1. American Heart Association Goal: 1500 mg/day Darwin R. Labarthe, MD, MPH, PhD, FAHA M1 Lecture 2/2016 c/o Donald M. Lloyd-Jones

2. American Heart Association Position: 1,500 mg per day of dietary sodium intake AKA: “The winning side”

3. AHA 2011 Presidential Advisory The AHA recommends 1,500mg of sodium intake per day based on the strength and totality of evidence relating excess sodium intake to: High blood pressure Cardiovascular disease Stroke and The capacity of reduced intake of sodium to prevent and treat hypertension and to reduce the risk of adverse CVD and stroke events. Appel LJ, et al. Circulation 2011; 123:1138.

4. Rationale for Update to AHA Advisory AHA recommendations are based on the totality of evidence: 1. Experimental and laboratory studies 2. Survey data 3. Risk association 4. Clinical trials 5. Nutritional adequacy 4 Whelton PK, et al. Circulation 2013; 126:2880.

5. Experimental and Laboratory Studies Short- and medium-term, well-controlled studies. Association between excess sodium intake and blood pressure has been demonstrated in humans and several species of experimental animals, including mice, rats, rabbits, dogs, pigs, green monkeys, baboons, and chimpanzees. Sodium is associated with cardiac, arteriolar, and renal hypertrophy, fibrosis, and dysfunction. Longer term exposure likely leads to greater effects. 5 Whelton PK, et al. Circulation 2013; 126:2880.

6. Survey Data Little change in dietary sodium intake among men (4,100 mg/day) and women (3,200 mg/day) between 1988 and 2000 using data from the National Health and Nutrition Examination Survey (NHANES). These data are limited by 24 hour recall, which is prone to reporting bias. 2008 NHANES estimates suggest that >99% of Americans consume more than the AHA’s recommendation. Forthcoming NHANES exam cycles will include 24 hour urinary sodium estimates. 6 Whelton PK, et al. Circulation 2013; 126:2880.

7. Risk Association (1) 3 key problems with the majority of risk association studies: 1.Measurement error 2.Confounding 3.Reverse causality #1a) Large within-person, day-to-day variability in sodium intake #1b) Spot/overnight urinary sodium estimates are inadequate substitutes for 24hr estimates (often with weak or absent validation) #1c) Databases used for dietary recall are not updated regularly enough to account for changing food supply 7 Whelton PK, et al. Circulation 2013; 126:2880.

8. Risk Association (2) 3 key problems with the majority of risk association studies: 1.Measurement error 2.Confounding 3.Reverse causality # 2) Collinearity between sodium intake and other individual (and collective) nutritional variables (energy, potassium, e.g.) #3) Cohorts that include individuals with prevalent disease can invert the relationship between sodium intake and disease, because individuals with prevalent disease have been told to reduce their sodium intake (ONTARGET, TRANSCEND) 8 Whelton PK, et al. Circulation 2013; 126:2880.

9. Risk Association (3) 9 O’Donnell, NEJM 2014 Individuals with HTN and other diseases included Single AM spot urine with calculation of 24 hour urinary sodium

10. Risk Association (4) 10 Cook, Circulation 2014 Individuals with pre-HTN, not HTN Multiple direct measures of 24 hour urinary sodium

11. Clinical Trials (1) The threshold of 1,500 mg per day was derived from the Dietary Approaches for Stopping Hypertension (DASH) Trial 11 Sacks FM, et al. N Engl J Med 2001;344:3-10.

12. 2011 meta-analysis including 167 trials of sodium reduction demonstrated reductions in systolic blood pressure across various sub-groups: Hypertensive Normotensive Whites 5.2 mmHgWhites 1.3 mmHg Blacks 6.4 mmHgBlacks 4.0 mmHg Asians: 10.2 mmHgAsians: 1.3 mmHg 28 trials of >4 weeks’ duration; 5mmHg and 2 mmHg reduction among hypertensive and normotensive individuals, respectively. Outcomes trials have been underpowered to date. 12 Whelton PK,et al. Circulation 2013; 126:2880. Clinical Trials (2)

13. Conclusions The AHA continues to recommend a daily intake of 1,500 mg per day of sodium and disagrees with the Institute of Medicine’s recommendation for 2,300 mg per day. Especially when >50% of the US population includes individuals who are African American, >51 years old, pre- hypertensive, hypertensive, or with prevalent CVD. Calls for additional research should not be used as a delay tactic given the totality of evidence, including the recent English experience where food manufacturers have reduced sodium in the packaged food supply by 15% from 2000 to 2011 (demonstrating feasibility and safety). 13 Whelton PK, et al. Circulation 2013; 126:2880.

