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Sodium and Potassium and the Pathogenesis of Hypertension

  • Pathogenesis of Hypertension (R Agarwal, Section Editor)
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Abstract

The evidence relating blood pressure to salt intake in humans originates from population studies and randomized clinical trials of interventions on dietary salt intake. Estimates from meta-analyses of trials in normotensive subjects generally are similar to estimates derived from prospective population studies (+1.7-mm Hg increase in systolic blood pressure per 100 mmol increment in 24-hour urinary sodium). This estimate, however, does not translate into an increased risk of incident hypertension in subjects consuming a high-salt diet. The meta-analyses of intervention trials have consistently shown that potassium supplementation is associated with lowering of blood pressure. However, prospective studies relating health outcomes to 24-hour urinary sodium and/or potassium excretion produced inconsistent results. Taken together, available evidence does not support the current recommendations of a generalized and indiscriminate reduction of salt intake at the population level, although the blood-pressure lowering effect of dietary sodium restriction might be of value in hypertensive patients. Potassium supplementation in hypertensive patients or healthy persons is not recommended by the current guidelines, but importance of adhering to healthy diet rich in vegetables and fruits is emphasized.

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References

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  1. Robertson JIS. Dietary salt and hypertension: a scientific issue or a matter of faith? J Eval Clin Pract. 2003;9:1–22.

    Article  PubMed  Google Scholar 

  2. Alderman MH. Reducing dietary sodium. The case for caution. JAMA. 2010;303:448–9.

    Article  PubMed  CAS  Google Scholar 

  3. Anonymous. Salt and cardiovascular disease mortality. Lancet. 2011;377:1626.

    Article  Google Scholar 

  4. 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. 2002;360:1903–13.

    Article  Google Scholar 

  5. Geerling JC, Loewy AD. Central regulation of sodium appetite. Exp Physiol. 2008;93:177–209.

    Article  PubMed  CAS  Google Scholar 

  6. Guyton AC. Long-term arterial pressure control: an analysis from animal experiments and computer and graphic models. Am J Phys. 1990;259:R865–77.

    CAS  Google Scholar 

  7. Visser FW, Boonstra AH, Titia Lely A, Boomsma F, Navis G. Renal response to angiotensin II is blunted in sodium-sensitive men. Am J Hypertens. 2008;21:323–8.

    Article  PubMed  CAS  Google Scholar 

  8. Luft FC. Molecular aspects of genetics of salt-sensitivity and hypertension. Drug Metab Dispos. 2003;29:500–4.

    Google Scholar 

  9. Staessen JA, Wang J, Bianchi G, Birkenhäger WH. Essential hypertension. Lancet. 2003;361:1629.

    Article  PubMed  Google Scholar 

  10. Beretta-Piccoli C, Weidmann P, Brown JJ, Davies DL, Lever AF, Robertson JIS. Body sodium and blood volume state in essential hypertension : abnormal relation of exchangeable sodium to age and blood pressure in male patients. J Cardiovasc Pharmacol. 1984;6(suppl 1):S134–S142.

    Google Scholar 

  11. Titze J, Machnik A. Sodium sensing in the interstitium and the relationship to hypertension. Curr Opin Nephrol Hypertens. 2010;19:385–62.

    Article  PubMed  Google Scholar 

  12. Campese VM. Salt-sensitive hypertension: renal and cardiovascular implications. Nutr Metab Cardiovasc Dis. 1999;9:143–56.

    PubMed  CAS  Google Scholar 

  13. Adrogué HJ, Madias NE. Sodium and potassium in the pathogenesis of hypertension. N Engl J Med. 2007;356:1966–78.

    Article  PubMed  Google Scholar 

  14. Intersalt Cooperative Research Group. Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. BMJ. 1988;297(6644):319–28.

    Google Scholar 

  15. • Graudal NA, Hubeck-Graudal T, Jürgens G. Effects of low-sodium diet vs. high-sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride (Cochrane Review). Am J Hypertens. 2012;25:1–15. A recent meta-analysis of low- versus high-sodium diets, included 167 studies. In White hypertensive patients and normotensive subjects, blood pressure on the sodium restricted diet decreased by 5.48 mm Hg systolic (p<0.0001) and 2.75 mm Hg for diastolic (p<0.00001) and by 1.27 mm Hg systolic (p=0.0001) and 0.05 mm Hg diastolic (p=0.85), respectively. The average trial duration was 4 weeks. Sodium reduction resulted in significant increases (p<0.001) in renin, aldosterone, noradrenaline, adrenaline, cholesterol, and triglyceride.

