Sodium, Potassium, Blood Pressure, and Cardiovascular Disease in Humans

  • Paul K. WheltonEmail author
Prevention of Hypertension: Public Health Challenges (P Muntner, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Prevention of Hypertension: Public Health Challenges


The scientific underpinning for recommended levels of dietary sodium and potassium intake is of great importance to healthcare providers and policy decision-makers. Recent clinical trials and meta-analyses confirm the capacity of dietary sodium reduction and potassium supplementation to reduce blood pressure with no harmful effects on blood lipid levels in customary clinical settings. Blood pressure is thought to be a good surrogate for cardiovascular disease events and the most important preventable risk factor for mortality and disability-adjusted life years. Cohort analyses and related pooling studies that have been used to explore the relationship between dietary Na and CVD were all based on secondary analyses of datasets that were not designed for this purpose. Most are of insufficient quality to provide dependable information. The limited information available from clinical trial experience and cohort studies of higher quality suggests a reduction in dietary Na decreases CVD morbidity and mortality. Modeling studies suggest that a small reduction in dietary sodium would result in a sizable general population health benefit. Some countries have experienced a progressive decline in average dietary sodium consumption. However, there is no evidence of a corresponding trend in the United States, and almost the entire population is failing to meet dietary sodium and potassium guideline recommendations.


Sodium Potassium Blood pressure Cardiovascular disease 


Compliance with Ethics Guidelines

Conflict of Interest Paul K. Whelton declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    IOM (Institute of Medicine). Panel on dietary reference intakes for electrolytes and water. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Food and Nutrition Board. Dietary reference intakes for water, potassium, sodium, chloride, and sulfate. Washington, D.C: The National Academies Press; 2005.Google Scholar
  2. 2.
    Lewington S, Clarke R, Qizilbash N, et al. Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2003;361:1903–13.Google Scholar
  3. 3.
    Stamler J, Stamler R, Neaton JD. Blood pressure, systolic and diastolic, and cardiovascular risks. US population data. Arch Intern Med. 1993;153:598–615.PubMedGoogle Scholar
  4. 4.
    He J, Gu D, Chen J, et al. Premature deaths attributable to blood pressure in China: a prospective cohort study. Lancet. 2009;374:1765–72.PubMedGoogle Scholar
  5. 5.
    Temple R. Are surrogate markers adequate to access cardiovascular disease drugs? JAMA. 1999;282:790–5.PubMedGoogle Scholar
  6. 6.
    Desai M, Stockbridge N, Temple R. Blood pressure as an example of a biomarker that functions as a surrogate. AAPS J. 2006;8:E146–52.PubMedPubMedCentralGoogle Scholar
  7. 7.
    IOM (Institute of Medicine). In: Micheel CM, Ball JR, editors. Evaluation of biomarkers and surrogate endpoints in chronic disease. Washington D.C: The National Academies Press; 2010.Google Scholar
  8. 8.
    Fleming TR, Powers JH. Biomarkers and surrogate endpoints in clinical trials. Stat Med. 2012;31:2973–84.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Lassere MN, Johnson KR, Schiff M, Rees D. Is blood pressure reduction a valid surrogate endpoint for stroke prevention? An analysis incorporating a systematic review of randomized controlled trials, a by-trial weighted errors-in-variables regression, the surrogate threshold effect (STE) and the biomarker-surrogacy (Biosurrogate) evaluation schema (BSES). BMC Med Res Methodol. 2012;12:27.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Kearney PM, Whelton M, Reynolds K, et al. Global burden of hypertension: analysis of worldwide data. Lancet. 2005;365:217–23.Google Scholar
  11. 11.
    Burt V, Whelton P, Roccella EJ, et al. Prevalence of hypertension in the U.S. adult population: results from the Third National Health and Nutrition Examination Survey, 1988-1991. Hypertension. 1995;25:305–13.PubMedGoogle Scholar
  12. 12.•
    Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease. Lancet. 2012;380:2224–60. A comparative risk assessment from the Global Burden of Disease Study that identifies BP as the leading risk factor for worldwide mortality and burden from disability-adjusted life years.PubMedPubMedCentralGoogle Scholar
  13. 13.
