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Curr Protein Pept Sci ; 23(5): 321-334, 2022.
Article in English | MEDLINE | ID: covidwho-1910825


Natriuretic peptide system (NPS) is a group of peptide hormones or paracrine factors, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and natriuretic peptide precursor C (NPC), that are structurally related. The physiological effects of NPS include natriuresis, increased glomerular filtration rate, inhibition release of renin, vasopressin, and aldosterone, sympathetic inhibition, vasodilatations, and prevents cardiac hypertrophy and remodeling. ANP has immunological effects, as it is produced locally from immune cells; it regulates innate and adaptive immune responses. Metabolism and degradation of ANP are achieved by neutral endopeptidase (NEP), also known as neprilysin. Coronavirus disease 2019 (Covid-19) pandemic may lead to acute lung injury (ALI) and/or respiratory distress syndrome (ARDS). The underlying causes of inflammatory and immunological disorders in patients with severe Covid-19 are connected to the immune over-stimulation with the subsequent release of pro-inflammatory cytokines. Covid-19 severity is linked with high ANP serum levels regardless of acute cardiac injury. Inflammatory stimuli appear to be linked with the release of NPs, which anti-inflammatory effects prevent the development of ALI/ARDS in Covid-19. Therefore, neprilysin inhibitors like sacubitril increase endogenous NPs and may reduce the risk of ALI in Covid-19 due to the potentiation of endogenous anti-inflammatory effects of NPs. However, sacubitril increases gastrin-releasing peptide, cathepsin G and release of pro-inflammatory cytokines that are inactivated by neprilysin. In conclusion, NPs and neprilysin have cardio-pulmonary protective effects against Covid-19-induced ALI/ARDS. Neprilysin inhibitor sacubitril has dual protective and harmful effects regarding metabolizing vasoactive peptides by neprilysin. These findings require potential reevaluation of the effect of neprilysin inhibitors in managing Covid-19.

COVID-19 Drug Treatment , Heart Failure , Respiratory Distress Syndrome , Aldosterone , Aminobutyrates , Anti-Inflammatory Agents , Atrial Natriuretic Factor/metabolism , Atrial Natriuretic Factor/therapeutic use , Biphenyl Compounds , Cathepsin G , Cytokines , Gastrin-Releasing Peptide/therapeutic use , Heart Failure/drug therapy , Humans , Natriuretic Peptide, Brain/metabolism , Natriuretic Peptide, Brain/therapeutic use , Natriuretic Peptides , Neprilysin/metabolism , Neprilysin/therapeutic use , Renin/therapeutic use , Tetrazoles/pharmacology , Tetrazoles/therapeutic use , Valsartan/therapeutic use
Heart ; 108(7): 543-549, 2022 04.
Article in English | MEDLINE | ID: covidwho-1286748


OBJECTIVE: Heart failure (HF) is a malignant condition requiring urgent treatment. Guidelines recommend natriuretic peptide (NP) testing in primary care to prioritise referral for specialist diagnostic assessment. We aimed to assess association of baseline NP with hospitalisation and mortality in people with newly diagnosed HF. METHODS: Population-based cohort study of 40 007 patients in the Clinical Practice Research Datalink in England with a new HF diagnosis (48% men, mean age 78.5 years). We used linked primary and secondary care data between 1 January 2004 and 31 December 2018 to report one-year hospitalisation and 1-year, 5-year and 10-year mortality by NP level. RESULTS: 22 085 (55%) participants were hospitalised in the year following diagnosis. Adjusted odds of HF-related hospitalisation in those with a high NP (NT-proBNP >2000 pg/mL) were twofold greater (OR 2.26 95% CI 1.98 to 2.59) than a moderate NP (NT-proBNP 400-2000 pg/mL). All-cause mortality rates in the high NP group were 27%, 62% and 82% at 1, 5 and 10 years, compared with 19%, 50% and 77%, respectively, in the moderate NP group and, in a competing risks model, risk of HF-related death was 50% higher at each timepoint. Median time between NP test and HF diagnosis was 101 days (IQR 19-581). CONCLUSIONS: High baseline NP is associated with increased HF-related hospitalisation and poor survival. While healthcare systems remain under pressure from the impact of COVID-19, research to test novel strategies to prevent hospitalisation and improve outcomes-such as a mandatory two-week HF diagnosis pathway-is urgently needed.

COVID-19 , Heart Failure , Aged , Biomarkers , COVID-19/diagnosis , COVID-19/epidemiology , Cohort Studies , Female , Heart Failure/drug therapy , Heart Failure/therapy , Hospitalization , Humans , Male , Natriuretic Peptide, Brain/therapeutic use , Peptide Fragments , SARS-CoV-2