Background: High intake of marine n-3 polyunsaturated fatty acids (PUFA) has been associated with reduced risk of cardiovascular events; however, this has not been confirmed in patients with a recent acute myocardial infarction (AMI). Elderly patients are at particularly increased cardiovascular risk after MI, but few trials address this group specifically. Omega-3 fatty acids hold the potential to reduce cardiovascular events with limited adverse effects in this vulnerable group. The hypothesis was that daily addition of 1.8g n-3 PUFA to standard of care secondary prophylaxis in elderly patients who have survived an AMI would reduce the risk of subsequent cardiovascular events during 2 years follow-up. Methods: The OMega-3 fatty acids in Elderly with Myocardial Infarction (OMEMI) trial is an investigator-initiated, multi-center, randomized clinical trial adding 1.8 g n-3 PUFA (930 mg EPA and 660 mg DHA) versus placebo (corn oil) daily to standard of care in 70-82 years old patients with recent (2-8 weeks) AMI. The primary endpoint was a composite of non-fatal AMI, unscheduled revascularization, stroke, all-cause death, heart failure hospitalization after two years. The secondary outcome was new atrial fibrillation. The safety outcome was major bleeding. Serum fatty acids were measured as biomarkers of adherence. Results: In total, 1,027 patients were randomized. Follow-up data were available for 1,014 patients who were included in the intention-to-treat analysis. Mean ± SD age was 75±3.6 years, 294 (29%) were female and mean triglycerides were 111.4±61.9 mg/dL. The primary endpoint occurred in 108 (21.4%) patients on n-3 PUFA vs 102 (20.0%) on placebo (HR 1.08 [95%CI 0.82-1.41], p=0.60). The secondary endpoint occurred in 28 (7.2%) patients on n-3 PUFA vs 15 (4.0%) on placebo (1.84 [0.98 -3.45], p=0.06). Median changes in EPA and DHA were +87% and +16% for n-3 PUFA vs -13% and -8% for placebo. Major bleeding occurred in 54 (10.7%) and 56 (11.0%) in the n-3 PUFA and placebo groups, respectively (p=0.87). Similar results were found in per-protocol analysis (n=893). Conclusions: We could not detect reduction in clinical events in our elderly patients with a recent AMI, treated with 1.8 g n-3 PUFAs daily for 2 years. Clinical Trial Registration: OMEMI Study; URL: https://clinicaltrials.gov Unique Identifier: NCT01841944

Background: Growth differentiation factor 15 (GDF-15) is a strong prognostic marker in sepsis and cardiovascular disease (CVD). The prognostic importance of GDF-15 in COVID-19 is unknown. Methods: Consecutive, hospitalized patients with laboratory-confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and symptoms of COVID-19 were enrolled in the prospective, observational COVID MECH study. Biobank samples were collected at baseline, day 3 and day 9. The primary endpoint was admission to the intensive care unit or death during hospitalization, and the prognostic performance of baseline and serial GDF-15 concentrations were compared with that of established infectious disease and cardiovascular biomarkers. Results: Of the 123 patients enrolled, 35 (28%) reached the primary endpoint; these patients were older, more often had diabetes mellitus, had lower oxygen saturations and higher National Early Warning Score on baseline. Baseline GDF-15 concentrations were elevated (>95th percentile in age-stratified healthy individuals) in 97 (79%), and higher concentrations were associated with detectable SARS-CoV-2 viremia and hypoxemia (both p<0.001). Patients reaching the primary endpoint had higher concentrations of GDF-15 (median 4225 [IQR 3197-5972] pg/mL vs 2187 [1344-3620] pg/mL, p<0.001). The C-statistic value was 0.78 (95% confidence interval 0.70-0.86). The association between GDF-15 and outcome persisted after adjusting for age, sex, race, body mass index, estimated glomerular filtration rate and previous myocardial infarction, heart failure or atrial fibrillation (p<0.001), and was superior and incremental to interleukin-6, C-reactive protein, procalcitonin, ferritin, D-dimer, cardiac troponin T and N-terminal pro-B-type natriuretic peptide. Increase in GDF-15 from baseline to day 3 was also greater in patients reaching the primary endpoint (median 1208 [IQR 0-4305] pg/mL versus -86 [IQR -322-491] pg/mL, p<0.001). Conclusions: GDF-15 is elevated in the majority of patients hospitalized with COVID-19, and higher concentrations are associated with SARS-CoV-2 viremia, hypoxemia and worse outcome. The prognostic importance of GDF-15 was additional and superior to established cardiovascular and inflammatory biomarkers.

Background: Diagnosing heart failure with preserved ejection fraction (HFpEF) can be challenging. The H2FPEF and HFA-PEFF scores have recently been developed to estimate the likelihood that HFpEF is present among patients with unexplained dyspnea.Objectives: To describe characteristics and risk of adverse outcomes associated with each score among participants in the community with unexplained dyspnea. Methods:We studied 4,892 Atherosclerosis Risk in Communities (ARIC) participants aged 67-90 at Visit 5 (2011)(2012)(2013) without other cardiopulmonary causes of dyspnea. We categorized participants as asymptomatic (76.6%), known HFpEF (10.3%), and tertiles of each score among those with ≥moderate, self-reported dyspnea (13.1%). H2FPEF≥6 and HFA-PEFF≥5 Results: Mean age was 75±5 years, 58% were women, and 22% were black. After a mean follow-up of 5.3±1.2 years, rates (95% CI) of HF hospitalization or death per 1000 person-years for asymptomatic and known HFpEF were 20.