Abdominal aortic aneurysm (AAA) is a progressive dilatation of the aorta that can lead to aortic rupture. The pathophysiology of the disease is not well characterized but is known to be caused by the general breakdown of the extracellular matrix within the aortic wall. In this comprehensive literature review, all current research on proteins that have been investigated for their potential prognostic capabilities in patients with AAA was included. A total of 45 proteins were found to be potential prognostic biomarkers for AAA, predicting incidence of AAA, AAA rupture, AAA growth, endoleak, and post-surgical mortality. The 45 proteins fell into the following seven general categories based on their primary function: (1) cardiovascular health, (2) hemostasis, (3) transport proteins, (4) inflammation and immunity, (5) kidney function, (6) cellular structure, (7) and hormones and growth factors. This is the most up-to-date literature review on current prognostic markers for AAA and their functions. This review outlines the wide pathophysiological processes that are implicated in AAA disease progression.

Carotid artery stenosis (CAS), an atherosclerotic disease of the carotid artery, is one of the leading causes of transient ischemic attacks (TIA) and cerebrovascular attacks (CVA). The atherogenic process of CAS affects a wide range of physiological processes, such as inflammation, endothelial cell function, smooth muscle cell migration and many more. The current gold-standard test for CAS is Doppler ultrasound; however, there is yet to be determined a strong, clinically validated biomarker in the blood that can diagnose patients with CAS and/or predict adverse outcomes in such patients. In this comprehensive literature review, we evaluated all of the current research on plasma and serum proteins that are current contenders for biomarkers for CAS. In this literature review, 36 proteins found as potential biomarkers for CAS were categorized in to the following nine categories based on protein function: (1) Inflammation and Immunity, (2) Lipid Metabolism, (3) Haemostasis, (4) Cardiovascular Markers, (5) Markers of Kidney Function, (6) Bone Health, (7) Cellular Structure, (8) Growth Factors, and (9) Hormones. This literature review is the most up-to-date and current comprehensive review of research on biomarkers of CAS, and the only review that demonstrated the several pathways that contribute to the initiation and progression of the disease. With this review, future studies can determine if any new markers, or a panel of the proteins explored in this study, may be contenders as diagnostic or prognostic markers for CAS.

Background/Objectives: Myokines have been demonstrated to be associated with cardiovascular diseases; however, they have not been studied as biomarkers for peripheral artery disease (PAD). We identified interleukin-7 (IL-7) as a prognostic biomarker for PAD from a panel of myokines and developed predictive models for 2-year major adverse limb events (MALEs) using clinical features and plasma IL-7 levels. Methods: A prognostic study was conducted with a cohort of 476 patients (312 with PAD and 164 without PAD) that were recruited prospectively. Their plasma concentrations of five circulating myokines were measured at recruitment, and the patients were followed for two years. The outcome of interest was two-year MALEs (composite of major amputation, vascular intervention, or acute limb ischemia). Cox proportional hazards analysis was performed to identify IL-7 as the only myokine that was associated with 2-year MALEs. The data were randomly divided into training (70%) and test sets (30%). A random forest model was trained using clinical characteristics (demographics, comorbidities, and medications) and plasma IL-7 levels with 10-fold cross-validation. The primary model evaluation metric was the F1 score. The prognostic model was used to classify patients into low vs. high risk of developing adverse limb events based on the Youden Index. Freedom from MALEs over 2 years was compared between the risk-stratified groups using Cox proportional hazards analysis. Results: Two-year MALEs occurred in 28 (9%) of patients with PAD. IL-7 was the only myokine that was statistically significantly correlated with two-year MALE (HR 1.56 [95% CI 1.12–1.88], p = 0.007). For the prognosis of 2-year MALEs, our model achieved an F1 score of 0.829 using plasma IL-7 levels in combination with clinical features. Patients classified as high-risk by the predictive model were significantly more likely to develop MALEs over a 2-year period (HR 1.66 [95% CI 1.22–1.98], p = 0.006). Conclusions: From a panel of myokines, IL-7 was identified as a prognostic biomarker for PAD. Using a combination of clinical characteristics and plasma IL-7 levels, we propose an accurate predictive model for 2-year MALEs in patients with PAD. Our model may support PAD risk stratification, guiding clinical decisions on additional vascular evaluation, specialist referrals, and medical/surgical management, thereby improving outcomes.

