Short-term mortality risk of serum potassium levels in hypertension: a retrospective analysis of nationwide registry data

Krogager ML, Torp-Pedersen C, Mortensen RN, et al.
Eur Heart J 2016; published online ahead of print

Background

Antihypertensive treatment with diuretics, beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) may lead to abnormal potassium levels and increased risk of death [1-3]. There are limited data about the optimal range of serum potassium in disease and the levels associated with increased risk [4,5]. According to current guidelines [2,6,7], the lower potassium limit ranges from 3.5 to 3.8 mmol/L, and the upper potassium limit is between 5.0 and 5.5 mmol/L.
However, in acute heart failure patients, potassium levels within the normal range are associated with increased risk of death, suggesting that the optimal level of potassium in these patients may differ from current definitions [8].
In this study, the relation between serum potassium and 90-day all-cause mortality was evaluated in 40.799 hypertensive individuals.

Main results

During 90-day follow-up, the mortality stratified by serum potassium interval was:

• 4.5% for K: 2.9-3.4 mmol/L
• 2.7% for K: 3.5-3.7 mmol/L
• 1.8% for K: 3.8-4.0 mmol/L
• 1.5% for K: 4.1-4.4 mmol/L
• 1.7% for K: 4.5-4.7 mmol/L
• 2.7% for K: 4.8-5.0 mmol/L
• 3.6% for K: 5.1-5.8 mmol/L

The risk for death (adjusted by age, sex, biologically relevant co-morbidities, concomitant medication) was statistically significantly different between patients that had serum potassium levels inside or outside the normal potassium range (4.1-4.4 mmol/L):

• hypokalaemia (HR: 2.80; 95% CI: 2.17–3.62, p<0.01)
• hyperkalaemia (HR: 1.70; 95% CI: 1.20–2.41, p<0.01)

Normal potassium levels were also associated with increased mortality:

• HR for K: 3.5–3.7 mmol/L: 1.70; 95% CI: 1.36–2.13
• HR for K: 3.8–4.0 mmol/L: 1.21; 95% CI: 1.00–1.47
• HR for K: 4.5-4.7 mmol/L: 1.09; 95% CI: 0.88-1.34
• HR for K: 4.8–5.0 mmol/L: 1.48; 95% CI: 1.15–1.92

The mortality in relation to the seven potassium ranges was U-shaped, with the lowest mortality in the interval of 4.1–4.4 mmol/L.

Antihypertensive drug combinations related to mortality:

• ACEIs/ARBs in combination with thiazide diuretics were a safe treatment (HR: 0.65; 95% CI: 0.42–1.01; P = 0.05)
• The combination of beta blockers with thiazide diuretics and potassium supplements was associated with an increased mortality risk (HR: 1.46; 95% CI: 1.03–2.08; P = 0.03).

Conclusion

In more than 40.000 hypertensive patients, potassium levels outside the interval of 4.1–4.7 mmol/L were associated with increased mortality risk. Even mild deviations within the normal potassium range were associated with increased mortality, suggesting that a narrower normal interval might improve outcomes in patients with hypertension.

Find this article online at Eur Heart J

References

1. Liamis G, Milionis H, Elisaf M. Blood pressure drug therapy and electrolyte disturbances. Int J Clin Pract 2008;62:1572–1580.
2. Sica DA. Antihypertensive therapy and its effects on potassium homeostasis. J Clin Hypertens (Greenwich) 2006;8:67–73.
3. Kotchen TA. Antihypertensive therapy-associated hypokalemia and hyperkalemia: clinical implications. Hypertension 2012;59:906–907.
4. Montoye CK, Eagle KA, Michigan ACC-GAP Investigators, ACC-GAP Steering Committee, American College of Cardiology. An organizational framework for the AMI ACC-GAP Project. J Am Coll Cardiol 2005;46:1–29.
5. Podrid PJ. Potassium and ventricular arrhytmias. Am J Cardiol 1990;65:12–33E.
6. Kjeldsen K. Hypokalemia and sudden cardiac death. Exp Clin Cardiol 2010;15:e96–e99.
7. Macdonald JE, Struthers AD. What is the optimal serum potassium level in cardiovascular patients? J Am Coll Cardiol 2004;43:155–161.
8. Krogager ML, Eggers-Kaas L, Aasbjerg K, et al. Short-term mortality risk of serum potassium levels in acute heart failure following myocardial infarction. Eur Heart J Cardiovasc Pharmacother 2015;1:245–251.