Background Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. Methods We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany ( n = 135), Spain ( n = 133), Switzerland ( n = 20) and the United States ( n = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID-19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). Findings We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1–2.1], odds ratio 3.5 [95% CI 1.9–6.6], adjusted p -value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. Interpretation HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2. Funding Funded by Roche Sequencing Solutions, Inc.

Aortic pulse wave velocity (PWV) is directly related to arterial stiffness. Different methods for the determination of PWV coexist. The aim of this prospective study was to evaluate the prognostic value of PWV in high-risk patients with suspected coronary artery disease undergoing invasive angiography and to compare 3 different methods for assessing PWV. In 1040 patients, invasive PWV (iPWV) was measured during catheter pullback. Additionally, PWV was estimated with a model incorporating age, central systolic blood pressure, and pulse waveform characteristics obtained from noninvasive measurements (estimated PWV). As a third method, PWV was calculated with a formula solely based on age and blood pressure (formula-based PWV). Survival analysis was based on continuous PWV as well as using cutoff values. After a median follow-up duration of 1565 days, 24% of the patients reached the combined end point (cardiovascular events or mortality). Cox proportional hazard ratios per 1 SD were 1.35 for iPWV, 1.37 for estimated PWV, and 1.28 for formula-based PWV ( P <0.0001 for all 3 methods) in univariate analysis, remaining statistically significant after comprehensive multivariable adjustments. In a model including a modified risk score for coronary artery disease, iPWV and estimated PWV remained borderline significant. The net reclassification improvement was significant for iPWV (0.173), formula-based PWV (0.181), and estimated PWV (0.230). All 3 methods for the determination of PWV predicted cardiovascular events and mortality in patients with suspected coronary artery disease. This indicates that iPWV as well as both noninvasive estimation methods are suitable for the assessment of arterial stiffness, bearing in mind their individual characteristics.

Objective: Patients with rheumatoid arthritis (RA) are at significantly higher risk of cardiovascular (CV) morbidity and mortality compared with the general population. Traditional CV risk factors cannot explain the total excess of CV morbidity and mortality in RA patients. At present, it is not clear whether treatment with statins might be of benefit in RA patients. The aim of the present systematic literature review is to summarize the published evidence concerning treatment with statins and its impact on CV events in RA patients.Methods: A systematic literature review of studies on RA and statins was carried out in the database PubMed. Search terms were 'simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR pravastatin OR rosuvastatin OR statin AND arthritis'. Papers were included in this review when the reported outcome was on CV events in RA patients. After exclusion of the studies not fulfilling our inclusion criteria four studies were finally analyzed. The total number of RA patients included in these studies was 4896.

Autoinflammatory syndromes (AIS) are characterized by recurring events of inflammation, leading to a variety of organ manifestations and fever attacks. A subgroup of AIS is commonly referred to as hereditary periodic fever syndromes (HPFS). There is substantial evidence that autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus are strongly associated with cardiovascular morbidity and mortality. The link between AIS and cardiovascular disease is not that clear, even if the concept of continuous inflammation as a risk factor for cardiovascular disease is widely accepted. Research on the association of AIS and cardiovascular disease is increasing within the last years. In this review, we will discuss the association of several AIS with cardiovascular disease. Based on the rarity of some entities, lack of data, however, led to exclusion of some rare AIS. Especially, for Behcet's disease (BD), adult-onset Still's disease (AOSD), and Familial Mediterranean fever (FMF), there is an association with a number of cardiovascular abnormalities. BD is the AIS, which is most strongly associated with manifestation in the arterial and venous system. AOSD is strongly associated with cardiac inflammation (peri-/myocarditis). FMF patients are likely to suffer from serositis. Of note, there seems to be a link between variants of AOSD as well as FMF and idiopathic recurrent acute pericarditis.

Background: Renal denervation (RDN) lowers blood pressure (BP), but BP response is variable in individual patients. We investigated whether measures of pulsatile hemodynamics, obtained during 24-hour ambulatory BP monitoring, predict BP drop following RDN. Methods: From the randomized, sham-controlled SPYRAL HTN-OFF MED Pivotal trial, we performed a post hoc analysis of BP waveforms from 111 RDN patients and 111 sham controls, obtained with a brachial cuff-based sphygmomanometer. Waveforms were acquired during ambulatory BP monitoring at diastolic BP level and processed with validated ARCSolver algorithms to derive hemodynamic parameters (augmentation index; augmentation pressure; backward and forward wave amplitude; estimated aortic pulse wave velocity). We investigated the relationship between averaged 24-hour values at baseline and the change in 24-hour BP at 3 months in RDN patients, corrected for observed trends in the sham group. Results: There was a consistent inverse relationship between baseline augmentation index/augmentation pressure/backward wave amplitude/forward wave amplitude/estimated aortic pulse wave velocity and BP response to RDN: the decrease in 24-hour systolic BP/diastolic BP was 7.8/5.9 (augmentation index), 8.0/6.3 (augmentation pressure), 6.7/5.4 (backward wave amplitude), 5.7/4.7 (forward wave amplitude), and 7.8/5.2 (estimated aortic pulse wave velocity) mm Hg greater for patients below versus above the respective median value ( P <0.001 for all comparisons, respectively). Taking augmentation index/augmentation pressure/backward wave amplitude/forward wave amplitude/estimated aortic pulse wave velocity into account, a favorable BP response following RDN, defined as a drop in 24-hour systolic blood pressure of ≥5 mm Hg, could be predicted with an area under the curve of 0.70/0.74/0.70/0.65/0.62 ( P <0.001 for all, respectively). Conclusions: These results suggest that pulsatile hemodynamics, obtained during 24-hour ambulatory BP monitoring, may predict BP response to RDN.