Search Results (49)

Background: This study presents an innovative approach to cardiovascular disease (CVD) risk prediction based on a comprehensive analysis of clinical, immunological and biochemical markers using mathematical modelling and machine learning methods. Baseline data include indices of humoral and cellular immunity (CD59, CD16, IL-10, CD14, CD19, CD8, CD4, etc.), cytokines and markers of cardiovascular disease, inflammatory markers (TNF, GM-CSF, CRP), growth and angiogenesis factors (VEGF, PGF), proteins involved in apoptosis and cytotoxicity (perforin, CD95), as well as indices of liver function, kidney function, oxidative stress and heart failure (albumin, cystatin C, N-terminal pro B-type natriuretic peptide (NT-proBNP), superoxide dismutase (SOD), C-reactive protein (CRP), cholinesterase (ChE), cholesterol, and glomerular filtration rate (GFR)). Clinical and behavioural risk factors were also considered: arterial hypertension (AH), previous myocardial infarction (PICS), aortocoronary bypass surgery (CABG) and/or stenting, coronary heart disease (CHD), atrial fibrillation (AF), atrioventricular block (AB block), and diabetes mellitus (DM), as well as lifestyle (smoking, alcohol consumption, physical activity level), education, and body mass index (BMI). Methods: The study included 52 patients aged 65 years and older. Based on the clinical, biochemical and immunological data obtained, a model for predicting the risk of premature cardiovascular aging was developed using mathematical modelling and machine learning methods. The aim of the study was to develop a predictive model allowing for the early detection of predisposition to the development of CVDs and their complications. Numerical methods of mathematical modelling, including Runge–Kutta, Adams–Bashforth and backward-directed Euler methods, were used to solve the prediction problem, which made it possible to describe the dynamics of changes in biomarkers and patients’ condition over time with high accuracy. Results: HLA-DR (50%), CD14 (41%) and CD16 (38%) showed the highest association with aging processes. BMI was correlated with placental growth factor (37%). The glomerular filtration rate was positively associated with physical activity (47%), whereas SOD activity was negatively correlated with it (48%), reflecting a decline in antioxidant defence. Conclusions: The obtained results allow for improving the accuracy of cardiovascular risk prediction, and form personalised recommendations for the prevention and correction of its development. Full article

Acute myocardial infarction (AMI) in young adults, though less common than in older populations, is an emerging clinical concern with increasing incidence and diverse etiologies. Unlike classic atherosclerotic presentations, a significant proportion of AMI cases in individuals under 45 years are due to nonatherothrombotic mechanisms such as coronary vasospasm, spontaneous coronary artery dissection (SCAD), vasculitis, hypercoagulable states, and drug-induced coronary injury. This manuscript aims to explore the multifactorial nature of AMI in young adults through a focused review of current evidence and a series of illustrative clinical cases. We present and analyze four distinct cases of young patients with AMI, each demonstrating different pathophysiological mechanisms and risk profiles—including premature atherosclerosis, substance use, human immunodeficiency virus (HIV)-related coronary disease, and SCAD. Despite the heterogeneity of underlying causes, early diagnosis, individualized management, and aggressive secondary prevention were key to favorable outcomes. Advanced imaging, lipid profiling, and risk factor modification played a central role in guiding therapy. AMI in young adults requires heightened clinical suspicion and a comprehensive, multidisciplinary approach. Early intervention and recognition of nontraditional risk factors are essential to improving outcomes and preventing recurrent events in this vulnerable population. Full article

