Biomarkers in Cardiovascular Disease—Chances and Risks, 2nd Volume

Atherosclerotic cardiovascular disease (ASCVD) has long been screened using the traditional lipid profile, mainly focusing on LDL cholesterol. However, despite growing evidence supporting lipoprotein(a) [Lp(a)] as an independent risk factor involved in atherosclerosis, its clinical use remains limited. This review examines the reasons behind the limited use of Lp(a) screening in clinical practice, assessing its role in cardiovascular risk, comparing it to traditional lipid markers and evaluating current assessment methods. It also explores existing and emerging treatments, including gene-silencing therapies, for managing elevated Lp(a) levels. One in four clinicians does not routinely check Lp(a) levels, which proves a lack of awareness amongst them. The reasons for that are implied to be that the cost is too high and that available treatments are scarce. The traditional lipid profile, including LDL, high-density lipoprotein (HDL) and triglycerides, continues to be the gold standard for CV risk assessment. One limitation of using Lp(a) in clinical practice is the significant variability in apo(a) sizes, which results from the presence of multiple isoforms determined by the number of kringle domains. This structural diversity poses challenges in standardizing measurement methods, affecting the accuracy and comparability of results. While statins have a minimal impact on Lp(a), PCSK9-i lowers its levels by 20–25%, although this class is not prescribed primarily for this reason. Lastly, gene-silencing therapies, which achieve the greatest reduction in Lp(a) levels, are still in phase III trials, and there is still a need to examine whether this reduction translates into CV benefits. These limitations should not discourage further research, because ASCVD’s complexity requires a more tailored approach. Current lipid-lowering therapy still fails in a minority of cases, as evidenced by new-onset cardiovascular events in patients with well-controlled LDL levels. There is a need for future interventional studies to assess whether a reduction in Lp(a) by PCSK9-i really translates into CV benefits, independent of LDL. Full article

Objectives: Risk stratification in coronary artery bypass grafting (CABG) remains challenging despite existing models. The Endothelial Activation and Stress Index (EASIX), originally developed for hematological conditions, has shown promise in various medical fields as a predictor of adverse outcomes. EASIX, calculated from lactate dehydrogenase, creatinine, and platelet count, reflects endothelial dysfunction and systemic inflammation. This study investigates EASIX’s potential in predicting mortality and morbidity in patients undergoing CABG. Methods: A total of 475 patients undergoing isolated CABG between January 2017 and June 2020 were retrospectively analyzed. EASIX scores were calculated from pre-operative blood samples. Patients were stratified based on an EASIX cut-off value of 1.16. Results: Patients with EASIX ≥ 1.16 were older and had more comorbidities. They experienced higher 30-day mortality (5.0% vs. 0.8%, p = 0.004), increased wound infections (6.7% vs. 2.5%, p = 0.035), and more frequent prolonged ventilation (9.2% vs. 4.2%, p = 0.040). The long-term survival analysis showed significant differences at 3 years (p = 0.030) and 5 years (p < 0.001). EASIX demonstrated moderate discriminatory power for long-term survival (AUROC 0.669, 95% CI: 0.598–0.740, p < 0.001). Importantly, the multivariable analysis revealed EASIX as an independent risk factor for long-term mortality, even after adjusting for traditional risk factors and comorbidities (HR: 2.65, 95% CI: 1.59–4.42, p < 0.001). Conclusions: EASIX ≥ 1.16 was associated with postoperative morbidity and poorer long-term survival in patients undergoing CABG. This easily calculable score could enhance risk stratification and guide personalized postoperative management. Full article

Background/Objectives: High-risk coronary plaques (HRP), identified through coronary CT angiography (CCTA), are closely linked to cardiovascular events. Nutritional status and systemic inflammation may play a critical role in the development of HRP. The Naples Prognostic Score (NPS), which integrates markers of nutritional status and systemic inflammation, has emerged as a potential predictor of outcomes in various cardiovascular conditions. This study aimed to investigate the association between NPS and HRP as assessed by CCTA. Methods: A retrospective analysis was performed on 753 patients with chronic coronary syndrome (CCS) who underwent CCTA. The patients were categorized into two groups: those with high-risk plaques (HRP present), and those without (HRP absent). Additionally, they were further stratified based on their NPS. Univariable and multivariable logistic regression analyses were conducted to identify the most relevant clinical factors and the role of NPS in relation to HRP and the need for revascularization. Results: The study population had a mean age of 56.9 ± 10.7 years, with 40% being female. The NPS was significantly higher in the HRP-present group compared to the HRP-absent group (p = 0.001). Stratification by NPS groups revealed that higher NPS groups were associated with increased coronary artery calcification scores (CAC) and revascularization rates (p < 0.001 and p = 0.003, respectively). Multivariable regression analysis demonstrated a significant association between NPS and HRP (OR = 1.228, 95% CI: 1.013–1.489, p = 0.036). Conclusions: The NPS is independently associated with the presence of high-risk coronary plaques in patients with chronic coronary syndrome. NPS may serve as a complementary risk stratification tool by reflecting systemic inflammation and nutritional status. Further prospective studies are needed to validate its prognostic value. Full article

