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| REVIEW ARTICLE |
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| Year : 2022 | Volume
: 6
| Issue : 1 | Page : 10-15 |
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The role of dietary potassium and sodium in hypertension and cardiovascular damage and protection: A narrative review
Qing Wang
Division of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland; Beijing Hypertension League Institute, Beijing; The 1st Affiliated Hospital of Shantou, University Medical College, Shantou, China
| Date of Submission | 17-Mar-2021 |
| Date of Acceptance | 16-Jun-2021 |
| Date of Web Publication | 06-Aug-2021 |
Correspondence Address:
Dr. Qing Wang
Division of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital (CHUV), Lausanne
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/hm.hm_23_21
This review focuses on the role of dietary potassium and sodium in hypertension and cardiovascular (CV) damage and protection. It briefly describes the burden of global hypertension and CV diseases; discusses some of the ways that sodium and potassium imbalance induce hypertension; provides some experimental evidence explaining how high-sodium and low-potassium diet induces target organ (kidney and heart, etc.) damage independent of blood pressure, and addresses the role that a low-sodium and high-potassium diet may play to reduce the incidence of hypertension, CV events, and death.
Keywords: Heart, hypertension, kidney, potassium, sodium
How to cite this article:
Wang Q. The role of dietary potassium and sodium in hypertension and cardiovascular damage and protection: A narrative review. Heart Mind 2022;6:10-5 |
| Burden of Global Hypertension and Cardiovascular Diseases | |  |
Noncommunicable diseases (NCDs), including heart disease, stroke, cancer, diabetes, and chronic lung disease, are collectively responsible for almost 70% of all deaths worldwide. An estimated 41 million people worldwide died of NCDs in 2016. Four NCDs caused most of those deaths: cardiovascular diseases (CVD) (17.9 million deaths), cancer (9.0 million deaths), chronic respiratory diseases (3.8 million deaths), and diabetes (1.6 million deaths).[1] To date, there is a relative paucity of measures to prevent this happening. A population strategy to prevent hypertension and CVD and death is required to reduce the burden of disease in the coming decades.
Hypertension affects more than 25% of the adult population worldwide and is the most important risk factor leading to CVD events and death. It is responsible for 62% of stroke and 49% of myocardial infarctions (or coronary heart disease).[2],[3] Hypertension is caused by genetic and environmental interactions and defined by the level of arterial blood pressure (systolic blood pressure [SBP]/diastolic blood pressure [DBP] >140/90 mm Hg). The precise role of genetic factors remains unclear. However, unhealthy diet, such as high-sodium and low-potassium and high-fat food, insufficient physical activity, and smoking have been recognized as major risk environmental factors leading to the development of hypertension and CVD. Thus, it is important to develop effective, economic strategies and approaches to reduce the incidence of hypertension and CV and cerebrovascular events. In particular, stopping smoking, reducing obesity, increasing exercise, and optimizing the dietary intake of sodium and potassium are critical measures that should be implemented to improve the situation.
