Risk of heart failure and subtypes with biomarker-calibrated protein intake: Women's health initiative cohort study

Introduction: Heart failure (HF) is a growing epidemic, with risk of HF with preserved ejection fraction (HFpEF) significantly higher in post-menopausal women compared to men. Data on its association with dietary protein intake is limited. Methods: To study the association of dietary protein intake with risk of HF and its subtypes in post-menopausal women, we included post-menopausal women from Women's Health Initiative's (WHI) HF cohort. Protein intake was assessed from the biomarker measurements in the WHI Nutrient Biomarker Study (WHI-NBS), and its calibration on Food-Frequency-Questionnaire (FFQ) based protein intake. Cox-proportional hazards regression analysis was used to study associations. Results: Total of 14,789 women were included with a mean age (SD) of 62 (7) years and follow-up of 14 (8) years. Participants were predominantly African American (48.5 %). Multivariable Cox-proportional hazards regression model adjusted for age, education, income, race/ethnicity, physical activity, smoking, alcohol, prevalent and incident CHD, hypertension, hyperlipidemia, and atrial fibrillation showed elevated risk of total incident hospitalized HF and HFpEF with higher intake of dietary protein across all quintiles (Q2-Q5) compared to Q1 in a dose-response relationship (HR of HF, Q5 compared to Q1: 2.26, 95 % CI: 1.66, 3.09, P<.0001; HR of HFpEF, Q5 compared to Q1: 2.50, 95 % CI 1.62, 3.84, P<.0001). When stratified by BMI, HF and HFpEF risk was elevated across quintiles of BMI > 30, indicating BMI may be an effect modifier. Conclusion: In conclusion, higher protein intake is associated with increased risk of HF and HFpEF, particularly in obese participants.