Search Results (133)

Background: Cardiovascular-kidney-metabolic syndrome (CKM) represents a multisystem condition involving obesity, diabetes, chronic kidney disease, and cardiovascular diseases. Frailty, as measured by the Frailty Index (FI), is linked to adverse outcomes, but its association with CKM severity and mortality remains unclear. This study aimed to evaluate the relationship between frailty status, CKM staging, and mortality risk. Methods: We analysed data from 19,407 adults aged ≥ 45 years from NHANES 1999–2018. Frailty status was assessed using a 49-item Frailty Index (FI) and categorised as robust (FI ≤ 0.08), pre-frail (0.08 < FI < 0.25), or frail (FI ≥ 0.25). CKM was staged from 1 to 4 based on established clinical criteria. Multinomial logistic regression assessed the association between frailty status and CKM staging. Cox proportional hazards models evaluated the associations between frailty status and all-cause, cardiovascular, and non-cardiovascular mortality among CKM patients. Results: A total of 19,407 participants (median [IQR] age: 63.00 [54.00–72.00] years, 50.77% male), with 19,089 CKM patients. Frail individuals exhibited significantly higher odds of being assigned to advanced CKM stages. Over a median follow-up of 8.4 years, 4794 participants died. Kaplan–Meier curves and restricted cubic spline analyses demonstrated a clear gradient in mortality risk across frailty categories. Compared with the robust group, pre-frail and frail individuals had significantly higher risks of all-cause (HR = 1.47 and 2.83, respectively), cardiovascular (HR = 1.71 and 3.78), and non-cardiovascular mortality (HR = 1.40 and 2.57). Conclusions: Frailty status demonstrated a significant association with CKM staging and mortality outcomes. Early identification of frailty may help guide risk stratification and inform tailored interventions for individuals with CKM. Full article

Background and Objectives: Type 2 diabetes (T2DM) substantially increases cardiovascular risk; beyond the well-recognized left-ventricular involvement in diabetic cardiomyopathy, emerging data indicate subclinical right-ventricular (RV) dysfunction may also be present. This study aimed to evaluate whether speckle-tracking echocardiography identifies subclinical right-ventricular systolic dysfunction in type 2 diabetes, despite normal conventional indices and preserved global systolic function. Materials and Methods: We conducted a cross-sectional, single-center study in accordance with STROBE recommendations, enrolling 77 participants, 36 adults with T2DM, and 41 non-diabetic controls, between December 2024 and July 2025. All participants underwent comprehensive transthoracic echocardiography, including conventional parameters (tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TV S’), right ventricular fractional area change (RVFAC)) and deformation imaging (right ventricular global longitudinal strain (RV GLS), right ventricular free wall longitudinal strain (RVFWS)) using speckle-tracking echocardiography. Biochemical and clinical data, including glycosylated hemoglobin (HbA1c), were recorded. Correlation and ROC curve analyses were performed to explore associations and predictive value. Results: The mean age was comparable between the two groups (62.08 ± 9.54 years vs. 60.22 ± 13.39 years; p = 0.480). While conventional RV parameters did not differ significantly between groups, diabetic patients had significantly lower RV GLS (−13.86 ± 6.07% vs. −18.59 ± 2.27%, p < 0.001) and RVFWS (−15.64 ± 4.30% vs. −19.03 ± 3.53%, p < 0.001). HbA1c levels correlated positively with RV strain impairment (RVFWS r = 0.41, p < 0.001). Both RV GLS and RVFWS were independent predictors of RV dysfunction in logistic regression analysis. ROC analysis showed good diagnostic performance for RV GLS, AUC = 0.84 with an optimal cut-off −17.2% (sensitivity 86.1% and specificity 80.5%) and RVFWS, AUC = 0.76 with cut-off −17.6% (sensitivity 77.8; specificity 80.5%) in identifying early myocardial involvement. Conclusions: RV systolic dysfunction may occur early in T2DM, even when traditional echocardiographic indices remain within normal limits. Speckle-tracking echocardiography, particularly RV GLS and RVFWS, offers sensitive detection of subclinical myocardial impairment, reinforcing its value in early cardiovascular risk stratification among diabetic patients. Full article

