The Renin–Angiotensin–Aldosterone System and Coronavirus Disease 2019

The renin–aldosterone–angiotensin system (RAAS) plays an important role in the pathogenesis of coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS-CoV-2 and the host’s expression of this membrane-bound protein could affect susceptibility to infection. The RAAS is an important regulator of cardiovascular physiology and ACE2 has an essential role. People with hypertension and other traits have shown to have an imbalance in ACE/ACE2 levels and reduced levels of ACE2 could enhance the risk of adverse outcome in patients with COVID-19. It has been hypothesised that the RAAS may mediate the interplay between cardiovascular disease and COVID-19 severity. Evidence shows that antihypertensive drugs that target the RAAS have no significant effect on the risk of infection and disease outcome. Variations in RAAS genes have been associated with the risk of developing hypertension and cardiovascular disease and could partly explain the heterogenous response to SARS-CoV-2 infection. This article explores the interplay between the RAAS and COVID-19, with emphasis on the possible relationship between genetic variations and disease severity

The Role of C-reactive Protein in Patient Risk Stratification and Treatment

Atherosclerosis is a chronic inflammatory disease. Several circulating inflammatory markers have been proposed for clinical use due to their ability to predict future cardiovascular events and may be useful for identifying people at high risk who might benefit from specific treatment to reduce this risk. Moreover, the identification of new therapeutic targets will allow the development of drugs that can help reduce the high residual risk of recurrence of cardiovascular events in patients with coronary artery disease. The clinical benefits of reducing recurrent major cardiovascular events recently shown by canakinumab and colchicine have renewed the cardiology community’s interest in inflammation as an aetiopathogenic mechanism for atherosclerosis. This review explores the use of C-reactive protein, which is the most frequently studied biomarker in this context; the concept of residual risk in primary and secondary cardiovascular prevention; and the current recommendations in international guidelines regarding the role of this inflammatory biomarker in cardiovascular risk stratification

Air pollution and heart failure: relationship with the ejection fraction

To study whether the concentrations of particulate matter in ambient air are associated with hospital admission due to heart failure in patients with heart failure with preserved ejection fraction and reduced ejection fraction

Rationale and design of the Concordance study between FFR and iFR for the assessment of lesions in the left main coronary artery. The ILITRO-EPIC-07 Trial

Introduction and objectives: Patients with left main coronary artery (LMCA) stenosis have been excluded from the trials that support the non-inferiority of the instantaneous wave-free ratio (iFR) compared to the fractional flow reserve (FFR) in the decision-making process of coronary revascularization. This study proposes to prospectively assess the concordance between the two indices in LMCA lesions and to validate the iFR cut-off value of 0.89 for clinical use. Methods: National, prospective, and observational multicenter registry of 300 consecutive patients with intermediate lesions in the LMCA (angiographic stenosis, 25% to 60%. A pressure gudiewire study and determination of the RFF and the iFR will be performed: in the event of a negative concordant result (FFR > 0.80/iFR > 0.89), no treatment will be performed; in case of a positive concordant result (FFR 0.80/iFR 0.89), an intravascular echocardiography will be performed and revascularization will be delayed if the minimum lumen area is > 6 mm(2). The primary clinical endpoint will be a composite of cardiovascular death, LMCA lesion-related non-fatal infarction or need for revascularization of the LMCA lesion at 12 months. Conclusions: Confirm that an iFR-guided decision-making process in patients with intermediate LMCA stenosis is clinically safe and would have a significant clinical impact. Also, justify its systematic use when prescribing treatment in these potentially high-risk patients

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden