Ticagrelor downregulates the expression of proatherogenic and proinflammatory miR125-b compared to clopidogrel: A randomized, controlled trial.

BACKGROUND: Platelet P2Y12 antagonist ticagrelor reduces cardiovascular mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets release proatherogenic and proinflammatory microRNAs, including miR-125a, miR-125b and miR-223, we hypothesized that the expression of these miRNAs is lower on ticagrelor, compared to clopidogrel. OBJECTIVES: We compared miR-125a, miR-125b and miR-223 expression in plasma of patients after AMI treated with ticagrelor or clopidogrel. METHODS: After percutaneous coronary intervention on acetylsalicylic acid and clopidogrel, 60 patients with first AMI were randomized to switch to ticagrelor or to continue with clopidogrel. Plasma expression of miR-223, miR-125a-5p, miR-125b was measured using quantitative polymerase chain reaction at baseline and after 72 h and 6 months of treatment with ticagrelor or clopidogrel in patients and one in 30 healthy volunteers. Multiple electrode aggregometry using ADP test was used to determine platelet reactivity in response to P2Y12 inhibitors. RESULTS: Expression of miR-125b was higher in patients with AMI 72 h and 6 months, compared to healthy volunteers (p = 0.001), whereas expression of miR-125a-5p and miR-223 were comparable. In patients randomized to ticagrelor, expression of miR-125b decreased at 72 h (p = 0.007) and increased back to baseline at 6 months (p = 0.005). Expression of miR-125a-5p and miR-223 was not affected by the switch from clopidogrel to ticagrelor. CONCLUSIONS: Ticagrelor treatment leads to lower plasma expression of miR-125b after AMI, compared to clopidogrel. Higher expression of miR-125b might explain recurrent thrombotic events and worse clinical outcomes in patients treated with clopidogrel, compared to ticagrelor.

Peripheral atherosclerosis evaluation through ultrasound: A promising diagnostic tool for coronary artery disease.

Effective treatment, but also proper diagnosis of cardiovascular diseases, remains a major challenge in everyday practice. A quick, safe, and economically acceptable non-invasive procedure should play a leading role in cardiovascular risk assessment before invasive diagnostics is performed. The staging of subclinical atherosclerosis may help in further clinical decisions. Safe, widely available, and relatively inexpensive, ultrasonography is a promising examination that should find wider application in clinical practice. The latest ESC guidelines emphasize the usefulness of carotid ultrasound in the diagnosis of coronary artery disease (CAD) and subclinical assessment of atherosclerosis, which help to determine the level of cardiovascular risk. Ultrasound examination of peripheral arteries, especially superficial vessels such as the femoral arteries, is quite easy, quick, and accurate. Other vascular beds, such as iliac and renal, are more demanding to examine, but can also provide valuable information. This review summarizes important studies comparing the severity of atherosclerosis in ultrasound-visible vascular beds in patients with established CAD. We especially emphasize the benefits of the combined assessment of atherosclerosis features, which were characterized by high sensitivity and specificity in the diagnosis of CAD and other serious cardiovascular diseases.

Diagnostic and Prognostic Value of miRNAs after Coronary Artery Bypass Grafting: A Review.

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.

Monocyte-to-Lymphocyte Ratio as a Predictor of Worse Long-Term Survival after Off-Pump Surgical Revascularization-Initial Report.

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.

Inclisiran-Silencing the Cholesterol, Speaking up the Prognosis.

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.