As the leading cause of global mortality, cardiovascular diseases demand improved and innovative strategies for early detection and risk assessment to enhance prevention and timely treatment. This comprehensive review examines the potential of combining high-sensitivity cardiac troponins (hs-cTns) and homocysteine (Hcy) as complementary biomarkers for enhanced cardiovascular risk prediction. hs-cTn assays have revolutionized cardiovascular diagnostics by enabling the detection of minimal myocardial injury, improving early diagnosis of acute coronary syndrome, and providing robust prognostic information in both symptomatic and asymptomatic populations. Hcy, while established as a marker of vascular dysfunction, presents an interpretative challenge due to multiple confounding factors and inconsistent therapeutic responses. Emerging evidence demonstrates significant correlations between elevated Hcy and troponins across various clinical conditions, suggesting that their combined assessment—reflecting both myocardial injury and vascular dysfunction—may improve cardiovascular risk stratification. While initial findings are promising, additional studies are required to validate the clinical value of the combined marker approach. Future development of personalized interpretation algorithms, and multi-marker panels incorporating these biomarkers, may significantly advance cardiovascular medicine and enable more effective population-specific risk management strategies. Full article

The growing success of oncologic therapies has led to a significant improvement in patient survival; however, this has been accompanied by an increasing incidence of cardiovascular adverse events, particularly cancer therapy-related cardiac dysfunction (CTRCD). Among these, left ventricular impairment represents a major concern due to its potential to compromise both cardiac and oncologic outcomes. This review provides an in-depth overview of the cardiotoxic adverse events associated with several classes of anticancer agents. Particular focus is given to the molecular mechanisms involved in myocardial injury, such as oxidative stress, mitochondrial dysfunction, calcium dysregulation, endothelial reticulum stress, autophagy, and apoptosis. In parallel, established and emerging cardioprotective strategies, from conventional to newer therapeutic approaches, are explored. The role of advanced imaging modalities, as well as cardiac biomarkers, is discussed in the context of early detection and monitoring of subclinical cardiac injury. Finally, the integration of pharmacogenomics and epigenetics is considered as a promising avenue to personalize risk stratification and preventive therapy. By elucidating the complex interplay between cancer treatments and cardiovascular health, this review underscores the importance of a multidisciplinary, precision medicine approach to optimizing the care of patients undergoing potentially cardiotoxic therapies. Full article

Cardiovascular disease (CVD) remains the leading global cause of morbidity and mortality, largely driven by atherosclerosis, a chronic inflammatory process involving lipids and immune cells. Although traditional lipid biomarkers such as low-density lipoprotein (LDL) and high-density lipoprotein (HDL) are well-established in CVD risk stratification, the interplay between cytokines, chemokines, growth factors (CCGFs), lipid metabolism, and hematological parameters in non-cardiac populations remains underexplored. We investigated associations between plasma cytokines and lipid-related biomarkers and their relationships with circulating blood cell counts in a cohort of 164 essentially healthy adults aged 18–44 years. CCGF profiling was performed using a proximity extension assay (PEA), and statistical correlations were adjusted for multiple testing using false discovery rate (FDR) correction. The CCGFs that were associated with HDL and apolipoprotein A1 all displayed negative associations. Several pro-inflammatory cytokines, including CCL3, IL-6, and TNFSF10, showed strong positive associations with triglycerides, remnants, non-HDL, and body mass index (BMI). Furthermore, triglycerides and remnants were consistently correlated with elevated leukocyte, neutrophil, and platelet counts. HGF and FGF-21, mainly considered as anti-inflammatory, were positively associated with BMI and negatively associated with HDL, which is compliant with a multitude of actions, depending on the local milieu and the cellular interplay. Our results support the existence of a complex immunometabolic network involving lipids, CCGFs, and blood cells, even in non-diseased individuals. The observed patterns underscore the importance of understanding the intricate cytokine–lipid–cell interactions that may occur in early pathophysiological processes and highlight their potential utility in refining cardiovascular risk assessment beyond traditional lipid metrics. Full article