| Pathophysiological Mechanisms and Significance of Sodium and Potassium Imbalance | | |
The renin–angiotensin–aldosterone system (RAAS) and the kidney have a key role to maintain sodium and potassium balance. Renin and aldosterone, synthesis and secretion, are modulated by dietary sodium and potassium. Angiotensin II (Ang. II) and aldosterone activate their specific receptors (angiotensin II type-I receptor [AT1] and mineralocorticoid receptor [MR]), which modulate the quantity and activity of the relevant enzymes and regulatory proteins (11 β HSD2, SGK1, WNK, ENaC, and ROMK) in target cells, particularly the renal tubular cells. These regulate the handling of sodium and potassium by the nephron to allow balance to be reached under widely different intakes of sodium and potassium, thereby maintaining body homeostasis of sodium and potassium.[4] If genes important for the management of sodium and potassium balance are mutated, they can cause sodium and potassium imbalance and abnormal blood pressure [Figure 1].[5],[6],[7],[8],[9],[10] Almost all the Mendelian dominant inherited forms of hypertension have involved disturbance of sodium and potassium handling. | Figure 1: Mutations and polymorphisms altering blood pressure levels in humans. They have been identified in rare Mendelian forms of hypertension or hypotension or have been linked to essential hypertension. Most of them are present in genes involved directly or indirectly in renal sodium handling, i.e., genes coding for tubular sodium transport systems or for proteins belonging to regulatory pathways (adapted from Meneton et al.[4])
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A sodium intake <5 mmol/day or 0.3 g NaCl/day causes maximal activation of RAAS. Ang II acts on the AT1 receptor in the proximal tubule of kidney increasing sodium and water reabsorption. Ang ll also acts on the AT1 receptor in the adrenal grand to increase aldosterone synthesis and secretion. Aldosterone then activates the MR in the distal convoluted tubule and collecting duct of kidney to increase sodium reabsorption thereby maintaining sodium and water balance and blood pressure level. A secondary effect of this action is increased excretion of potassium. When sodium intake is about 50 mmol/day or ~3 g NaCl/day, plasma renin activity (PRA) and aldosterone excretion are inhibited by 50%. A sodium intake of 100 mmol/day or ~6 g NaCl/day almost completely suppresses the RAAS [Figure 2].[11],[12] This suggests that in humans on a sodium intake <100 mmol/day (≤6 g of NaCl/day), the RAAS can effectively regulate sodium and potassium balance and maintain blood pressure. However, on a high salt (≥9 g of NaCl/day), the capacity of the RAAS to regulate sodium balance is exceeded and requires other mechanisms such as an increase in blood pressure (hypertension) to increase sodium excretion via the kidney. | Figure 2: Relationship of the 24-h urine sodium excretion (a reflection of the daily sodium intake) to the ambulatory plasma renin activity level and to the 24-h urinary aldosterone excretion values in normal subjects. The current cutoff for low renin is now an ambulatory PRA level < 0.65 ng/ml/h. Balance–outpatient = all meals contained known sodium content and were eaten in the metabolic ward. Balance–metabolic ward = subjects were ambulatory but confined to the metabolic ward for several weeks and ate diets of known sodium content. Random sample = no dietary or life style restrictions[11]
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| A High-sodium and Low-potassium Diet Contributes to Hypertension and Related Diseases | | |
A large number of animal experiments, clinical research, and epidemiological investigations have confirmed that a high-sodium and low-potassium diet can elevate arterial blood pressure and exacerbate CV and cerebrovascular disease and diabetes, etc.[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28] In contrast, a low-sodium and high-potassium diet can reduce blood pressure and CV and cerebrovascular events and death.[29],[30],[31],[32],[33],[34],[35],[36],[37] One should realize that in the evolution of man that our diet has altered. Prehistoric humans and hominids (from 3.5 million to 10,000 years ago) lived as hunter gatherers and ate a natural diet, mainly vegetables and fruits and raw meat containing a very low sodium (25 -30mmol Na/day or 0.58 - 0.69g Na/day or 1.5 -1.8g NaCl /day) and a very high potassium (200- 285mmol K/day or 8-11 g K/day). This gives a Na/K ratio of about 0.1 using the mmol intake of each variable. As society has developed and particularly in recent times (in the last 200 years) most food consumed has been processed and the diet contains a very high sodium (150–200 mmol Na/day, or 9–12 g NaCl/day) and a very low potassium (30–65 mmol K/day or 1.2–2.5 g K/day).The Na/K ratio of such a modern diet is more than 3, about 30 times greater than that of natural diet [Figure 3].[13] This high-sodium and low-potassium modern diet exceeds the regulatory capacity of the RAAS and may cause high blood pressure or hypertension to increase sodium excretion by the kidney. | Figure 3: Left panel (image source: https://en.wikipedia.org/wiki/Paleolithic, free encyclopedia): Primitive humans living from the Paleolithic ~3½ million to ~10,000 years ago eat natural diet;[38] Right panel: Sodium, potassium, calcium, and magnesium contents in natural diet and modern diet (or industrial food really occurred in the last 200 years, calculated per 2100 kcal daily)[13]
