The effects of angiotensin converting enzyme inhibitors (ACEI) on human N-acetylseryl-aspartyl-lysyl-proline (AcSDKP) levels : a systematic review

Background: Tuberculous pericardial effusion is a pro-fibrotic condition that is complicated by constrictive pericarditis in 4-8% of cases. N-acetyl-seryl-aspartyl-lysylproline (Ac-SDKP) is a ubiquitous tetrapeptide with antifibrotic properties that is low in tuberculous pericardial effusion, thus providing a potential mechanism for the heightened fibrotic state. Angiotensin converting enzyme inhibitors (ACEI), which increase Ac-SDKP levels with antifibrotic effects in animal models, are candidate drugs for preventing constrictive pericarditis if they can be shown to have similar effects on AcSDKP and fibrosis in human tissues. Objective: To systematically review the effects of ACEIs on Ac-SDKP levels in human tissues. Methods: We searched five electronic databases (1996-2014) and conference abstracts with no language restrictions. Two reviewers independently selected studies, extracted data and assessed methodological quality. The protocol was registered in PROSPERO

The Effects of Angiotensin Converting Enzyme Inhibitors (ACE-I) on Human N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) Levels: A Systematic Review and Meta-Analysis

BACKGROUND: Tuberculous pericardial effusion is a pro-fibrotic condition that is complicated by constrictive pericarditis in 4% to 8% of cases. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a ubiquitous tetrapeptide with anti-fibrotic properties that is low in tuberculous pericardial effusion, thus providing a potential mechanism for the heightened fibrotic state. Angiotensin-converting enzyme inhibitors (ACE-I), which increase Ac-SDKP levels with anti-fibrotic effects in animal models, are candidate drugs for preventing constrictive pericarditis if they can be shown to have similar effects on Ac-SDKP and fibrosis in human tissues. Objective To systematically review the effects of ACE-Is on Ac-SDKP levels in human tissues. METHODS: We searched five electronic databases (1996 to 2014) and conference abstracts with no language restrictions. Two reviewers independently selected studies, extracted data and assessed methodological quality. The protocol was registered in PROSPERO. RESULTS: Four studies with a total of 206 participants met the inclusion criteria. Three studies (106 participants) assessed the change in plasma levels of Ac-SDKP following ACE-I administration in healthy humans. The administration of an ACE-I was associated with an increase in Ac-SDKP levels (mean difference (MD) 5.07 pmol/ml (95% confidence intervals (CI) 0.64 pmol/ml to 9.51 pmol/ml)). Two studies with 100 participants further assessed the change in Ac-SDKP level in humans with renal failure using ACE-I. The administration of an ACE-I was associated with a significant increase in Ac-SDKP levels (MD 8.94 pmol/ml; 95% CI 2.55 to 15.33; I 2 = 44%). CONCLUSION: ACE-I increased Ac-SDKP levels in human plasma. These findings provide the rationale for testing the impact of ACE-I on Ac-SDKP levels and fibrosis in tuberculous pericarditis

Change in Ac-SDKP levels in participants with renal failure.

<p>ACE-I, Angiotensin Converting Enzyme Inhibitors; IV, inverse variance.</p

Change in Ac-SDKP levels in healthy participants.

<p>ACE-I, Angiotensin Converting Enzyme Inhibitors; IV, inverse variance.</p

Flow diagram of search results.

<p>Flow diagram of search results.</p

Interventions.

BackgroundCOVID-19 experiences on noncommunicable diseases (NCDs) from district-level hospital settings during waves I and II are scarcely documented. The aim of this study is to investigate the NCDs associated with COVID-19 severity and mortality in a district-level hospital with a high HIV/TB burden.MethodsThis was a retrospective observational study that compared COVID-19 waves I and II at Khayelitsha District Hospital in Cape Town, South Africa. COVID-19 adult patients with a confirmed SARS-CoV-2 polymerase chain reaction (PCR) or positive antigen test were included. In order to compare the inter wave period, clinical and laboratory parameters on hospital admission of noncommunicable diseases, the Student t-test or Mann-Whitney U for continuous data and the X2 test or Fishers’ Exact test for categorical data were used. The role of the NCD subpopulation on COVID-19 mortality was determined using latent class analysis (LCA).FindingsAmong 560 patients admitted with COVID-19, patients admitted during wave II were significantly older than those admitted during wave I. The most prevalent comorbidity patterns were hypertension (87%), diabetes mellitus (65%), HIV/AIDS (30%), obesity (19%), Chronic Kidney Disease (CKD) (13%), Congestive Cardiac Failure (CCF) (8.8%), Chronic Obstructive Pulmonary Disease (COPD) (3%), cerebrovascular accidents (CVA)/stroke (3%), with similar prevalence in both waves except HIV status [(23% vs 34% waves II and I, respectively), p = 0.022], obesity [(52% vs 2.5%, waves II and I, respectively), p ConclusionEven though clinical and laboratory characteristics differed significantly between the two waves, mortality remained constant. According to LCA, the cardiovascular, diabetes, and CKD phenotypes had the highest death probability.</div

