Sodium Intake and Cardiovascular Disease: Rationale for Policy Action Thomas Farley, MD MPH Joan H. Tisch Distinguished Fellow in Public Health Policy Roosevelt House at Hunter College

InterventionIncidence of CHD Death from any cause Salt reduction: 3 g/day Low estimate66,000 ± ,000 ± 7100 High estimate110,000 ± ,000 ± 11,000 Smoking cessation41,000 ± 10,00084,000 ± 9300 Weight loss59,000 ± ,000 ± 2000 Statin therapy52,000 ± ± 540 Pharmacologic treatment of HTN100,000 ± 11,00080,000 ± 10,000 Source: Bibbins-Domingo K et al. Projected Effect of Dietary Salt Reductions on Future Cardiovascular Disease New England Jounral of Medicine. 362: Annual Estimated Reductions in Deaths and Cardiovascular Events: Comparison Across Various Interventions

Background Extremely common in U.S. and other “modern” populations: High sodium consumption High blood pressure Cardiovascular disease Questions: Does chronic high level of sodium consumption contribute to high blood pressure and to cardiovascular mortality? Would reductions in sodium consumption lead to reductions in blood pressure and reductions in cardiovascular mortality?

Evidence Supporting Na+ Intake Increases Cardiovascular Disease Risk Animal studies  Na ->  BP in many species, including primates Observational studies in humans  BP ->  Cardiovascular disease (CVD) Prospective Studies Collaboration, Lancet, 2002 He FJ and MacGregor GA. A comprehensive review of salt and health. J Hum Hypertension 2009;23:363 Appell LJ et al. The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke. Circulation 2011;123:1138 Whelton PK et al. Sodium, blood pressure, and cardiovascular disease. Circulation 2012;126

Stroke Mortality by Systolic BP Prospective Studies Collaboration, Lancet, 2002: Meta-analysis of 61 prospective studies with 2.7m person-yrs, 11.9k deaths Definition of Hypertension

Heart Disease Mortality by Systolic BP Prospective Studies Collaboration, Lancet, 2002: Meta-analysis of 61 prospective studies with 2.7m person-yrs, 11.9k deaths

Evidence Supporting Na+ Intake Increases Cardiovascular Disease Risk Animal studies  Na ->  BP in many species, including primates Observational studies in humans  BP ->  Cardiovascular disease (CVD)  Na ->  BP in cross-sectional, multi-population studies Prospective Studies Collaboration, Lancet, 2002 He FJ and MacGregor GA. A comprehensive review of salt and health. J Hum Hypertension 2009;23:363 Appell LJ et al. The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke. Circulation 2011;123:1138 Whelton PK et al. Sodium, blood pressure, and cardiovascular disease. Circulation 2012;126

Sodium Intake vs. Blood Pressure in 24 Populations Law MR et al, BMJ 1991;302:811-5 Isolated primitive tribes USA

Evidence Supporting Na+ Intake Increases Cardiovascular Disease Risk Animal studies  Na ->  BP in many species, including primates Observational studies in humans  BP ->  Cardiovascular disease (CVD)  Na ->  BP in cross-sectional, multi-population studies  Na ->  BP in migration studies  Na ->  CVD across most samples Intervention trials (short term) Treatment to  BP ->  CVD  Na intake ->  BP in meta-analyses Prospective Studies Collaboration, Lancet, 2002 He FJ and MacGregor GA. A comprehensive review of salt and health. J Hum Hypertension 2009;23:363 Appell LJ et al. The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke. Circulation 2011;123:1138 Whelton PK et al. Sodium, blood pressure, and cardiovascular disease. Circulation 2012;126

Limiting Sodium Intake Reduces Blood Pressure DASH-Sodium Trial Sacks FM et al. Effects on Blood Pressure of Reduced Dietary Sodium. NEJM Jan 4;344(1):3-10 High Intermediate Low 3,450 mg/day 2,300 mg/day 1,150mg/day Systolic Blood Pressure (mm Hg)

Evidence Supporting Na+ Intake Increases Cardiovascular Disease Risk Animal studies  Na ->  BP in many species, including primates Observational studies in humans  BP ->  Cardiovascular disease (CVD)  Na ->  BP in cross-sectional, multi-population studies  Na ->  BP in migration studies  Na ->  CVD across most samples Intervention trials (short term) Treatment to  BP ->  CVD  Na intake ->  BP in meta-analyses  Na intake ->  CVD across most samples Prospective Studies Collaboration, Lancet, 2002 He FJ and MacGregor GA. A comprehensive review of salt and health. J Hum Hypertension 2009;23:363 Appell LJ et al. The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke. Circulation 2011;123:1138 Whelton PK et al. Sodium, blood pressure, and cardiovascular disease. Circulation 2012;126

Effects of Reduced Na on CVD Events: Results from 3 Randomized Trials INTERVENTIONOUTCOMEFU TONE (2001) 639 Elderly ↓ Na 21% ↓ CVD events 2.3 yrs Taiwan Veterans (2006) 1,981 Elderly ↓ Na /↑ K Salt 41%* ↓ CVD Mortality 2.6 yrs TOHP Follow-up (2007) 3,126 Prehypertensives ↓ Na 30%* ↓ CVD events yrs *p<0.05

Evidence Supporting Na+ Intake Increases Cardiovascular Disease Risk Animal studies  Na ->  BP in many species, including primates Observational studies in humans  BP ->  Cardiovascular disease (CVD)  Na ->  BP in cross-sectional, multi-population studies  Na ->  BP in migration studies  Na ->  CVD across most samples Intervention trials (short term) Treatment to  BP ->  CVD  Na intake ->  BP in meta-analyses  Na intake ->  CVD across most samples Population interventions  Na intake associated with  CVD mortality in Japan, Finland, U.K. Prospective Studies Collaboration, Lancet, 2002 He FJ and MacGregor GA. A comprehensive review of salt and health. J Hum Hypertension 2009;23:363 Appell LJ et al. The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke. Circulation 2011;123:1138 Whelton PK et al. Sodium, blood pressure, and cardiovascular disease. Circulation 2012;126

