RESUMO
BACKGROUND: Patients with chronic heart failure have vulnerable myocardial function and are susceptible to electrolyte disturbances. In these patients, diuretic treatment is frequently prescribed, though it is known to cause electrolyte disturbances. Therefore, we investigated the association between altered calcium homeostasis and the risk of all-cause mortality in chronic heart failure patients. METHODS: From Danish national registries, we identified patients with chronic heart failure with a serum calcium measurement within a minimum 90 days after initiated treatment with both loop diuretics and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Patients were divided into 3 groups according to serum calcium levels, and Cox regression was used to assess the mortality risk of <1.18 mmol/L (hypocalcemia) and >1.32 mmol/L (hypercalcemia) compared with 1.18 mmol/L-1.32 mmol/L (normocalcemia) as reference. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. RESULTS: Of 2729 patients meeting the inclusion criteria, 32.6% had hypocalcemia, 63.1% normocalcemia, and 4.3% hypercalcemia. The highest mortality risk was present in early deaths (≤30 days), with a HR of 2.22 (95% CI; 1.74-2.82) in hypocalcemic patients and 1.67 (95% CI; 0.96-2.90) in hypercalcemic patients compared with normocalcemic patients. As for late deaths (>30 days), a HR of 1.52 (95% CI; 1.12-2.05) was found for hypocalcemic patients and a HR of 1.87 (95% CI; 1.03-3.41) for hypercalcemic patients compared with normocalcemic patients. In adjusted analyses, hypocalcemia and hypercalcemia remained associated with an increased mortality risk in both the short term (≤30 days) and longer term (>30 days). CONCLUSION: Altered calcium homeostasis was associated with an increased short-term mortality risk. Almost one-third of all the heart failure patients suffered from hypocalcemia, having a poor prognosis.
Assuntos
Cálcio/sangue , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Doença Crônica , Dinamarca/epidemiologia , Diuréticos/uso terapêutico , Insuficiência Cardíaca/epidemiologia , Homeostase , HumanosRESUMO
The TRPA1 and TRPV1 receptors are important pharmaceutical targets for antipruritic and analgesic therapy. Obtaining further knowledge on their roles and interrelationship in humans is therefore crucial. Preclinical results are contradictory concerning coexpression and functional interdependency of TRPV1 and TRPA1, but no human evidence exists. This human experimental study investigated whether functional responses from the subpopulation of TRPA1 nociceptors could be evoked after defunctionalization of TRPV1 nociceptors by cutaneous application of high-concentration capsaicin. Two quadratic areas on each forearm were randomized to pretreatment with an 8% topical capsaicin patch or vehicle for 24 hours. Subsequently, areas were provoked by transdermal 1% topical capsaicin (TRPV1 agonist) or 10% topical allyl isothiocyanate ("AITC," a TRPA1 agonist), delivered by 12 mm Finn chambers. Evoked pain intensities were recorded during pretreatments and chemical provocations. Quantitative sensory tests were performed before and after provocations to assess changes of heat pain sensitivity. Imaging of vasomotor responses was used to assess neurogenic inflammation after the chemical provocations. In the capsaicin-pretreated areas, both the subsequent 1% capsaicin- and 10% AITC-provoked pain was inhibited by 92.9 ± 2.5% and 86.9 ± 5.0% (both: P < 0.001), respectively. The capsaicin-ablated skin areas showed significant heat hypoalgesia at baseline (P < 0.001) as well as heat antihyperalgesia, and inhibition of neurogenic inflammation evoked by both 1% capsaicin and 10% AITC provocations (both: P < 0.001). Ablation of cutaneous capsaicin-sensitive afferents caused consistent and equal inhibition of both TRPV1- and TRPA1-provoked responses assessed psychophysically and by imaging of vasomotor responses. This study suggests that TRPA1 nociceptive responses in human skin strongly depend on intact capsaicin-sensitive, TRPV1 fibers.
Assuntos
Limiar da Dor/fisiologia , Psicofísica/métodos , Pele/metabolismo , Canal de Cátion TRPA1/metabolismo , Canais de Cátion TRPV/metabolismo , Administração Cutânea , Adulto , Capsaicina/farmacologia , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Isotiocianatos/farmacologia , Masculino , Inflamação Neurogênica/induzido quimicamente , Inflamação Neurogênica/patologia , Medição da Dor , Resistência Física , Estimulação Física/efeitos adversos , RNA Mensageiro/metabolismo , Distribuição Aleatória , Fármacos do Sistema Sensorial/farmacologia , Fatores Sexuais , Pele/efeitos dos fármacos , Canal de Cátion TRPA1/genética , Adulto JovemRESUMO
AIMS: Medication prescribed to patients suffering from chronic heart failure carries an increased risk of impaired potassium homeostasis. We examined the relation between different levels of serum potassium and mortality among patients with chronic heart failure. METHODS AND RESULTS: From Danish National registries, we identified 19 549 patients with a chronic heart failure diagnosis who had a measurement of potassium within minimum 90 days after initiated medical treatment with loop diuretics and angiotensin converting enzyme inhibitors or angiotensin-II receptor blockers. All-cause mortality was examined according to eight predefined potassium levels: 2.8-3.4 mmol/L, 3.5-3.8 mmol/L, 3.9-4.1 mmol/L, 4.2-4.4 mmol/L, 4.5-4.7 mmol/L, 4.8-5.0 mmol/L, 5.1-5.5 mmol/L, and 5.6-7.4 mmol/L. Follow-up was 90 days from potassium measurement. We estimated the risk of all-cause mortality using multivariable adjusted Cox proportional hazard model, with normal serum potassium level at 4.2-4.4 mmol/L as reference. After 90 days, the mortality in the eight strata was 14.4, 8.0, 6.3, 5.0, 5.8, 7.9, 10.3, and 21.1% respectively. In multivariable adjusted analysis, patients with potassium levels of 2.8-3.4 mmol/L [hazard ratio (HR): 3.16; confidence interval (CI): 2.43-4.11], 3.5-3.8 mmol/L (HR: 1.62; CI: 1.31-1.99), 3.9-4.1 mmol/L (HR: 1.29; CI: 1.08-1.55), 4.8-5.0 mmol/L (HR: 1.34; CI: 1.10-1.63), 5.1-5.5 mmol/L (HR: 1.60; CI: 1.29-1.97), and 5.6-7.4 mmol/L (HR: 3.31; CI: 2.61-4.20) had an increased risk of all-cause mortality. CONCLUSION: Levels within the lower and upper levels of the normal serum potassium range (3.5-4.1 mmol/L and 4.8-5.0 mmol/L, respectively) were associated with a significant increased short-term risk of death in chronic heart failure patients. Likewise, potassium below 3.5 mmol/L and above 5.0 mmol/L was also associated with increased mortality.