Hooper et al recently published a new meta-analysis, this
one entitled “Reduction
in saturated fat intake for cardiovascular disease”. This meta-analysis focused on the effect of
reducing saturated fat (SFA), as opposed to their previous
meta-analysis that looked at the effect of reducing and/or modifying fat
for CVD.
This new meta-analysis included many of the original
trials from the previous meta-analysis (from all three categories), but had more
selective inclusion criteria than the previous, such as an intention to reduce
SFA and the intervention lasting at least 24 months. This led to the exclusion of many of the
trials that were included in the previous meta-analysis
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Trials in 2012
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Included in 2015
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Reason for Exclusion
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Modified Fat Trials
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RCOT
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X
|
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LAVAT
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X
|
|
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ODHS
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X
|
|
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NDHS
|
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Follow-up less than 24
months
|
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MRCT
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X
|
|
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MCS
|
|
Although the study
proceeded for over 4 years participants (patients) came and went and mean
follow-up was only 1 year
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SDHS
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X
|
|
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Houtsmuller
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X
|
|
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Reduced Fat Trials
|
Ball
|
|
Study aim was to assess
effects of a low-fat diet and methods state that the "nature of the fat
consumed was not altered". Saturated fat content of diet was not
reported.
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WINS
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X
|
|
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Black
|
X
|
|
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Polyp Prevention
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Neither mortality nor
cardiovascular morbidity data available (only decided after contact with at
least 1 author)
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Ley
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X
|
|
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Moy
|
X
|
|
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BRIDGES
|
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Follow-up less than 24
months
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PREMIER
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Follow-up less than 24
months
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DO IT
|
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Intervention aim was for
a "mediterranean diet" with total fat 27 - 30%E, protein 15 - 18%E,
CHO 50 - 55%E, no specific aim to reduce saturated fat (though
polyunsaturated margarine given to intervention group), and intervention
group saturated fat was more than 80% of that in the control.
|
|
WHI
|
X
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|
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WHEL
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Study aimed to reduce
total fat, but saturated fat goals were not mentioned, and saturated fat
intake in the intervention group was more than 80% of that in the control
(81%)
|
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Modified and Reduced Fat Trials
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DART
|
X
|
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STARS
|
X
|
|
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Sondergaard
|
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Follow up less than 24
months
|
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MeDiets
|
|
Follow-up less than 24
months
|
|
NDHS
|
|
Follow-up less than 24
months
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This meta-analysis included the same figures as the
previous one. This means they generally included
minor events (angina, surgery, increased anti-anginal treatment) and the same
error in total mortality in ODHS (48 vs. 65 should be 41 vs. 55)
This meta-analysis got a very similar result to the
previous one, with a significant reduction in combined
CVD events and no effect for CVD
mortality or total
mortality (the links take you to the Forest plots)
|
CVD Events
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CVD Mortality
|
Total Mortality
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Hooper, et al
(2012)
(modified fat)
|
0.82
(0.66-1.02)
P = 0.073
|
0.92 (0.73-1.15)
P = 0.46
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1.02 (0.88-1.18)
P = 0.81
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Hooper, et al
(2012)
(modified and reduced
fat)
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0.77
(0.57-1.03)
P = 0.077
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0.98 (0.76-1.27)
P = 0.88
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0.97 (0.76-1.23)
P = 0.78
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Hooper, et al
(2015)
(reduced SFA)
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0.83 (0.72-0.96)
P = 0.013
|
0.95 (0.80-1.12)
P = 0.51
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0.97 (0.90-1.05)
P = 0.47
|
The lack of effect for CVD mortality and total mortality
is predictable. The inclusion of the
Finnish Mental Hospital Study (FMHS) is the major determinant of whether a
meta-analysis finds a significant reduction in CHD or CVD mortality as
evidenced by Skeaff & Miller and Mozaffarian et al (blog). If FMHS is not included, as is the case with
this meta-analysis, it’s very hard to get a significant effect. Similarly almost every meta-analysis has
found no effect for total mortality. The
only exception is the meta-analysis by Skeaff & Miller because they incorrectly calculated the risk ratio for FMHS using group size rather than by using
person years. If FMHS is not included or
its risk ratio is calculated using person years then you get a risk ratio very
close to 1.0 (blog).
The significant effect for CVD events is similar to their
previous result, significant this time probably due to the inclusion of more
trials under one category. This
significant result is particularly interesting because the inclusion of the
Women’s Health Initiative (WHI) would be expected to strongly
draw the pooled RR close to 1.0 as it did previously in the pooled result of reduced fat trials. There are some reasons that can explain this
significant result:
1) In the analysis for total mortality the WHI had 2404/4376
(55%) of all deaths and 59.6% of the weighting.
However, in the analysis for CVD events the WHI had 3445/4377 (79%) of
all CVD events, but only 32.7% of the weighting.
2) The trials that drove the significant result included
Houtsmuller, MRC, ODHS, STARS and LAVAT.
Neither of these trials are a particularly accurate representation of
reducing SFA. The control group in LAVAT
had a vitamin E intake that was 9.4-fold lower than the experimental group and
only 16% of the RDI, ODHS and STARS used a multifactorial diet intervention,
and the control group in Houtsmuller likely had a very high intake of TFA. Even though I have categorised both MRC and DART
as ‘adequately controlled trials’ they aren’t perfect either as the method to
reduce SFA included forbidding “…most biscuits and cakes” (MRC) and limiting “..cakes,
pastries, biscuits, meat pies and pasties, crisps, chocolates and toffees”
(DART), which confounds the results due to the unhealthy and/or lack of healthy
components of those foods.
3) Unlike their previous meta-analysis, none of the sensitivity
analyses excluded studies that “were not free of dietary differences other than
fat (or unclear)”, which excluded ODHS and STARS in their previous
meta-analysis. This criteria of bias
assessment wasn’t even present in this meta-analysis
So I still think that the most accurate representation of
the effect of reducing SFA or replacing it with PUFA is my analysis of ‘adequately
controlled trials’ (with or without the Sydney Diet Heart Study) (blog)
Finally, I am waiting for the same people who criticised the meta-analyses by Ramsden et al and Harcombe et al to also criticise this meta-analysis because it is inconsistent with
the results of several meta-analyses of observational studies that find no
independent association between intake of SFA and CHD (which is close enough to CVD) [1] [2] [3] [4] [5] [6]
Steven: "Unlike their previous meta-analysis, none of the sensitivity analyses excluded studies that “were not free of dietary differences other than fat (or unclear)”, which excluded ODHS and STARS in their previous meta-analysis. This criteria of bias assessment wasn’t even present in this meta-analysis"
ReplyDeleteI don't understand their reasoning for this:
"we have omitted this factor from the formal validity assessment as we did not consider confounding changes in types of fat other than saturated fats".
I don't understand their reasoning either as it doesn't really match up with first part of the paragraph where they say :
Delete"...for example, some studies encouraged intervention participants to make changes to their fat intake as well as changes to fruit and vegetable or fibre or salt intakes"
(They began the paragraph talking about there being other differences in fats besides SFA and differences in other things besides fat, but then they follow up with only talking about differences in fats besides SFA)
It's probably because its purpose is to be a meta-analysis of trials that intended to and successfully reduced SFA intake regardless of any other dietary differences. Not exactly a step in the right direction