Electrolyte Biomarkers: Potassium

Optimal Takeaways

Potassium is an essential mineral and major electrolyte. It plays a vital role in cell function, muscle contractions, heart rate, blood pressure regulation, and nerve impulse transmission. Serum levels are maintained within a fairly tight range. The kidneys are instrumental in maintaining serum levels and can retain or excrete potassium as needed. Excursions considerably above or below standard can be detrimental or even fatal. Potassium can also be lost through excessive sweating and diuretic use and may be depleted under stress.

Standard Range: 3.5 - 5.3 mEq/L (3.5 – 5.3 mmol/L)

The ODX Range: 4.0 – 5.0 mEq/L (4.0 – 5.0 mmol/L)      

Low levels of potassium can be associated with insufficient intake, gastrointestinal losses, metabolic alkalosis, cardiac arrhythmias, hyperaldosteronism, Cushing syndrome, cystic fibrosis, licorice ingestion, ascites, and excess sodium reabsorption and retention by the kidneys. Medications that can deplete potassium include many diuretics, antibiotics, salicylates, insulin, laxatives, cisplatin, and lithium carbonate (Pagana 2021). Low serum potassium is also associated with hypertension (Liamis 2013), ventricular fibrillation, heart failure, and hypomagnesemia (Macdonald 2004).

High levels of potassium can be associated with dehydration, excess intake, renal failure, hypoaldosteronism, tissue injury, hemolysis, infection, acidosis, and cardiac arrhythmias. Medications that can increase potassium include antibiotics, chemotherapy, heparin, histamine, captopril, lithium, mannitol, succinylcholine, potassium-sparing diuretics, and potassium supplements (Pagana 2021). Muscle weakness may also be observed with high serum potassium (Lanham-New 2012). High blood pressure may be also associated with hyperkalemia (Xi 2015), especially in those with compromised renal function (Macdonald 2004).

Overview

Potassium is an essential mineral with a wide range of functions in the body. It is involved in acid-base balance, electrodynamic cellular function, tissue synthesis, nerve impulse transmission, gastric secretion, blood pressure regulation, and muscle contraction including cardiac, smooth, and skeletal muscle (Sur 2021). Adequate potassium intake can significantly decrease blood pressure and help retain calcium and support bone mass (EFSA 2019).

Potassium is the most abundant cation found inside cells. Since most potassium is within the cell, the extracellular and serum levels are relatively low at approximately 4.0 mEq/L. However, small changes can have a significant impact on health. Serum levels could drop significantly if potassium lost in the urine is not replaced by dietary intake. On the other hand, serum levels can increase to fatal levels quickly if the kidneys are unable to excrete potassium regularly. A high serum potassium will trigger an increase in aldosterone which facilitates potassium excretion through the kidneys if they are functioning properly (Pagana 2021).

Stress can also trigger increased aldosterone, potentially causing increased excretion and depletion of potassium. Research suggests that increased aldosterone is also associated with anxiety and depression and may be mitigated with the use of stress reduction techniques such as meditation (Kubzansky 2010).

Heart rate and contractility are significantly affected by potassium and small variations in serum levels can cause abnormalities that can be identified by electrocardiogram. Atrial fibrillation may occur with a potassium below 3.5 mEq/L and sudden death is associated with a level below 3.0 mEq/L or above 6.0 mEq/L. A review of 911,698 medical records revealed that lowest mortality occurred with a potassium of 4.0-5.0 mEq/L in those with and without heart failure, chronic kidney disease, diabetes, and CVD. All-cause mortality increased significantly for every 0.1 mEq/L increment in potassium below 4.0 mEq/L or above 5.0 mEq/L (Collins 2017). Researchers confirm tight control of serum potassium in the range of 4.0-5.0 mEq/L in those with heart failure to reduce the risk of negative outcomes (Palaka 2020).

Evaluation of 9,651 individuals initially free of CVD found that all-cause mortality, CVD deaths, and non-CVD deaths were highest with serum potassium of 5 mEq/L or above or a level below 3.5 mEq/L. All-cause mortality was lowest in those with a potassium of 4.0-4.4 mEq/L in this group (Hughes-Austin 2017). Concurrent diuretic use and magnesium insufficiency amplified the negative effects of dyskalemia.

Potassium status in individuals with heart failure and those experiencing acute myocardial infarction (MI) is affected by several factors including medication use, potassium-sparing versus non-potassium-sparing diuretics, adrenaline levels, and renal status. One review assessing optimal potassium levels in these groups suggested that those with hypertension maintain a serum potassium between 3.5-5.0 mEq/L and those with acute MI and heart failure maintain a level above 4.5 mEq/L to avoid sudden cardiac death (Macdonald 2004).