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Previously, populations in South America, Africa, and Oceania had similarities with our ancestors and had a habitually low-sodium and high-potassium intake. These people were normotensive and did not exhibit increased blood pressure with age. The prevalence of hypertension was <1%. The most striking example was the Yanomamo Indian tribe population living in Brazil and Venezuela. The data showed that their urinary excretions of sodium (Na) and potassium (K) were 1 mmol/24 h and 152 mmol/24 h, respectively, urinary Na/K = 0.007. PRA was 13 ng/ml/h and aldosterone excretion was 74 μg/24 h, both extremely high. In 50-year-old Yanomamo Indians, blood pressure was 100/64 mmHg. In a control population, sodium intake was 104 mmol/day and potassium 38 mmol/day, Na/K = 2.7, PRA = 2.5 ng/ml/h, and aldosterone excretion, 3.8 μg/24 h. The chronic elevation of renin in the Yanomamo Indians was appropriate for a low level of body sodium and important to maintain normal blood pressure.[14]
| Sodium and Potassium Effects Independent of Raised Blood Pressure | | |
High-sodium intake may also damage target tissue independent of blood pressure thereby speeding up the process of left ventricular hypertrophy, myocardial infarction, etc.[15],[26],[27] We found that increased sodium intake induces cardiac hypertrophy and cardioperivascular fibrosis and dysfunction in absence of hypertension in one-renin gene mice [Figure 4].[26] | Figure 4: Cardiac histology and function in DOCA-HS-and DOCA-LS-treated mice. (a) 20-fold magnification of elastic van Gieson-stained cardiac artery of a DOCA-LS-treated mouse. (b) 20-fold magnification of VGEL-stained cardiac artery of a DOCA-HS treated mouse. (c) Left ventricular contractility in DOCA-HS- and DOCA-LS-treated mice. LVdP/dtmax and LVdP/dtmin: Maximal rates of left ventricular pressure rise and fall, which indicates left systolic and diastolic function (own data)[26]
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We have shown that long-term administration of deoxycorticosterone acetate (DOCA)/salt induces cardiac and renal hypertrophy and fibrosis and dysfunction in one-renin gene mice without hypertension [Figure 5].[25],[26],[29],[30] Dietary potassium supplementation reduces cardiac and renal hypertrophy in DOCA/salt-treated one-renin gene normotensive mice. In addition, there are significant correlations between urinary Na/K ratio and cardiac- and kidney-weight index (heart or kidney weight/body weight) in both one-renin gene normotension and two-renin gene hypertensive mice [Figure 5].[29] The urinary Na/K ratio may be considered as a risk marker for salt-induced target organ damage. | Figure 5: Left panel: Representative examples of heart and kidney weight and index in one-renin-gene normotensive mice. Middle panel: Dietary potassium supplementation for 6 weeks reduces heart and kidney weight index in DOCS one-renin normotensive mice. HW/BW and KW/BW: Heart and kidney weight to body weight ratio. TAP: Tap water, DOCS: DOCA implant + 1% NaCl drinking fluid, DOCS + KCl: DOCA implant + 1% NaC/0.4% KCl drinking fluid. Data were presented as mean ± SEM and analyzed by one-way ANOVA and unpaired t-test. P <0.05 was considered statistically significant, n = 9–12 for each group (own data).[33] Right panel C: Correlations between urinary Na/K and cardiac-and kidney-weight in both one-renin gene (filled dots) normotensive and two-renin gene (open dots) hypertensive mice (own data).[29] SEM = Standard error of mean
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| High-potassium and Low-sodium Diet Reduces Incidence of Hypertension, Cardiovascular Events, and Death | | |
