Sunday, January 5, 2014

The Sydney Diet Heart Study

Studies Associated with the Trial

Low fat, low cholesterol diet in secondary prevention of coronary heart disease (1978) [1]
The synergistic effect of weight loss and changes in dietary lipids on the serum cholesterol of obese men with hypercholesterolaemia: implications for prevention of coronary heart disease (1979) [2]

Participants and Diets

458 men who had recently had a heart attack or definite angina were randomised to two groups: an experimental group and a control group.

The experimental group (the ‘F group’) “were advised and tutored individually to reduce saturated fat intake to approximately 10% of calories and dietary cholesterol to 300 mg or less per day. They were encouraged to use food containing polyunsaturated fatty acids to 15% or more of daily calories”

Whereas the control group (the ‘P group’) “were given no specific dietary instruction apart from restriction of calories if thought to be overweight. As a concession to the popular and medical beliefs of the time they were allowed to use polyunsaturated margarine instead of butter if they wished”

After they had their heart attack and before the trial, many of the men lost weight (average of ~3kg), stopped or reduced smoking (70% vs. 38%) and/or made dietary changes (replacing SFA with PUFA and presumably other changes too).  However, both groups were similar at baseline.  As a result of the dietary change before the trial, the two groups didn’t have a very large difference in fat composition (note the high PUFA in the control group) [1]

[1]
Experimental
Control
Calories
2289
2191
Protein
15.2
15.7
Fat
SFA*/MUFA*/PUFA*
P/S*
38.3
9.8/11.5/15.1
1.7
38.1
13.5/13.8/8.9
0.8
Carbohydrate
40.9
40.3
Alcohol
5.4
5.7
Cholesterol*
248
342
* Significant difference between groups

Results

On average, both groups lost weight and decreased cholesterol and triglycerides, though to a slightly greater extent in the experimental group [1].



Experimental
Control
Weight
(kg)
At Infarct
76.4
75.9
Baseline
73.1
73.2
Follow-up
71.4
71.3
Total Cholesterol (mg/dl)
Baseline
281.3
282.0
Follow-up*
250.2
262.3
Triglycerides
(mg/dl)
Baseline
189.0
185.9
Follow-up
144.4
154.5
The people who lost weight also reduced their cholesterol and triglyceride levels [2]
* Significant difference between groups

There were 67 deaths during follow up, 37 in the experimental group and 28 in the control group.  60 of the deaths were from CHD, 3 from stroke, 2 to cancer and 2 to motor accidents, but we don’t know the breakdown within each groups.  Survival was significantly better in the control group [1]


Experimental
(n=221)
Control
(n=237)
Total Mortality
39 (17.6%)
28 (11.8%)

Fortunately Ramsden et al recovered some data from the SDHS


Experimental
(n=221)
Control
(n=237)
CVD Mortality
38 (17.2%)
26 (11.0%)
CHD Mortality
36 (16.3%)
24 (10.1%)
* There seems to be an extra stroke death in Ramsden et al

The breakdown didn’t make much difference, but there was slightly more non-CVD mortality in the control group (2 vs. 1) so, while total mortality was not significant (p=0.051), CVD mortality and CHD mortality was.

Many of the participants made diet and lifestyle changes following infarct, which led the authors to conclude “that because of multiple changes in lifestyle men who have had myocardial infarction are not a good choice for testing the lipid hypothesis”  Weight loss, reduction in cigarette smoking, increase in physical activity and other readjustments may well have more important beneficial effects than change in dietary lipids.” [1]  

While lifestyle changes can be a confounding variable, this is less of a concern in larger randomised trials.  Even though the prevalence of smoking and physical activity in each group was not reported, given that the groups were similar at baseline and lost a similar amount of weight between infarct and starting the trial (3.3kg vs. 2.7kg) [1], it can reasonably be assumed that the degree of lifestyle change was similar in each group.  There was also a large enough difference in the PUFA:SFA ratio (1.7 vs. 0.8) to make the the trial a meaningful comparison

Following Ramsden et al’s publication there was a bit of an uproar in the mainstream (see here).  One of the better objections was that the experimental group had a large intake of artificial TFA from the brand of margarine they were given.  However, Ramsden et al. did discuss this:

“Another factor that could have been altered by the intervention is dietary trans fatty acids, which are known to raise total and low density lipoprotein cholesterol and have been associated with increased cardiovascular risk in observational studies. This association was not widely appreciated during the SDHS, and the trans fatty acid content of participants’ diets was not recorded. Restriction of common margarines and shortenings (major sources of trans fatty acids) in the intervention group would be expected to substantially reduce consumption of trans fatty acids compared with the control group.”

“Conversely, some of this reduction in trans fatty acids in the intervention group may have been offset by small amounts of trans fatty acids in the safflower oil polyunsaturated margarine. Although the precise composition of this margarine was not specified, it was selected for the study because of its ability to lower blood cholesterol and its high PUFA to SFA ratio, two characteristics of margarines that contain comparatively low amounts of trans fatty acids.”

“Because dietary trans fatty acids are predominantly 18-carbon MUFA isomers, the recorded changes in MUFAs probably included small amounts of trans fatty acids in both groups.  Statistical adjustment for changes in MUFAs (an imperfect surrogate for trans fatty acids) in sensitivity analyses did not noticeably alter the observed relation between LA and increased risk of cardiovascular death in the intervention group (data not shown).”

“Collectively, these observations indicate that changes in trans fatty acid were unlikely to play a substantial role in the findings reported here. Nevertheless, the SDHS dataset does not contain sufficient information to rule out the possibility that changes in nutrients other than n-6 LA and SFAs could have contributed to, or reduced, the observed unfavorable effects of the LA intervention.”

In other words: possible, but not certain.  It’s really annoying that there are a number of ‘experts’, some with conflicts of interest, that have set out to debunk the SDHS because of its unfavourable results, yet aren’t critical at all with the other trials that are so obviously multifactorial in favour of the experimental group

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