Eating Pattern Response to a Low-Fat Diet Intervention and Cardiovascular Outcomes in Normotensive Women: The Women's Health Initiative

Abstract

Background: Women without cardiovascular disease (CVD) or hypertension at baseline assigned to intervention in the Women's Health Initiative Dietary Modification (DM) trial experienced 30% lower risk of coronary heart disease (CHD), whereas results in women with hypertension or prior CVD could have been confounded by postrandomization use of statins.

Objectives: Intervention participants reported various self-selected changes to achieve the 20% total fat goals. Reviewed are intervention compared with comparison group HRs for CHD, stroke, and total CVD in relation to specific dietary changes in normotensive participants.

Methods: Dietary change was assessed by comparing baseline with year 1 FFQ data in women (n = 10,371) without hypertension or CVD at baseline with intake of total fat above the median to minimize biases due to use of the FFQ in trial eligibility screening.

Results: Intervention participants self-reported compensating reduced energy intake from total fat by increasing carbohydrate and protein. Specifically they increased plant protein, with those in the upper quartile (increased total protein by ≥3.3% of energy) having a CHD HR of 0.39 (95% CI: 0.22, 0.71), compared with 0.92 (95% CI: 0.57, 1.48) for those in the lower quartile of change (decreased total protein ≥0.6% of energy), with P-trend of 0.04. CHD HR did not vary significantly with change in percentage energy from carbohydrate, and stroke HR did not vary significantly with any macronutrient changes. Scores reflecting adherence to recommended dietary patterns including the Dietary Approaches to Stop Hypertension Trial and the Healthy Eating Index showed favorable changes in the intervention group.

Conclusions: Intervention group total fat reduction replaced with increased carbohydrate and some protein, especially plant-based protein, was related to lower CHD risk in normotensive women without CVD who reported high baseline total fat intake. This trial was registered at clinicaltrials.gov as NCT00000611. Link to the WHI trial protocol: https://www.whi.org/about/SitePages/Dietary%20Trial.aspx.

Keywords: cardiovascular outcomes; food choices; low-fat diet; normotensive women; self-selected dietary change; vegetable protein.

Copyright © The Author(s) 2020.

Figures

FIGURE 1

Participant flow diagram. Participant flow diagram for the Women's Health Initiative trial of a low-fat dietary pattern in women without hypertension or prior history of CVD at baseline but who reported intake of total fat above the median. All participants were postmenopausal and in the age range 50–79 y when enrolled during 1993–1998 at 40 US clinical centers. 1Hypertension was defined as self-report of ever taking medication for hypertension before randomization, or clinic-measured systolic/diastolic blood pressure ≥140/90 mm Hg. 2Prior history of CVD was defined as self-report before randomization of MI, CABG/PCI, or stroke. 3Time-origin for Cox regression models began at year 1. 4Implausible energy intakes of <600 kcal/d or >5000 kcal/d. CABG/PCI, coronary artery bypass graft/percutaneous coronary intervention; CVD, cardiovascular disease; MI, myocardial infarction.

FIGURE 2

Diet quality scores by randomization group among normotensive participants consuming a high-fat diet at baseline. Mean (SD) change (year 1 minus baseline) and effect size of diet quality scores by randomization group in normotensive participants who consumed ≥36.6% energy from fat without a history of CVD (n = 10,371); diet quality scores are summarized in Supplemental Table S1. Changes in diet quality scores are ranked by effect size (best to worst) to facilitate comparisons between scores. Likewise, components are ranked to facilitate within-score comparisons. Vertical reference lines indicate effects that are large (0.8 SD), median (0.5 SD), and small (0.2 SD) (17). Diet quality scores and components can have different ranges, so mean (SD) should not be compared across or within scores. AHEI, Alternative Healthy Eating Index; aMed, Alternate Mediterranean Diet; CVD, cardiovascular disease; DASH, Dietary Approaches to Stop Hypertension Trial; HEI, Healthy Eating Index.

FIGURE 3

HRs in normotensive participants consuming a high-fat diet at baseline. Forest plot of HR estimates by pertinent study subject characteristics in normotensive participants who consumed ≥36.6% energy from fat without a history of CVD (n = 10,371). Fitted HRs (lower half; intervention vs. comparison) for CHD risk are based on the estimated regression coefficients (Supplemental Table S2) evaluated at the average eating patterns reported by the intervention group overall and for increasing changes in energy from protein (Supplemental Table S3) and carbohydrates (Supplemental Table S4). For example, the HRs (0.92, 0.67, 0.55, 0.39) that correspond to increasing change in energy from protein (quartiles: <−0.6%, −0.6 to <1.3%, 1.3 to <3.3%, ≥3.3%) were computed from the regression coefficients at the observed (average) change in energy from protein (−2.6, 0.4, 2.2, 5.3%), carbohydrates (17.1, 14.6, 14.1, 11.9%), and alcohol (0.7, 0.4, 0.3, 0.1%); these changes offset the observed decrease in energy from total fat (−15.3, −15.3, −16.6, −17.3%). P values for fitted HRs correspond to tests for trend of the observed eating pattern and are intended to complement, not supersede, P values for specific HR interactions shown in Supplemental Table S2. CHD, coronary heart disease; CVD, cardiovascular disease.

FIGURE 4

Changes in metabolic syndrome components among normotensive participants consuming a high-fat diet at baseline. Forest plot of estimated average change (intervention vs. comparison) for metabolic syndrome components in normotensive participants who consumed ≥36.6% energy from fat without a history of CVD (n = 10,371). Estimates of change are based on the estimated regression coefficients evaluated at the average eating patterns reported by the intervention group for increasing changes in energy from protein (Supplemental Table S3) and carbohydrates (Supplemental Table S4). Laboratory measurements based on a 5.8% subsample of trial participants. Because of skewed distributions glucose and triglycerides were log-transformed and ratios of geometric means were presented. BP, blood pressure; CVD, cardiovascular disease; HDL-C, HDL-cholesterol.