Addison reported nearly 70 years ago that a high potassium intake could exert an antihypertensive effect.[31] Meta-analyses of 33 randomized controlled trials (2565 participants) have identified that potassium supplementation (60–200 mmol potassium in diet) was associated with a significant reduction in mean (95% confidence interval) systolic and diastolic blood pressure of − 3.11 mmHg (−1.91 to − 4.31 mmHg) and-1.97 mm Hg (−0.52 to − 3.42 mmHg), respectively.[32] Dietary approaches to stop hypertension (DASH) found that a potassium-enriched fruit and vegetable diet (4.7 g K and 3 g Na/day) decreased SBP/DBP to 5.5 and 3 mmHg, respectively, in normotensive compared to one with modern diet or typical American diet (1.7 g K and 3 g Na/day), the drop of blood pressure is higher in hypertensive patients 11. 4/5.5 mmHg.[33] The DASH diet combined with a low salt intake causes a greater fall in blood pressure.[34] In Taiwan, a study used a potassium-enriched cooking salt (NaCl/KCl = 1:1) in a hospitalized veteran's population. After 31-month follow–up, the patients in the high-potassium reduced sodium intake group compared with the control population in a nursing home had a 40% decline in cerebrovascular disease mortality, there were significantly reductions in outpatient and inpatient medical expenses.[35]
Dietary salt reduction to prevent hypertension and CV events and death has been recommended and carried out in many countries for decades; however, the achievement of a population salt intake <5 g per day for adults has seldom been reached. Changes in lifestyle are a huge challenge for humans and alteration in salt intake may take a very long time. China is a country with a very high sodium-to-potassium ratio in the diet.[21] The recommended intake of sodium and potassium by the World Health Organization (WHO) is 5 gNaCl or 85 mmol Na/day and 3.5 g or 90 mmol K/day, Na/K = 0.94.[39] However, China is an important country to study the effect of Na/K ratio on blood pressure, target organ damage, CV events, and death today. The author believes that reducing the dietary sodium/potassium ratio may be more important and easier than only reducing sodium intake to prevent hypertension, CV event, and death.[40] A recent study has shown that the association between sodium excretion and CV events was J-shaped. Compared with baseline sodium excretion of 4–5.99 g/day, sodium excretion of >7 g/day was associated with an increased risk of all CV events, and a sodium excretion of <3 g/day was associated with increased risk of CV mortality and hospitalization for CHF. A higher potassium excretion was associated with a reduced risk of stroke. A higher sodium-to-potassium excretion ratio was associated with an increased risk of subsequent CVD, with an effect stronger than that of sodium or potassium alone.[41]
An important intervention study was performed in Finland to attempt to reduce hypertension, CV diseases, events, and death. Finnish experts in cooperation with government, media, and food industry used extensive media campaigns among other measures to reduce salt intake. This included food salt labeling regulations and production of low-sodium and high-potassium mixed salt (Pansalt®: 56% NaCl + 28% KCl + 12% MgSO4). The investigators provided evidence for a dramatic decrease in all-cause and CV mortality among the 5.4 million people in Finland during the past 40 years. This corresponds with the decrease in sodium intake and increase in potassium intake.[13],[42] Changes in the intake of sodium have been carefully monitored by measurement of 24-h urinary sodium excretion in representative population samples. As a result of the continuous decrease of salt intake, the average intake of sodium is now about 30% lower than it was 40 years ago. Despite an increase in obesity and consumption of alcohol and smoking among women between 1972 and 2002, there has been a remarkable 10 mmHg fall in the average diastolic blood pressure of the population. In the middle-aged population (men and women aged 30–59 years), the death rate from stroke and ischemic heart diseases has decreased by approximately 70%, and the life expectancy has increased by 5 years in Finland
| Conclusion and Perspectives | | |
Death from CV disease is extremely prevalent in all countries and worldwide is the leading cause of death. Hypertension is the major risk factor causing the above. Hypertension is a disease of modern society and is predominantly due to lifestyle events though genetics influence who will be most affected. Thus, hypertension and the subsequent events should be able to be prevented. Most attention has been focused on reducing sodium (salt) intake, but widespread adoption is hard to achieve. This review has discussed how sodium affects the CV system and the kidney independent of the effect on blood pressure. It also presents evidence that these and the blood pressure effects can be ameliorated or prevented by a high potassium intake. Instead of attempting to achieve a very low-sodium intake, it may be preferable to reduce sodium and increase potassium in the diet. Such a diet may be more acceptable to the general population and its implementation would lead to a major reduction in CV events and death.
Ethical approval
Ethical Statement is not applicable for this article.
