Getting the science right on the health outcomes of salt reduced diets

1. Sodium intake and mortality Perspectives on the evidence from the U.S. National Health and Nutrition Examination Surveys (NHANES) Hillel W. Cohen, MPH, DrPH Associate Professor of Epidemiology and Population Health Albert Einstein College of Medicine, Bronx NY

2. The Sodium Hypothesis Higher Sodium (Na) Intake Elevated Blood Pressure (BP) Excess Cardiovascular Disease (CVD) Events

3. Blood pressure: a demonstrated, modifiable risk factor of CVD Elevated Blood Pressure Excess CVD Events Consistent evidence Meaningful effect

4. How strong is the association between higher Na and BP? Elevated Blood Pressure Higher Sodium Intake Data suggest the magnitude of the association is modest

9. What is the relationship of sodium intake with CVD events? A mount B P sodium ? B P C vd A mount C vd sodium Does association of BP with both Na and CVD answer the question?

13. Na and CVD: cohort studies MRFIT* Outcome: All-cause mortality Population: males Median urinary sodium ~ 117 mmol/d Results: no association *Cutler JA. ASH 1997 (presentation).

14. Na and CVD: cohort studies Hawaiian Japanese Men* Outcome: Stroke Population: men, Japanese ancestry, n=7895 Median dietary sodium: approx. 2000 mg/d Results: no association *Kagan et al. Stroke, 1985.

15. Na and CVD: cohort studies Worksite Hypertension Program* Outcome: Myocardial Infarction Population: Treated hypertensives n=2937 Median urinary sodium (mmol/d): Men: 126 mmol Women 97 mmol Results: Inverse association for men No association for women *Alderman et al. Hypertension, 1995.

16. Na and CVD: cohort studies Scottish Heart Health Study* Outcome: All CHD, CHD & All-Cause Mortality Population: Scottish adults n= 11,629 Mean urinary sodium mmol/d males ~ 186 mmol females ~ 136 mmol Results Males: Indirect assoc., All-Cause Mortality Females: Direct assoc., All CHD No assoc. for other outcomes, either sex *Tunstall-Pedoe et al., BMJ 1997.

17. Na and CVD: cohort studies Finland study* Outcome: CHD; CHD, CVD & All Mortality Population: Finish adults n= 2533 Median urinary sodium mmol/d males = 206 mmol females = 155 mmol Results: Direct associations *Tuomilehto et al. Lancet, 2001.

18. Na and CVD: cohort studies Takayama Study* Outcome: Stroke Mortality Population: Japanese adults n= 39,079 Mean dietary sodium ** males = 5.7 gm females = 5.2 gm Results: Direct association with stroke *Nagata et al. Stroke, 2004. **Mean Na for middle tertile

19. Na and CVD: cohort studies TOHP (Trials of hypertension prevention)* Outcome: All CVD; All cause mortality Population: 3126 U.S. adults 30-54 y.o. Diastolic 80-89 mmHg; BMI ≥25 in >90% participants Results for lower Na group: Significant (p=.044) protection for all CVD Not significant (p=.35) for all mortality *Cook et al. BMJ 2007

20. The NHANES Experience National Health and Nutrition Examination Surveys Representative samples of non-institutionalized adults in the U.S. Outcome follow-up added after. Sodium and calories from 24-hr dietary recall. Baseline surveys conducted NHANES I 1971-1975 NHANES II 1976-1980 NHANES III 1988-1994

21. The NHANES Experience NHANES I (a) * Outcome: CVD and All-Cause Mortality Population: U.S. adults n= 11,346 Mean dietary sodium: (mg/d) Men: 2515 mg Women 1701 mg Results: Inverse association for Na Direct association for Na/Cal *Alderman et al. Lancet, 1998.

22. The NHANES Experience NHANES I (b) * Outcome: Stroke, CVD & All-Cause Mortality Population: U.S. adults n= 9,485 BMI <27.8 kg/m 2 n=6797 BMI > 27.8 n=2688 Results: Direct associations in Overweight (28%) No associations in Non-overweight (72%) *He et al. JAMA, 1999.

23. The NHANES Experience NHANES II* Outcome: CVD and All-Cause Mortality Population: U.S. adults ages 30-74 at entry n= 7154 representing 78.9 million Mean dietary sodium: 2718 mg/d Median: 2360 mg/d *Cohen et al. Sodium intake and mortality in the NHANES II Follow-up Study. American Journal of Medicine (2006) 119: 275.e7-275.e14.

