Background: Observational and small, randomized studies suggest that influenza vaccine may reduce future cardiovascular events in patients with cardiovascular disease. Methods: We conducted an investigator-initiated, randomized, double-blind trial to compare inactivated influenza vaccine with saline placebo administered shortly after myocardial infarction (MI; 99.7% of patients) or high-risk stable coronary heart disease (0.3%). The primary end point was the composite of all-cause death, MI, or stent thrombosis at 12 months. A hierarchical testing strategy was used for the key secondary end points: all-cause death, cardiovascular death, MI, and stent thrombosis. Results: Because of the COVID-19 pandemic, the data safety and monitoring board recommended to halt the trial before attaining the prespecified sample size. Between October 1, 2016, and March 1, 2020, 2571 participants were randomized at 30 centers across 8 countries. Participants assigned to influenza vaccine totaled 1290 and individuals assigned to placebo equaled 1281; of these, 2532 received the study treatment (1272 influenza vaccine and 1260 placebo) and were included in the modified intention to treat analysis. Over the 12-month follow-up, the primary outcome occurred in 67 participants (5.3%) assigned influenza vaccine and 91 participants (7.2%) assigned placebo (hazard ratio, 0.72 [95% CI, 0.52–0.99]; P =0.040). Rates of all-cause death were 2.9% and 4.9% (hazard ratio, 0.59 [95% CI, 0.39–0.89]; P =0.010), rates of cardiovascular death were 2.7% and 4.5%, (hazard ratio, 0.59 [95% CI, 0.39–0.90]; P =0.014), and rates of MI were 2.0% and 2.4% (hazard ratio, 0.86 [95% CI, 0.50–1.46]; P =0.57) in the influenza vaccine and placebo groups, respectively. Conclusions: Influenza vaccination early after an MI or in high-risk coronary heart disease resulted in a lower risk of a composite of all-cause death, MI, or stent thrombosis, and a lower risk of all-cause death and cardiovascular death, as well, at 12 months compared with placebo. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02831608.

Aim. This study was designed to evaluate the relationship between microRNAs (miRNAs), miR-126-3p and miR-223-3p, as new biomarkers of platelet activation, and predicting recurrent thrombotic events after acute myocardial infarction (AMI). Methods and Results. The analysis included 598 patients randomized in the PRAGUE-18 study (ticagrelor vs. prasugrel in AMI). The measurements of miRNAs were performed by using a novel miRNA immunoassay method. The association of miRNAs with the occurrence of the ischemic endpoint (EP) (cardiovascular death, nonfatal MI, or stroke) and bleeding were analyzed. The miR-223-3p level was significantly related to an increased risk of occurrence of the ischemic EP within 30 days (odds ratio (OR) = 15.74, 95% confidence interval (CI): 2.07–119.93, p = 0.008) and one year (OR = 3.18, 95% CI: 1.40–7.19, p = 0.006), respectively. The miR-126-3p to miR-223-3p ratio was related to a decreased risk of occurrence of EP within 30 days (OR = 0.14, 95% CI: 0.03–0.61, p = 0.009) and one year (OR = 0.37, 95% CI: 0.17–0.82, p = 0.014), respectively. MiRNAs were identified as independent predictors of EP even after adjustment for confounding clinical predictors. Adding miR-223-3p and miR-126-3p to miR-223-3p ratios as predictors into the model calculating the ischemic risk significantly increased the predictive accuracy for combined ischemic EP within one year more than using only clinical ischemic risk parameters. No associations between miRNAs and bleeding complications were identified. Conclusion. The miR-223-3p and the miR-126-3p are promising independent predictors of thrombotic events and can be used for ischemic risk stratification after AMI.

