LncRNAs as Regulators of Atherosclerotic Plaque Stability.

Current clinical data show that, despite constant efforts to develop novel therapies and clinical approaches, atherosclerotic cardiovascular diseases (ASCVD) are still one of the leading causes of death worldwide. Advanced and unstable atherosclerotic plaques most often trigger acute coronary events that can lead to fatal outcomes. However, despite the fact that different plaque phenotypes may require different treatments, current approaches to prognosis, diagnosis, and classification of acute coronary syndrome do not consider the diversity of plaque phenotypes. Long non-coding RNAs (lncRNAs) represent an important class of molecules that are implicated in epigenetic control of numerous cellular processes. Here we review the latest knowledge about lncRNAs' influence on plaque development and stability through regulation of immune response, lipid metabolism, extracellular matrix remodelling, endothelial cell function, and vascular smooth muscle function, with special emphasis on pro-atherogenic and anti-atherogenic lncRNA functions. In addition, we present current challenges in the research of lncRNAs' role in atherosclerosis and translation of the findings from animal models to humans. Finally, we present the directions for future lncRNA-oriented research, which may ultimately result in patient-oriented therapeutic strategies for ASCVD.

Development and Validation of a Multivariable Predictive Model for Mortality of COVID-19 Patients Demanding High Oxygen Flow at Admission to ICU: AIDA Score.

INTRODUCTION: Risk stratification is an important aspect of COVID-19 management, especially in patients admitted to ICU as it can provide more useful consumption of health resources, as well as prioritize critical care services in situations of overwhelming number of patients. MATERIALS AND METHODS: A multivariable predictive model for mortality was developed using data solely from a derivation cohort of 160 COVID-19 patients with moderate to severe ARDS admitted to ICU. The regression coefficients from the final multivariate model of the derivation study were used to assign points for the risk model, consisted of all significant variables from the multivariate analysis and age as a known risk factor for COVID-19 patient mortality. The newly developed AIDA score was arrived at by assigning 5 points for serum albumin and 1 point for IL-6, D dimer, and age. The score was further validated on a cohort of 304 patients admitted to ICU due to the severe form of COVID-19. RESULTS: The study population included 160 COVID-19 patients admitted to ICU in the derivation and 304 in the validation cohort. The mean patient age was 66.7 years (range, 20-93 years), with 68.1% men and 31.9% women. Most patients (76.8%) had comorbidities with hypertension (67.7%), diabetes (31.7), and coronary artery disease (19.3) as the most frequent. A total of 316 patients (68.3%) were treated with mechanical ventilation. Ninety-six (60.0%) in the derivation cohort and 221 (72.7%) patients in the validation cohort had a lethal outcome. The population was divided into the following risk categories for mortality based on the risk model score: low risk (score 0-1) and at-risk (score > 1). In addition, patients were considered at high risk with a risk score > 2. By applying the risk model to the validation cohort (n = 304), the positive predictive value was 78.8% (95% CI 75.5% to 81.8%); the negative predictive value was 46.6% (95% CI 37.3% to 56.2%); the sensitivity was 82.4% (95% CI 76.7% to 87.1%), and the specificity was 41.0% (95% CI 30.3% to 52.3%). The C statistic was 0.863 (95% CI 0.805-0.921) and 0.665 (95% CI 0.598-0.732) in the derivation and validation cohorts, respectively, indicating a high discriminative value of the proposed score. CONCLUSION: In the present study, AIDA score showed a valuable significance in estimating the mortality risk in patients with the severe form of COVID-19 disease at admission to ICU. Further external validation on a larger group of patients is needed to provide more insights into the utility of this score in everyday practice.

Improvement of Ventricular-Arterial Coupling in Elderly Patients with Heart Failure After Beta Blocker Therapy: Results from the CIBIS-ELD Trial.

UNLABELLED: The interaction between the heart and the arterial system (ventricular-arterial coupling - VA) is an important determinant of cardiovascular performance. Vascular stiffness (Ea) and left ventricular (LV) endsystolic stiffness (Elv) augment with age and in heart failure (HF). Beta blockers (BB) are recommended therapy for patients with HF. However, data about the effects of BB on VA coupling are scarce. AIMS OF THE STUDY: TO ASSESS: 1) changes in VA after BB therapy; 2) interactions between VA and LV functions, 3) predictive factors influencing VA change. METHODS: Eight hundred seventy-seven elderly patients with HF (aged ≥ 65, NYHA ≥ II, LV ejection fraction (LVEF) ≤ 45%), treated with BB according to the CIBIS-ELD protocol of up-titration, underwent Doppler echocardiography with clinical and laboratory assessment before and after 12 weeks of BB. VA coupling was calculated as Ea/Elv ratio. RESULTS: Ventriculo-arterial interaction improved after 12 weeks of BB in elderly patients with HF. Values of Ea significantly decreased from 2.73 ± 1.16 to 2.40 ± 1.01, p < 0.001, resulting in a VA level close to the optimal range i.e. from 1.70 ± 1.05 (1.46) to 1.50 ± 0.94 (1.29), p < 0.001. A similar degree of VA change was found in the patients with ischemic and non-ischemic HF after the treatment. Improvement in the clinical stage of HF closely correlated with VA coupling change after BB (p = 0.006). The strongest predictor of VA coupling alteration during BB was the improvement in global LVEF (p < 0.001) followed by the age of patients (p = 0.014). CONCLUSIONS: The beneficial effect of BB in elderly patients with HF was achieved by optimizing VA coupling close to recommended range, associated with an improvement in LVEF and contractility.

