1. Omega-3 Fatty Acid/Fish Intake and Brachial Artery Flow-Mediated Dilation Jennifer S. Anderson, MD, PhD, MEd Cardiology Fellow/Research Fellow in the Multi-Ethnic Study of Atherosclerosis

2. Background Multiple studies have shown an inverse relationship between fish/omega-3 fatty acid consumption and cardiovascular events/death One potential mechanism includes omega-3 fatty acids’ impact on endothelial function Flow-mediated dilation (FMD) is a noninvasive surrogate for endothelial function Few studies have examined the relationship between dietary fish and FMD

3. Study Hypotheses 1. Consumption of non-fried fish foods rich in long- chain omega-3 fatty acids (eicosapentanoic acid (EPA), docosahexanoic acid (DHA)) will be positively associated with larger FMD across ethnic groups. Omega-3 rich (EPA, DHA) dietFlow-mediated dilation (FMD) 2.Concentrations of EPA and DHA in plasma phospholipids will demonstrate positive associations with FMD.

4. Cross-sectional analysis of MESA participants – n=6,814 men and women aged 45-85 years, free of CVD – Multi-center participation, 6 U.S. sites Baseline data collection including: – 120-item food frequency questionnaire – FMD measures (n = 3,137) – plasma phospholipid/fatty acid measures (n = 1,642) Study Design

5. Exposure Measures: Dietary Fish Non-fried fish tuna, salmon, sardines, sashimi or sushi; other broiled, steamed, baked, or raw fish including trout, sole, halibut, poke, grouper Shellfish (non-fried) shrimp, lobster, crab, oysters, mussels Fish in mixed dishes (non-fried) fish in enchiladas, burritos, quesadilla, pasta, stew, gumbo, paella, or salad Fried fish fried fish or fish sandwich, fried shrimp, calamari

6. Exposure Measures: Plasma EPA and DHA

7. Outcome: Brachial Artery Measures  Baseline brachial artery diameter  Maximum brachial artery diameter

8. Multivariate linear regression Stepwise approach Final model included: Stratified by gender, race/ethnicity Statistics  Age  Gender  Race/ethnicity  Smoking  Education  Income level  Physical activity  Systolic & diastolic BP  Lipid levels  BMI

9. Non-fried Fish & Brachial Measures: Overall Results, Baseline Artery Diameter (n = 642) (n = 943) (n = 838) (n = 714) *p < 0.001

10. Non-fried Fish & Brachial Measures: Baseline Diameter, Stratification by Gender* MenWomen *p = 0.02 (n = 338) (n = 455) (n = 411) (n = 344)(n = 304) (n = 488) (n = 427) (n = 370) p = 0.10 *adjusted for age, race, BMI, smoking, diabetes, SBP, DBP, total:HDL, exercise, income, education, and HRT (women)

11. Non-fried Fish & Brachial Measures: FMD, Stratification by Gender* MenWomen  Test for gender-fish interaction significant (p = 0.008 and 0.05 for baseline diameter & FMD, respectively) (n = 304) (n = 488) (n = 427) (n = 370)(n = 338) (n = 455) (n = 411) (n = 344) *p = 0.007 p = 0.23 *adjusted for age, race, BMI, smoking, diabetes, SBP, DBP, total:HDL, exercise, income, education, and HRT (women)

12. Non-fried Fish & Brachial Measures: FMD, Stratification by Gender* & Race/Ethnicity *results for women shown, fully adjusted model *p = 0.02

13. Plasma EPA+DHA & Brachial Measures: FMD, Stratification by Gender* p = 0.33 (n = 221) (n = 173) (n = 203) (n = 178) *adjusted for age, race, BMI, smoking, diabetes, SBP, DBP, total:HDL, exercise, income, education, and HRT (women)

14. Plasma EPA+DHA & Brachial Measures: FMD, Stratification by Gender* p = 0.33 (n = 221) (n = 173) (n = 203) (n = 178) *adjusted for age, race, BMI, smoking, diabetes, SBP, DBP, total:HDL, exercise, income, education, and HRT (women)

15. Summary 1.Gender differences were observed in the relationship between non-fried fish and both baseline artery diameter and FMD within the MESA cohort 2.Results examining plasma EPA+DHA levels corroborated results observed in dietary non- fried fish intake 3.Some race/ethnic differences were suggested

16. Next Steps 1.Are gender differences in brachial measures explained by variation in plasma %EPA vs %DHA? 2.Gender differences in the relationship between fish consumption & clinical events within MESA? 3.Gender differences in fish consumption & other markers of subclinical CVD (i.e. IMT, LV structure/function)? 4.Results replicable in other large cohorts with mixed race/ethnic groups?

17. Acknowledgements Mentors & MESA coauthors: David Herrington, MD, MHS Jennifer Nettleton, PhD David Siscovick, MD, MPH Craig Johnson, MPH Michael Tsai, PhD And special thanks to: Georgia Saylor

18. Thank You! Questions?