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Aging-induced pathological alterations of the circulatory system play a critical role in morbidity and mortality of older adults. While the importance of cellular and molecular mechanisms of arterial aging for increased cardiovascular risk in older adults is increasingly appreciated, aging processes of veins are much less studied and understood than those of arteries. In this review, age-related cellular and morphological alterations in the venous system are presented. Similarities and dissimilarities between arterial and venous aging are highlighted, and shared molecular mechanisms of arterial and venous aging are considered. The pathogenesis of venous diseases affecting older adults, including varicose veins, chronic venous insufficiency, and deep vein thrombosis, is discussed, and the potential contribution of venous pathologies to the onset of vascular cognitive impairment and neurodegenerative diseases is emphasized. It is our hope that a greater appreciation of the cellular and molecular processes of vascular aging will stimulate further investigation into strategies aimed at preventing or retarding age-related venous pathologies.

Prior research has identified abnormal platelet procoagulant responses in COVID-19. Coated-platelets, a form of procoagulant platelets, support thrombin formation and are elevated in ischemic stroke patients with increased risk for recurrent infarction. Our goal was to examine changes in coated-platelet levels over the course of COVID-19 infection and determine their association with disease severity, thrombosis, and death. Coated-platelet levels were assayed after admission and repeated weekly in COVID-19 patients, and in COVID-19 negative controls. Receiver operator characteristic (ROC) analysis was used to calculate area under the curve (AUC) values for a model including baseline coated-platelets to predict death. Kaplan–Meier and Cox proportional hazards analysis was used to predict risk for death at 90 days. We enrolled 33 patients (22 with moderate and 11 with severe infection) and 20 controls. Baseline coated-platelet levels were lower among moderate (mean ± SD; 21.3 ± 9.8%) and severe COVID-19 patients (28.5 ± 11.9%) compared to controls (38.1 ± 10.4%, p < 0.0001). Coated-platelet levels increased during follow-up in COVID-19 patients by 7% (relative) per day from symptom onset (95% CI 2–12%, p = 0.007). A cut-off of 33.9% for coated-platelet levels yielded 80% sensitivity and 96% specificity for death at 90 days, with resulting AUC of 0.880 (95% CI 0.680–1.0, p = 0.0002). The adjusted hazard ratio for death in patients with coated-platelet levels > 33.9% was 40.99 when compared to those with levels ≤ 33.9% (p < 0.0001). Platelet procoagulant potential is transiently decreased in most patients during COVID-19; however, increased baseline platelet procoagulant levels predict death. Defining the mechanisms involved and potential links with aging may yield novel treatment targets.

Mean levels of coated‐platelets, a subset of highly procoagulant platelets, are decreased in patients with lacunar as compared to those with non‐lacunar stroke. Elevated coated‐platelets are associated with increased risk for recurrent infarction in non‐lacunar stroke and predict incident stroke after transient ischemic attack (TIA).

Introduction:Coated-platelets are a subset of highly procoagulant platelets observed upon dual-agonist stimulation with collagen and thrombin. Coated-platelet levels are elevated in patients with ischemic stroke and associated with stroke recurrence. Lower levels of coated-platelets are present in ischemic stroke patients with early hemorrhagic transformation or in those with microbleeds. We now investigate if the number and location of microbleeds are associated with coated-platelet levels following non-lacunar stroke.Methods:Coated-platelet levels, reported as percent of cells converted to coated-platelets, were assayed in consecutive stroke patients. The number and location of microbleeds (deep vs lobar/mixed) on 1.5 T MRI was recorded by two independent reviewers. Correlations between number of microbleeds and demographics, vascular risk factors, stroke subtype, medications and laboratory values (platelet count, MPV, Hgb, WBC, CRP) were calculated using the Spearman correlation coefficient. Logistic regression was used to identify factors independently associated with location.Results:There were 249 stroke patients analyzed, with a mean age of 65.7 years (range 42 to 91). Microbleeds were present in 72/249 patients (29%), ranged from 1 to 14 lesions and were classified as deep (47) or lobar/mixed (25) distribution. Inter-rater agreement was excellent (91%). The number of microbleeds correlated negatively with coated-platelet levels (adjusted r = -0.41, p < 0.001) after adjusting for age (r = 0.11, p = 0.09). Variables independently associated with lobar/mixed as opposed to deep location of microbleeds included coated-platelet levels (47.0±35.0% vs 26.7±10.2%, p = 0.005) and prior stroke (10/25 vs 9/47, p = 0.028).Conclusions:Lower levels of coated-platelets are associated with increased number of microbleeds. In addition, coated-platelet levels are higher in patients with lobar/mixed as compared to those with deep distribution of microbleeds, a finding possibly linked to amyloid metabolism abnormalities described in this subset of procoagulant platelets. These data support a role for differential involvement of platelet procoagulant potential in mechanisms leading to development of cerebral microbleeds.

Coated-platelets, a subset of procoagulant platelets observed on dual agonist stimulation with collagen and thrombin, support a robust prothrombinase activity and provide a unique measure of platelet thrombotic potential. Coated-platelet levels are increased in large artery stroke, and higher levels are associated with early stroke recurrence, suggesting a potential role for risk stratification in asymptomatic patients with carotid artery stenosis.