Background: Myocardial fibrosis leads to ventricular dysfunction and worsened prognosis, especially after ST-segment elevation myocardial infarction (STEMI). Sodium–glucose cotransporter 2 inhibitors (SGLT2is) offer cardiovascular benefits by reducing markers of myocardial fibrosis and fibroblast activity. However, the effects of SGLT2i on myocardial fibrosis deposition among STEMI patients undergoing primary percutaneous coronary intervention (PCI) have not yet been evaluated. Study and Design: The effect of DAPAgliflozin on myocardial fibrosis and ventricular function in patients with STEMI (DAPA-STEMI) trial is a phase III, multicenter, randomized, double-blind, placebo-controlled trial. The study aims to assess the effects of dapagliflozin on myocardial fibrosis and ventricular function, evaluated using cardiac magnetic resonance (CMR), in STEMI patients undergoing primary PCI. Eligible patients were 30 to 85 years old and exhibited a left ventricular ejection fraction ≤ 50%. A total of 120 patients with STEMI were expected to be randomized 1:1 to receive dapagliflozin 10 mg or placebo daily for six months. The primary endpoint is the change in the extracellular volume fraction of the remote myocardium from baseline to six months, as measured by CMR. The secondary endpoints include changes in the circulating C-terminal propeptide of type I procollagen, N-terminal propeptide of type III procollagen, and Galectin-3 from baseline to six months. The study was stopped prematurely due to slow recruitment, with 54 enrolled patients, limiting the statistical power to detect changes in the primary endpoint between groups. Conclusions: The DAPA-STEMI trial will provide insights into the impact of dapagliflozin on myocardial fibrosis and ventricular remodeling in patients with STEMI undergoing primary PCI. Clinical Trial Registration Unique Identifier: NCT06619600 Full article

Despite significant advancements in the primary and secondary prevention of cardiovascular disease, evidence shows a rising incidence of premature coronary artery disease (CAD) and myocardial infarction (MI) in patients aged < 50 years. This increase is linked to the growing prevalence of traditional cardiovascular risk factors among younger people, such as type 2 diabetes, hypertension, obesity, and hyperlipidaemia, which have led to a rise in atherosclerotic CAD. Additionally, emerging research points to the influence of less traditional risk factors, including chronic inflammation, autoimmune diseases, drug use, psychosocial factors, and novel biomarkers in the early onset of CAD. These factors collectively contribute to the rise in premature CAD, highlighting the need for improved prevention strategies and public health efforts focused on younger populations. In this review, we explore the aetiology, risk factor profile, role of novel biomarkers, and how each of these impact outcomes among younger patients with MI. Full article

Premature myocardial infarction (MI) risk factors, including genetic ones, are crucial for an individual risk stratification. The aim of this study was to investigate the role of genetic variants in young patients with MI and a family history of premature atherosclerosis (FHpa). The studied group consisted of 70 patients aged 26–49 (mean 43.1, SD ± 4.3; 17 women, 53 men), with MI and with FHpa. The targeted enrichment library was prepared and analyzed using the Next-Generation Sequencing method. The results of sequencing were compared to data from the reference control population, consisting of 597 people with no history of MI (418 women, 179 men) aged 18–83 (mean 40.5, SD ± 12.4), using Propensity Score Matching. SYNE1 gene variant NM_182961.4:c.20396+22A>G occurs with a significantly higher incidence in the studied group compared to the control population (OR 4.80 95%CI 1.43–14.45; p = 0.005) as a whole and when matched by age and gender (OR 9.31 95%CI 1.64–95.41; p = 0.004). There were no statistically significant differences in the incidence of variants related to familial hypercholesterolemia (LDLR NM_001195800.2:c.667G>A, PCSK9 NM_182961.4:c.658−36G>A NM_174936.3:c.658−36G>A, and APOB NM_000384.3:c.12382G>A) between both cohorts. A novel variant of the SYNE1 gene is associated with MI in young patients with FHpa. Full article