Successful Labeling Model: Finland 1970s: begin focus on sodium reduction 1993: required "high salt content" warning on packaged food : salt intake ↓ 23% in men and 28% in women Over three decades coronary heart disease deaths reduced by 80% in middle aged adults Karppanen, H., and Mervaala, E. Sodium Intake and Hypertension. Progress in Cardiovascular Diseases. 2006; 49 (2): Laatikainen, T. et al. Sodium in the Finnish Diet: 20-year trends in urinary sodium excretion among the adult population. Euro J Clin Nutr. 2006; 60:

Evidence Supporting Na+ Intake Increases Cardiovascular Disease Risk Animal studies  Na ->  BP in many species, including primates Observational studies in humans  BP ->  Cardiovascular disease (CVD)  Na ->  BP in cross-sectional, multi-population studies  Na ->  BP in migration studies  Na ->  CVD across most samples Intervention trials (short term) Treatment to  BP ->  CVD  Na intake ->  BP in meta-analyses  Na intake ->  CVD across most samples Population interventions  Na intake associated with  CVD mortality in Japan, Finland, U.K. Prospective Studies Collaboration, Lancet, 2002 He FJ and MacGregor GA. A comprehensive review of salt and health. J Hum Hypertension 2009;23:363 Appell LJ et al. The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke. Circulation 2011;123:1138 Whelton PK et al. Sodium, blood pressure, and cardiovascular disease. Circulation 2012;126

Leading Health Care Organizations Agree: Na Intake Must be Reduced American Medical Association (AMA) American Heart Association (AHA) American Public Health Association (APHA) Institute of Medicine (IOM) National Heart, Lung, and Blood Institute (NHLBI) World Health Organization (WHO)

Evidence Supporting Na+ Intake Increases Cardiovascular Disease Risk Animal studies  Na -> BP in many species, including primates Observational studies in humans  BP ->  Cardiovascular disease (CVD)  Na ->  BP in cross-sectional, multi-population studies  Na ->  BP in migration studies  Na ->  CVD across most samples Intervention trials (short term) Treatment to  BP ->  CVD  Na intake ->  BP in meta-analyses  Na intake ->  CVD across most samples Population interventions  Na intake associated with  CVD mortality in Japan, Finland, U.K. Prospective Studies Collaboration, Lancet, 2002 He FJ and MacGregor GA. A comprehensive review of salt and health. J Hum Hypertension 2009;23:363 Appell LJ et al. The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke. Circulation 2011;123:1138 Whelton PK et al. Sodium, blood pressure, and cardiovascular disease. Circulation 2012;126

“Definitive” Intervention Trial? Randomized controlled trial of 28,000 people for >5 yrs to low vs. high Na intake Not feasible Compliance? 80% Na comes from processed food 5 years? Ethics?

Current U.S. Recommendations And Disagreements U.S. Dietary Guidelines for Na intake <2,300 mg/day for low-risk 50 yrs, blacks, those with hypertension, renal disease, diabetes IOM recommendations (new) <2,300 mg/day for all “insufficient evidence to determine” if < 1,500 mg

Sodium Consumption in U.S. Briefel RR, Johnson CL. Secular trends in dietary intake in the United States. Annu Rev Nutr. 2004;24: U.S. adults, years Salt consumption (mg/day) 2005 U.S. Dietary Guidelines recommendation for adults Recommended limit for people with hypertension, blacks, middle aged and older NSRI 5 yr Goal

Not All Disagreement is Healthy Scientific Skepticism Salt Institute Membership is global salt-producing companies E.g. Cargill, Morton Salt, International Salt Company, United Salt Corporation Attack science showing that salt intake is unhealthy Some leading critics funded by Salt Institute E.g. David McCarron (220 scientific publications)

Lead Poisoning: Symptom of A Deeper Problem? “[LIA’s lead expert at Harvard Joseph Aub] felt that children that have subnormal appetites, or the disease known as ‘pica’ which caused them to chew on inedible articles, were subnormal to start with!” Felix Wormser, Secretary of Lead Industry Association (LIA) in response to study on association between lead levels and learning/behavior problems, 1944 Markowitz & Rosner, “Deceit and Denial: The deadly politics of industrial pollution.” U of CA Press, Chapter 2

Value of Scientific Doubt Strong tendency in public policy-making toward inaction Opponents need not prove anything Doubt is often sufficient to paralyze action Think climate change

Na Consumption in Paleolithic Era Humans hunter-gatherers Diet – all low in Na Fruit & berries Nuts Seeds Roots, tubers Meat Fish Insects Salt in short supply -> craving Estimated Na consumption < 1,000 mg/day Lindeberg S. Am J Hum Biol 2012;24: Konner M, Eaton SB. Nutr Clin Practice 2010;25:594

Key Questions - Reframed Does chronic high level of sodium consumption contribute to high blood pressure and to cardiovascular mortality? Would reductions in sodium consumption lead to reductions in blood pressure and reductions in cardiovascular mortality? Is it safe to feed people 3-4x as much Na as we evolved eating?

Conclusions Scientific evidence, taken in its entirety, makes compelling case that Na intake is far too high Leading to high blood pressure and unnecessary heart disease and stroke We should reduce Na in food supply Inaction is dangerous Tens of thousands of unnecessary deaths per year