Acknowledgments
The author is very grateful to Trefor Morgan (Emeritus Professor, University of Melbourne, Australia) for critical reading and correction of the manuscript.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | |
| 2. | Adrogué HJ, Madias NE. Sodium and potassium in the pathogenesis of hypertension. N Engl J Med 2007;356:1966-78.  |
| 3. | Soler EP, Ruiz VC. Epidemiology and risk factors of cerebral ischemia and ischemic heart diseases: similarities and differences. Curr Cardiol Rev 2010;6:138-49. |
| 4. | Meneton P, Jeunemaitre X, Wardener HE, Marcgregor GA. Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases. Physiol Rev 2005;85:679-715. |
| 5. | Pradervand S, Wang Q, Burnier M, Beermann F, Horisberger JD, Hummler E, et al. A mouse model for Liddle's syndrome. J Am Soc Nephrol 1999;10:2527-33. |
| 6. | Pradervand S, Barker PM, Wang Q, Ernst SA, Beermann F, Grubb BR, et al. Salt restriction induces pseudohypoaldosteronism type 1 in mice expressing low levels of the beta-subunit of the amiloride-sensitive epithelial sodium channel. Proc Natl Acad Sci U S A 1999;96:1732-7. |
| 7. | Hummler E, Barker P, Talbot C, Wang Q, Verdumo C, Grubb B, et al. A mouse model for the renal salt-wasting syndrome pseudohypoaldosteronism. Proc Natl Acad Sci U S A 1997;94:11710-5. |
| 8. | Wang WH, Giebisch G. Regulation of potassium (K) handling in the renal collecting duct. Pflugers Arch 2009;458:157-68. |
| 9. | McCormick JA, Yang CL, Ellison DH. WNK kinases and renal sodium transport in health and disease: An integrated view. Hypertension 2008;51:588-96. |
| 10. | Lifton RP, Gharavi AG, Geller DS. Molecular mechanisms of human hypertension. Cell 2001;104:545-56. |
| 11. | Laragh JH, Baer L, Brunner HR, Buhler FR, Sealey JE, Vaughan ED Jr. Renin, angiotensin and aldosterone system in pathogenesis and management of hypertensive vascular disease. Am J Med 1972;52:633-52. |
| 12. | Laragh JH, Sealey JE. The plasma renin test reveals the contribution of body sodium-volume content (V) and renin-angiotensin (R) vasoconstriction to long-term blood pressure. Am J Hypertens 2011;24:1164-80. |
| 13. | Karppanen H, Karppanen P, Mervaala E. Why and how to implement sodium, potassium, calcium, and magnesium changes in food items and diets? J Hum Hypertens 2005;19 Suppl 3:S10-9. |
| 14. | Oliver WJ, Cohen EL, Neel JV. Blood pressure, sodium intake, and sodium related hormones in the Yanomamo Indians, a “no-salt” culture. Circulation 1975;52:146-51. |
| 15. | Tobian L. Potassium and hypertension. Nutr Rev 1988;46:273-83. |
| 16. | Reddy V, Sridhar A, Machado RF, Chen J. High sodium causes hypertension: Evidence from clinical trials and animal experiments. J Integr Med 2015;13:1-8. |
| 17. | Gonçalves C, Abreu S. Sodium and potassium intake and cardiovascular disease in older people: A systematic review. Nutrients 2020;12:3447. |
| 18. | Willey J, Gardener H, Cespedes S, Cheung YK, Sacco RL, Elkind MS. Dietary sodium to potassium ratio and risk of stroke in a multiethnic urban population: The northern manhattan study. Stroke 2017;48:2979-83. |
| 19. | Okayama A, Okuda N, Miura K, Okamura T, Hayakawa T, Akasaka H, et al. Dietary sodium-to-potassium ratio as a risk factor for stroke, cardiovascular disease and all-cause mortality in Japan: the NIPPON DATA80 cohort study. BMJ Open 2016;6:e011632. |
| 20. | Aaron KJ, Sanders PW. Role of dietary salt and potassium intake in cardiovascular health and disease: A review of the evidence. Mayo Clin Proc 2013;88:987-95. |
| 21. | Zhou BF, Stamler J, Dennis B, Moag-Stahlberg A, Okuda N, Robertson C, et al. Nutrient intakes of middle-aged men and women in China, Japan, United Kingdom, and United States in the late 1990s: The INTERMAP study. J Hum Hypertens 2003;17:623-30. |
| 22. | Vinceti M, Filippini T, Crippa A, Sesmaisons A, Wise LA, Nicola Orsini N. Meta-analysis of potassium intake and the risk of stroke. J Am Heart Assoc 2016;5:e004210. |
