Aspirin resistance describes a phenomenon where patients receiving aspirin therapy do not respond favorably to treatment, and is categorized by continued incidence of adverse cardiovascular events and/or the lack of reduced platelet reactivity. Studies demonstrate that one in four patients with vascular disease are resistant to aspirin therapy, placing them at an almost four-fold increased risk of major adverse limb and adverse cardiovascular events. Despite the increased cardiovascular risk incurred by aspirin resistant patients, strategies to diagnose or overcome this resistance are yet to be clinically validated and integrated. Currently, five unique laboratory assays have shown promise for aspirin resistance testing: Light transmission aggregometry, Platelet Function Analyzer-100, Thromboelastography, Verify Now, and Platelet Works. Newer antiplatelet therapies such as Plavix and Ticagrelor have been tested as an alternative to overcome aspirin resistance (used both in combination with aspirin and alone) but have not proven to be superior to aspirin alone. A recent breakthrough discovery has demonstrated that rivaroxaban, an anticoagulant which functions by inhibiting active Factor X when taken in combination with aspirin, improves outcomes in patients with vascular disease. Current studies are determining how this new regime may benefit those who are considered aspirin resistant.

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.

Background: Peripheral artery disease (PAD) involves atherosclerosis of the lower extremity arteries and is a major contributor to limb loss and death worldwide. Several studies have demonstrated that interleukins (ILs) play an important role in the development and progression of PAD; however, a comprehensive literature review has not been performed. Methods: A systematic review was conducted and reported according to PRISMA guidelines. MEDLINE was searched from inception to 5 December 2022, and all studies assessing the association between ILs and PAD were included. Results: We included 17 studies from a pool of 771 unique articles. Five pro-inflammatory ILs (IL-1β, IL-2, IL-5, IL-6, and IL-8) and one pro-atherogenic IL (IL-12) were positively correlated with PAD diagnosis and progression. In contrast, two anti-inflammatory ILs (IL-4 and IL-10) were protective against PAD diagnosis and adverse limb events. Specifically, IL-6 and IL-8 were the most strongly associated with PAD and can act as potential disease biomarkers to support the identification and treatment of PAD. Conclusions: Ongoing work to identify and validate diagnostic/prognostic inflammatory biomarkers for PAD has the potential to assist clinicians in identifying high-risk patients for further evaluation and management which could reduce the risk of adverse cardiovascular and limb events.

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.

Chronic limb-threatening ischemia (CLTI) results in devastating complications such as lower-limb amputations. In this study, a genome-wide plasma microRNAs (miRNA) sequencing was performed to identify miRNA(s) associated with CLTI. Blood samples were collected from early stage CLTI patients (ABI < 0.9) and non-PAD controls (ABI ≥ 0.9) for 3 experiments: discovery phase (n = 23), confirmatory phase (n = 52) and validation phase (n = 20). In the discovery phase, next generation sequencing (NGS) was used to identify miRNA circulating in the plasma CLTI (n = 13) patients, compared to non-PAD controls (n = 10). Two down-regulated miRNAs (miRNA-6843-3p and miRNA-6766-5p) and three upregulated miRNAs (miRNA-1827, miRNA-320 and miRNA-98-3p) were identified (≥2-fold change). In the confirmatory phase, these 5 deregulated miRNAs were further investigated in non-PAD (n = 21) and CTLI (n = 31) patients using qRT-PCR. Only miRNA-1827 was found to be significantly upregulated (≥3-fold, p-value < 0. 001) in the CLTI group. Lastly, to minimize the influence of confounding factors, miRNA-1827 plasma levels were validated in a third cohort of CLTI patients (n = 10) matched to non-PAD controls (n = 10). Our analysis demonstrated that miRNA-1827 expression was increased in the CLTI cohort (≥2-folds, p-value < 0.001). In summary, circulating miRNA-1827 is significantly elevated in patients with CLTI.

Diabetic patients with peripheral arterial disease (PAD) often suffer from poor clinical outcomes such as limb-loss. Fatty acid binding protein 4 (FABP4) is mainly expressed by adipocytes and is known to play a significant role in the development of atherosclerosis. In this study, we sought to investigate whether FABP4 is associated with PAD in patients with type 2 diabetes mellitus (DM). FABP4 plasma levels were studied in 119 diabetic patients with PAD (DM-PAD) and 49 diabetic patients without PAD (DM-noPAD) presenting to St. Michael’s Hospital between October 2017 and September 2018. Levels of FABP4 in DM-PAD patients (23.34 ± 15.27 ng/mL) were found to be over two-fold higher than the levels in DM-noPAD patients (10.3 ± 7.59 ng/mL). Regression analysis demonstrated a significant association between FABP4 levels and DM-PAD after adjusting for age, sex, prior history of coronary arterial disease and white blood cells count (OR, 2.77; 95% CI, 1.81–4.31; p-value = 0.001). Relative to DM-noPAD controls, plasma FABP4 levels in DM-PAD patients were noted to be inversely correlated with the ankle brachial index (ABI; r= −0.374, p-value < 0.001). The diagnostic ability of FABP4 was investigated using receiver operator curves (ROC) and area under the curve (AUC) analysis. FABP4 had an AUC of 0.79, which improved to 0.86 after adjusting for age, sex and prior history of coronary arterial disease. This raises a possibility of utilizing FABP4 as a biomarker for diagnosing PAD in diabetic patients.