Familial hypercholesterolemia (FH) is relatively prevalent in myocardial infarction (MI) sufferers, and its diagnosis could improve preventive treatment in family members. We aim to analyze the diagnosis of FH and the rate of genetic testing in a prospective cohort of 245 patients submitted to our Cardiac Rehabilitation Program (CRP) after MI. Baseline characteristics were registered, and basal low-density lipoprotein cholesterol (LDL-C) was calculated after correction for lipid-lowering therapies (LLT) before or during admission. Simplified Dutch Lipid Clinic Network Scores (sDLCNS) were retrospectively calculated based on personal and familial history of premature cardiovascular disease and basal LDL-C levels. Mean age was 62.19 ± 13.93 years, and most patients were male (81.6%). Mean LDL-C before admission and basal LDL-C corrected for LLT were 131.79 ± 45.34 mg/dL and 162.87 ± 44.17 mg/dL, respectively. Patients in the cohort were retrospectively categorized in the “unlikely” (<3 points; n = 162, 66.1%), “possible” (3–5 points; n = 72, 29.4%) and “probable” (6–8 points; n = 11, 4.5%) sDLCNS categories. Genetic testing for FH was requested in four (1.6%) patients, and no clinically significant genetic variants were detected. Patients who underwent genetic testing depicted significantly higher basal LDL-C (233 ± 49.09 vs. 161.71 ± 43.25 mg/dL, p = 0.001). However, the rate of individuals undergoing genetic testing was negligible even in the “possible” (n = 2, 2.8%) and “probable” (n = 1, 9.1%) sDLCNS categories. In conclusion, genetic testing for FH in our CRP after MI is largely underutilized, even in patients with a “possible” or “probable” diagnosis based on sDLCNS criteria, which represent about a third of the cohort. Strategies to improve screening for FH should be prospectively implemented. Full article

Background: Patients suffering from chronic kidney disease (CKD) have a high risk of premature cardiovascular morbidity and mortality. It has been suggested that elevated homocysteine (Hcy) or disturbances in the transmethylation pathway may contribute to this high cardiovascular risk burden due to epigenetic mechanisms. The objective of this study was to explore the prognostic value of Hcy, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) (one-carbon (C1)-metabolites) among patients with CKD. Methods: Plasma concentrations of Hcy, SAM and SAH were measured among 297 participants with CKD (KDIGO GFR category G2–G5). The predefined endpoint was the occurrence of major cardiovascular events (MACE), defined as carotid, coronary and peripheral arterial revascularization, stroke, acute myocardial infarction, major amputation, cardiovascular death and all-cause mortality during a median (IQR) follow-up period of 4.0 [3.2; 4.3] years. Results: Among all participants, the median (IQR) of plasma Hcy, SAH, and SAM levels were 16.6 [13.5; 21.2] µmol/L, 41.5 [26.6; 63.9] nmol/L, 183.4 [151.1; 223.5] nmol/L, respectively. Estimated glomerular filtration rate (eGFR) correlated more strongly with plasma SAH (r = −0.588) than with SAM (r = −0.497) and Hcy (r = −0.424). During the follow-up period, 55 participants experienced MACE. In a univariate Kaplan Meier analysis, all three C1-metabolites were significantly associated with the occurrence of the primary outcome. In a Cox-regression analysis, the association between Hcy and MACE was not significant after adjustment for age and sex (hazard ratio (HR) and 95% confidence intervals (95% CI) for the 3rd vs. 1st tertile = 1.804 (0.868–3.974)). Both SAH and SAM were not associated with MACE after adjustment for age, sex and additionally for renal function markers (SAH: HR 3rd vs. 1st tertile 1.645 95% (0.654–4.411); SAM: HR 3rd vs. 1st tertile 1.920 95% CI (0.764–5.138)). Conclusions: In people with CKD, plasma Hcy, SAH and SAM were not independent predictors of MACE after adjustment for age, sex and renal function. Disturbed renal function may explain elevated C1-metabolites and disturbed transmethylation, while this pathway is not likely to be an appropriate access point to modify the risk of cardiovascular events in CKD patients. Full article