| 23. | Chatterjee R, Yeh HC, Edelman D, Brancati F. Potassium and risk of type 2 diabetes. Expert Rev Endocrinol Metab 2011;6:665-72. |
| 24. | Radzeviciene L, Ostrauskas R. Adding salt to meals as a risk factor of type 2 diabetes mellitus: A case-control study. Nutrients 2017;9:1-10. |
| 25. | Wang Q, Hummler E, Nussberger J, Clément S, Gabbiani G, Brunner HR, et al. Blood pressure, cardiac, and renal responses to salt and deoxycorticosterone acetate in mice: Role of Renin genes. J Am Soc Nephrol 2002;13:1509-16. |
| 26. | Wang Q, Domenighetti AA, Schäfer SC, Weber J, Simon A, Maillard MP, et al. Impact of salt on cardiac differential gene expression and coronary lesion in normotensive mineralocorticoid-treated mice. Am J Physiol Regul Integr Comp Physiol 2012;302:R1025-33. |
| 27. | Nista F, Gatto F, Albertelli M, Musso N. Sodium intake and target organ damage in hypertension-an update about the role of a real villain. Int J Environ Res Public Health 2020;17:2811. |
| 28. | Wang Q, Bode C, van den Berghe L. Funding: Pfizer Foundation Award for Research. “The Dietary Sodium/Potassium Ratio May Be More Important Than Only Reducing Sodium Intake for Preventing Hypertension and Target Organ Damage”. Circulation. 2011;124:f7–f12. Doi: 10.1161/CIR.0b013e3182137ea9. |
| 29. | Wang Q, Domenighetti AA, Pedrazzini T, Burnier M. Potassium supplementation reduces cardiac and renal hypertrophy independently of blood pressure in DOCA/salt mice. Hypertension 2005;46:547-54. |
| 30. | Wang Q, Alonso F, Haefliger JA. Matrix metalloproteinase-2 and plasminogen activator inhibitor-1 contribute to deoxycorticosterone-acetate/salt induced renal lesion and potassium mediated protection in one-renin normotensive mice. J Hypertens 2016;34:e429-430. |
| 31. | Addison WL. The use of sodium chloride, potassium chloride, sodium bromide, and potassium bromide in cases of arterial hypertension which are amenable to potassium chloride. Can Med Assoc J 1928;18:281-5. |
| 32. | 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. |
| 33. | Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Engl J Med 1997;336:1117-24. |
| 34. | Obarzanek E, Proschan MA, Vollmer WM, Moore TJ, Sacks FM, Appel LJ, et al. Individual blood pressure responses to changes in salt intake: results from the DASH-sodium trial. Hypertension 2003;42:459-67. |
| 35. | Chang HY, Hu YW, Yue CS, Wen YW, Yeh WT, Hsu LS, et al. Effect of potassium-enriched salt on cardiovascular mortality and medical expenses of elderly men. Am J Clin Nutr 2006;83:1289-96. |
| 36. | Adrogué HJ, Madias NE. The impact of sodium and potassium on hypertension risk. Semin Nephrol 2014;34:257-72. |
| 37. | Zhang HY, Wang Q, Brunner HR, Li WW, Zhang BQ, Liu LS, et al. Effects of long-term enriched potassium salt consumption on premature death in Chinese living in nursing houses – Preliminary analysis. J Hypertens 2018;36:e286-7. |
| 38. | Toth N, Schick K. Overview of paleolithic anthropology. In: Henke HC, Hardt T, Tatersall I, editors. Handbook of Paleoanthropology. Vol. 3. Berlin; Heidelberg; New York: Springer; 2007. p. 1943-63. |
| 39. | WHO. Guideline: Sodium and potassium intake for adults and children. Geneva, World Health Organization (WHO), 2012. |
| 40. | Wang Q. The dietary sodium/potassium ratio may be more important than only reducing sodium intake for preventing hypertension and target organ damage. In Funding: Pfizer foundation award for research. European Perspectives in Cardiology. Circulation 2011;124:f12. |
| 41. | Cook NR, Obarzanek E, Cutle 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 follow-up study. Arch Intern Med 2009;169:33-40. |
| 42. | Karppanen H, Mervaala E. Adherence to and population impact of nonpharmacological and pharmacological antihypertensive therapy. J Hum Hypertens 1996;10 Suppl 1:S57-61. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
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