Long COVID is a persistent post-viral syndrome with the significant involvement of both the cardiovascular and pulmonary systems, often extending well beyond the acute phase of SARS-CoV-2 infection. Emerging evidence has highlighted a spectrum of chronic alterations, including endothelial dysfunction, microvascular inflammation, perivascular fibrosis, and in some cases, the persistence of viral components in the cardiac and pulmonary tissues. At the molecular level, a sustained inflammatory milieu—characterized by elevated pro-inflammatory cytokines such as interleukin 6 (IL-6)—and chronic platelet hyperreactivity contribute to a prothrombotic state. These mechanisms are implicated in microvascular damage, cardiac strain, and impaired gas exchange, correlating with clinical manifestations such as fatigue, dyspnea, chest discomfort, and reduced exercise capacity. In certain patients, especially those who were not hospitalized during the acute phase, cardiac MRI and myocardial biopsy may reveal signs of myocardial inflammation and autonomic dysregulation. These often subclinical cardiovascular alterations underscore the need for improved diagnostic strategies, integrating molecular and histopathological markers during post-COVID evaluations. Recognizing persistent inflammatory and thrombotic activity may inform risk stratification and individualized therapeutic approaches. The interdependence between pulmonary fibrosis and cardiac dysfunction highlights the importance of multidisciplinary care. In this context, molecular and tissue-based diagnostics play a pivotal role in elucidating the long-term cardio-pulmonary sequelae of long COVID and guiding targeted interventions. Early identification and structured follow-up are essential to mitigate the burden of chronic complications in affected individuals. Full article

As people with cystic fibrosis (PwCF) live longer, kidney disease is emerging as a significant comorbidity that is increasingly linked to cardiovascular complications and progression to end-stage kidney disease. In our recent review, we proposed the unifying term CF-related kidney disease (CFKD) to encompass the spectrum of kidney dysfunction observed in this population. Early detection of kidney injury is critical for improving long-term outcomes, yet remains challenging due to the limited sensitivity of conventional laboratory tests, particularly in individuals with altered muscle mass and unique CF pathophysiology. Emerging approaches, including novel blood and urinary biomarkers, urinary extracellular vesicles, and genetic risk profiling, offer promising avenues for identifying subclinical kidney damage. When integrated with machine learning algorithms, these tools may enable the development of personalized risk stratification models and targeted therapeutic strategies. This precision medicine approach has the potential to transform kidney disease management in PwCF, shifting care from reactive treatment of late-stage disease to proactive monitoring and early intervention. Full article

Background and Objectives: Type 2 diabetes mellitus (T2DM) is associated with subclinical cardiovascular changes, such as increased arterial stiffness and myocardial dysfunction. Vitamin D deficiency has been recognized as a potential contributing factor to vascular disease; however, its impact on early cardiac changes associated with T2DM remains poorly understood. Our aim was to evaluate the association between serum levels of 25-hydroxyvitamin D3 [25(OH)D3], arterial stiffness, and left ventricular global longitudinal strain (LV GLS) in patients with T2DM who do not have a clinically evident cardiovascular disease. Material and methods: This cross-sectional study evaluated the carotid intima–media thickness (IMT), aortic pulse wave velocity (PWVao), LV GLS, and serum 25(OH)D3 levels in patients diagnosed with T2DM (n = 65) compared to healthy control subjects (n = 55). Independent predictors of arterial stiffness were identified by a multivariate logistic regression analysis. Results: Patients with T2DM showed a significant increase in IMT and PWVao, a reduction in LV GLS, and low levels of 25(OH)D3 compared to subjects in the control group (all p < 0.05). Both vitamin D deficiency and T2DM were found to be independently associated with an increased arterial stiffness, with odds ratios of 2.4 and 4.8, respectively. A significant inverse relationship was identified between 25(OH)D3 levels and markers of arterial stiffness, as well as LV GLS, suggesting a possible association between the vitamin D status and the early onset of cardiovascular dysfunction. Conclusions: Patients with T2DM show early signs of heart and blood vessel problems, even with an ejection fraction that remains within normal limits. There is a significant correlation between vitamin D deficiency and increased arterial stiffness, along with impaired LV GLS, indicating its possible involvement in cardiovascular complications associated with diabetes. These findings support the utility of integrating vascular, myocardial, and vitamin D assessments in early cardiovascular risk stratification for T2DM patients. Full article

