Objective: To investigate the association between hypertension and outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. Methods: We performed a systematic literature search from several databases on studies that assess hypertension and outcome in COVID-19. Composite of poor outcome, comprising of mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care and disease progression were the outcomes of interest. Results: A total of 6560 patients were pooled from 30 studies. Hypertension was associated with increased composite poor outcome (risk ratio (RR) 2.11 (95% confidence interval (CI) 1.85, 2.40), p < 0.001; I2, 44%) and its sub-group, including mortality (RR 2.21 (1.74, 2.81), p < 0.001; I2, 66%), severe COVID-19 (RR 2.04 (1.69, 2.47), p < 0.001; I2 31%), ARDS (RR 1.64 (1.11, 2.43), p = 0.01; I2,0%, p = 0.35), ICU care (RR 2.11 (1.34, 3.33), p = 0.001; I2 18%, p = 0.30), and disease progression (RR 3.01 (1.51, 5.99), p = 0.002; I2 0%, p = 0.55). Meta-regression analysis showed that gender ( p = 0.013) was a covariate that affects the association. The association was stronger in studies with a percentage of males < 55% compared to ⩾ 55% (RR 2.32 v. RR 1.79). Conclusion: Hypertension was associated with increased composite poor outcome, including mortality, severe COVID-19, ARDS, need for ICU care and disease progression in patients with COVID-19.

Background-Daily rhythms of mammalian physiology and endocrinology are regulated by circadian pacemakers. The master circadian pacemaker resides in the suprachiasmatic nucleus, which is located in the hypothalamus of the brain, but circadian oscillators also exist in peripheral tissues. Because many studies have demonstrated apparent circadian variations in the frequency of cardiovascular disorders, it is of great interest to investigate a possible relation between circadian gene expression and cardiovascular function. We examined whether a circadian oscillation system exists in the aorta and/or in cultured vascular smooth muscle cells (VSMCs). Methods and Results-The mRNA levels of clock genes were assayed by northern blot analysis. The mouse aorta showed a clear circadian oscillation in the expression of mPer2, dbp, and Bmal1. Brief treatment of VSMCs with angiotensin II induced a robust increase in mPer2 gene expression, followed by a marked reduction in mPer2 mRNA levels and subsequent synchronous cycling of mPer2, dbp, and Bmal1 mRNAs. The induction of mPer2 in VSMCs by angiotensin II was completely abolished by treatment with CV11947, a specific angiotensin II type1 receptor antagonist. Conclusions-The present results demonstrate that the aorta and VSMCs possess a circadian oscillation system which is comparable to that of the suprachiasmatic nucleus and that the circadian gene expression in VSMCs is induced by angiotensin II through the angiotensin II type1 receptor. Our in vitro system will provide a useful tool to further analyze the physiological significance of the peripheral clock in cardiovascular function. Key Words: angiotensin Ⅲ circadian rhythm Ⅲ molecular biology Ⅲ muscle, smooth I n mammals, behavioral and physiological processes display Ϸ24-hour rhythms that are regulated by circadian pacemakers. On the basis of surgical ablation and transplantation experiments, the central circadian pacemaker is thought to reside in the hypothalamic suprachiasmatic nucleus. 1 However, several lines of evidence indicate that peripheral tissues and immortalized cells also contain circadian oscillators; the molecular mechanisms of these oscillators are virtually identical to those in the suprachiasmatic nucleus. [2][3][4][5] The molecular mechanism of this circadian oscillator is based on interacting transcriptional-translational autoregulatory feedback loops. The feedback loop involves 3 homologs of the Drosophila gene period (mPer1, mPer2, and mPer3) and 2 cryptochrome genes (mCry1 and mCry2). The rhythmic transcription of the mPer and mCry genes is driven by the transcription activator genes Clock and Bmal1. 6 Various cardiovascular functions, including blood pressure, heart rate, and coagulation parameters, are known to show a diurnal variation. 7 In addition, several cardiovascular events, such as myocardial infarction, sudden cardiac death, and stroke, show well-defined patterns in their occurrence throughout the day. 8 Although such diurnal variations are widely known, the underlying molecular mechanisms...

In vitro enzymological analysis of the recombinant soluble form of SEP demonstrated that it hydrolyzes a variety of vasoactive peptides, including endothelin-1, atrial natriuretic peptide, and angiotensin I. This activity of SEP was inhibited by phosphoramidon and the neutral endopeptidase 24.11 specific inhibitor thiorphan, but it was only partially inhibited by the endothelin-converting enzyme specific inhibitor FR901533. These findings suggest that SEP is a novel metalloprotease that possesses a broad substrate specificity and that it may be involved in the metabolism of biologically active peptides intracellulary as well as extracellularly.

Our study showed that for persistent AF ablation, a specified substrate modification guided by nonlinear phase mapping could eliminate localized re-entry and non-pulmonary focal sources after pulmonary vein isolation.

ObjectivesThis systematic review and meta-analysis aimed to assess the association between N-terminal pro-brain natriuretic peptide (NT-proBNP) and mortality in patients with COVID-19.MethodsSystematic literature search from several electronic databases were performed. The outcome was mortality (non-survivor) in patients with COVID-19 pneumonia. NT-proBNP data were in continuous variable (pg/mL), dichotomous data (elevated/non-elevated) and effect estimate adjusted to cardiac injury/elevated biomarkers of cardiac injury.ResultsA total of 967 patients from six studies were included in this analysis. NT-proBNP was higher in non-survivor group (standardised mean difference 0.75 (0.44, 1.07), p<0.001; I2: 61%). Elevated NT-proBNP was associated with increased mortality (RR 3.63 (92.21, 5.95), p<0.001; I2: 60%). Sensitivity analysis by removing a study reduces heterogeneity (risk ratio 3.47 (2.36, 5.11), p<0.001; I2: 49%). Pooled adjusted HR (adjusted to cardiac injury/elevated biomarkers of cardiac injury) showed that elevated NT-proBNP was independently associated with mortality (HR 1.37 (1.19, 1.57), p<0.001; I2: 0%, p=0.77). Pooled analysis of multiple cut-off point resulted in a sensitivity of 76% (46%–92%) and specificity of 88% (71%–96%). Summary receiver operating characteristic curve analysis demonstrates an area under curve of 0.90 (0.87–0.93). Elevated NT-proBNP has a likelihood ratio (LR) +6.4 and LR -0.3.ConclusionElevated NT-proBNP level was associated with increased mortality in COVID-19 pneumonia.