Angiogenic Microvascular Wall Shear Stress Patterns Revealed Through Three-dimensional Red Blood Cell Resolved Modeling.

The wall shear stress (WSS) exerted by blood flowing through microvascular capillaries is an established driver of new blood vessel growth, or angiogenesis. Such adaptations are central to many physiological processes in both health and disease, yet three-dimensional (3D) WSS characteristics in real angiogenic microvascular networks are largely unknown. This marks a major knowledge gap because angiogenesis, naturally, is a 3D process. To advance current understanding, we model 3D red blood cells (RBCs) flowing through rat angiogenic microvascular networks using state-of-the-art simulation. The high-resolution fluid dynamics reveal 3D WSS patterns occurring at sub-endothelial cell (EC) scales that derive from distinct angiogenic morphologies, including microvascular loops and vessel tortuosity. We identify the existence of WSS hot and cold spots caused by angiogenic surface shapes and RBCs, and notably enhancement of low WSS regions by RBCs. Spatiotemporal characteristics further reveal how fluctuations follow timescales of RBC "footprints." Altogether, this work provides a new conceptual framework for understanding how shear stress might regulate EC dynamics in vivo.

Disparities in PCSK9 Initiation Among US Veterans with Peripheral Arterial Disease or Cerebrovascular Disease.

BACKGROUND: Effective lipid lowering is essential in patients with peripheral arterial disease (PAD) and cerebrovascular disease (CeVD). Proprotein convertase subtilsin/kexin type 9 inhibitors (PCSK9i) efficiently lower low-density lipoprotein (LDL) levels; however, use in PAD and CeVD patients is limited. Therefore, our aim was to evaluate the use of PCSK9i among US Veterans and compare rates between patients with PAD, CeVD, and coronary artery disease (CAD). METHODS: We evaluated PCSK9i initiation (2016-2019) in US Veterans with CAD, PAD, or CeVD treated at 124 Veterans Affairs (VA) hospitals. We fit a hierarchical logistic regression model to evaluate the association of the patient's primary diagnosis, baseline low-density lipoprotein cholesterol (LDL-C) levels, socioeconomic indicators, and the Department of Veterans Affairs medical center enrollment with PCSK9i initiation. RESULTS: Of 519,566 patients with atherosclerotic vascular disease, 337,766 (65%), 79,926 (15%) and 101,874 (20%) had CAD, PAD, and CeVD, respectively. Among 2115/519,566 (0.4%) initiated on PCSK9i therapy, 84.3% had CAD, while only 7.2% and 8.5% had PAD and CeVD, respectively. Compared with CAD patients, PAD {odds ratio [OR] 0.50 (0.36-0.70)} and CeVD [OR 0.24 (0.15-0.37)] patients were less likely to receive PCSK9i. Relative to under $40K per year, PCSK9i initiation was higher if earning $40,000-$80,000 [OR 1.13 (1.01-1.27)] or > $80,000 [OR 1.41 (1.14-1.75)]. Even moderate community deprivation [OR 0.87 (0.77-0.97)] was associated with lower PCSK9i therapy. CONCLUSIONS: Adjusted for LDL-C levels, PAD and CeVD patients are much less likely to receive PCSK9i therapy. Despite low co-pay, PCSK9i initiation rates among US veterans, nationwide, is low, with household income and community deprivation appearing to predict PCSK9i use.