    James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507–20.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Mancia G, Fagard R, Narkiewicz K, Task Force Members, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31:1281–357.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Pereira M, Lunet N, Azevedo A, Barros H. Differences in prevalence, awareness, treatment and control of hypertension between developing and developed countries. J Hypertens. 2009;27:963–75.PubMedGoogle Scholar
  16. 16.
    Egan BM, Zhao Y, Axon RN. US trends in prevalence, awareness, treatment, and control of hypertension, 1988-2008. JAMA. 2010;303:2043–50.PubMedGoogle Scholar
  17. 17.
    Gu Q, Burt VL, Dillon CF, Yoon S. Trends in antihypertensive medication use and blood pressure control among United States adults with hypertension: the National Health and Nutrition Examination Survey, 2001 to 2010. Circulation. 2012;126:2105–14.PubMedGoogle Scholar
  18. 18.
    Xi B, Liang Y, Reilly KH, et al. Trends in prevalence, awareness, treatment, and control of hypertension among Chinese adults 1991-2009. Int J Cardiol. 2012;158:326–9.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Grudal NA, Hubeck-Graudal T, Jurgens G. Effects of low-sodium diet vs. high-sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride (Cocherane Review). Am J Hypertens. 2012;25:1–15.Google Scholar
  20. 20.••
    He FJ, Li J, MacGregor GA. Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomized trials. BMJ. 2013;346:f1325. Meta-analysis of 34 randomized controlled clinical trials, relevant to clinical practice and public health, which documents the BP lowering effect of Na reduction and identifies factors that modify the response.PubMedGoogle Scholar
  21. 21.••
    Aburto NJ, Ziolkovska A, Hooper L, et al. Effect of lower sodium intake on health: systematic review and meta-analyses. BMJ. 2013;346:f1326. Meta-analysis of 36 randomized controlled trials, relevant to clinical practice and public health, which documents the BP lowering effect of Na reduction, identifies no adverse effect on total cholesterol or catecholamine, and suggests a beneficial effect on renal protein excretion. This study served a major resource in setting the new WHO guidelines for Na intake.PubMedPubMedCentralGoogle Scholar
  22. 22.••
    Aburto NJ, Hanson S, Gutierrez H, et al. Effect of increased potassium on cardiovascular risk factors and disease: systematic review and meta-analyses. BMJ. 2013;346:f1378. Meta-analysis of 21 randomized controlled trials, relevant to clinical practice and public health, which documents the BP lowering effect of K supplementation and identifies no adverse effect on lipid levels, catecholamines, or renal function. This study served a major resource in setting the new WHO guidelines for K intake.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Van Bommel E, Cleophas T. Potassium treatment for hypertension in patients with high salt intake: a meta-analysis. Int J Clin Pharmacol Ther. 2012;50:478–82.PubMedGoogle Scholar
  24. 24.
    Whelton PK, He J, Cutler JA, et al. Effect of oral potassium on blood pressure. Meta-analysis of randomized controlled clinical trials. JAMA. 1997;277:1624–32.PubMedGoogle Scholar
  25. 25.
    Cappuccio FP, MacGregor GA. Does potassium supplementation lower blood pressure – a metaanalysis of published trials. J Hypertens. 1991;9:465–73.PubMedGoogle Scholar
  26. 26.
    Rodrigues SL, Baldo MP, Machado RC, et al. High potassium intake blunts the effect of elevated sodium intake on blood pressure levels. J Am Soc Hypertens. 2014;8:232–8.PubMedGoogle Scholar
  27. 27.
    Khaw KT, Barrett-Connor E. The association between blood pressure, age, and dietary sodium and potassium: a population study. Circulation. 1988;77:53–61.PubMedGoogle Scholar
  28. 28.