Atherosclerosis is accompanied by inflammation that underlies cardiovascular disease (CVD) and its vascular manifestations, including acute stroke, myocardial infarction, and peripheral artery disease, the leading causes of morbidity/mortality worldwide. The monolayer of endothelial cells formed on the luminal surface of arteries and veins regulates vascular tone and permeability, which supports vascular homeostasis. Endothelial dysfunction, the first step in the development of atherosclerosis, is caused by mechanical and biochemical factors that disrupt vascular homeostasis and induce inflammation. Together with increased plasma levels of low-density lipoprotein (LDL), diabetes, hypertension, cigarette smoking, infectious microorganisms, and genetic factors, epidemiological studies established that dysregulated metabolism of homocysteine (Hcy) causing hyperhomocysteinemia (HHcy) is associated with CVD. Patients with severe HHcy exhibit severe CVD and die prematurely due to vascular complications. Biochemically, HHcy is characterized by elevated levels of Hcy and related metabolites such as Hcy-thiolactone and N-Hcy-protein, seen in genetic and nutritional deficiencies in Hcy metabolism in humans and animals. The only known source of Hcy in humans is methionine released in the gut from dietary protein. Hcy is generated from S-adenosylhomocysteine (AdoHcy) and metabolized to cystathionine by cystathionine β-synthase (CBS) and to Hcy-thiolactone by methionyl-tRNA synthetase. Hcy-thiolactone, a chemically reactive thioester, modifies protein lysine residues, generating N-homocysteinylated (N-Hcy)-protein. N-Hcy-proteins lose their normal native function and become cytotoxic, autoimmunogenic, proinflammatory, prothrombotic, and proatherogenic. Accumulating evidence, discussed in this review, shows that these Hcy metabolites can promote endothelial dysfunction, CVD, and stroke in humans by inducing pro-atherogenic changes in gene expression, upregulating mTOR signaling, and inhibiting autophagy through epigenetic mechanisms involving specific microRNAs, histone demethylase PHF8, and methylated histone H4K20me1. Clinical studies, also discussed in this review, show that cystathionine and Hcy-thiolactone are associated with myocardial infarction and ischemic stroke by influencing blood clotting. These findings contribute to our understanding of the complex mechanisms underlying endothelial dysfunction, atherosclerosis, CVD, and stroke and identify potential targets for therapeutic intervention. Full article

Atrial fibrillation (AF) is a common arrhythmia in clinical practice, and oral anticoagulation is the cornerstone of stroke prevention in AF. Direct oral anticoagulants (DOAC) significantly reduce the incidence of intracerebral hemorrhage with preserved efficacy for preventing stroke compared to vitamin K antagonists (VKA). However, the pivotal randomized controlled trials (RCTs) of DOAC excluded patients with valvular heart disease, especially mitral stenosis, which remains an exclusion criterion for DOAC use. The INVICTUS study was a large multicenter global RCT aimed at evaluating the role of DOAC compared to VKA in stroke prevention among patients with rheumatic valvular AF. In this study, rivaroxaban failed to prove superiority over VKA in preventing the composite primary efficacy endpoints of stroke, systemic embolism, myocardial infarction, and death. Unfortunately, the bleeding rates were not lower with rivaroxaban either. The death and drug discontinuation rates were higher in the DOAC arm. Close to the heels of the dismal results of INVICTUS, an apixaban trial in prosthetic heart valves, PROACT-Xa, was also prematurely terminated due to futility. Hence, for AF complicating moderate-to-severe mitral stenosis or prosthetic valve VKA remains the standard of care. However, DOAC can be used in patients with surgical bioprosthetic valve implantation, TAVR, and other native valve diseases with AF, except for moderate-to-severe mitral stenosis. Factor XI inhibitors represent a breakthrough in anticoagulation as they aim to dissociate thrombosis from hemostasis, thereby indicating a potential to cut down bleeding further. Multiple agents (monoclonal antibodies—e.g., osocimab, anti-sense oligonucleotides—e.g., fesomersen, and small molecule inhibitors—e.g., milvexian) have garnered positive data from phase II studies, and many have entered the phase III studies in AF/Venous thromboembolism. Future studies on conventional DOAC and new-generation DOAC will shed further light on whether DOAC can dethrone VKA in valvular heart disease. Full article

