1. Sugar-Sweetened Beverage Consumption and Incident Cardiovascular Risk Factors: The Multi-Ethnic Study of Atherosclerosis (MESA) Christina Shay PhD MA 1 Jennifer Nettleton PhD 2 ; Pamela Lutsey PhD MPH 3 ; Tamar Polonsky MD 4 ; Mercedes Carnethon PhD 4 ; Linda Van Horn PhD RD 4, Gregory Burke MD MSc 5 1 Dept of Biostatistics and Epidemiology, Univ of Oklahoma Health Sciences Ctr, Oklahoma City, OK ; 2 Div of Epidemiology, Human Genetics and Environmental Sciences, Univ of Texas School of Public Health, Houston, TX; 3 Div of Epidemiology and Community Health, Univ of Minnesota, School of Public Health, Minneapolis 4 Dept of Preventive Medicine, Feinberg School of Medicine, Northwestern Univ, Chicago, IL; 5 Div of Public Health Sciences, Wake Forest Univ Health Science, Winston-Salem, NC Corresponding Author: christina-shay@ouhsc.edu

2. Background Sugar-sweetened beverage (SSB) consumption has been associated with weight gain and obesity, dyslipidemia, hyperglycemia, type 2 diabetes, and increased risk for cardiovascular (CV) events The association between SSB consumption and development of CV risk factors has not been extensively examined in large, prospective, multi-ethnic cohorts

3. Objective To quantify the association between SSB consumption and risk for developing individual CV risk factors in men and women in the Multi- Ethnic Study of Atherosclerosis (MESA)

4. MESA Study Description 6,814 participants recruited in 2000-2002 Field Centers: - Baltimore- New York - Chicago- St. Paul - Los Angeles - Winston-Salem 45-84 years, free of clinical cardiovascular disease 57% women 38% Non-Hispanic White, 28% African-American, 22% Hispanic, 12% Chinese American

5. Assessment of SSB Intake Food Frequency Questionnaire (FFQ) was used to measure SSB consumption at the first exam (2000-2002) The FFQ specifically asked about consumption of “regular soft drinks, soda, sweetened mineral water (not diet), and nonalcoholic beer” SSB intake was categorized into the following groups: 0-<1, 1-<2, and 2+ servings per day

6. CV Risk Factors Definitions (1) Weight Gain: Weight on any follow-up exam or average of all exam weight measurements >3% higher than baseline Increased Waist Circumference (WC): WC from any follow-up exam or average of all exam WC measurements >3% higher than baseline High Triglycerides: HDL >40 mg/dL (men), > 50mg/dL (women), LDL 150mg/dL

7. Low HDL cholesterol: HDL <40mg/dL (men), <50 mg/dL (women), LDL <160mg/dL, and triglycerides <150mg/dL Impaired Fasting Glucose: Fasting plasma glucose 100- 125 mg/dL Type 2 Diabetes (T2D): Fasting glucose ≥126 mg/dL, medication use for T2D or self-reported T2D CV Risk Factors Definitions (2)

8. Selection of Study Participants for the Current Study 8 6,814 MESA participants ages 45-84 and free of clinical CVD at first exam General Analysis Sample (n=4,166) Lipid Analyses (n=1,614) IGT Analyses (n=3,437) Excluded Participants No follow up exams (n=761) Type 2 diabetes at baseline(n=773) BMI <18.5 kg/m 2 at baseline (n=37) Missing covariates of interest (n=1,077) Additional Exclusions Lipid Medication Use (n=2,552) Impaired fasting glucose at baseline (n=729)

9. Statistical Analyses Cox proportional hazards regression used estimate hazard ratios All risk estimates adjusted for: Age Sex Race/ethnicity Study center Educational attainment Intentional exercise Smoking status Dietary intake (i.e., total energy, fiber, saturated fat, cholesterol, fruits and vegetables, sodium) Family history of T2D (for T2D incidence) Time-varying BMI and WC

10. Results

11. Table 1: MESA Baseline Characteristics According to SSB Consumption Sugar-sweetened beverage consumption (s/day) 0 - <11 - <22+ Number of Participants3418490258 Male sex (%)**44.556.154.6 Age (years)**61.7 (10.3)58.8 (9.8)56.2 (8.9) Current smokers (%)**11.317.819.0 Body Mass Index (kg/m 2 )**27.5 (5.0)29.3 (5.3)30.0 (6.1) Waist Circumference (cm)**95.6 (13.6)100.2 (13.2)101.1 (14.9) Total Intentional Exercise, MET-min/wk [median (IQR)]** 945.0 (210.0 - 2175.0) 630.0 (0.0 -1635.0)495.0 (0.0 - 1680.0) HDL Cholesterol (mg/dL)**52.7 (15.5)48.8 (13.9)46.9 (12.9) LDL Cholesterol (mg/dL)120.0 (30.8)119.4 (31.1)122.1 (30.0) Triglycerides [median (IQR)]*106.0 (75.0-153.0)108.0 (79.0-153.0)113.0 (81.0-167.0) Fasting Plasma Glucose (mg/dL) 88.8 (10.4)89.6 (10.3)90.1 (10.3) Systolic Blood Pressure (mmHg)124.6 (21.0)124.7 (20.7)123.1 (19.5) Diastolic Blood Pressure (mmHg) **71.5 (10.2)73.4 (10.9)73.6 (9.9) Follow-Up Time, years4.7 (0.8) 4.6 (0.8) IQR, interquartile range; Significantly different across groups, *p-value < 0.01, **p-value < 0.001

12. Hazard Ratios (95% CI) for Weight Gain According to Level of Sugar-Sweetened Beverage Consumption: The Multi-Ethnic Study of Atherosclerosis (MESA) Men Women Hazard Ratios (95% C.I.)