    Whelton PK. Urinary sodium and cardiovascular disease risk. Informing guidelines for sodium consumption. 2011;306:2262–4.Google Scholar
  29. 29.••
    Whelton PK, Appel LJ, Sacco RL, et al. Sodium, blood pressure, and cardiovascular disease. Further evidence supporting the American Heart Association sodium reduction recommendations. Circulation. 2012;126:2880–9. A qualitative assessment of methodological challenges in the interpretation of observational cohort studies that have related dietary Na to CVD.Google Scholar
  30. 30.••
    Cobb LK, Anderson CAM, Elliott P, et al. Methodological issues in cohort studies that relate sodium intake and cardiovascular disease outcomes. Circulation. 2014;129:1173–86. A quantitative assessment of methodological challenges in the interpretation of observational cohort studies that have related dietary Na to CVD. It underscores the poor quality of data from most such studies.PubMedGoogle Scholar
  31. 31.
    IOM (Institute of Medicine). In: Strom BL, Yaktine AL, Oria M, editors. Sodium intake in populations: assessment of evidence. Washington, D.C: The National Academies Press; 2013.Google Scholar
  32. 32.
    Strazzullo P, D’Elia L, Kandala NM, Cappuccio FP. Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies. BMJ. 2009;339:b4567.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:924–6.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Graudal N, Jurgens J, Baslund B, Alderman MH. Compared with usual sodium intake, low-and excessive-sodium diets are associated with increased mortality: a meta-analysis. Am J Hypertens. 2014. doi: 10.1093/ajh/hpu028.PubMedGoogle Scholar
  35. 35.
    He J, Ogden LG, Vupputuri S, et al. Dietary sodium intake and subsequent risk of cardiovascular disease in overweight adults. JAMA. 1999;282:2027–34.PubMedGoogle Scholar
  36. 36.
    Yang Q, Liu T, Kuklina EV, et al. Sodium and potassium intake and mortality among US adults: prospective data from the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2011;171:1183–91.PubMedGoogle Scholar
  37. 37.
    Alderman MH, Cohen H, Madhavan S. Dietary sodium intake and mortality: the National Health and Nutrition Examination Survey (NHANES I). Lancet. 1998;351:781–5.PubMedGoogle Scholar
  38. 38.
    Cohen HW, Hailpern SM, Alderman MH. Sodium intake and mortality follow-up in the Third National Health and Nutrition Examination Survey (NHANES III). J Gen Intern Med. 2008;23:1297–302.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Appel LJ, Whelton PK. Flawed evidence should not derail sound policy: the case remains strong for population-wide sodium reduction. Am J Hypertens. 2013;26:1183–6.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Joosten MM, Gansevoort RT, Mukamal KJ, PREVEND Study Group, et al. Sodium excretion and risk of developing coronary heart disease. Circulation. 2014;129:1121–8.PubMedGoogle Scholar
  41. 41.••
    Cook NR, Appel LJ, Whelton PK. Lower levels of sodium intake and reduced cardiovascular risk. Circulation. 2014;129:981–9. This study avoids many of the methodological concerns that have plagued other cohort analyses of the relationship between Na and CVD. It suggests the presence of a direct linear relationship between Na and CVD throughout the entire distribution of Na consumption.PubMedPubMedCentralGoogle Scholar
  42. 42.
    He J, Ogden LG, Vupputuri S, Bazzano LA, Loria C, Whelton PK. Dietary sodium intake and subsequent risk of cardiovascular disease in overweight adults. JAMA. 1999;282:2027–34.PubMedGoogle Scholar
  43. 43.
    Klag MJ, He J, Coresh J, Whelton PK, Chen JY, Mo JP, et al. The contribution of urinary cations to the blood pressure differences associated with migration. Am J Epidemiol. 1995;142:295–303.PubMedGoogle Scholar
  44. 44.
    Chang HY, Hu YW, Yue CS, et al. Effect of potassium-enriched salt on cardiovascular mortality and medical expenses of elderly men. Am J Clin Nutr. 2006;83:1289–96.PubMedGoogle Scholar
  45. 45.
    Whelton PK, Appel LJ, Espeland MA, et al. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). TONE Collaborative Research Group. JAMA. 1998;279:839–46.PubMedGoogle Scholar
  46. 46.