Demographic, lifestyle, and clinical characteristics of the sample.

Demographic, lifestyle, and clinical characteristics of the sample.</p

Fraction dead vs. time from triage, by wave.

BackgroundCOVID-19 experiences on noncommunicable diseases (NCDs) from district-level hospital settings during waves I and II are scarcely documented. The aim of this study is to investigate the NCDs associated with COVID-19 severity and mortality in a district-level hospital with a high HIV/TB burden.MethodsThis was a retrospective observational study that compared COVID-19 waves I and II at Khayelitsha District Hospital in Cape Town, South Africa. COVID-19 adult patients with a confirmed SARS-CoV-2 polymerase chain reaction (PCR) or positive antigen test were included. In order to compare the inter wave period, clinical and laboratory parameters on hospital admission of noncommunicable diseases, the Student t-test or Mann-Whitney U for continuous data and the X2 test or Fishers’ Exact test for categorical data were used. The role of the NCD subpopulation on COVID-19 mortality was determined using latent class analysis (LCA).FindingsAmong 560 patients admitted with COVID-19, patients admitted during wave II were significantly older than those admitted during wave I. The most prevalent comorbidity patterns were hypertension (87%), diabetes mellitus (65%), HIV/AIDS (30%), obesity (19%), Chronic Kidney Disease (CKD) (13%), Congestive Cardiac Failure (CCF) (8.8%), Chronic Obstructive Pulmonary Disease (COPD) (3%), cerebrovascular accidents (CVA)/stroke (3%), with similar prevalence in both waves except HIV status [(23% vs 34% waves II and I, respectively), p = 0.022], obesity [(52% vs 2.5%, waves II and I, respectively), p ConclusionEven though clinical and laboratory characteristics differed significantly between the two waves, mortality remained constant. According to LCA, the cardiovascular, diabetes, and CKD phenotypes had the highest death probability.</div

Comorbid patterns by latent disease class.

BackgroundCOVID-19 experiences on noncommunicable diseases (NCDs) from district-level hospital settings during waves I and II are scarcely documented. The aim of this study is to investigate the NCDs associated with COVID-19 severity and mortality in a district-level hospital with a high HIV/TB burden.MethodsThis was a retrospective observational study that compared COVID-19 waves I and II at Khayelitsha District Hospital in Cape Town, South Africa. COVID-19 adult patients with a confirmed SARS-CoV-2 polymerase chain reaction (PCR) or positive antigen test were included. In order to compare the inter wave period, clinical and laboratory parameters on hospital admission of noncommunicable diseases, the Student t-test or Mann-Whitney U for continuous data and the X2 test or Fishers’ Exact test for categorical data were used. The role of the NCD subpopulation on COVID-19 mortality was determined using latent class analysis (LCA).FindingsAmong 560 patients admitted with COVID-19, patients admitted during wave II were significantly older than those admitted during wave I. The most prevalent comorbidity patterns were hypertension (87%), diabetes mellitus (65%), HIV/AIDS (30%), obesity (19%), Chronic Kidney Disease (CKD) (13%), Congestive Cardiac Failure (CCF) (8.8%), Chronic Obstructive Pulmonary Disease (COPD) (3%), cerebrovascular accidents (CVA)/stroke (3%), with similar prevalence in both waves except HIV status [(23% vs 34% waves II and I, respectively), p = 0.022], obesity [(52% vs 2.5%, waves II and I, respectively), p ConclusionEven though clinical and laboratory characteristics differed significantly between the two waves, mortality remained constant. According to LCA, the cardiovascular, diabetes, and CKD phenotypes had the highest death probability.</div

Fraction dead vs time from triage, by latent class.

Fraction dead vs time from triage, by latent class.</p