The impact of the metabolic syndrome on the outcome after aortic valve replacement.

OBJECTIVES: The aim of this study was to examine the influence of the metabolic syndrome on the left ventricular geometry as well as on the early and mid-time outcome in patients with aortic stenosis who underwent aortic valve replacement. METHODOLOGY: The study included 182 patients who underwent aortic valve replacement due to aortic stenosis. The metabolic syndrome was defined by the presence of at least three AHA-NHLB (American Heart Association/National Heart, Lung and Blood Institute) criteria. All the patients were followed for at least 2 years after the surgery. RESULTS: The metabolic syndrome did not influence the severity of aortic stenosis (mean gradient and aortic valve area). However, the metabolic syndrome was associated with the reduced prevalence of the normal left ventricular geometry and the increased risk of concentric left ventricular hypertrophy in patients with aortic stenosis. Among the metabolic syndrome criteria, only increased blood pressure was simultaneously associated with the short-term and mid-term outcome, independently of other risk factors. Increased fasting glucose level was an independent predictor of the only 30-day outcome after the valve replacement. The metabolic syndrome and left ventricular hypertrophy were, independently of hypertension and diabetes, associated with the 30-day outcome, as well as incidence of major cerebrovascular and cardiovascular events in the 2-year postoperative period. CONCLUSION: The metabolic syndrome does not change severity of the aortic stenosis, but significantly impacts the left ventricular remodeling in these patients. The metabolic syndrome and left ventricular hypertrophy, irrespective of hypertension and diabetes, are predictors of the short-term and mid-term outcome of patients with aortic stenosis who underwent aortic valve replacement.

Myocardial hypertrophy in hypertensive patients with and without metabolic syndrome.

BACKGROUND/AIM: Beside arterial hypertension as the most important factor of a myocardial hypertension development, very important risk factors are obesity, hypercholesterolemia, insulin resistance, etc. The aim of the study was to examine the influence of metabolic syndrome (MetS) on left ventricular hypertrophy in patients with arterial hypertension. METHODS: We checked medical records for 138 patients with arterial hypertension, and compared them with the control group of 44 normotensive subjects. The patients with arterial hypertension were divided into two groups considering the presence of MetS: with MetS (59 patients), and without MetS (79 patients). We defined MetS as presence of three (or more) within five criteria: central obesity (> 102 cm male, > 88 cm female), raised triglycerides (> 1.7 mmol/L, or drug treatment for elevated triglycerides), reduced high density lipoprotein (HDL) cholesterol (< 1.03 mmol/L male, < 1.3 mmol/L female), raised blood pressure (> 130 mmHg systolic, > 90mmHg diastolic), raised fasting glucose (> 6.11 mmol/L, or drug treatment for elevated glucose level). In each group routine laboratory, echocardiography and 24-hour ambulatory blood pressure monitoring were performed. RESULTS: We found statisticaly significant higher left ventricular mass in both subgroups hypertensive patients in comparison with the control group (p < 0.05). We did not find statistically significant difference (227.31 +/- 63.44 vs 219 +/- 59.5, p > 0.05) in left ventricular mass between these two groups of patients. In the patients with arterial hypertension and MetS we found hypertrophy more frequently than in the subgroup without MetS (43/57 vs 34/69, p < 0.001). CONCLUSION: Our results suggest that associated cardiometabolic risks increase the prevalence of myocardial hypertrophy, but do not influence left ventricular mass.

Ambulatory arterial blood pressure monitoring in patients before and after thyroidectomy.

BACKGROUND/AIM: [corrected] Increased values of thyroid hormones in the clinical syndrome of hyperthyreosis affect blood pres sure values and its circadial variation. The aim of this study was to define the influence of hyperthyreosis on the values and circadial variations of arterial blood pressure, as well as to investigate the effect of thyroid surgery on blood pressure values. METHODS: We compared the 24-hour averages of systolic and diastolic blood pressure, their variations and their reduction during the night between 20 female patients with hyperthyroidism and hypertension de novo and 20 healthy females. We compared the values of 24-hour ambulatory monitoring performed before the surgery with the values gathered two weeks after the surgery. RESULTS: The 24-hour average systolic and diastolic blood pressure values were higher in the patients with hyperthyroidism than in the control group (p < 0.001). In the group of patients, the variations in blood pressure were significantly higher than they were in the group of healthy people (p < 0.001). The amplitude of the nocturnal reduction of blood pressure was also significantly lower in the patients with hyperthyroid status and hypertension, in comparison to the healthy persons (p < 0.001). Two weeks after the surgery, a significant reduction of blood pressure values (both for systolic and diastolic) appeared. CONCLUSION: The patients with hyperthyroidism caused hypertension had higher systolic and dia stolic blood pressure, higher variations in blood pressure and lower nocturnal reduction of blood pressure than healthy subjects. Thyroid surgery, as a control of thyroid function, optimised blood pressure very rapidly.