    Cook NR, Cutler JA, Obarzanek E, et al. Long-term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the Trials of Hypertension Prevention (TOHP). BMJ. 2007;334:885–92.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Cook NR, Kumanyika SK, Cutler JA, Whelton PK, for the Trials of Hypertension Prevention Collaborative Research Group. Dose–response of sodium excretion and blood pressure change among overweight, nonhypertensive adults in a 3-year dietary intervention study. J Hum Hypertens. 2005;19:47–54.PubMedGoogle Scholar
  48. 48.
    D’Elia L, Barba G, Cappuccio FP, Strazzullo P. Potassium intake, stroke, and cardiovascular disease. A meta-analysis of prospective studies. J Am Coll Cardiol. 2011;57:1210–9.PubMedGoogle Scholar
  49. 49.
    Hunt BD, Cappuccio FP. Potassium intake and stroke risk. A review of the evidence and practical considerations for achieving a minimum target. Stroke. 2014;45:1519–22.PubMedGoogle Scholar
  50. 50.
    Cook NR, Obarzanek E, Cutler JA, et al. Joint effects of sodium and potassium intake on subsequent cardiovascular disease: the Trials of Hypertension Prevention (TOHP) follow-up study. Arch Intern Med. 2009;169:32–40.PubMedPubMedCentralGoogle Scholar
  51. 51.••
    Coxon PG, Cook NR, Joffres M, et al. Mortality benefits from US population-wide reduction in sodium consumption. Projections from 3 modeling approaches. Hypertension. 2013;61:564–70. The most recent modeling analysis that identifies the potential CVD health benefits of reducing dietary Na consumption.Google Scholar
  52. 52.
    Danaei G, Ding EL, Mozaffarian D, et al. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med. 2009;6(4):e1000058.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Palar K, Sturm R. Potential societal savings from reduced sodium consumption in the U.S. adult population. Am J Health Promot. 2009;24:49–57.PubMedGoogle Scholar
  54. 54.
    Bibbins-Domingo K, Chertow GM, Coxson PG, et al. Projected effect of dietary salt reductions on future cardiovascular disease. N Engl J Med. 2010;362:590–9.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Cappuccio FP, Capewell S, Lincoln P, McPherson K. Policy options to reduce population salt intake. BMJ. 2011;343:402–5.Google Scholar
  56. 56.
    U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary guidelines for Americans, 2010. 7th ed. Washington, DC: U.S. Government Printing Office; 2010.Google Scholar
  57. 57.
    Lloyd-Jones DM, Hong Y, Labarthe D, on behalf of the American Heart Association Strategic Planning Force and Statistics Committee, et al. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic impact goal through 2020 and beyond. Circulation. 2010;121:586–613.PubMedGoogle Scholar
  58. 58.
    Appel LJ, Frohlich ED, Hall JE, et al. The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke. A call for action from the American Heart Association. Circulation. 2011;123:1138–43.PubMedGoogle Scholar
  59. 59.
    IOM (Institute of Medicine). In: Henney JE, Taylor CL, Boon CS, editors. Committee on strategies to reduce sodium intake. Strategies to reduce sodium intake in the United States. Washington, D.C: The National Academy Press; 2010.Google Scholar
  60. 60.
    Whelton PK, He J. The health effects of sodium and potassium in humans. Curr Opin Lipidol. 2014;25:75–9.PubMedGoogle Scholar
  61. 61.•
    Strom BL, Anderson CAM, Ix JH. Sodium reduction in populations. Insights from the Institute of Medicine Committee. JAMA. 2013;310:31–2. Brief article that summarizes the findings and conclusions of the 2013 IOM report on observational studies that have investigated the CVD health consequences of Na reduction.PubMedGoogle Scholar
  62. 62.
    NHS National Institute for Health and Clinical Excellence. Prevention of cardiovascular disease at the population level. NICE public health guidance 25. 2010.
  63. 63.
    WHO. Guideline: sodium intake for adults and children. Geneva: World Health Organization (WHO); 2012.Google Scholar
  64. 64.
    WHO. Guideline: potassium intake for adults and children. Geneva: World Health Organization (WHO); 2012.Google Scholar
  65. 65.