The quest for prompt and effective diagnosis of acute myocardial infarction (AMI) has been in the spotlight for decades. Ongoing research focuses on refined biomarker strategies for the early identification and disposition of patients with symptoms suggestive of AMI. Copeptin, a surrogate of the hormone arginine vasopressin, has emerged as a novel biomarker that could potentially aid in the diagnostic approach of patients with chest pain presenting to the emergency department. Observational studies have demonstrated that copeptin is upregulated in patients with AMI, although the exact pathophysiological mechanisms implicated in its release during myocardial ischemia remain unclear. Following these observations, copeptin was proposed as an adjunct to troponin in an effort to augment the diagnostic accuracy of conventional troponin assays. However, after the introduction of high-sensitivity troponin assays, the diagnostic utility of copeptin has been debated. This narrative review aims to elucidate plausible pathophysiological mechanisms involved in copeptin release during myocardial ischemia and to summarize the most recent evidence regarding its diagnostic potential in combination with high-sensitivity troponin assays. Full article

Background/Objectives: An increase in body fat is linked to abnormalities in energy metabolism. We aimed at determining cardiometabolic risk in Algerian participants with obesity alone and with or without type 2 diabetes. The study measured the concentrations of circulating adipocytokines (leptin, adiponectin, resistin), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) to identify and examine how imbalances in adipocytokines may affect the parameters of cardiometabolic health. Methods: Algerian participants (n = 300) were recruited and divided into three groups: control, obese, and type 2 diabetics (with two sub-groups: with and without obesity). Insulin resistance was evaluated using HOMA-IR, while ELISA was used to measure adipocytokines. Atherogenic index in plasma (AIP), adiponectin-leptin ratio (ALR), and visceral adiposity index (VAI) were also assessed. One-way ANOVA was used to compare obesity and diabetes groups to the control one (p < 0.05). Logistic regression analysis was conducted to strengthen the robustness of statistical correlations. Results: Participants with reduced adiponectin-leptin ratio (ALR) and elevated levels of resistin, TNF-α, and IL-6 are found to be at higher risk of cardiovascular diseases. An imbalance in adipocytokine levels is caused by a decrease in adiponectin concentrations, and an increase in pro-inflammatory adipocytokines that maintain and exacerbate energy imbalance and induces hyperinsulinemia, exposing individuals to a high risk of cardiovascular diseases. Conclusions: Given that ALR is a functional biomarker of inflammation, insulin resistance, and adipose tissue dysfunction, targeting ALR could potentially be a therapeutic approach to coping with obesity-related cardiometabolic risks. Mediterranean diet, weight loss, and increased physical activity can be key components to promote healthy adipose tissue through the increase in ALR. Full article

Background: Pulmonary function impairment significantly affects quality of life, work ability, and healthcare utilization. Among patients with COVID-19, respiratory symptoms vary in severity. This study aimed to assess whether biomarkers related to respiratory function and inflammation at emergency department (ED) admittance can predict long-term pulmonary function impairment in COVID-19 survivors. Methods: This prospective single-center study recruited patients 4–5 months post-COVID-19 infection using consecutive sampling. All attendees at the respiratory outpatient clinic were invited to participate. Pulmonary function tests, including diffusing capacity of the lungs for carbon monoxide (DL_CO), total lung capacity (TLC), forced expiratory volume in the first second (FEV1), and forced vital capacity (FVC), were performed, with DL_CO < 80% as the key indicator of impairment. Baseline biomarkers—C-Reactive Protein (CRP), leukocyte counts, and soluble urokinase Plasminogen Activator Receptor (suPAR)—were correlated with post-discharge DL_CO values. Results: This study enrolled 110 patients with COVID-19; 58.2% were female, the median age was 61.5, and the average BMI was 27.2. Smoking history showed that 53.7% were never smokers, 43.5% were former smokers, and 2.8% were current smokers. A diffusion deficit (DL_CO < 80%) was present in 48.6% of patients. Leukocyte counts and suPAR had the highest sensitivity (>0.80) for predicting DL_CO impairment but showed low specificity and a positive predictive value (PPV) of around 0.50. However, combining all biomarkers improved prediction accuracy, with a negative predictive value (NPV) of 0.93. Conclusions: The chosen inflammatory biomarkers by themselves had a limited ability to predict long-term pulmonary function impairment in COVID-19 survivors. However, when combined, they demonstrated a high negative predictive value (NPV) for identifying DL_CO impairment. This strategy could help clinicians better tailor follow-up care for patients with COVID-19. Full article

