Sodium Intake and Cardiovascular Disease Rationale for Policy

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

Annual Estimated Reductions in Deaths and Cardiovascular Events: Comparison Across Various Interventions Incidence of CHD Death from any cause Low estimate 66, 000 ± 5800 51, 000 ± 7100 High estimate 110, 000 ± 9200 81, 000 ± 11, 000 Smoking cessation 41, 000 ± 10, 000 84, 000 ± 9300 Weight loss 59, 000 ± 3500 36, 000 ± 2000 Statin therapy 52, 000 ± 5600 5400 ± 540 100, 000 ± 11, 000 80, 000 ± 10, 000 Intervention Salt reduction: 3 g/day Pharmacologic treatment of HTN Source: Bibbins-Domingo K et al. Projected Effect of Dietary Salt Reductions on Future Cardiovascular Disease. 2010. New England Jounral of Medicine.

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 Mac. Gregor 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 Definition of Hypertension Prospective Studies Collaboration, Lancet, 2002: Meta-analysis of 61 prospective studies with 2. 7 m person-yrs, 11. 9 k 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 Mac. Gregor 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 USA Isolated primitive tribes Law MR et al, BMJ 1991; 302: 811 -5

• • • 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 Mac. Gregor 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 135 130 125 120 (mm Hg) Systolic Blood Pressure DASH-Sodium Trial High Intermediate 3, 450 mg/day 2, 300 mg/day Low 1, 150 mg/day Sacks FM et al. Effects on Blood Pressure of Reduced Dietary Sodium. NEJM. 2001 Jan 4; 344(1): 3 -10

• • • 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 Mac. Gregor 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 INTERVENTION OUTCOME TONE (2001) 639 Elderly Taiwan Veterans (2006) 1, 981 Elderly TOHP Follow-up (2007) 3, 126 Prehypertensives ↓ Na /↑ K Salt ↓ Na FU 21% ↓ CVD events 2. 3 yrs 41%* ↓ CVD Mortality 2. 6 yrs 30%* ↓ CVD events 10 -15 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 Mac. Gregor 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 • • 1970 s: begin focus on sodium reduction 1993: required "high salt content" warning on packaged food 1979 -2002: 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): 59 -75. Laatikainen, T. et al. Sodium in the Finnish Diet: 20 -year trends in urinary sodium excretion among the adult

• • 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 Mac. Gregor 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 Mac. Gregor 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 • <1, 500 mg/day for those >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

U. S. adults, 20 -74 years Salt consumption (mg/day) Sodium Consumption in U. S. NSRI 5 yr Goal 2005 U. S. Dietary Guidelines recommendation for adults Recommended limit for people with hypertension, blacks, middle aged and older Briefel RR, Johnson CL. Secular trends in dietary intake in the United States. Annu Rev Nutr. 2004; 24: 401 -431

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 Mc. Carron (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, 2002. 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: 110 -115 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 -4 x 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