One systemic literature review confirmed adverse outcomes with serum potassium above or below “normal range” and even at the high and low end of normal. Risk of hyperkalemia was most apparent in subjects with chronic kidney disease, heart failure, type 2 diabetes, hypertension, and those using certain medications including renin–angiotensin–aldosterone system inhibitors (RAASi) and mineralocorticoid receptor antagonists (MRAs). In those with heart failure, all-cause mortality was significantly increased when potassium was 3.5-4.0 mEq/L, or 5.0-5.5 mEq/L in those with heart failure and chronic kidney disease, suggesting an optimal range of 4.0-5.0 mEq/L, especially in these groups (Palaka 2020).

A retrospective study of 1,924 acute MI patients found that 3-year mortality was highest in those with serum potassium below 3.5 mEq/L or above 4.5 mEq/L. Mortality was significantly increased with a potassium of 5.0 mEq/L or above. The lowest long-term mortality was associated with serum potassium of 3.5 to 3.9 mEq/L in this group (Choi 2014).

A study of 34,026 MI subjects indicated that lowest in-hospital all-cause mortality was associated with serum potassium between 3.5 and 4.5 mEq/L, while mortality doubled with a level above 4.5 mEq/L. Ventricular fibrillation and cardiac arrest where more frequent in those with potassium below 3.0 or above 5.0 mEq/L, and in-hospital mortality followed a similar U-shaped curve (Goyal 2012).

Although hypokalemia and low potassium intake are associated with increased risk of hypertension, increasing serum potassium is also associated with higher blood pressure. A serum potassium of 4.80 mEq/L or above was associated with an 84% increased risk of hypertension compared to 4.2-4.79 mEq/L in a 5-year community-based cohort study of 839 normotensive subjects free of CVD. The lowest incidence of hypertension was in the group with a serum potassium of 4.4-4.59 mEq/L. Researchers observed a 75% increased risk of hypertension with each 1 mEq/L increase in potassium above baseline (Xi 2015).

Assessment of potassium status is complex and must take into account comorbidities, renal function, medication use, and nutritional status. Levels should be closely monitored in those with acute pathology, while trends above or below optimal should be evaluated further in healthy individuals.

References

Choi, Joon Seok et al. “Relation of serum potassium level to long-term outcomes in patients with acute myocardial infarction.” The American journal of cardiology vol. 113,8 (2014): 1285-90. doi:10.1016/j.amjcard.2014.01.402

Collins, Allan J et al. “Association of Serum Potassium with All-Cause Mortality in Patients with and without Heart Failure, Chronic Kidney Disease, and/or Diabetes.” American journal of nephrology vol. 46,3 (2017): 213-221. doi:10.1159/000479802

EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) et al. “Dietary reference values for chloride.” EFSA journal. European Food Safety Authority vol. 17,9 e05779. 4 Sep. 2019, doi:10.2903/j.efsa.2019.5779

Goyal, Abhinav, et al. "Serum potassium levels and mortality in acute myocardial infarction." Jama 307.2 (2012): 157-164.

Hughes-Austin, Jan M et al. “The Relation of Serum Potassium Concentration with Cardiovascular Events and Mortality in Community-Living Individuals.” Clinical journal of the American Society of Nephrology : CJASN vol. 12,2 (2017): 245-252. doi:10.2215/CJN.06290616

Kubzansky, Laura D, and Gail K Adler. “Aldosterone: a forgotten mediator of the relationship between psychological stress and heart disease.” Neuroscience and biobehavioral reviews vol. 34,1 (2010): 80-6. doi:10.1016/j.neubiorev.2009.07.005

Lanham-New, Susan A et al. “Potassium.” Advances in nutrition (Bethesda, Md.) vol. 3,6 820-1. 1 Nov. 2012, doi:10.3945/an.112.003012

Liamis, George et al. “Electrolyte disorders in community subjects: prevalence and risk factors.” The American journal of medicine vol. 126,3 (2013): 256-63. doi:10.1016/j.amjmed.2012.06.037

Macdonald, John E, and Allan D Struthers. “What is the optimal serum potassium level in cardiovascular patients?.” Journal of the American College of Cardiology vol. 43,2 (2004): 155-61. doi:10.1016/j.jacc.2003.06.021

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Palaka, Eirini et al. “Associations between serum potassium and adverse clinical outcomes: A systematic literature review.” International journal of clinical practice vol. 74,1 (2020): e13421. doi:10.1111/ijcp.13421

Sur, Moushumi. and Shamim S. Mohiuddin. “Potassium.” StatPearls, StatPearls Publishing, 21 December 2021.

Xi, Lu et al. “Associations between serum potassium and sodium levels and risk of hypertension: a community-based cohort study.” Journal of geriatric cardiology : JGC vol. 12,2 (2015): 119-26. doi:10.11909/j.issn.1671-5411.2015.02.009