    Bernstein AM, Willett WC. Trends in 24-h urinary sodium excretion in the United States, 1957–2003: a systematic review. Am J Clin Nutr. 2010;92:1172–80.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Briefel RB, Johnson CL. Secular trends in dietary intake in the United States. Annu Rev Nutr. 2004;24:401–31.PubMedGoogle Scholar
  67. 67.•
    Cogswell ME, Zhang Z, Carriquiry AL, et al. Sodium and potassium intakes among US adults: NHANES 2003-2008. Am J Clin Nutr. 2012;96:647–57. Estimation of adherence to Na reduction guidelines by US adults. It suggests very poor adherence to guideline recommendations, even in population subgroups who are most likely to benefit from a reduced intake of dietary Na.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Espland MA, Kumanyika S, Wilson AC, et al. Statistical issues in analyzing 24-hour dietary recall and 24-hour urine collection data for sodium and potassium intakes. Am J Epidemiol. 2001;153:996–1006.Google Scholar
  69. 69.•
    Powles P, Fahimi S, Micha R, on behalf of the Global Burden of Diseases Nutrition and Chronic Diseases Expert Group (NutriCoDE) et al. Global, regional and national sodium intakes in 1990 and 2010: a systematic analysis of 24 h urinary sodium excretion and dietary surveys worldwide. BMJ Open. 2013;e003733. First study to estimate global, regional and national consumption of dietary Na. Despite weaknesses in the underlying database, the study is innovative and suggests Na intake in excess of guideline recommendations in all world regions.Google Scholar
  70. 70.•
    Jacobson MF, Havas S, McCarter R. Changes in sodium levels in processed and restaurant foods, 2005 to 2011. JAMA Intern Med. 2013;173:1285–91. Study that identifies an absence of any appreciable change in Na content of processed and restaurant foods in the US between 2005 and 2011.PubMedGoogle Scholar
  71. 71.•
    Dunford E, Wester J, Woodward M, et al. The variability of reported salt levels in fast foods across six countries: opportunities for salt reduction. CMAJ. 2012;184:1023–8. Study that documents wide variability in fast foods Na content within country and across country, even for identical food products being sold by the same company. It highlights the opportunity for reducing the Na content of fast food products.PubMedPubMedCentralGoogle Scholar
  72. 72.•
    Scourboutakos MJ, Semnani-Azad Z, L’Abbe MR. Restaurant meals: almost a full day’s worth of calories, fats, and sodium. JAMA Intern Med. 2013;173:1373–4. Report of Na content in meals served at Canadian sit-down restaurants indicating only 1 % of the meals meet the FDA criterion for a healthy meal.PubMedGoogle Scholar
  73. 73.
    Anderson CAM, Appel LJ, Okuda N, et al. Dietary sources of sodium in China, Japan, the United Kingdom, and the United States, women and men 40 to 59 years: the INTERMAP Study. J Am Diet Assoc. 2010;110:736–45.PubMedPubMedCentralGoogle Scholar
  74. 74.
    James WP, Ralph A, Sanchez-Castillo CP. The dominance of salt in manufactured food in the sodium intake of affluent societies. Lancet. 1987;1:426–9.PubMedGoogle Scholar
  75. 75.
    Sanchez-Castillo CP, Warrender S, Whitehead TP, James WP. An assessment of the sources of dietary salt in a British population. Clin Sci. 1987;72:95–102.PubMedGoogle Scholar
  76. 76.•
    He FJ, Pombo-Rodrigues S, MacGregor GA. Salt reduction in England from 2003 to 2011: its relationship to blood pressure, stroke and ischaemic heart disease mortality. BMJ Open 2014;e004549. Quantitative assessment of reduction in dietary Na attained through a structured national initiative centered on voluntary reductions in the addition of Na during food processing. Also, related Na reduction to concurrent declines in CVD mortality.Google Scholar
  77. 77.
  78. 78.
    Antman EM, Appel LJ, Balentine D et al. Stakeholder discussion to reduce population-wide sodium intake and decrease sodium in the food supply: a conference report from the American Heart Association Sodium Conference 2013 Planning Group. Circulation. 2014;

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of EpidemiologyTulane University School of Public Health and Tropical MedicineNew OrleansUSA

Personalised recommendations