Antihypertensive treatment changes and related clinical outcomes in older hospitalized patients.

BACKGROUND: Hypertension management in older patients represents a challenge, particularly when hospitalized. OBJECTIVE: The objective of this study is to investigate the determinants and related outcomes of antihypertensive drug prescription in a cohort of older hospitalized patients. METHODS: A total of 5671 patients from REPOSI (a prospective multicentre observational register of older Italian in-patients from internal medicine or geriatric wards) were considered; 4377 (77.2%) were hypertensive. Minimum treatment (MT) for hypertension was defined according to the 2018 ESC guidelines [an angiotensin-converting-enzyme-inhibitor (ACE-I) or an angiotensin-receptor-blocker (ARB) with a calcium-channel-blocker (CCB) and/or a thiazide diuretic; if >80 years old, an ACE-I or ARB or CCB or thiazide diuretic]. Determinants of MT discontinuation at discharge were assessed. Study outcomes were any cause rehospitalization/all cause death, all-cause death, cardiovascular (CV) hospitalization/death, CV death, non-CV death, evaluated according to the presence of MT at discharge. RESULTS: Hypertensive patients were older than normotensives, with a more impaired functional status, higher burden of comorbidity and polypharmacy. A total of 2233 patients were on MT at admission, 1766 were on MT at discharge. Discontinuation of MT was associated with the presence of comorbidities (lower odds for diabetes, higher odds for chronic kidney disease and dementia). An adjusted multivariable logistic regression analysis showed that MT for hypertension at discharge was associated with lower risk of all-cause death, all-cause death/hospitalization, CV death, CV death/hospitalization and non-CV death. CONCLUSIONS: Guidelines-suggested MT for hypertension at discharge is associated with a lower risk of adverse clinical outcomes. Nevertheless, changes in antihypertensive treatment still occur in a significant proportion of older hospitalized patients.

Correlations between IL-6 serum level and olfactory dysfunction severity in COVID-19 patients: a preliminary study.

BACKGROUND: Interleukin 6 (IL-6) is a proinflammatory cytokine that is secreted by cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is widely recognized as a negative prognostic factor. The purpose of this study was to analyze the correlations between the olfactory scores determined by psychophysical tests and the serum levels of IL-6 in patients affected by coronavirus disease 2019 (COVID-19) METHODS: Patients underwent psychophysical olfactory assessment with Connecticut Chemosensory Clinical Research Center test and IL-6 plasma level determination within 10 days of the clinical onset of COVID-19. RESULTS: Seventy-four COVID-19 patients were included in this study. COVID-19 staged as mild in 34 patients, moderate in 26 and severe in 14 cases. There were no significant differences in olfactory scores across the different COVID-19 severity groups. In the patient series, the median plasma level of IL-6 was 7.7 pg/mL (IQR 3.7-18.8). The concentration of IL-6 was found to be significantly correlated with the severity of COVID-19 with a directly proportional relationship. The correlation between IL-6 plasma concentrations and olfactory scores was weak (rs = 0.182) and not significant (p = 0.12). CONCLUSIONS: In COVID-19 patients, psychophysical olfactory scores did not show significant correlations with the plasma levels of a well-recognized negative prognostic factor such as IL-6. This observation casts some shadows on the positive prognostic value of olfactory dysfunctions.

Theoretical investigation of action potential duration dependence on extracellular Ca2+ in human cardiomyocytes.

Reduction in [Ca2+]o prolongs the AP in ventricular cardiomyocytes and the QTc interval in patients. Although this phenomenon is relevant to arrhythmogenesis in the clinical setting, its mechanisms are counterintuitive and incompletely understood. To evaluate in silico the mechanisms of APD modulation by [Ca2+]o in human cardiomyocytes. We implemented the Ten Tusscher-Noble-Noble-Panfilov model of the human ventricular myocyte and modified the formulations of the rapidly and slowly activating delayed rectifier K+ currents (IKr and IKs) and L-type Ca2+ current (ICaL) to incorporate their known sensitivity to intra- or extracellular Ca2+. Simulations were run with the original and modified models at variable [Ca2+]o in the clinically relevant 1 to 3 mM range. The original model responds with APD shortening to decrease in [Ca2+]o, i.e. opposite to the experimental observations. Incorporation of Ca2+ dependency of K+ currents cannot reproduce the inverse relation between APD and [Ca2+]o. Only when ICaL inactivation process was modified, by enhancing its dependency on Ca2+, simulations predict APD prolongation at lower [Ca2+]o. Although Ca2+-dependent ICaL inactivation is the primary mechanism, secondary changes in electrogenic Ca2+ transport (by Na+/Ca2+ exchanger and plasmalemmal Ca2+-ATPase) contribute to the reversal of APD dependency on [Ca2+]o. This theoretical investigation points to Ca2+-dependent inactivation of ICaL as a mechanism primarily responsible for the dependency of APD on [Ca2+]o. The modifications implemented here make the model more suitable to analyze repolarization mechanisms when Ca2+ levels are altered.

Calcium and potassium changes during haemodialysis alter ventricular repolarization duration: in vivo and in silico analysis.

BACKGROUND: Alterations of ventricular repolarization duration, as measured by the QT interval, are frequently observed in haemodialysis (HD) patients. The nature and the sign of these changes are not yet fully understood. METHODS: Different dialysate K(+) and Ca(2+) levels, leading to different end-HD plasma concentrations in the patient, have been tested in the present study in terms of their impact on QTc. A model of the human cardiomyocyte action potential (AP) has been used to assess in silico whether the changes in Ca(2+) and K(+) were able to justify at the cellular level the observed alterations of QTc. RESULTS: QTc was prolonged in HDs with low (1.25 mM) versus high (2 mM) Ca(2+) (424 +/- 33 versus 400 +/- 28 ms, P < 0.05) and in HDs with low (2 mM) versus high (3 mM) K(+) (420 +/- 35 versus 399 +/- 36 ms, P < 0.05). These alterations were confirmed at the cellular level by computational analysis showing prolongation of ventricular AP at low K(+) and low Ca(2+) at the same extent of the measured QTc variations. Numerical simulation predicted a critically long AP (and QT) when considering low K(+) and Ca(2+) simultaneously, suggesting the concurrent lowering of Ca(2+) and K(+) as a potential arrhythmogenic factor. CONCLUSIONS: Numerical simulations of the ventricular AP may be useful to quantitatively predict the complex dependence of AP duration on simultaneous changes in Ca(2+) and K(+). Moreover, Ca(2+) content in the dialysate should be designed not to critically lower serum Ca(2+), especially in sessions at risk of end-dialysis hypokalaemia.