14. “High quality evidence in non-acutely ill adults shows that reduced sodium intake reduces blood pressure and has no adverse effect on blood lipids, catecholamine levels, or renal function, and moderate quality evidence in children shows that a reduction in sodium intake reduces blood pressure. Lower sodium intake is also associated with a reduced risk of stroke and fatal coronary heart disease in adults. The totality of evidence suggests that most people will likely benefit from reducing sodium intake.” 14 Aburto NJ, et al. BMJ 2013; 346:f1326. 2013 systematic review 5 RCTs/14 cohorts reporting events 37 RCTs reporting blood pressure changes 9 RCTs and 1 cohort in children 2g/day = 3.47 mm Hg (0.76 to 6.18) change in SBP

15. American Heart Association Position: 1,500 mg per day of dietary sodium intake AKA: “The winning side” Rebuttal slides – The AHA position

16. When is a surrogate not a surrogate? When should you ask for evidence behind the evidence? Who said 1500 mg/less should be the upper limit? And for whom? What has “the IOM” said about sodium? What ‘s REALLY holding us back? 16

17. High blood pressure is common, and prevalence increases with age. Prevalence of high blood pressure in adults by age and sex – NHANES, 2005- 2006

18. The risk of death from IHD increases with blood pressure at every age, 40-89.

19. U Na excretion and CVD outcomes O’Donnell et al. JAMA 2011

20. Evidence behind the evidence... 20

21. 17 global communities; similar results O’Donnell et al. N Eng J Med 2014.

22. Different dietary patterns show the lowest BP with lowest sodium intake, and conversely. 9.7 mmHg

23. A seemingly small difference in BP predicts large differences in deaths.

24. Sodium Recommendation: DGA 2005 2005 Dietary Guidelines for Americans (DGA) recommendation: <2,300 mg/day. http://www.health.gov/dietaryguidelines/dga2005/document/pdf/DGA2005.pdf “Specific populations” recommended to consume ≤1,500 mg/day: Hypertensives Blacks Middle-aged or older Americans “Specific populations”: 70% of American adults. Source: Ayala C, et al. Application of lower sodium intake recommendations to adults—United States, 1999–2006. MMWR Morb Mortal Wkly Rep. 2009;58(11):281–283.

25. Institute of Medicine Report and Recommendations - 2010

26. Findings – 1: Adverse health effects “…excess sodium intake is strongly associated with elevated blood pressure, a serious public health concern related to increased risk of heart disease, stroke, congestive heart failure, and renal disease.”

27. Findings – 2: Excess dietary intake “ The current level of sodium added to the food supply—by food manufacturers, foodservice operators, and restaurants—is simply too high to be “safe” for consumers.”

28. Findings – 3: Individual change limited “…instructing consumers to select lower-sodium foods and making available reduced-sodium “niche” products cannot result in intakes consistent with the Dietary Guidelines for Americans.”

29. IOM Recommendations Primary Strategy FDA should expeditiously initiate a process to set mandatory national standards for the sodium content of foods Applies to processed and restaurant foods Utilize generally recognized as safe (GRAS) status of salt

30. The Global Picture  A global public health issue – not just for the United States.  Reformulation of products has occurred in other countries.  Some countries, such as the United Kingdom, Australia, and Canada, are leaders in sodium-reduction efforts.  Sodium reduction and tobacco control – the two foremost strategies to reduce chronic disease deaths in developing countries.

31. Global Cost Savings Chronic disease prevention: health effects and financial costs of strategies to reduce salt intake and control tobacco use (Asaria et al., 2007) Investigated number of deaths that could potentially be averted over 10 years by implementation of selected population-based interventions Calculated the financial costs of implementation of interventions Used methods from the WHO Comparative Risk Assessment project to estimate shifts in the distribution of risk factors associated with salt intake Model the effects on chronic disease mortality for 23 countries that account for 80% of chronic disease burden in the developing world Source: The Lancet 2007;370,;2044-2053

32. Global Cost Savings Projected results over 10 years (2006-2015) 13.8 million deaths could be averted by implementation of interventions Cost is less than $0.40 per person per year Could substantially reduce mortality from chronic diseases and make a major (and affordable) contribution towards achievement of the global goal to prevent and control chronic diseases Source: The Lancet 2007;370,;2044-2053

33.  Excess salt masks other flavors  Salt taste changes with changing intake  Gradual changes go largely unnoticed  Resetting the palate: Less sodium means more natural flavors 33 Myths and Misconceptions 5. Food Will Lose Its Taste DARE TO TASTE THE TOMATO!