24. NHANES II * CVD and all-cause mortality *Cohen et al. AJM, 2006 . ** rates without weighting;RR with weighting Age-sex adjusted rates**

25. NHANES II * Adjusted CVD Mortality Hazard Ratios *Cohen et al. AJM, 2006 . Adjusted for age, sex, race, smoking, alcohol, SBP, BP-txt, BMI, education, physical activity, dietary K, Hx diabetes, cholesterol, (calories) .03 0.80, 0.99 0.89 Na per 1000 mg .04 1.01, 1.49 1.22 Na <residuals adjusted median .03 1.03, 1.81 1.37 Na < 2300 mg .008 0.68, 0.94 0.80 Na mg per calorie P 95% CI H.R. Sodium

26. NHANES II * All-Cause Mortality Hazard Ratios *Cohen et al. AJM, 2006 . Adjusted for age, sex, race, smoking, alcohol, SBP, BP-txt, BMI, education, physical activity, dietary K, Hx diabetes, cholesterol, (calories) .06 0.87, 1.00 0.93 Na per 1000 mg .13 0.97, 1.30 1.12 Na <residuals adjusted median .003 1.10, 1.50 1.28 Na < 2300 mg .05 0.79, 1.00 0.89 Na mg per calorie P 95% CI H.R. Na

27. Adjusted hazard ratios of CVD mortality for Na intake <2300 mg in 27 selected subgroups estimated by Cox models

28. Adjusted hazard ratios of CVD mortality for Na intake <2300 mg in 27 selected subgroups estimated by Cox models

30. NHANES III* Population: U.S. adults age >30 at entry Exclusions: CVD at baseline or on low salt diet for BP Remaining n = 8699 (representing about 100 million) Mean dietary sodium: 3207 ± 1608 mg/d Median: 2922 mg/d (IQR: 2060, 4048) *Cohen et al. Sodium intake and mortality follow-up in the Third National Health and Nutrition Examination Survey (NHANES III), JGIM 2008.

31. NHANES III* Outcomes: CVD deaths: 436 (236 CHD, 82 CVA, 118 other) All-Cause Mortality: 1150 deaths Mean follow-up time: 8.7 ±2.3 years Hazard ratios adjusted for age, sex, race/ethnicity, education, smoking, diabetes, cancer, SBP, alcohol, physical activity, dietary K, weight, cholesterol, txt for hypertension and calories *Cohen et al. Sodium intake and mortality follow-up in the Third National Health and Nutrition Examination Survey (NHANES III), JGIM 2008.

32. NHANES III * Adjusted CVD Mortality Hazard Ratios *Cohen et al. JGIM, 2008. Adjusted for age, sex, race/ethnicity, education, smoking, diabetes, cancer, SBP, alcohol, physical activity, dietary K, weight, cholesterol, txt for hypertension (calories for 1 st row) .07 0.77, 1.01 0.88 Na per 1000 mg .07 0.77, 1.01 0.88 Na residuals adjusted per 1000 mg .40 0.72, 1.14 0.91 Na mg per calorie P 95% CI H.R. Sodium

33. NHANES III * Adjusted All-Cause Mortality HRs *Cohen et al. JGIM, 2008. Adjusted for age, sex, race/ethnicity, education, smoking, diabetes, cancer, SBP, alcohol, physical activity, dietary K, weight, cholesterol, txt for hypertension (calories for 1 st row) .11 0.88, 1.01 0.94 Na per 1000 mg .11 0.88, 1.02 0.95 Na residuals adjusted per 1000 mg .94 0.88, 1.12 1.00 Na mg per calorie P 95% CI H.R. Sodium

34. NHANES III* 99% CI for Hazard Ratios per 1000 mg Na CVD mortality: (.73, 1. 06 ) All cause mortality: (.86, 1. 04 ) Very small probability of meaningful increased risk of mortality per 1000 mg Na *Cohen et al. Sodium intake and mortality follow-up in the Third National Health and Nutrition Examination Survey (NHANES III). JGIM, 2008.

39. No strong evidence for either benefit or harm of sodium restriction With regard to clinical outcomes of morbidity and mortality:

41. Should government restrict sodium in processed food? With little and contradictory evidence regarding benefit or harm, does the rationale of “can’t hurt” apply?

46. Contact information: Dr. Hillel W. Cohen Dept. of Epidemiology and Population Health Albert Einstein College of Medicine Bronx, NY 10461, USA 718-430-3745 [email_address]