Background/Objectives: Major adverse cardiovascular events (MACE)—including heart attacks and strokes—are the leading cause of death in patients with peripheral artery disease (PAD), yet biomarker research for MACE prediction in PAD patients remains limited. Inflammatory proteins play a key role in the progression of atherosclerosis and may serve as useful prognostic indicators for systemic cardiovascular risk in PAD. The objective of this study was to evaluate a broad panel of circulating inflammatory proteins to identify those independently associated with 2-year MACE in patients with PAD. Methods: We conducted a prospective cohort study involving 465 patients with PAD. Plasma concentrations of 15 inflammatory proteins were measured at baseline using validated immunoassays. Patients were followed over a two-year period for the development of MACE, defined as a composite endpoint of myocardial infarction, stroke, or mortality. Protein levels were compared between patients with and without MACE using the Mann–Whitney U test. Cox proportional hazards regression was used to determine the independent association of each protein with MACE after adjusting for baseline demographic and clinical variables, including existing coronary and cerebrovascular disease. To validate the findings, a random forest machine learning model was developed to assess the relative importance of each protein for predicting 2-year MACE. Results: The mean age of the cohort was 71 years (SD 10), and 145 participants (31.1%) were female. Over the two-year follow-up, 84 patients (18.1%) experienced MACE. Six proteins were significantly elevated in PAD patients who developed MACE: interferon gamma (IFN-γ; 42.55 [SD 15.11] vs. 33.85 [SD 12.46] pg/mL, p < 0.001), tumor necrosis factor alpha (TNF-α; 9.00 [SD 5.00] vs. 4.65 [SD 4.29] pg/mL, p < 0.001), chemokine (C-X-C motif) ligand 9 (CXCL9; 75.99 [SD 65.14] vs. 5.38 [SD 64.18] pg/mL, p = 0.002), macrophage inflammatory protein-1 beta (MIP-1β; 20.88 [SD 18.10] vs. 15.67 [SD 16.93] pg/mL, p = 0.009), MIP-1δ (25.29 [SD 4.22] vs. 17.98 [SD 4.01] pg/mL, p = 0.026), and interleukin-6 (IL-6; 12.50 [SD 40.00] vs. 6.72 [SD 38.98] pg/mL, p = 0.035). After adjusting for all baseline covariates, only two proteins—TNF-α (adjusted HR 1.66, 95% CI 1.28–2.33, p = 0.001) and IFN-γ (adjusted HR 1.25, 95% CI 1.12–2.29, p = 0.033)—remained significantly and independently associated with 2-year MACE. These findings were corroborated by the random forest model, where TNF-α and IFN-γ received the highest importance scores for predicting 2-year MACE: (TNF-α: 0.15 [95% CI 0.13–0.18], p = 0.002; IFN-γ: 0.19 [95% CI 0.17–0.21], p = 0.001). Conclusions: From a panel of 15 proteins, TNF-α and IFN-γ emerged as inflammatory biomarkers associated with 2-year MACE in PAD patients. Their measurement may aid in cardiovascular risk stratification, helping to identify high-risk individuals who could benefit from early multidisciplinary referrals to cardiology, neurology, and/or vascular medicine specialists to provide intensified medical therapy. Incorporating these biomarkers into PAD management may improve systemic cardiovascular outcomes through more personalized and targeted treatment approaches.

