Hiding unhealthy heart outcomes in a low-fat diet trial: the Women's Health Initiative Randomized Controlled Dietary Modification Trial finds that postmenopausal women with established coronary heart disease were at increased risk of an adverse outcome if they consumed a low-fat 'heart-healthy' diet

Abstract

The Women's Health Initiative Randomized Controlled Dietary Modification Trial (WHIRCDMT) was designed to test whether the US Department of Agriculture's 1977 Dietary Guidelines for Americans protects against coronary heart disease (CHD) and other chronic diseases. The only significant finding in the original 2006 WHIRCDMT publication was that postmenopausal women with CHD randomised to a low-fat 'heart-healthy' diet in 1993 were at 26% greater risk of developing additional CHD events compared with women with CHD eating the control diet. A 2017 WHIRCDMT publication includes data for an additional 5 years of follow-up. It finds that CHD risk in this subgroup of postmenopausal women had increased further to 47%-61%. The authors present three post-hoc rationalisations to explain why this finding is 'inadmissible': (1) only women in this subgroup were less likely to adhere to the prescribed dietary intervention; (2) their failure to follow the intervention diet increased their CHD risk; and (3) only these women were more likely to not have received cholesterol-lowering drugs. These rationalisations appear spurious. Rather these findings are better explained as a direct consequence of postmenopausal women with features of insulin resistance (IR) eating a low-fat high-carbohydrate diet for 13 years. All the worst clinical features of IR, including type 2 diabetes mellitus (T2DM) in some, can be 'reversed' by the prescription of a high-fat low-carbohydrate diet. The Women's Health Study has recently reported that T2DM (10.71-fold increased risk) and other markers of IR including metabolic syndrome (6.09-fold increased risk) were the most powerful predictors of future CHD development in women; blood low-density lipoprotein-cholesterol concentration was a poor predictor (1.38-fold increased risk). These studies challenge the prescription of the low-fat high-carbohydrate heart-healthy diet, at least in postmenopausal women with IR, especially T2DM. According to the medical principle of 'first do no harm', this practice is now shown to be not evidence-based, making it scientifically unjustifiable, perhaps unethical.

Keywords: coronary artery disease; diabetes mellitus; epidemiology; risk factors.

Figure 1

Changes in mean minimal coronary artery diameter measured in postmenopausal women participating in the Estrogen Replacement and Atherosclerosis trial. Note that increased rates of coronary artery narrowing were associated with increasing intake of polyunsaturated fats (arrow 2) and carbohydrates (arrow 3). The highest intake of saturated fat was associated with a slight regression of coronary artery narrowing (arrow 1). Redrawn and reproduced from Mozaffarian et al with permission from the American Journal of Clinical Nutrition.

Figure 2

Percentage of postmenopausal women in the three different subgroups who were using statin drugs at the start (year 0) and end (year 6) of WHIRCDMT. Figure drawn from data in figure 3 in Prentice et al. CHD, coronary heart disease; WHIRCDMT, Women’s Health Initiative Randomized Controlled Dietary Modification Trial.

Figure 3

HR for the six most important risk factors and the six biochemical markers for the development of CHD in 28 024 postmenopausal women who were healthy on entry to the Women’s Heart Study. Drawn from data from Dugani et al. CHD, coronary heart disease; HDL, high-density lipoprotein; LDL, low-density lipoprotein.