13. Hazard Ratios (95% CI) for Increased Waist Circumference According to Level of Sugar-Sweetened Beverage Consumption: The Multi-Ethnic Study of Atherosclerosis (MESA) Men Women Hazard Ratios (95% C.I.)

14. Hazard Ratios (95% CI)* for High Triglycerides According to Level of Sugar-Sweetened Beverage Consumption: The Multi-Ethnic Study of Atherosclerosis (MESA) Men Women Hazard Ratios (95% C.I.)

15. Hazard Ratios (95% CI) for Low HDL Cholesterol According to Level of Sugar-Sweetened Beverage Consumption: The Multi-Ethnic Study of Atherosclerosis (MESA) Men Women Hazard Ratios (95% C.I.)

16. Hazard Ratios (95% CI) for Impaired Fasting Glucose According to Level of Sugar-Sweetened Beverage Consumption: The Multi-Ethnic Study of Atherosclerosis (MESA) Men Women Hazard Ratios (95% C.I.)

17. Hazard Ratios (95% CI) for Type 2 Diabetes According to Level of Sugar-Sweetened Beverage Consumption: The Multi-Ethnic Study of Atherosclerosis (MESA) Men Women Hazard Ratios

18. Summary Women who consumed 2+ SSBs per day exhibited higher risk for developing: –high triglycerides –impaired glucose tolerance –increased waist circumference compared to women who consumed <1 SSB per day These associations remained even after accounting for baseline and time varying BMI and WC 18

19. Strengths and Limitations Strengths The MESA study is a large, population-based cohort designed to examine the development of CVD risk factors Limitations Food frequency item used likely to not have captured all types of SSBs consumed

20. American Beverage Association "This type of study cannot show that drinking sugar-sweetened beverages causes increased risk for cardiovascular disease. It simply looks at associations between the two, which could be the result of numerous other confounding factors.”

21. Conclusions The influence of SSBs consumption on cardiovascular risk is complex and may not be the same between middle- and older-aged men and women Women exhibit lower energy requirements compared to men and may therefore experience higher CV risk when a greater proportion of calories is consumed in the form of SSBs 21

22. Acknowledgements Co-Authors: Jennifer Nettleton, Pamela Lutsey, Tamar Polonsky, Linda Van Horn, Gregory Burke MESA’s Funding Agency: National, Heart, Lung, and Blood Institute (NHLBI) THANK YOU

23. Table 1: Characteristics According to SSB Consumption at First Exam Sugar-sweetened beverage consumption (s/day) 0 - <11 - <22+ Number of Participants3418490258 Sugar-sweetened beverage consumption (s/day) [median]** 0.01.02.5 Male sex (%)**44.556.154.6 Age (years)**61.7 (10.3)58.8 (9.8)56.2 (8.9) Education > high school (%)68.065.163.6 Current smokers (%)**11.317.819.0 Body Mass Index (kg/m 2 )**27.5 (5.0)29.3 (5.3)30.0 (6.1) Waist Circumference (cm)**95.6 (13.6)100.2 (13.2)101.1 (14.9) Total Intentional Exercise, MET-min/wk [median (IQR)]* 945.0 (210.0 - 2175.0)630.0 (0.0 -1635.0)495.0 (0.0 - 1680.0) HDL Cholesterol (mg/dL)**52.7 (15.5)48.8 (13.9)46.9 (12.9) LDL Cholesterol (mg/dL)120.0 (30.8)119.4 (31.1)122.1 (30.0) Triglycerides [median (IQR)]*106.0 (75.0-153.0)108.0 (79.0-153.0)113.0 (81.0-167.0) Fasting Plasma Glucose (mg/dL)88.8 (10.4)89.6 (10.3)90.1 (10.3) Systolic Blood Pressure (mmHg)124.6 (21.0)124.7 (20.7)123.1 (19.5) Diastolic Blood Pressure (mmHg)**71.5 (10.2)73.4 (10.9)73.6 (9.9) Anti-Hypertensive Medication use (%)29.928.829.1 Follow-Up Time, years4.7 (0.8) 4.6 (0.8) IQR, interquartile range; Significantly different across groups, *p-value < 0.01, **p-value < 0.001

24. CV Risk Factors Sugar-Sweetened Beverage Consumption WomenMen 0 - <11 - <22+0 - <11 - <22+ Weight gain >3% N17591951021412253129 # Cases69489475087851 WC gain >3% N17591951021412253129 # Cases953108655869457 Hypertriglyceridemia 1 N79083375768147 # Cases7911979105 Low HDL 1 N79083375768147 # Cases116196731310 Type 2 diabetes N18972151171521275141 # Cases13820151092212 Impaired Fasting Glucose N1621179931215217112 # Cases33139253245124 Sample Sizes