    Article  PubMed  CAS  Google Scholar 

  16. • Stolarz-Skrzypek K, Kuznetsova T, Thijs L, Tikhonoff V, Seidlerová J, Richart T, et al. Fatal and nonfatal outcomes, incidence of hypertension and blood pressure changes in relation to urinary sodium excretion in White Europeans. JAMA. 2011;305:1777–85. A longitudinal population-based study included 3681 people without cardiovascular disease at baseline, all White Europeans, who were members of families randomly enrolled in the FLEMENGHO or in the EPOGH studies. During a median follow up of 7.9 years, cardiovascular deaths decreased across increasing tertiles of 24-hour sodium excretion. This significant inverse association between cardiovascular mortality and tertile of sodium excretion was retained in multivariable analyses (p for trend =0.02), with a HR of 1.56 in the low tertile versus the overall risk in the whole study population (p=0.04). The 24-hour sodium excretion at baseline did not predict either total mortality or fatal combined with nonfatal cardiovascular events. In a subgroup of 1499 participants who had both blood pressure and sodium excretion measured at baseline and at last follow-up and who were followed up for a median of 6.1 years, in multivariable-adjusted analyses of individual participants, a 100-mmol increment in 24-hour sodium excretion was associated with a significant 1.71 mmHg increase in systolic blood pressure (p<0.001), without concomitant change in diastolic blood pressure.

    Article  PubMed  CAS  Google Scholar 

  17. Whelton PK, Appel LJ, Espeland MA, Applegate WB, Ettinger Jr WH, Kostis JB, 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). JAMA. 1998;279:839–46.

    Article  PubMed  CAS  Google Scholar 

  18. Grobbee DE, Hofman A. Does sodium restriction lower blood pressure? BMJ. 1986;293:27–9.

    Article  PubMed  CAS  Google Scholar 

  19. Midgley JP, Matthew AG, Greenwood CMT, Logan AG. Effect of reduced dietary sodium on blood pressure. A meta-analysis of randomized controlled trials. JAMA. 1996;275:1590–7.

    Article  PubMed  CAS  Google Scholar 

  20. Cutler JA, Follmann DF, Allender PS. Randomized trials of sodium reduction: an overview. Am J Clin Nutr. 1997;65(suppl):643S–51S.

    PubMed  CAS  Google Scholar 

  21. He FJ, MacGregor GA. Effect of longer-term modest salt reduction on blood pressure. Cochrane Database Syst Rev. 2004; Issue 3. Art. No.: CD004937.

  22. He J, Whelton PK, Appel LJ, Charleston J, Klag MJ. Long-term effects of weight loss and dietary sodium reduction on incidence of hypertension. Hypertension. 2000;35(2):544–9.

    Article  PubMed  CAS  Google Scholar 

  23. Chien KL, Hsu HC, Chen PC, Su TC, Chang WT, Chen MF, et al. Urinary sodium and potassium excretion and risk of hypertension in Chinese: report from a community-based cohort study in Taiwan. J Hypertens. 2008;26(9):1750–6.

    Article  PubMed  CAS  Google Scholar 

  24. Alderman MH, Madhavan S, Cohen H, Sealey JE, Laragh JH. Low urinary sodium is associated with greater risk of myocardial infarction among treated hypertensive men. Hypertension. 1995;25(6):1144–52.

    Article  PubMed  CAS  Google Scholar 

  25. Tunstall-Pedoe H, Woodward M, Tavendale R, A’Brook R, McCluskey MK. Comparison of the prediction by 27 different factors of coronary heart disease and death in men and woman of the Scottish Heart Health Study: cohort study. BMJ. 1997;315(7110):722–9.

    Article  PubMed  CAS  Google Scholar 

  26. Tuomilehto J, Jousilahti P, Rastenyte D, Moitchanov V, Tanskanen A, Pietinen P, et al. Urinary sodium excretion and cardiovascular mortality in Finland: a prospective study. Lancet. 2001;357(9259):848–51.

    Article  PubMed  CAS  Google Scholar 

  27. Cook NR, Cutler JA, Obarzanek E, Buring JE, Rexrode KM, Kumanyika SK, 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(7599):885–8.

    Article  PubMed  Google Scholar 

  28. Cook NR, Obarzanek E, Cutler JA, Buring JE, Rexrode KM, Kumanyika SK, 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.

    Article  PubMed  Google Scholar 

  29. Staessen JA, Wang JG, Brand E, Barlassina C, Birkenhäger WH, Herrmann SM, et al. Effects of three candidate genes on prevalence and incidence of hypertension in a Caucasian population. J Hypertens. 2001;19(8):1349–58.

    Article  PubMed  CAS  Google Scholar 

  30. Kuznetsova T, Staessen JA, Kawecka-Jaszcz K, Babeanu S, Casiglia E, Filipovský J, et al. Quality control of the blood pressure phenotype in the European Project on Genes in Hypertension. Blood Press Monit. 2002;7:215–24.

