Abnormal serum calcium levels are associated with clinical response to maximization of heart failure therapy

INTRODUCTION Abnormal serum calcium levels are associated with adverse cardiovascular effects. Therapy of heart failure (HF) may result in urinary calcium excretion and calcium apposition to bones, and consequently, in calcemia.

OBJECTIVES The aim of the study was to assess the prevalence of abnormal calcium levels in the blood of patients receiving maximized HF therapy, to explore clinical and laboratory determinants of abnormal serum calcium levels, and to analyze the relation of abnormal calcium levels to prognosis. 

PATIENTS AND METHODS The study included 722 patients with HF classified as New York Heart Association (NYHA) classes III–IV at baseline (age 53 ±10 years, 13% of women), who underwent HF therapy optimization to maximum tolerated doses.

RESULTS After therapy maximization, the NYHA class improved in 66.7% of the patients, while it did not change in 31.0% and worsened in 2.4%. Hypocalcemia occurred in 166 patients (22.9%) and was more prevalent in patients in whom the NYHA class improved. Hypercalcemia was diagnosed in 63 patients (8.7%) and was more common in patients with no functional improvement or worsening of the NYHA class. This effect was independent of age, sex, etiology of HF, body mass index, kidney function, or the use of thiazides. Hypercalcemia was associated with increased catabolism, hemodynamic compromise, more intensive inflammation, and lower bone mineral density. Lower albumin and higher phosphorus levels, were significant predictors of hypercalcemia, independently of kidney function. Hypocalcemia was associated with reduced catabolism, higher albumin and lower phosphorus levels, use of thiazides, and smoking history. Neither hypocalcemia nor hypercalcemia was associated with poor prognosis. 

CONCLUSIONS Our study shows that abnormal serum calcium levels are associated with a clinical response to treatment maximization in patients with HF. Mild hypocalcemia after maximization of therapy is not associated with poorer prognosis. Hypercalcemia is associated with lack of response to treatment, and its prognostic value remains unclear.