The reduction of circulating low-density lipoprotein-cholesterol (LDL-C) is a primary target in cardiovascular risk reduction due to its well-established benefits in terms of decreased mortality. Despite the use of statin therapy, 10%–20% of high- and very-high-risk patients do not reach their LDL-C targets. There is an urgent need for improved strategies to manage dyslipidemia, especially among patients with homozygous familial hypercholesterolemia, but also in patients with established cardiovascular disease who fail to achieve LDL goals despite combined statin, ezetimibe, and PCSK9 inhibitor (PCSK9i) therapy. Inclisiran is a disruptive, first-in-class small interfering RNA (siRNA)-based therapeutic developed for the treatment of hypercholesterolemia that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9) synthesis, thereby upregulating the number of LDL receptors on the hepatocytes, thus lowering the plasma LDL-C concentration. Inclisiran decreases the LDL-C levels by over 50% with one dose every 6 months, making it a simple and well-tolerated treatment strategy. In this review, we summarize the general information regarding (i) the role of LDL-C in atherosclerotic cardiovascular disease, (ii) data regarding the role of PCSK9 in cholesterol metabolism, (iii) pleiotropic effects of PCSK9, and (iv) the effects of PCSK9 silencing. In addition, we focus on inclisiran, in terms of its (i) mechanism of action, (ii) biological efficacy and safety, (iii) results from the ORION trials, (iv) benefits of its combination with statins, and (v) its potential future role in atherosclerotic cardiovascular disease.

MiRNAs are noncoding, 21–24 nucleotide-long RNA particles that control over 60% of genes. MiRNAs affect gene expression through binding to the 3’-untranslated region of messenger RNA (mRNA), thus inhibiting mRNA translation or inducing mRNA degradation. MiRNAs have been associated with various cardiovascular diseases, including heart failure, hypertension, left ventricular hypertrophy, or ischemic heart disease. In addition, miRNA expression alters during coronary artery bypass grafting (CABG) surgery, which could be used to predict perioperative outcomes. CABG is an operation in which complex coronary arteries stenosis is treated by bypassing atherosclerotic lesions with venous or arterial grafts. Despite a very low perioperative mortality rate and excellent long-term survival, CABG is associated with postoperative complications, including reperfusion injury, graft failure, atrial fibrillation and perioperative myocardial infarction. So far, no reliable diagnostic and prognostic tools to predict prognosis after CABG have been developed. Changes in the perioperative miRNA expression levels could improve the diagnosis of post-CABG myocardial infarction and atrial fibrillation and could be used to stratify risk after CABG. Herein, we describe the expression changes of different subtypes of miRNAs during CABG and review the diagnostic and prognostic utility of miRNAs in patients undergoing CABG.

Background and objective: Coronary artery disease is one of the leading causes of deaths nowadays and the trends in diagnosis and revascularization are still in plateau despite well-known factors. Simple whole blood count parameters may be used to measure inflammatory reactions that are involved in processes of atherosclerosis progression. The aim of our study was to analyse the association between simply available hematologic indices and long-term mortality following off-pump coronary artery bypass grafting (OPCAB). Material and Methods: The study group comprised 129 consecutive patients (16 females and 113 males, mean age 66 ± 6 years) who underwent surgical revascularization with off-pump technique between January 2014 and September 2019. The mean follow-up was 4.7 +/−1.9 years. A receiver operating characteristics curve was applied to estimate demographical and perioperative parameters including MLR for mortality. Results: Cox regression analysis revealed chronic pulmonary obstructive disease (HR = 2.86, 95%CI 1.05–7.78), MLR (HR = 3.81, 95%CI 1.45–10.06) and right coronary artery blood flow (HR = 1.06, 95%CI 1.00–1.10) as significant factors predicting increased mortality risk. In the presented model, the MLR > 1.44 on 1st postoperative day was a significant predictor of late mortality after the OPCAB procedure (HR = 3.82, 95%CI 1.45–10.06). Conclusions: Pronounced inflammatory reaction after off-pump surgery measured by MLR > 1.44 can be regarded as a worse long-term prognostic factor.