Background: Metabolic-associated fatty liver disease (MAFLD) is a spectrum of liver diseases linked to insulin resistance (IR), type 2 diabetes, and metabolic disorders. IR accelerates fat accumulation in the liver, worsening MAFLD. Regular physical activity and weight loss can improve liver function, reduce fat, and lower cardiovascular risk. This study examines the role of sex hormone-binding globulin (SHBG) in MAFLD, focusing on its potential as a biomarker and its relationship with insulin resistance. Methods: The study included 98 male patients (ages 30–55) with MAFLD, identified through systematic examinations, and 74 healthy male controls. All participants underwent abdominal ultrasound and blood tests after fasting, assessing markers such as glucose, liver enzymes (AST, ALT, γGT), lipids (cholesterol, triglycerides), insulin, SHBG, estradiol, and testosterone. SHBG levels were analyzed in relation to body mass index (BMI) and age. Results: A significant association was found between low SHBG levels and the presence of fatty liver. Individuals with MAFLD had lower SHBG levels compared to controls. BMI and age were key factors influencing SHBG, with higher BMI linked to lower SHBG in younger men, while SHBG remained stable in older individuals regardless of BMI. Conclusion: SHBG may serve as a valuable biomarker for early detection and risk assessment of MAFLD. The complex relationship between SHBG, BMI, and age highlights the importance of considering both hormonal and metabolic factors when assessing fatty liver risk. Our findings support the need for comprehensive metabolic evaluations in clinical practice. Full article

Background and Objectives: Studies have shown that inflammation markers can be used as prognostic tools in predicting acute ischemic stroke. In this study, we conducted a comparison of several inflammation scores in predicting left atrial thrombosis (LAT) in patients with ischemic stroke without AF. Materials and Methods: In this single-center, retrospective study, we included 303 consecutive patients with ischemic stroke. Each patient underwent a transesophageal echocardiography (TEE) examination within 10 days of admission to detect the presence of LAT. To identify independent predictors of LAT, we conducted a multivariate logistic regression analysis. Results: In total, 303 patients who had ischemic stroke were included in the analysis. LAT was detached in 34 patients at the time of the TEE examination. The patients were categorized into two groups based on their LAT status. The Prognostic Nutritional Index (PNI), HALP score, and C-reactive Protein–Albumin Ratio (CAR) were identified as statistically significant predictors of LAT. Based on the results of the multivariate regression analysis, the CAR emerged as the only independent predictor of LAT. Conclusions: Among several inflammation scores, the PNI, HALP, and CAR were statistically significant predictors of LAT in ischemic stroke patients without AF. CAR was identified as the optimal score for the prediction of LAT in patients with stroke and without AF. Full article

Background: Coronary heart disease is the most common cause of death worldwide. It is responsible for almost a third of deaths in patients over the age of 35. Various biomarkers are currently being studied in detail for their value in predicting postoperative mortality in patients undergoing CABG. Aim: The aim of this study is to analyze the predictive value of certain blood morphological parameters in CABG and off-pump coronary artery bypass grafting (OPCAB). Methods: A total of 520 patients who underwent surgery in two consecutive years and underwent CABG (404) or OPCAB (116) were included in this retrospective study. Gender, age, comorbidities, five-year survival rate, detailed information on hospitalization, surgery, intensive care unit parameters and preoperative blood samples from the cubital vein were recorded. Inverse propensity treatment weighting was applied to adjust for confounding factors at baseline. Results: No differences were found between OPCAB and CABG as an isolated comparison. In the standardized population, patients with abnormal lymphocyte counts had an increased risk of death at one-year and five-year follow-up. In the standardized population, abnormal red blood cell distribution width (RDW-SD), neutrocyte-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were associated with increased mortality in each period analyzed. Conclusions: Abnormal PLR, RDW-SD and NLR are associated with increased early and late mortality in patients undergoing CABG and OPCAB. Abnormal lymphocytes are only associated with increased late mortality. Full article