Background: Myocardial ischemia remains a major cause of morbidity and mortality worldwide. Although traditional risk factors are well-established, genetic predisposition—particularly involving MTHFR polymorphisms—has garnered increasing attention. This study investigates the association between MTHFR C677T and A1298C polymorphisms and first-episode myocardial ischemia in a Romanian population. Methods: This study included 69 adult patients with first-episode myocardial ischemia and 55 healthy controls, matched by age and sex. Participants were recruited from southeastern Romania between 2023 and 2025. Clinical data—such as blood pressure, body mass index, smoking, and alcohol consumption—were recorded. Genotyping for MTHFR C677T and A1298C polymorphisms was performed using a real-time PCR-based assay (Bosphore^® MTHFR 677-1298 Detection Kit v2), following the manufacturer’s protocol. Results: A significantly higher frequency of homozygous mutant genotypes was observed in patients with myocardial ischemia. The TT genotype of MTHFR C677T was present in 71% of patients, compared to only 7.3% of controls. Similarly, the CC genotype of A1298C was detected in 59.4% of patients, versus 7.3% in controls. These genotypic patterns suggest a strong genetic predisposition among affected individuals. The association between MTHFR polymorphisms and myocardial ischemia was particularly evident in participants over 50 years of age, indicating a possible interaction between genetic vulnerability and age-related cardiovascular risk. Conclusions: Our findings indicate a strong association between MTHFR C677T and A1298C homozygous mutant genotypes and the risk of first-episode myocardial ischemia, particularly in older adults. These results underscore the potential role of genetic screening in early cardiovascular risk stratification. Full article

Background: Blood pressure (BP) variability has been increasingly recognized as a predictor of cardiovascular and renal outcomes. However, the relevance of specific dynamic indices such as the maximum slope of systolic blood pressure (max SBP slope), derived through partial Fourier series modeling, in relation to early renal damage remains underexplored. Methods: A total of 389 patients with essential hypertension were enrolled and stratified according to the estimated glomerular filtration rate (eGFR) ≥ or <90 mL/min/1.73 m² and the presence of subclinical renal damage, defined by elevated urinary albumin excretion (AER) and/or reduced eGFR. All participants underwent clinical and biochemical evaluation, as well as 24-h ambulatory blood pressure monitoring (ABPM), including advanced hemodynamic analysis using Fourier-based modeling. Results: Patients with eGFR < 90 mL/min/1.73 m² were older and exhibited higher waist circumference, uricemia, albuminuria, and systolic BP values, including the elevated max SBP slope (12.8 vs. 10.8 mmHg/h, p = 0.028). Subclinical renal damage was associated with older age; male sex; smoking; and higher levels of uricemia, clinical, and ambulatory BP, and the max SBP slope (14.2 vs. 10.7 mmHg/h, p = 0.007). The max SBP slope positively correlated with AER (r = 0.215, p < 0.001) and inversely with eGFR (r = −0.153, p = 0.002). In multivariate linear regression, the max SBP slope remained independently associated with AER (β = 0.220, p < 0.001), along with mean 24-h SBP, male sex, and the day–night SBP percentage dip. Logistic regression confirmed these associations with subclinical renal damage (max SBP slope OR: 1.536; 95% CI: 1.241–2.004; p = 0.001). Conclusions: The max SBP slope, a dynamic index of BP derived via Fourier analysis, is independently associated with markers of subclinical renal damage in hypertensive patients. This suggests that incorporating such advanced metrics into ABPM evaluation may improve early risk stratification and help identify individuals at greater risk of renal impairment, even in the absence of overt kidney disease. Full article