Existing data have described benefits and drawbacks of alcohol consumption on cardiovascular diseases (CVD), but no research has evaluated its association with the cardiovascular health (CVH) score proposed by the American Heart Association. Here, we conducted a cross-sectional analysis on the Kardiovize cohort (Brno, Czech Republic), to investigate the relationship between alcohol consumption and CVH. We included 1773 subjects (aged 25–64 years; 44.2% men) with no history of CVD. We compared CVD risk factors, CVH metrics (i.e., BMI, healthy diet, physical activity level, smoking status, blood pressure, fasting glucose, and total cholesterol) and CVH score between and within several drinking categories. We found that the relationship between drinking habits and CVH was related to the amount of alcohol consumed, drinking patterns, and beverage choices. Heavy drinkers were more likely to smoke tobacco, and to report diastolic blood pressure, fasting glucose, triglycerides, and low-density lipoprotein (LDL)-cholesterol at higher level than non-drinkers. Among drinkers, however, people who exclusively drank wine exhibited better CVH than those who exclusively drank beer. Although our findings supported the hypothesis that drinking alcohol was related to the CVH in general, further prospective research is needed to understand whether the assessment of CVH should incorporate information on alcohol consumption.

Yes-associated protein 1 (YAP1) is a transcriptional co-activator downstream of Hippo pathway. The pathway exerts crucial roles in organogenesis and its dysregulation is associated with the spreading of different cancer types. YAP1 gene encodes for multiple protein isoforms, whose specific functions are not well defined. We demonstrate the splicing of isoform-specific mRNAs is controlled in a stage- and tissue-specific fashion. We designed expression vectors encoding for the most-represented isoforms of YAP1 with either one or two WW domains and studied their specific signaling activities in YAP1 knock-out cell lines. YAP1 isoforms display both common and unique functions and activate distinct transcriptional programs, as the result of their unique protein interactomes. By generating TEAD-based transcriptional reporter cell lines, we demonstrate individual YAP1 isoforms display unique effects on cell proliferation and differentiation. Finally, we illustrate the complexity of the regulation of Hippo-YAP1 effector in physiological and in pathological conditions of the heart.

Purpose: To investigate the prognostic significance of diabetes mellitus (DM) in patients with high risk acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (pPCI) in the era of potent antithrombotics. Methods: Data from 1230 ST-segment elevation myocardial infarction (STEMI) patients enrolled in the PRAGUE-18 (prasugrel vs. ticagrelor in pPCI) study were analyzed. Ischemic and bleeding event rates were calculated for patients with and without diabetes. The independent impact of diabetes on outcomes was evaluated after adjustment for outcome predictors. Results: The prevalence of DM was 20% (N = 250). Diabetics were older and more often female. They were more likely to have hypertension, hyperlipoproteinemia, multivessel coronary disease and left main disease, and be obese. The primary net-clinical endpoint (EP) containing death, spontaneous nonfatal MI, stroke, severe bleeding, and revascularization at day 7 occurred in 6.1% of patients with, and in 3.5% of patients without DM (HR 1.8; 95% CI 0.978–3.315; P = 0.055). At one year, the key secondary endpoint defined as cardiovascular death, spontaneous MI, or stroke occurred in 8.8% with, and 5.5% without DM (HR 1.621; 95% CI 0.987–2.661; P = 0.054). In those with DM the risk of total one-year mortality (6.8% vs. 3.9% (HR 1.773; 95% CI 1.001–3.141; P = 0.047)) and the risk of nonfatal reinfarction (4.8% vs. 2.2% (HR 2.177; 95% CI 1.077–4.398; P = 0.026)) were significantly higher compared to in those without DM. There was no risk of major bleeding associated with DM (HR 0.861; 95% CI 0.554–1.339; P = 0.506). In the multivariate analysis, diabetes was independently associated with the one-year risk of reinfarction (HR 2.176; 95% Confidence Interval, 1.055–4.489; p = 0.035). Conclusion: Despite best practices STEMI treatment, diabetes is still associated with significantly worse prognoses, which highlights the importance of further improvements in the management of this high-risk population.