Background: Obstructive sleep apnea syndrome (OSA) is a chronic inflammatory disease characterized by endothelial dysfunction and cardiovascular complications. Continuous positive airway pressure (CPAP) is the standard treatment, hence poor adherence has prompted interest in mandibular advancement devices (MAD) as an alternative. This comprehensive review aimed to explore the effects of MAD therapy on oxidative stress, inflammation, endothelial function, and its impact on the cardiovascular risk in OSA patients. Results: MAD therapy significantly reduces the apnea-hypopnea index (AHI), improves serum nitric oxide (NOx) concentrations, reduces oxidative stress markers, and enhances endothelial function. Animal studies indicated that MAD reduces myocardial fibrosis and attenuates inflammatory markers. While both CPAP and MADs improve endothelial function and heart rate variability, CPAP is more effective in reducing OSA severity. Nevertheless, MAD has higher compliance, contributing to its positive impact on cardiovascular function. Moreover, CPAP and MADs have similar effectiveness in reducing cardiovascular risk. Conclusions: MAD therapy is an effective alternative to CPAP, particularly for patients with mild to moderate OSA as well as those intolerant to CPAP. It offers significant improvements in endothelial function and oxidative stress. Further studies are needed to assess MAD therapy in comprehensive OSA management. Full article

Background: Erectile dysfunction (ED) can stem from various organic and functional causes but is often linked to vascular health and cardiovascular disease. Limited data exist on how cardiovascular disease markers correlate with objective ED tests like the Nocturnal Penile Tumescence and Rigidity (NPTR) test and Penile Color Doppler Ultrasound (PCDU). Methods: A prospective observational study was performed, and 58 men with ED were assessed using the International Index of Erectile Function-15 (IIEF-15), NPTR test, and PCDU. Peripheral vascular health was evaluated through carotid intima-media thickness (cIMT) and brachial flow-mediated dilation (FMD). Results: Out of the participants, 44 had normal NPTR results, while 14 had abnormal results. The group with abnormal NPTR results was significantly older and had higher rates of hypertension and diabetes. Although the IIEF-15 scores were similar between the two groups, those with abnormal NPTR results had a lower peak systolic velocity (PSV) and a higher prevalence of impaired PSV. Correlations between the IIEF, NPTR, PCDU, and peripheral vascular markers lost significance after the age adjustment. Conclusions: This study suggests that abnormal NPTR results, combined with cardiovascular risk factors, may signal vascular ED and generalized vasculopathy, highlighting the need for cardiovascular assessment. An accurate ED diagnosis should integrate clinical evaluation with multiple tests while considering aging as a key risk factor. Full article

Background: Placental cadherin (CDH3) is an adhesion molecule expressed in many malignant tumors. The role of serum CDH3 in atherosclerosis is unclear. Methods: This 3-year follow-up study measured atherosclerosis and serum CDH3 in 218 angiography inpatients. Coronary stenosis was assessed as the Gensini score. The brachiocephalic and femoral plaques were quantified by ultrasound. Microarray serum profiling was conducted in selected samples. CDH3 in the serum was measured using an indirect ELISA. The odds ratio (OR), ROC analysis, and logistic regressions were used to evaluate the associations between CDH3 content, atherosclerotic lesions, and various serum biomarkers. Results: Serum CDH3 was associated with the severity of atherosclerosis and diastolic blood pressure. The levels of CDH3 were able to discriminate patients with total subclinical and hemodynamically significant atherosclerotic lesions in all circulation pools (coronary, brachiocephalic, and femoral). Elevated serum CDH3 appeared to be a risk factor for cardiovascular outcomes after 3-year follow up with OR = 1.81 (95% CI: 1.07–3.72; p = 0.022). Endothelin-1 and NOx were associated with the content of CDH3 in the serum, suggesting the involvement of certain signal transduction pathways that may participate in plaque formation. Conclusions: CDH3 was associated with cardiovascular outcomes adjusted for coronary plaque presence, indicating a role of CDH3 in plaque biology. Full article