Background: The performance of an everolimus-eluting bioresorbable scaffold (BRS) was inferior to an everolimus-eluting metallic drug-eluting stent (DES) with permanent polymer, mainly due the mechanical features of BRS technology. The performance of BRS as compared to metallic DES with bioresorbable polymers remains unstudied. Methods: This prospective, randomized, multicenter, clinical trial enrolled patients who underwent coronary stenting for de novo coronary lesions. Patients were randomly assigned to bioresorbable polymer everolimus-eluting stents (BP-EES) or everolimus-eluting BRS. The primary endpoint was percentage diameter stenosis (in-device) at 6- to 8-month angiographic surveillance. The main secondary endpoint was the device-oriented composite endpoint (DOCE) of cardiac death/target vessel-myocardial infarction/target lesion revascularization assessed after 12 months and 5 years. Results: The trial was prematurely terminated after the enrollment of 117 of 230 patients (BP-EES, n = 60; BRS, n = 57) due to safety issues associated with BRS technology. The primary endpoint of in-device diameter stenosis at angiographic surveillance was 12.5 ± 7.7% with BP-EES versus 19.3 ± 16.5% with BRS (p = 0.01). The DOCE occurred in 5.0% in the BP-EES group versus 12.3% of patients in the BRS group (hazard ratio [HR] 2.48, 95% confidence interval [CI] 0.64–9.58, p = 0.19) after 12 months and in 11.7% in the BP-EES group versus 26.4% of patients in the BRS group (HR 2.38, 95% CI 0.97–5.84, p = 0.06) after 5 years. Conclusions: BP-EES showed superior mid-term angiographic performance compared with BRS. Clinical event rates did not differ significantly between the groups up to 5 years of follow-up. These results should be interpreted with caution in view of the premature discontinuation of the study. Full article

Leukocytosis in neonates can occur because of infectious, inflammatory, malignant, or physiological processes. Hyperleukocytosis is defined as a total leukocyte count (TLC) exceeding 100,000 per mm³, warranting immediate evaluation. Neonates with hyperleukocytosis are at risk of leukostasis and the associated severe complications, including respiratory distress, myocardial ischemia, hyperuricemia, acute renal failure, infarction, and hemorrhage. Differentiating leukemia and leukemoid reactions in neonates presenting with elevated TLC is challenging but critical. We present a unique case of a preterm male neonate with hyperleukocytosis, initially suspected to have an underlying malignancy. The neonate’s clinical course was complicated by respiratory distress syndrome and anemia of prematurity, necessitating neonatal intensive care unit management. Further investigation revealed high human herpesvirus 6 (HHV-6) DNA levels in the whole blood, leading to a chromosomally integrated HHV-6 (ciHHV-6) diagnosis. CiHHV-6 is characterized by HHV-6 DNA integration into the host genome. Accurate diagnosis relies on whole-blood quantitative PCR, distinguishing ciHHV-6 from an active infection. The neonate remained asymptomatic, and antiviral treatment was deemed unnecessary. This case underscores the importance of recognizing ciHHV-6 as a potential cause of hyperleukocytosis in neonates and highlights the value of whole-blood PCR for differentiation. Understanding the spectrum of HHV-6 infection in neonates is vital for appropriate management and prognostication. Full article

Familial hypercholesterolemia, a genetic disorder marked by elevated low-density lipoprotein cholesterol (LDL-C), poses significant risks for premature atherosclerosis and cardiovascular diseases, particularly during pregnancy. One of the safe methods of treating this condition in pregnancy is with the use of LDL apheresis. We present a 38-year-old primigravida with homozygous Familial Hypercholesterolemia (HoFH), ischemic cardiomyopathy, and angina pectoris. Two years before conception, extremely elevated lipid levels prompted statin therapy and lifestyle changes. Stent placements followed acute myocardial infarction. When planning pregnancy, statins were discontinued, but lipid levels elevated. LDL apheresis was initiated, achieving a 60% reduction. Throughout pregnancy, 16 LDL apheresis sessions were performed every 14 days, maintaining optimal lipid profiles. A cesarean section was performed in the 38th week of gestation, delivering a healthy infant. The patient resumed statin therapy after 8 months of breastfeeding. The patient maintained cardiovascular health, demonstrating the feasibility of controlled HoFH pregnancies. This case highlights the successful management of HoFH during pregnancy using LDL apheresis, ensuring maternal and fetal well-being. Future research on novel treatments and their safety during pregnancy is essential for refining therapeutic approaches in similar cases. Full article