Background and Objectives: Inflammatory proteins and their prognostic value in patients with carotid artery stenosis (CAS) have not been adequately studied. Herein, we identified CAS-specific biomarkers from a large pool of inflammatory proteins and assessed the ability of these biomarkers to predict adverse events in individuals with CAS. Materials and Methods: Samples of blood were prospectively obtained from 336 individuals (290 with CAS and 46 without CAS). Plasma concentrations of 29 inflammatory proteins were determined at recruitment, and the patients were followed for 24 months. The outcome of interest was a major adverse cardiovascular event (MACE; composite of stroke, myocardial infarction, or death). The differences in plasma protein concentrations between patients with vs. without a 2-year MACE were determined using the independent t-test or Mann–Whitney U test to identify CAS-specific prognostic biomarkers. Kaplan–Meier and Cox proportional hazards analyses with adjustment for baseline demographic and clinical characteristics were performed to assess the prognostic value of differentially expressed inflammatory proteins in predicting a 2-year MACE in patients with CAS. Results: The mean age of the cohort was 68.8 (SD 10.2) years and 39% were female. The plasma concentrations of two inflammatory proteins were significantly higher in individuals with a 2-year MACE relative to those without a 2-year MACE: IL-6 (5.07 (SD 4.66) vs. 3.36 (SD 4.04) pg/mL, p = 0.03) and CD163 (233.825 (SD 230.306) vs. 159.673 (SD 175.669) pg/mL, p = 0.033). Over a follow-up period of 2 years, individuals with elevated levels of IL-6 were more likely to develop MACE (HR 1.269 (95% CI 1.122–1.639), p = 0.042). Similarly, over a 2-year period, patients with high levels of CD163 were more likely to develop MACE (HR 1.413 (95% CI 1.022–1.954), p = 0.036). Conclusions: The plasma levels of inflammatory proteins IL-6 and CD163 are independently associated with adverse outcomes in individuals with CAS. These CAS-specific prognostic biomarkers may assist in the risk stratification of patients at an elevated risk of a MACE and subsequently guide further vascular evaluation, specialist referrals, and aggressive medical/surgical management, thereby improving outcomes for patients with CAS.

Background/Objectives: Peripheral artery disease (PAD) is associated with an increased risk of major adverse cardiovascular events (MACE), such as myocardial infarction and stroke, which are the top mortality causes in the PAD population. However, the identification of reliable biomarkers for predicting MACE in PAD patients remains limited. Proteins involved in extracellular matrix (ECM) remodeling have been implicated in atherosclerosis and may serve as potential indicators of cardiovascular risk. This study aimed to evaluate a panel of circulating proteins involved in ECM remodeling to identify those predictive of 2-year MACE in individuals with PAD. Methods: A prospective cohort of 465 PAD patients was enrolled and followed for 24 months. At baseline, plasma levels of nine ECM-related proteins were quantified. The outcome of interest was a 2-year MACE, defined as a composite of myocardial infarction, stroke, or mortality. Protein level differences between MACE vs. non-MACE patients were analyzed using Mann–Whitney U tests. Cox proportional hazards models, adjusted for baseline variables (including known cerebrovascular and coronary disease), were used to determine the independent associations between each protein and 2-year MACE. Subgroup analyses were conducted for diabetic and female patients, who are known to be at high risk for adverse events. Results: The mean age of the participants was 71 (SD 10) years, with 31.1% identifying as female and 47.2% having diabetes. Over two years, 84 patients (18.1%) experienced MACE. Among the proteins analyzed, matrix metalloproteinase-10 (MMP-10) and matrix metalloproteinase-7 (MMP-7) were significantly elevated in those who developed MACE compared to those who did not: MMP-10 (710.60 pg/mL [SD 46.09] vs. 672.40 pg/mL [SD 45.04], p = 0.032) and MMP-7 (5.20 pg/mL [SD 4.11] vs. 4.76 pg/mL [SD 3.86], p = 0.048). Both independently correlated with 2-year MACE after adjustment for all baseline factors: MMP-10 (HR 1.32, 95% CI 1.16–1.51, p = 0.023) and MMP-7 (HR 1.17, 95% CI 1.05–2.68, p = 0.026). Subgroup analyses revealed that MMP-10 was associated with MACE in diabetic patients (HR 1.18, 95% CI 1.13–1.53, p = 0.019), while MMP-7 was associated with MACE among females (HR 1.31, 95% CI 1.15–1.69, p = 0.009). Conclusions: MMP-10 and MMP-7 emerged as independent biomarkers for prognosticating 2-year MACE in PAD patients, suggesting their utility in systemic cardiovascular risk stratification. Measuring these proteins could enhance clinical decision-making by identifying high-risk individuals with PAD who may benefit from multidisciplinary vascular evaluation and intensified treatment strategies, ultimately aiming to reduce cardiovascular complications in the PAD population.