Background and Objectives: Atherosclerosis, driven by dyslipidaemia and oxidative stress, is a leading cause of cardiovascular morbidity and mortality. This study evaluates the effects of vigorous-intensity bodybuilding exercise (VIBBE) on atherosclerosis biomarkers—including paraoxonase-1 (PON1) and arylesterase (ARE) activities—and lipid profiles in male bodybuilders who do not use anabolic-androgenic steroids. Comparisons were made with individuals engaged in moderate-intensity aerobic exercise (MIAE), as well as overweight/obese sedentary (OOS) and normal-weight sedentary (NWS) individuals. Materials and Methods: A cross-sectional study was conducted involving 122 healthy male participants aged 18–45 years, divided into four groups: VIBBE (n = 31), OOS (n = 30), MIAE (n = 32), and NWS (n = 29). Anthropometric assessments were performed, and fasting blood samples were collected for biochemical analyses, including lipid profiles and PON1 and ARE activities. Statistical analyses compared the groups and evaluated correlations between adiposity measures and atherosclerosis biomarkers. Results: The VIBBE group exhibited significantly lower levels of low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and logarithm of the TG to high-density lipoprotein cholesterol (HDL-C) ratio [log(TG/HDL-C)] compared to the OOS group (p < 0.05 for all), indicating improved lipid profiles. However, these improvements were not significant when compared to the NWS group (p > 0.05), suggesting that VIBBE may not provide additional lipid profile benefits beyond those associated with normal weight status. PON1 and ARE activities were significantly lower in the VIBBE group compared to the MIAE group (p < 0.05 for both), suggesting that VIBBE may not effectively enhance antioxidant defences. Correlation analyses revealed significant inverse relationships between PON1 and ARE activities and adiposity measures, including body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body fat percentage (BFP), fat mass index (FMI), and obesity degree (OD) (p < 0.05 for all). Positive correlations were observed between oxLDL and log(TG/HDL-C) and adiposity measures (p < 0.05 for all). Conclusions: Vigorous-intensity bodybuilding exercise improves certain lipid parameters compared to sedentary obese individuals but does not significantly enhance antioxidant enzyme activities or further improve lipid profiles beyond those observed in normal-weight sedentary men. Conversely, moderate-intensity aerobic exercise significantly enhances PON1 and ARE activities and improves lipid profiles, offering superior cardiovascular benefits. These findings underscore the importance of incorporating moderate-intensity aerobic exercise into physical activity guidelines to optimize cardiovascular health by balancing improvements in lipid metabolism with enhanced antioxidant defences. Full article

Background: Transgender men use exogenous androgen for male pattern virilization. Hysterectomy and bilateral salpingo-oophorectomy (HBSO) is performed to stop the endogenous estrogen secretion. Cardiovascular disease (CVD) risk has been shown to increase with long-term use of androgens and the removal of estrogen. We aimed to investigate the CVD risk in these individuals by measuring internal and common carotid artery intima–media thicknesses (CIMT). Methods: In this cohort study, data were collected from transgender men who had undergone HBSO and used androgens for at least two years (median treatment duration was 5 years in our research). Cisgender women in the same age range were selected as the control group. Demographics, vital signs, and hematological values of transgender patients and cisgender women subjects in the control group were noted. CVD markers were compared with sonographically measured CIMT values. Results: The mean age and body mass index (BMI) of the study group were 32.6 and 25.3, respectively. Weight, systolic–diastolic blood pressure, hemoglobin, hematocrit, low-density lipoprotein (LDL), serum triglyceride (TG), HbA1c levels, internal CIMT, and common CIMT values of the study group were higher, while the high-density lipoprotein (HDL) level was significantly lower compared the control group (p1 = 0.025, p2 = 0.010, p3 = 0.002, p4 = 0.001, p5 = 0.001, p6 = 0.012, p7 = 0.008, p8 = 0.007, p9 = 0.013, and p10 = 0.001). There was also an increase in the body weight, BMI, LDL, and TG levels of the study group after the testosterone treatment (p1 = 0.025, p2 = 0.019, p3 = 0.001, p4 = 0.001, and p5 = 0.001). Conclusions: We demonstrated that the use of testosterone therapy in transgender men is associated with higher CIMT values. While further investigation is needed to assess morbidity and mortality rates, we recommend that regular clinical and radiological examinations be performed in these individuals to accurately evaluate the risk of CVD. Full article