Chronic coronary syndrome (CCS) and atrial fibrillation (AF) are prevalent cardiovascular conditions that share numerous risk factors and pathophysiological mechanisms. While clinical scores commonly used in AF—such as CHA₂DS₂VA (which includes congestive heart failure, hypertension, age ≥ 75, diabetes, stroke/TIA, vascular disease, and age 65–74), HAS-BLED (which incorporates hypertension, abnormal renal/liver function, stroke, bleeding history, labile INR, elderly age, and drug/alcohol use), and C₂HEST (incorporating coronary artery disease, COPD, hypertension, elderly age ≥ 75, systolic heart failure, and thyroid disease)—are traditionally applied to rhythm or bleeding risk prediction, their value in estimating the angiographic severity of coronary artery disease (CAD) remains underexplored. We conducted a prospective, single-center study including 131 patients with suspected stable CAD referred for coronary angiography, stratified according to coronary angiographic findings into two groups: significant coronary stenosis (S-CCS) and non-significant coronary stenosis (N-CCS). At admission, AF-related scores (CHA₂DS₂, CHA₂DS₂VA, CHA₂DS₂VA-HSF, CHA₂DS₂VA-RAF, CHA₂DS₂VA-LAF, HAS-BLED, C₂HEST, and HATCH) were calculated. CAD severity was subsequently assessed using the SYNTAX and Gensini scores. Statistical comparisons and Pearson correlation analyses were performed to evaluate the association between clinical risk scores and angiographic findings. Patients in the S-CCS group had significantly higher scores in CHA₂DS₂VA (4.09 ± 1.656 vs. 3.20 ± 1.338, p = 0.002), HAS-BLED (1.98 ± 0.760 vs. 1.36 ± 0.835, p < 0.001), CHA₂DS₂VA-HSF (6.00 ± 1.854 vs. 5.26 ± 1.712, p = 0.021), and C₂HEST (3.49 ± 1.501 vs. 2.55 ± 1.279, p < 0.001). Multivariate logistic regression identified HAS-BLED and C₂HEST as independent predictors of significant coronary lesions. A threshold value of HAS-BLED ≥ 1.5 and C₂HEST ≥ 3.5 demonstrated moderate discriminative ability (AUC = 0.694 and 0.682, respectively), with acceptable sensitivity and specificity. These scores also demonstrated moderate to strong correlations with both Gensini and SYNTAX scores. AF-related clinical scores, especially HAS-BLED and C₂HEST, may serve as practical and accessible tools for early CAD risk stratification in patients with suspected CCS. Their application in clinical practice may serve as supplementary triage tools to help prioritize patients for further diagnostic evaluation, but they are not intended to replace standard imaging or testing. Full article

Heart failure (HF) is a global health burden characterized by high morbidity and mortality, necessitating advancements in diagnostic and therapeutic approaches. Molecular diagnostics, encompassing genomics, transcriptomics, proteomics, metabolomics, and epigenetics, offer unprecedented insights into HF pathogenesis, aiding early diagnosis, risk stratification, and personalized management. This state-of-the-art review critically examines recent developments in molecular diagnostics in HF, evaluates their translational potential, and highlights key challenges in clinical implementation. Emerging tools such as liquid biopsy, multi-omics integration, and artificial intelligence (AI)-driven platforms are explored. We propose strategies to enhance clinical translation, equity in access, and utility in guiding treatment, thereby advancing precision cardiovascular medicine Full article

Myocardial injury following polytrauma is a significant yet often underdiagnosed condition that contributes to acute cardiac dysfunction and long-term cardiovascular complications. This review examines the role of systemic inflammation, oxidative stress, neuro-hormonal activation, and immune dysregulation in trauma-induced myocardial damage. Key immunological markers, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and adhesion molecules (ICAM-1, VCAM-1), are implicated in endothelial dysfunction, myocardial apoptosis, and ventricular remodeling. The interplay between these factors potentially exacerbates cardiac injury, increasing the risk of heart failure. Biomarker-guided approaches for early detection, combined with advanced imaging techniques such as speckle-tracking echocardiography and cardiac MRI, offer promising avenues for risk stratification and targeted interventions. Anti-inflammatory and oxidative stress-modulating therapies may mitigate myocardial damage and improve outcomes. This article highlights the clinical relevance of integrating immunological markers into diagnostic and therapeutic strategies to enhance the management of trauma-related cardiac dysfunction and reduce long-term morbidity. Full article

