What is the clinical significance of hypercalcemia?

From the Guidelines

The significance of hyperkalaemia in patients with cardiovascular disease is substantial, as it can lead to cardiac arrhythmias, cardiac arrest, and death, especially in those with renal function impairment, diabetes, and advanced age. The severity of hyperkalaemia can be classified as mild, moderate, or severe, with the risk of arrhythmic emergencies and sudden arrhythmic death varying between different patients 1. Hyperkalaemia is a common electrolyte disorder that may develop due to increased potassium intake, reduced potassium excretion, and shift of potassium from intracellular to extracellular space.

Classification and Prevalence

The classification of hyperkalaemia is based on serum or plasma potassium levels, with mild hyperkalaemia defined as >5.0 to <5.5 mEq/L, moderate as 5.5 to 6.0 mEq/L, and severe at thresholds >6.0 mEq/L 1. The prevalence of hyperkalaemia differs between in- and outpatients, with a higher prevalence in patients hospitalized for any cause, and it increases with the severity of renal impairment.

Clinical Implications

Hyperkalaemia frequently occurs in patients with cardiovascular diseases, such as heart failure, arterial hypertension, and coronary artery disease, particularly when combined with renal function impairment, diabetes, and advanced age 1. It leads to more frequent hospitalizations and increased mortality, especially when stringent monitoring is not performed. The choice of treatment for hyperkalaemia should be based on the severity of the condition, the presence of comorbidities, and the patient's preferences.

Management

The management of hyperkalaemia involves the use of mineralocorticoid antagonists, such as spironolactone, and other treatments, such as potassium-binding resins and hemodialysis in severe cases 1. The goal of treatment is to reduce serum potassium levels, prevent cardiac arrhythmias, and improve patient outcomes. A multi-disciplinary approach, including cardiologists, nephrologists, and other healthcare professionals, is crucial in the management of hyperkalaemia in patients with cardiovascular disease.

Key Considerations

In clinical practice, hyperkalaemia occurs in up to 73% of patients with advanced chronic kidney disease and in up to 40% of patients with chronic heart failure 1. The incidence of hyperkalaemia increases with the severity of renal impairment, and it is often iatrogenic, caused by concurrent drugs and nutritional/herbal supplements. Therefore, it is essential to monitor serum potassium levels regularly in patients with cardiovascular disease, especially those with renal function impairment, diabetes, and advanced age, to prevent and manage hyperkalaemia effectively.

From the Research

Significance of ACE Inhibitors and Other Antihypertensive Agents

• ACE inhibitors are commonly prescribed medications for the management of hypertension (HTN) and other chronic conditions, including heart failure and chronic kidney disease 2.
• They work by inhibiting the synthesis of angiotensin II, causing arterial and venous vasodilation, natriuresis, and a decrease in sympathetic activity, resulting in the reduction of blood pressure 2.
• ACE inhibitors are first-line therapy in HTN management, along with thiazide diuretics, calcium channel blockers, and angiotensin receptor blockers (ARBs) 2.
• Recent evidence has shown that ARBs may have neuroprotective effects compared to other antihypertensives, including ACE inhibitors, although this warrants further study 2.
• Combination therapy with a calcium channel blocker (CCB) and an ACE inhibitor has been shown to be effective in preventing composite cardiovascular events, even in patients achieving aggressive systolic blood pressure targets and those with apparent resistant hypertension 3.

Comparison of Antihypertensive Agents

• A study comparing the long-term relative risk of antihypertensive treatments found that cardiovascular disease mortality was similar between patients treated with a thiazide-type diuretic, a CCB, or an ACE inhibitor 4.
• However, the study found that ACE inhibitors increased the risk of stroke outcomes by 11% compared to diuretics, and this effect persisted well beyond the trial period 4.
• Another study found no increased cancer mortality with the use of CCBs, and the suggestion that ACE inhibitors reduce cancer mortality was not supported 5.

Emerging Therapies

• A new class of 1,4-dihydropyridines has been developed that selectively and potently inhibits the intermediate-conductance calcium-activated K+ channel KCa3.1, a validated therapeutic target for diseases affecting many organ systems 6.
• One of these 1,4-dihydropyridines, DHP-103, has shown promise in reducing infarct volume and improving outcomes in a rat model of acute ischemic stroke 6.