    Article  PubMed  Google Scholar 

  31. Thomas MC, Moran J, Forsblom C, Harjutsalo V, Thorn L, Ahola A, et al. The association between dietary sodium intake, ESRD, and all-cause mortality in patients with type 1 diabetes. Diabet Care. 2011;34:861–6.

    Article  CAS  Google Scholar 

  32. Ekinci EL, Clarke S, Thomas MC, Moran JL, Cheong K, MacIsaac RJ, et al. Dietary salt intake and mortality in patients with type 2 diabetes. Diabet Care. 2011;34:703–9.

    Article  Google Scholar 

  33. Kagan A, Popper JS, Rhoads GG, Yano K. Dietary and other risk factors for stroke in Hawaiian Japanese men. Stroke. 1985;16(3):390–6.

    Article  PubMed  CAS  Google Scholar 

  34. 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(21):2027–34.

    Article  PubMed  CAS  Google Scholar 

  35. Alderman MH, Cohen H, Madhavan S. Dietary sodium intake and mortality: the National Health and Nutrition Examination Survey (NHANES I). Lancet. 1998;351(9105):781–5.

    Article  PubMed  CAS  Google Scholar 

  36. 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(9):1297–302.

    Article  PubMed  Google Scholar 

  37. Cohen HW, Hailpern SM, Fang J, Alderman MH. Sodium intake and mortality in the NHANES II follow-up study. Am J Med. 2006;119:275.e7–275.e14.

    Article  Google Scholar 

  38. Geleijnse JM, Witteman JCM, Stijnen T, Kloos MW, Hofman A, Grobbee DE. Sodium and potassium intake and risk of cardiovascular events and all-cause mortality: the Rotterdam study. Eur J Epidemiol. 2007;22(11):763–70.

    Article  PubMed  CAS  Google Scholar 

  39. Umesawa M, Iso H, Date C, Yamamoto A, Toyoshima H, Watanabe Y, et al. Relations between dietary sodium and potassium intakes and mortality from cardiovascular disease: the Japan Collaborative Cohort Study for Evaluation of Cancer Risks. Am J Clin Nutr. 2008;88(1):195–202.

    PubMed  CAS  Google Scholar 

  40. Yang Q, Liu T, Kuklina E, Flanders D, Hong Y, Gillespie C, et al. Sodium and potassium intake and mortality among US adults. Arch Intern Med. 2011;171:1183–91.

    Article  PubMed  Google Scholar 

  41. •• O’Donnell MJ, Yusuf S, Mente A, Gao P, Mann JF, Teo K, et al. Urinary sodium and potassium excretion and risk of cardiovascular events. JAMA. 2011;306:2229–38. An observational analysis of two cohorts of high-risk patients (n=28,880) included in the ONTARGET and the TRANSCEND trials. The 24-hour urinary sodium and potassium excretion was estimated from a morning fasting urine sample. The association between cardiovascular outcomes and salt intake had a J shape with a nadir at 4 to 5.99 g per day; a sodium excretion of greater than 7 g per day was associated with increased risk of all cardiovascular events, whereas a sodium excretion of less than 3 g per day was associated with increased cardiovascular mortality and hospitalisation for congestive heart failure.

    Article  PubMed  Google Scholar 

  42. Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358:1547–59.

    Article  PubMed  CAS  Google Scholar 

  43. Yusuf S, Teo K, Anderson C, Pogue J, Dyal L, Copland I, et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular eventsin high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet. 2008;372:1174–83.

    Article  PubMed  CAS  Google Scholar 

  44. •• Taylor RS, Ashton KE, Moxham T, Hooper L, Ebrahim S. Reduced dietary salt for the prevention of cardiovascular disease: a meta-analysis of randomized controlled trials (Cochrane Review). Am J Hypertens. 2011. doi:10.1038/ajh.2011.115:1-10. A quantitative review of seven randomised clinical trials that addressed the effect of restricting salt intake on cardiovascular disease: three in normotensive volunteers, two in hypertensive patients, one in a mixed population of normo- and hypertensive participants, and one in heart failure. Salt reduction was associated with reductions in urinary salt excretion of between 27 and 39 mmol per 24 hour and reductions in systolic blood pressure between 1 and 4 mm Hg. Pooled relative risks (RRs) comparing the intervention with the reference groups for all-cause mortality were 0.90 (CI, 0.581.40; 79 deaths) and 0.96 (CI, 0.831.11; 565 deaths) in normotensive and hypertensive participants, respectively. Salt restriction increased the risk of all-cause mortality in patients with heart failure (RR, 2.59; CI, 1.046.44; 21 deaths).

  45. Strazzullo P, D’Elia L, Kandala NB, Cappuccio FP. Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies. BMJ. 2009;339:b4567.

