Low-fat dietary pattern and cardiovascular disease: results from the Women's Health Initiative randomized controlled trial

Abstract

Background: The influence of a low-fat dietary pattern on the cardiovascular health of postmenopausal women continues to be of public health interest.Objective: This report evaluates low-fat dietary pattern influences on cardiovascular disease (CVD) incidence and mortality during the intervention and postintervention phases of the Women's Health Initiative Dietary Modification Trial.Design: Participants comprised 48,835 postmenopausal women aged 50-79 y; 40% were randomly assigned to a low-fat dietary pattern intervention (target of 20% of energy from fat), and 60% were randomly assigned to a usual diet comparison group. The 8.3-y intervention period ended in March 2005, after which >80% of surviving participants consented to additional active follow-up through September 2010; all participants were followed for mortality through 2013. Breast and colorectal cancer were the primary trial outcomes, and coronary heart disease (CHD) and overall CVD were additional designated outcomes.Results: Incidence rates for CHD and total CVD did not differ between the intervention and comparison groups in either the intervention or postintervention period. However, CHD HRs comparing these groups varied strongly with baseline CVD and hypertension status. Participants without prior CVD had an intervention period CHD HR of 0.70 (95% CI: 0.56, 0.87) or 1.04 (95% CI: 0.90, 1.19) if they were normotensive or hypertensive, respectively (P-interaction = 0.003). The CHD benefit among healthy normotensive women was partially offset by an increase in ischemic stroke risk. Corresponding HRs in the postintervention period were close to null. Participants with CVD at baseline (3.4%) had CHD HRs of 1.47 (95% CI: 1.12, 1.93) and 1.61 (95% CI: 1.02, 2.55) in the intervention and postintervention periods, respectively. However, various lines of evidence suggest that results in women with CVD or hypertension at baseline are confounded by postrandomization use of cholesterol-lowering medications.Conclusions: CVD risk in postmenopausal women appears to be sensitive to a change to a low-fat dietary pattern and, among healthy women, includes both CHD benefit and stroke risk. This trial was registered at clinicaltrials.gov as NCT00000611.

Keywords: LDL cholesterol; cardiovascular disease; cholesterol-lowering medications; coronary heart disease; low-fat dietary pattern; nutritional behavioral intervention; postrandomization confounding; randomized controlled trial; stroke.

© 2017 American Society for Nutrition.

Figures

FIGURE 1

CVD outcomes in the Dietary Modification Trial during the intervention period: overall, by baseline hypertension status among women without a history of CVD, and among women with a history of CVD. Summary statistics and forest plots are shown for the overall cohort (all women randomly assigned; left panel), baseline hypertension subgroups among women without a history of CVD (middle panels), and women with a history of CVD (right panel) during the intervention period. 1Self-report before randomization of MI, CABG/PCI, or stroke; may also have baseline hypertension. 2Self-report of ever taking antihypertensive medication before randomization, or clinic-measured systolic/diastolic blood pressure ≥140/90 mm Hg; excludes women with missing baseline hypertension status data. 3Sample size of the overall cohort and baseline subgroups at randomization. 4P1 corresponds to a 1-df test for the interaction between HR and baseline hypertension status among women without prior CVD. 5P2 corresponds to a 2-df test for the interaction between HR and baseline hypertension or prior CVD strata. CABG/PCI, coronary artery bypass graft/percutaneous coronary intervention; CHD, coronary heart disease; CVD, cardiovascular disease; MI, myocardial infarction.

FIGURE 2

Statin usage in the Dietary Modification Trial during the intervention period: overall, by baseline hypertension status among women without a history of CVD, and among women with a history of CVD. Summary statistics are shown for the overall cohort (all women randomly assigned; left panel), baseline hypertension subgroups among women without a history of CVD (middle panels), and women with a history of CVD (right panel) during the intervention period. Sample size indicates the number of participants with a baseline medication collection. To summarize statin usage during the 3 follow-up visits by randomization group (intervention or comparison), a mean OR (95% CI) was computed for all women and by subgroup through the use of generalized estimating equations with an unstructured correlation matrix. For the visual display, statin usage at each visit was computed as the percentage of women taking statins divided by the number of women with a medication collection; bow ties represent ∼95% confidence limits. 1Sample size of the overall cohort and baseline subgroups at randomization. 2Self-report of MI, CABG/PCI, or stroke before randomization; may also have baseline hypertension. 3Self-report of ever taking antihypertensive medication before randomization, or clinic-measured systolic/diastolic blood pressure ≥140/90 mm Hg; excludes women with missing baseline hypertension status data. 4P-interaction corresponds to a 2-df test for the interaction between OR and baseline hypertension or prior CVD strata. CABG/PCI, coronary artery bypass graft/percutaneous coronary intervention; CVD, cardiovascular disease; MI, myocardial infarction.

FIGURE 3

CVD outcomes in the Dietary Modification Trial during the postintervention period: overall, by baseline hypertension status among women without a history of CVD, and among women with a history of CVD. Summary statistics and forest plots are shown for the overall cohort (all randomly assigned women; left panel), baseline hypertension subgroups among women without a history of CVD (middle panels), and women with a history of CVD (right panel) during the postintervention period. 1Self-report of MI, CABG/PCI, or stroke before randomization; may also have baseline hypertension. 2Self-report before randomization of ever taking antihypertensive medication, or clinic-measured systolic/diastolic blood pressure ≥140/90 mm Hg; excludes women with missing baseline hypertension status data. 3Sample size of the overall cohort with active (upper panel) or passive (i.e., NDI linkage; lower panel) follow-up and baseline subgroups at randomization. 4P1 corresponds to a 1-df test for the interaction between HR and baseline hypertension status among women without prior CVD. 5P2 corresponds to a 2-df test for the interaction between HR and baseline hypertension or prior CVD strata. CABG/PCI, coronary artery bypass graft/percutaneous coronary intervention; CHD, coronary heart disease; CVD, cardiovascular disease; MI, myocardial infarction; NDI, National Death Index.

FIGURE 4

CVD outcomes in the Dietary Modification Trial during the cumulative intervention and postintervention periods: overall, by baseline hypertension status among women without a history of CVD, and among women with history of CVD. Summary statistics and forest plots are shown for the overall cohort (all women randomly assigned; left panel), baseline hypertension subgroups among women without a history of CVD (middle panels), and women with a history of CVD (right panel) during the postintervention period. 1Self-report of MI, CABG/PCI, or stroke before randomization; may also have baseline hypertension. 2Self-report of ever taking antihypertensive medication before randomization, or clinic-measured systolic/diastolic blood pressure ≥140/90 mm Hg; excludes women with missing baseline hypertension status data. 3Sample size of the overall cohort and baseline subgroups at randomization. 4P1 corresponds to a 1-df test for the interaction between HR and baseline hypertension status among women without prior CVD. 5P2 corresponds to a 2-df test for the interaction between HR and baseline hypertension or prior CVD strata. CABG/PCI, coronary artery bypass graft/percutaneous coronary intervention; CHD, coronary heart disease; CVD, cardiovascular disease; MI, myocardial infarction.