Dietary Inflammatory Potential and Risk of Cardiovascular Disease Among Men and Women in the U.S

Abstract

Background: Inflammation plays an important role in cardiovascular disease (CVD) development. Diet modulates inflammation; however, it remains unknown whether dietary patterns with higher inflammatory potential are associated with long-term CVD risk.

Objectives: This study sought to examine whether proinflammatory diets are associated with increased CVD risk.

Methods: We prospectively followed 74,578 women from the Nurses' Health Study (NHS) (1984-2016), 91,656 women from the NHSII (1991-2015), and 43,911 men from the Health Professionals Follow-up Study (1986-2016) who were free of CVD and cancer at baseline. Diet was assessed by food frequency questionnaires every 4 years. The inflammatory potential of diet was evaluated using a food-based empirical dietary inflammatory pattern (EDIP) score that was pre-defined based on levels of 3 systemic inflammatory biomarkers.

Results: During 5,291,518 person-years of follow-up, we documented 15,837 incident CVD cases, including 9,794 coronary heart disease (CHD) cases and 6,174 strokes. In pooled analyses of the 3 cohorts, after adjustment for use of anti-inflammatory medications and CVD risk factors including body mass index, a higher dietary inflammatory potential, as indicated by higher EDIP scores, was associated with an increased risk of CVD (hazard ratio [HR] comparing the highest to lowest quintiles: 1.38; 95% confidence interval [CI]: 1.31 to 1.46; p for trend <0.001), CHD (HR: 1.46; 95% CI: 1.36 to 1.56; p for trend <0.001), and stroke (HR: 1.28; 95% CI: 1.17- to 1.39; p for trend <0.001). These associations were consistent across cohorts and between sexes, and they remained significant after further adjustment for other dietary quality indices. In a subset of study participants (n = 33,719), a higher EDIP was associated with a higher circulating profile of proinflammatory biomarkers, lower levels of adiponectin, and an unfavorable blood lipid profile (p < 0.001).

Conclusions: Dietary patterns with a higher proinflammatory potential were associated with higher CVD risk. Reducing the inflammatory potential of the diet may potentially provide an effective strategy for CVD prevention.

Keywords: cardiovascular disease; chronic inflammation; coronary heart disease; dietary patterns; predictive biomarkers; stroke.

figure 1. Dose-response relationship of the EDIP scores with risk of (A) CVD, (B) CHD, and (C) stroke

We combined data from NHS, NHSII, and HPFS for the cubic spline analyses. Models were stratified by cohort, age in months, and follow-up period and were adjusted for race, smoking, menopausal status and post-menopausal hormone use (in women), multivitamin use, regular aspirin use, regular use of other anti-inflammatory medications, physical activity, hypercholesterolemia, hypertension, diabetes, family history of myocardial infarction, and body mass index. Reference levels were set to the median EDIP values of the first quintile. Vertical dashed lines indicate cutoff values of EDIP quintiles (i.e., −0.74, −0.19, 0.24, and 0.75). Solid curves indicate HRs, and dashed curves depict 95% CIs. The axis for HR is nature log-scaled with original labels. CHD = coronary heart disease; CI = confidence interval; CVD = cardiovascular disease; EDIP = empirical dietary inflammatory pattern; HPFS = Health Professionals Follow-Up Study; HR = hazard ratio; NHS = Nurses’ Health Study.

figure 2. HR (95% CI) for CVD, CHD, and Stroke Associated With a 1-SD Increase in EDIP Scores, Stratified by Pre-selected Cardiovascular Risk Factors

Multivariable adjusted HRs (indicated by blue dots) and 95% CIs (indicated by black horizonal lines) were calculated separately in each cohort and combined using a fixed-effects meta-analysis. The full model in Table 2 was used, with the exception of not adjusting for a categorical covariate when it was used as strata. The p values for differences across subgroups of risk factors are presented to the right. The axis for HR is nature log-scaled with original labels. Abbreviations as in Figure 1

figure 3. Associations Between EDIP Scores and Levels of Inflammatory Biomarkers

Linear regressions were used to analyze associations between cumulatively averaged EDIP scores (average of 1984 and 1986 in NHS, 1991 and 1995 in NHSII, and 1986 and 1990 in HPFS) and levels of inflammatory biomarkers measured using blood samples collected several years later (1989 and 1990 in NHS, 1996 to 1999 in NHSII, and 1993 to 1995 in HPFS). Multivariable models were adjusted for study cohort, age, fasting status, body mass index, race, smoking, regular aspirin use, regular use of other anti-inflammatory medications, steroid use, multivitamin use, menopausal status and post-menopausal hormone use (in women), physical activity, hypercholesterolemia, diabetes, hypertension, family history of CHD, and case-control status in original substudies. Dots represent SD differences in biomarkers comparing higher to the lowest EDIP quintiles, and vertical lines represent 95% CIs. hsCRP = high-sensitive C-reactive protein; sICAM-1 = soluble intercellular adhesion molecule-1; TNFα-R1 = tumor necrosis factor-a receptor 1; TNFα-R2 = tumor necrosis factor-α receptor 2; other abbreviations as in Figure 1.

CENTRAL ILLUSTRATION. Adherence to Proinflammatory Dietary Patterns and Cardiovascular Disease Incidence

Dietary patterns with a higher inflammatory potential were significantly associated with a higher incidence of cardiovascular disease and subtypes, including coronary heart disease and stroke, in 3 prospective cohorts including 210,145 U.S. women and men and followed up for up to 32 years. Secondary analyses further showed that higher dietary inflammatory potential was significantly associated with biomarkers indicating higher systemic, vascular, and metabolic inflammation and an unfavorable lipid profile. The axis for hazard ratio is nature log-scaled with original labels.