    Article  PubMed  Google Scholar 

  46. Grassi G, Dell’Oro R, Seravalle G, Foglia G, Trevano FQ, Mancia G. Short- and long-term neuroadrenergic effects of moderate dietary sodium restriction in essential hypertension. Circulation. 2002;106:1957–61.

    Article  PubMed  CAS  Google Scholar 

  47. Garg K, Williams GH, Hurwitz S, Brown NJ, Hopkins PN, Adler GK. Low-salt diet increases insulin resistance in healthy subjects. Metabolism. 2011;60:965–8.

    Article  PubMed  CAS  Google Scholar 

  48. Alderman MH, Madhavan S, Ooi WL, Cohen H, Sealey JE, Laragh JH. Association of the renin-sodium profile with the risk of myocardial infarction in patients with hypertension. N Engl J Med. 1991;324:1098–104.

    Article  PubMed  CAS  Google Scholar 

  49. Appel LJ, Frohlich ED, Hall JE, Pearson TA, Sacco RL, Seals DR, et al. The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke. A call to action from the American Heart Association. Circulation. 2011;123:1138–43.

    Article  PubMed  Google Scholar 

  50. Staessen J, Bulpitt CJ, Fagard R, Joossens JV, Lijnen P, Amery A. Salt intake and blood pressure in the general population: a controlled intervention trial in two towns. J Hypertens. 1988;6:965–73.

    Article  PubMed  CAS  Google Scholar 

  51. Staessen JA, Lijnen P, Thijs L, Fagard R. Salt and blood pressure in community-based intervention trials. Am J Clin Nutr. 1997;65(suppl):661S–70S.

    PubMed  CAS  Google Scholar 

  52. 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.

    Article  PubMed  Google Scholar 

  53. Smith-Spangler CM, Juusola JL, Enns EA, Owens DK, Garber AM. Population strategies to decrease sodium intake and the burden of cardiovascular disease. A cost-effectiveness analysis. Ann Intern Med. 2010;152(8):481–7.

    PubMed  Google Scholar 

  54. Bibbins-Domingo K, Chertow GM, Coxson PG, Moran A, Lightwood JM, Pletcher MJ, et al. Projected effect of dietary salt reductions on future cardiovascular disease. N Engl J Med. 2010;362(7):590–9.

    Article  PubMed  CAS  Google Scholar 

  55. Staessen J, Bulpitt C, Fagard R, Joossens JV, Lijnen P, Amery A. Four urinary cations and blood pressure. A population study in two Belgian towns. Am J Epidemiol. 1983;117(6):676–87.

    PubMed  CAS  Google Scholar 

  56. Smith WCS, Crombie IK, Tavendale RT, Gulland SK, Tunstall-Pedoe HD. Urinary electrolyte excretion, alcohol consumption, and blood pressure in the Scottish heart health study. BMJ. 1988;297:329–30.

    Article  PubMed  CAS  Google Scholar 

  57. Giebisch G. Renal potassium transport: mechanisms and regulation. Am J Physiol. 1998;274:F817–33.

    PubMed  CAS  Google Scholar 

  58. Agarwal R, Afzalpurkar R, Fordtran JS. Pathophysiology of potassium absorption and secretion by the human intestine. Gastroenterology. 1994;107:548–71.

    PubMed  CAS  Google Scholar 

  59. Zhou MS, Kosaka H, Yoneyama H. Potassium augments vascular relaxation mediated by nitric oxide in the carotid arteries of hypertensive Dahl rats. Am J Hypertens. 2000;13:666–72.

    Article  PubMed  CAS  Google Scholar 

  60. Cappuccio FP, MacGregor GA. Does potassium supplementation lower blood pressure ? A meta-analysis of published trials. J Hypertens. 1991;9:465–73.

    Article  PubMed  CAS  Google Scholar 

  61. Whelton PK, He J, Cutler JA, Brancati FL, Appel LJ, Follmann D, et al. Effects of oral potassium on blood pressure. Meta-analysis of randomized controlled clinical trials. JAMA. 1997;277:1624–32.

    Article  PubMed  CAS  Google Scholar 

  62. Geleijnse JM, Kok FJ, Grobbee DE. Blood pressure response to changes in sodium and potassium intake: a metaregression analysis of randomised trials. J Hum Hypertens. 2003;17:471–80.

    Article  PubMed  CAS  Google Scholar 

  63. Appel LJ, Brands MW, Daniels SR, Karanja N, Elmer PJ, Sacks FM, et al. Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association. Hypertension. 2006;47:296–308.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We gratefully acknowledge the expert assistance of Mrs. Sandra Covens, Studies Coordinating Centre, Leuven, Belgium.

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Stolarz-Skrzypek, K., Bednarski, A., Czarnecka, D. et al. Sodium and Potassium and the Pathogenesis of Hypertension. Curr Hypertens Rep 15, 122–130 (2013). https://doi.org/10.1007/s11906-013-0331-x

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