Peripheral artery disease (PAD) is associated with an elevated risk of major adverse cardiovascular events (MACE). Despite this, few reliable biomarkers exist to identify patients at heightened risk of MACE. Growth differentiation factor 15 (GDF15), a stress-responsive cytokine implicated in inflammation, atherosclerosis, and thrombosis, has been broadly studied in cardiovascular disease but remains underexplored in PAD. This study aimed to evaluate the prognostic utility of GDF15 for predicting 2-year MACE in PAD patients using explainable statistical and machine learning approaches. We conducted a prospective analysis of 1192 individuals (454 with PAD and 738 without PAD). At study entry, patient plasma GDF15 concentrations were measured using a validated multiplex immunoassay. The cohort was followed for two years to monitor the occurrence of MACE, defined as stroke, myocardial infarction, or death. Baseline GDF15 levels were compared between PAD and non-PAD participants using the Mann–Whitney U test. A machine learning model based on extreme gradient boosting (XGBoost) was trained to predict 2-year MACE using 10-fold cross-validation, incorporating GDF15 and clinical variables including age, sex, comorbidities (hypertension, diabetes, dyslipidemia, congestive heart failure, coronary artery disease, and previous stroke or transient ischemic attack), smoking history, and cardioprotective medication use. The model’s primary evaluation metric was the F1 score, a validated measurement of the harmonic mean of the precision and recall values of the prediction model. Secondary model performance metrics included precision, recall, positive likelihood ratio (LR+), and negative likelihood ratio (LR-). A prediction probability histogram and Shapley additive explanations (SHAP) analysis were used to assess model discrimination and interpretability. The mean participant age was 70 ± SD 11 years, with 32% (n = 386) female representation. Median plasma GDF15 levels were significantly higher in PAD patients compared to the levels in non-PAD patients (1.29 [IQR 0.77–2.22] vs. 0.99 [IQR 0.61–1.63] pg/mL; p < 0.001). During the 2-year follow-up period, 219 individuals (18.4%) experienced MACE. The XGBoost model demonstrated strong predictive performance for 2-year MACE (F1 score = 0.83; precision = 82.0%; recall = 83.7%; LR+ = 1.88; LR− = 0.83). The prediction histogram revealed distinct stratification between those who did vs. did not experience 2-year MACE. SHAP analysis identified GDF15 as the most influential predictive feature, surpassing traditional clinical predictors such as age, cardiovascular history, and smoking status. This study highlights GDF15 as a strong prognostic biomarker for 2-year MACE in patients with PAD. When combined with clinical variables in an interpretable machine learning model, GDF15 supports the early identification of patients at high risk for systemic cardiovascular events, facilitating personalized treatment strategies including multidisciplinary specialist referrals and aggressive cardiovascular risk reduction therapy. This biomarker-guided approach offers a promising pathway for improving cardiovascular outcomes in the PAD population through precision risk stratification. Full article

C-reactive protein (CRP) has emerged as a valuable biomarker in acute myocardial infarction (AMI), offering multiple insights into diagnosis, prognosis, and therapeutic strategies. In the diagnostic domain, elevated CRP levels serve as an early indicator of AMI, aiding in prompt identification and initiation of treatment. Prognostically, CRP is a strong predictor of adverse outcomes post-AMI, correlating with increased mortality and cardiovascular events. Beyond its diagnostic and prognostic roles, CRP also exposes therapeutic avenues in AMI management. Targeting CRP through pharmacological interventions has shown promise in reducing inflammatory responses, thereby mitigating myocardial damage and improving clinical outcomes. However, CRP’s low specificity, influenced by elevation in non-cardiac conditions, remains a clinical limitation that warrants consideration. This review comprehensively examines the evolving role of CRP in AMI, exploring its diagnostic accuracy, prognostic significance, and potential as a therapeutic target. The understanding of the complex role of CRP in AMI provides clinicians with valuable tools for risk stratification, treatment optimization, and personalized patient care in the acute setting. Full article