Background: A significant percentage of younger patients with myocardial infarction have premature coronary artery disease (CAD). The aims of this study were to analyze all-cause mortality and major adverse cardiovascular events (MACEs cardiovascular death, non-fatal reinfarction, stroke, target vessel revascularization) during eight-year follow-up in patients with ST-elevation myocardial infarction (STEMI) and premature CAD. Method: We analyzed 2560 STEMI patients without previous CAD and without cardiogenic shock at admission who were treated with primary PCI. CAD was classified as premature in men aged <50 years and women <55 years. Results: Premature CAD was found in 630 (24.6%) patients. Patients with premature CAD have fewer comorbidities and better initial angiographic findings compared to patients without premature CAD. The incidence of non-fatal adverse ischemic events was similar to the incidence in older patients. Premature CAD was an independent predictor for lower mortality (HR 0.50 95%CI 0.28–0.91) and MACEs (HR 0.27 95%CI 0.15–0.47). In patients with premature CAD, EF < 40% was the only independent predictor of mortality (HR 5.59 95%CI 2.18–8.52) and MACEs (HR 4.18, 95%CI 1.98–8.13). Conclusions: Premature CAD was an independent predictor for lower mortality and MACEs. In patients with premature CAD, EF < 40% was an independent predictor of eight-year mortality and MACEs. Full article

Background: Familial hypercholesterolemia (FH) is an inherited metabolic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-c) from birth. About 85% of all FH cases are caused by pathogenic variants in the LDLR gene. Individuals with FH have increased cardiovascular risk, including a high risk of premature myocardial infarction (PMI). Methods: We conducted an opportunistic exome screening to identify variants in the LDLR gene among Vietnamese patients with PMI treated at a general hospital in southern Vietnam. A cascade testing for LDLR variants was conducted in their relatives within three generations, and the effects of the LDLR variant on the response to rosuvastatin treatment were also studied using a comparative before-and-after study design on those who were eligible. Results: A total of 99 participants from the three generations of four PMI patients were recruited, mean age 37.3 ± 18.5 years, 56.6% males. Sanger sequencing revealed two variants in the LDLR gene: variant rs577934998 (c.664T>C), detected in 17 individuals within one family, and variant rs12710260 (c.1060+10G>C), found in 32 individuals (49.5%) in the other three families tested. Individuals harboring the variant c.664T>C had significantly higher baseline LDL-c and total cholesterol levels compared to those with variant c.1060+10G>C (classified as benign) or those without LDLR variants, and among the 47 patients subjected to a 3-month course of rosuvastatin therapy, those with variant c.664T>C had a significantly higher risk of not achieving the LDL-c target after the course of treatment compared to the c.1060+10G>C carriers. Conclusions: These findings provide evidence supporting the existence of pathogenic LDLR variants in Vietnamese patients with PMI and their relatives and may indicate the need for personalizing lipid-lowering therapies. Further studies are needed to delineate the extent and severity of the problem. Full article

Over the past four decades, percutaneous coronary intervention (PCI) safety and efficacy have significantly improved, particularly with the advent of the drug-eluting stent (DES). First-generation DESs reduced in-stent restenosis rates and targeted lesion revascularization; however, safety issues emerged, due to high incidences of stent thrombosis (ST) linked to death, myocardial infarction, and repeat revascularization. Second-generation DESs were developed to overcome these issues, reducing late-thrombotic-event risk while maintaining anti-restenosis efficacy. Nevertheless, ST still occurs with second-generation DES use. Stent thrombosis etiology is multifaceted, encompassing lesion-, patient-, procedural-, and stent-related factors. Overall, most early-stent-thrombosis cases are linked to procedural and patient-related aspects. Factors like premature discontinuation of dual antiplatelet therapy, resistance to clopidogrel, smoking, diabetes mellitus, malignancy, reduced ejection fraction or undertaking coronary angioplasty for an acute coronary syndrome can increase the risk of stent thrombosis. The aim of this study is to assess patient-related factors that potentially heighten the risk of stent thrombosis, with the objective of pinpointing and addressing modifiable contributors to this risk. By focusing on both patient- and procedure-related factors, a multifaceted approach to coronary revascularization can help minimize complications and maximize long-term benefits in managing ST. Full article