Abstract

Introduction: Ultra-processed foods (UPF) are associated with cardiovascular disease (CVD) in European populations. Evidence is limited from U.S. populations, for specific UPF subgroups, and in the diet quality context. Hypothesis: We hypothesized that U.S. women with higher UPF intake have higher CVD risk and evaluated this association by UPF subgroup and diet quality. Methods: Women from the Nurses' Health Study (NHS; n=75,639; 30-55y) and NHSII (n=90,770; 25-42y) with complete dietary intake data and without CVD/cancer at baseline were prospectively followed (1984-2014 and 1991-2015). Diet, demographics, lifestyle, and medical history were assessed every 2-4y using validated food frequency questionnaires and follow-up questionnaires. NOVA-classified UPF (% of energy) included ten subgroups: bread and cereals; sauces, spreads, and condiments; sweet snacks and desserts; savory snacks; sugar-sweetened beverages; animal-based products; ready-to-eat/heat dishes; yogurt and dairy desserts; hard liquors, and artificially sweetened beverages. The Alternative Healthy Eating Index (AHEI) measured diet quality. Primary outcomes were non-fatal myocardial infarction, fatal coronary heart disease (CHD), and non-fatal/fatal stroke. Multivariable-adjusted Cox regression estimated the associations of cumulatively-averaged UPF and subgroup intake quintiles with CVD risk. Each cohort was analyzed separately, and data were meta-analyzed (fixed effects models). Results: We identified 7,659 CVD cases (CHD=3,889; stroke=3,855) in NHS during 2,002,986 person-years of follow-up, and 1,588 CVD cases (CHD=807; stroke=786) in NHSII during 2,308,569 person-years. Pooled multivariable-adjusted hazard ratios [HRs (95%CIs)] of CVD, CHD, and stroke for the highest quintile of UPF intake ( vs. lowest) were 1.11 (1.04, 1.19; p-trend =0.002), 1.18 (1.08, 1.30; p-trend <0.001), and 1.05 (0.95, 1.15; p-trend =0.37), respectively. Positive associations remained for participants with higher diet quality (AHEI above the sample median): CVD [HR=1.15 (1.05, 1.25; p-trend =0.009)] and CHD [HR=1.24 (1.09, 1.41; p-trend =0.007)]. Values of I 2 were non-significant. For UPF subgroups, intake for the highest quintile of sugar-sweetened beverages and animal-based products was significantly associated with higher risk of CVD, CHD, and stroke. Significant inverse associations were noted for bread and cereals and yogurt and dairy dessert with CVD, CHD, and stroke, for savory snacks with CHD, and for ready-to-eat/heat dishes with stroke. Conclusion: U.S. women with long-term higher total UPF intake had a higher CHD risk, even with a high-quality diet. Sugary drinks and animal-based products were predominant for CVD risk. Some UPF subgroups may contain beneficial components, warranting more nuanced food subgroup analyses. Replication is needed in racially/ethnically-diverse populations.

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