Sunday, April 26, 2015

Testing the Diet Heart Hypothesis in Women

Most of the diet heart trials were only conducted in men probably because CHD is thought to be the ‘fat, middle-aged man’s disease’, but CHD is the leading cause of death in Australian [1] and American [2] women as well.  In Australia, 45.5% of all deaths from CHD occur in women [1].  So while CHD certainly does affect more men than women, this difference seems to be greatly exaggerated.

Despite these statistics, only two of the trials included women (Finnish Mental Hospital Study (FMHS) and Minnesota Coronary Survey (MCS)) and consequently the weighting of events/deaths for women is far below 45.5%


Weighting in ‘Adequately Controlled Trials’
Weighting in All Trials
Men (%)
Women (%)
Men (%)
Women (%)
Major CHD Events (E)
82.6
17.4
86.8
13.2
Major CHD Events (P)
82.5
17.5
86.5
13.5
Total CHD Events (E)
83.8
16.2
83.0
17.0
Total CHD Events (P)
84.1
15.9
83.0
17.0
CHD Mortality
85.0
15.0
79.7
20.3
Total Mortality
77.0
23.0
67.7
32.3

This goes to larger issue in medicine where women are often underrepresented in clinical trials, sometimes even to the extent where women are prescribed a drug which hasn’t even been tested in a single woman in a clinical trial [3].  A lot of small, short term studies are done only using men, as the menstrual cycle may affect the results.  While this is a legitimate concern of small, short term studies, it would have little to no impact in larger, long term studies such as the diet heart trials, particularly if they included mainly postmenopausal women

This is important because certain interventions can affect women differently.  There are a few examples in [3] and [4] and plenty on Suppversity if you do a few searches.  Another example may be statins, as a meta-analysis found that in secondary prevention trials statins don’t significantly reduce total mortality in women, whereas they do with men [5].

Replacing SFA with PUFA may be another example where women respond differently as there was a fairly consistent pattern in MCS and FMHS: when the RRs for men were compared with those for women: men do better than women or women do worse than men (depending on how you look at it).

FMHS
RR for Men
RR for Women
Difference
Major CHD Events
0.330
0.393
+19.1%
Total CHD Events
0.557
0.635
+14.0%
CHD Mortality
0.469
0.659
+40.5%
Total Mortality
0.882
1.064
+20.6%

MCS
RR for Men
RR for Women
Difference
Major CHD Events
0.895
1.317
+47.2%
CHD Mortality
1.102
1.097
-0.5%
Total Mortality
0.992
1.164
+17.3%

Given that women were very underrepresented in the diet heart trials and respond to replacing SFA with PUFA less favourably/worse than men do, I wonder what the results would be if more of the trials included women:

  • Would this pattern persist?  Is this a real effect?
  • Would the pooled result be completely neutral even without excluding inadequately randomised and/or inadequately controlled trials?
  • If there were some repeats of MCS, would health authorities be urging women away from vegetable oils?

The answers to those questions is debatable, simply because we don’t know and I don’t think we can draw too strong a conclusion from two trials (especially because one of them (FMHS) was both inadequately randomised and inadequately controlled).  This is an additional reason to conduct another trial where SFA is replaced with PUFA, one which is randomised, well controlled and includes both men and women.  Conventional dietitians/doctors should be motivated to do so, not only do they have the burden of proof, but also because the current results for women aren't too favourable.

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