
studies contributed 2 dose-response
curves each.)
•Two studies contributed 4 curves (1
study reported results separately for 2
ethnic groups and sexes, and another for
age groups and sexes.)
37 Male
19 Female
Define a Drink
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The amount of a drink was taken as quantified by each author
whenever possible; otherwise (7 studies) it was considered
equivalent to 10 g of ethanol.
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Considering a drink equivalent to either 12 or 14 g of ethanol
did not change our results (data not shown).
A Standard Drink
•U.S. DEPARTMENT OF HEALTH & HUMAN SERVICES, National Institutes of Health National Institute on Alcohol Abuse and Alcoholism,
Helping Patients Who Drink Too Much : A CLINICIAN’S GUIDE 2005 Edition
Helpful Conversions
•U.S. DEPARTMENT OF HEALTH & HUMAN SERVICES, National Institutes of Health National Institute on Alcohol Abuse and Alcoholism,
Helping Patients Who Drink Too Much : A CLINICIAN’S GUIDE 2005 Edition
SUMMARY
•Over 1 million Subjects
•Studies representative of 5
countries
•Follow up years ranged from
5.5 – 26 years
•Level of Adjustment
identified for over 20 factors.
Deriving the J-curve
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The regression models were log (relative risk
[RR])=1xp2xq ; exponents p and q were
selected among the following set:
{−2.0, −1.0, −0.5, 0.0, 0.5, 1.0, 2.0}.
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When p=0, xp is replaced by log(x).
When p=q, the model becomes
log(RR|x) =1xp2xq log(x).
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Data Analysis
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(1) the value x of alcohol intake (measured in grams per day)
assigned as the midpoint of the reported ranges; x was defined
as 1.2 times the lower boundary for the open-ended upper
categories.
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(2) frequency counts, adjusted relative risks, and 95% CIs for
each x level
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(3) covariates describing the characteristics of the study.
Inverse variance–weighted methods, taking into account the
correlation between estimates within each study, were used.
Subgroup Analysis
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Level of Adjustment
Sex
Country
Sample size
Duration of follow up
Subgroup Analysis
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Level of Adjustment
Sex
Country
Sample size
Duration of follow up
_____________________
Reversion point: the dose of
alcohol at which the
protection against total
mortality is no longer
statistically significant at the
99% confidence level.
•Mortality benefit could be
associated with up to 42 g/d of
alcohol consumption (approx 4
drinks/ day)
6 g/d
42 g/d
•Lowest risk of to total mortality
associated with 6g/d (approx 0.5
drinks/day)
•Dose response curves are similar for both sexes when
alcohol intake is light, but differs with heavier alcohol
consumption
•Protection apparent up to 3 drinks/day in MEN
•Protection apparent up to 2 drinks/day in WOMEN
•Obvious differences between women from different
countries. (p >.54 for differences between countries)
•However the differences between men from different
countries were significant (p >.003)
•Maximum risk reduction for European Men (20 -28%)
•Maximum risk reduction for US Men (14-19%)
•** no explanation was offered to explain this relationship
Why is there a difference between
the Sexes?
Key Findings
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Low levels of ETOH intake are significantly
associated with reduced total mortality.
While both sexes benefit from moderate
ETOH intake, the dose of ETOH at which this
benefit is realized is different for men (3
drinks/day) and women (2 drinks/day)
The relationship of ETOH intake and
decreased mortality is lower in US-based
studies as opposed to European (men only)
Discussion
The Big Picture
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Why a meta-analysis? (and by the way, what is
a meta-analysis?)
How should this type of study be applied to
your clinical decision-making?
Other Related Resourcs
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National Institute on Alcohol Abuse and
Alcoholism