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As the COVID-19 pandemic took hold in the USA in early 2020, it became clear that knowledge of the prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among asymptomatic individuals could inform public health policy decisions and provide insight into the impact of the infection on vulnerable populations. Two Clinical and Translational Science Award (CTSA) Hubs and the National Institutes of Health (NIH) set forth to conduct a national seroprevalence survey to assess the infection’s rate of spread. This partnership was able to quickly design and launch the project by leveraging established research capacities, prior experiences in large-scale, multisite studies and a highly skilled workforce of CTSA hubs and unique experimental capabilities at the NIH to conduct a diverse prospective, longitudinal observational cohort of 11,382 participants who provided biospecimens and participant-reported health and behavior data. The study was completed in 16 months and benefitted from transdisciplinary teamwork, information technology innovations, multimodal communication strategies, and scientific partnership for rigor in design and analytic methods. The lessons learned by the rapid implementation and dissemination of this national study is valuable in guiding future multisite projects as well as preparation for other public health emergencies and pandemics.

Objective: Rheumatoid arthritis (RA) is associated with increased risk of cardiovascular disease. Adventitial vasa vasorum density (aVVD), the vessel density of the vasa vasorum, is a surrogate measure for atherosclerotic plaque vulnerability. The purpose of this study was to compare the adventitial vasa vasorum density (aVVD) in RA and non-RA control participants using novel carotid artery contrast-enhanced ultrasound (CEUS). In addition, we investigate associations of aVVD with traditional cardiovascular (CV) risk factors, vascular and inflammatory biomarkers, and RA disease activity. Methods: The study was a cross-sectional analysis of patients with RA and control participants without RA or other autoimmune disease. CV disease risk, biomarkers, and CEUS images were collected on all patients. Results: aVVD was quantified in 86 patients with RA and 95 non-RA control participants. Nitrite, CD40L, E-selectin, matrix metalloproteinase 9, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, myeloperoxidase (MPO), high-sensitivity C-reactive protein (hsCRP), and erythrocyte sedimentation rate were measured. Median aVVD was higher in patients with RA (0.59 [0.47–0.69] vs 0.64 [0.54–0.62]; P = .02). In patients with RA, MPO was lower (253.5 [153.2–480] vs 470.8 [274.2–830.1] ng/mL; P = .0002) and ESR was higher (15.5 [11–25] vs 13 [9–20] mm/h; P = .02). aVVD was correlated with MPO ( r = −0.33, P = .001) and hsCRP ( r = 0.25, P = .02) in control participants only, associations that remained significant after adjusting for number of CV risk factors and age. No significant correlations were found between aVVD and RA disease activity measures. Conclusions: Using a novel application of CEUS, we found that aVVD, an early measure of plaque vulnerability, was significantly higher in RA than control subjects, even after adjusting for CV risk factors. Differences in correlation of aVVD with vascular biomarkers and CV risk factors suggest RA-related differences in atherosclerotic progression.

Lower FEV1 is associated with increased prevalence of atherosclerosis; however, causal mechanisms remain elusive.To determine if systemic endothelial dysfunction mediates the association between reduced FEV1 and increased atherosclerosis.Brachial artery endothelial function, pulmonary function, coronary artery calcium, and carotid plaque were assessed in 231 Pittsburgh SCCOR (Specialized Centers for Clinically Oriented Research) study participants; peripheral arterial endothelial function, pulmonary function, and coronary artery calcium were assessed in 328 HeartSCORE (Heart Strategies Concentrating on Risk Evaluation) study participants.Lower FEV1 was independently associated with increased atherosclerosis in both cohorts (per 25% lower % predicted FEV1: odds ratio [OR], 1.76; 95% confidence interval [CI], 1.30-2.40; P 0.001 for carotid plaque in SCCOR participants) (per 25% lower % predicted FEV1: OR, 1.35; 95% CI, 1.02-1.77; P = 0.03 for coronary artery calcium in HeartSCORE participants). Similarly, reduced endothelial function was independently associated with increased atherosclerosis in both cohorts (per SD lower endothelial function: OR, 1.30; 95% CI, 1.01-1.67; P = 0.04 for carotid plaque in SCCOR participants) (per SD lower endothelial function: OR, 1.38; 95% CI, 1.09-1.76; P = 0.008 and OR, 1.41; 95% CI, 1.07-1.86; P = 0.01 for coronary artery calcium in SCCOR and HeartSCORE participants, respectively). However, there was no association between endothelial dysfunction and FEV1, FEV1/FVC, low-attenuation area/visual emphysema, and diffusing capacity in SCCOR participants, and between endothelial dysfunction and FEV1 or FEV1/FVC in HeartSCORE participants (all P 0.05). Adjusting the association between FEV1 and atherosclerosis for endothelial dysfunction had no impact.Endothelial dysfunction does not mediate the association between airflow limitation and atherosclerosis. Instead, airflow limitation and endothelial dysfunction seem to be unrelated and mutually independent predictors of atherosclerosis.