Michael A. Nardi

Introduction: Environmental determinants of health, such as greenness, play an increasing role in our understanding of cardiovascular disease, and can inform how to address geographic cardiovascular disparities. This study assesses the impact of greenness and changes in greenness on cardiovascular disease. Purpose: The purpose of this study is to investigate the impact of greenness and changes in greenness on cardiovascular disease diagnoses. Methods: The sample for this prospective, longitudinal study was comprised of 243,558 U.S. Medicare beneficiaries 65 years or older, residing on the same Census Block from 2011 through 2016, and who had a Miami-Dade residential 9-digit zip code. Analyses examined the impact of greenness, measured by mean block-level Normalized Difference Vegetation index (NDVI) from satellite imagery to incidence of new cardiovascular conditions including: acute myocardial infarction, atrial fibrillation, heart failure, ischemic heart disease, hypertension, and stroke/ transient ischemic attack. Zero-inflated poisson regression was used to model the odds of developing any new cardiovascular disease and number of new cardiovascular conditions based on block level greenness while adjusting for individual age, gender, race/ethnicity, number of baseline cardiovascular conditions, and neighborhood characteristics including income and walkability. Results: Living in a higher greenness Census Block was associated with lower odds of having at least one new cardiovascular condition and having a small number of new conditions, adjusting for individual and neighborhood level characteristics. When compared to individuals living in the lowest tertile of greenness throughout the study, those individuals living in the highest tertile of greenness throughout the study had a 16% lower odds of having any new cardiovascular conditions (OR=0.84, 95% CI: 0.79–0.90, p<0.001) and among individuals developing at least one new cardiovascular disease, 4% fewer new cardiovascular conditions (OR=0.96, 95% CI: 0.92–0.99, p<0.05). When compared to individuals living in the lowest tertile of greenness throughout the study, those individuals living in areas that increased their greenness from the lowest tertile to the highest tertile of greenness had a 15% lower odds of having any new cardiovascular conditions (OR=0.85, 95% CI: 0.75–0.97, p<0.001) and among individuals developing at least one new cardiovascular disease, 9% fewer new cardiovascular conditions (OR=0.91, 95% CI: 0.83–0.99, p<0.05). Conclusions: High greenness is associated with lower rates of cardiovascular conditions over time, both when greenness increases and when a Census Block maintains high greenness. It is remarkable that these effects appear in five years, a relatively short amount of time for a positive environmental impact; and that even for those who began in the lowest greenness tertile, an increase to the high greenness tertile had a significant effect. Funding Acknowledgement: Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Robert Wood Johnson Evidence for Action Grant

Summary: Introduction: Von Willebrand disease (VWD) is the most prevalent inherited bleeding disorder. Diagnosis requires measurement of VWF–platelet binding function, for which VWF ristocetin cofactor activity (VWF:RCo) is the reference method. Recently, an automated latex particle‐enhanced immunoturbidimetric von Willebrand factor activity assay (VWF:Ab) has been validated showing superior characteristics. We further validate VWF:Ab in a prospective study including post‐treatment patient samples.Methods: A total of 1151 samples were collected from patients tested for VWD, including 119 samples from patients treated with desmopressin or VWF replacement product. All samples were tested for VWF:Ab and VWF:RCo, and the methods were compared using linear regression. Imprecision, linearity and lower detection limit were determined for both assays.Results: VWF:Ab showed improved precision compared to VWF:RCo. Linear regression of VWF:Ab and VWF:RCo across all samples exhibited good agreement (R² = 0.89) with statistical significance (P < 0.001) and bias of −8.7. Concordance was high in classifying samples as normal or abnormal. Analysis of treated samples showed excellent agreement (R² = 0.91) with statistical significance (P < 0.001) and bias of −4.3.Conclusions: Our analysis validates the VWF:Ab assay in a prospective study of a large cohort of patient samples and extends these results to post‐treatment patient samples.

Platelet markers [soluble CD40 ligand (sCD40L) and soluble p selectin (sPselectin)] are associated with platelet activation and cardiovascular events. We sought to investigate the reproducibility of these markers over time and the effect of low-dose aspirin on sCD40L and sPselectin in plasma and serum. Following an overnight fast, 40 healthy volunteers had weekly phlebotomy and were administered aspirin 81 mg/day between weeks 3 and 4. Reproducibility over time was assessed by coefficient of variation (CV) and inter-class correlation coefficient. Correlation between markers was assessed using Pearson r statistic. Difference between levels pre- and post-aspirin was measured with Wilcoxon signed-rank test. Data are presented as median (interquartile range). sCD40L and sPselectin measurements were reproducible over time in plasma and serum (CV < 10 %). Measurement of sCD40L and sPselectin in plasma correlated with levels in serum before aspirin and after aspirin. There was no significant correlation between sCD40L and sPselectin. After 1-week of aspirin 81 mg/day, there was a reduction in sCD40L and sPselectin in serum and plasma, respectively. Soluble CD40L and sPselectin are independent markers that are reproducible over time in both plasma and sera and are reduced by 1-week of low-dose aspirin.

Hemostasis is a major concern during the perioperative period. Changes in platelet aggregation and coagulation factors may contribute to the delicate balance between thrombosis and bleeding. We sought to better understand perioperative hemostasis by investigating the changes in platelet aggregation and coagulation factors during the perioperative period. We performed a prospective cohort analysis of 70 subjects undergoing non-emergent orthopedic surgery of the knee (n = 28), hip (n = 35), or spine (n = 7) between August 2011 and November 2011. Plasma was collected preoperatively (T1), 1-h intraoperatively (T2), 1-h (T3), 24-h (T4) and 48-h (T5) postoperatively. Platelet function testing was performed using whole blood impedance aggregometry. Coagulation assays were performed for factor VII, factor VIII, von Willebrand Factor (vWF), and fibrinogen. Of the 70 patients, mean age was 64.1 ± 9.8 years, 61 % were female, and 74 % were Caucasian. Platelet activity decreased until 1 h postoperatively and then significantly increased above baseline at 24- and 48-h postoperatively. Compared to baseline, coagulation factors decreased intraoperatively. Factor VII activity continued to decrease, while FVIII, vWF, and fibrinogen all increased above baseline postoperatively. The results of our study indicate significant changes in platelet activity and coagulation factors during the perioperative period. Both platelet activity and markers of coagulation decrease during the intraoperative period and then some increase postoperatively. These changes may contribute to the hypercoagulabity and/or bleeding risk that occurs in the perioperative period. Future prospective studies aimed at correlating hemostatic changes with perioperative outcomes are warranted.

Background: Mechanisms for increased cardiovascular risk in HIV-1-infected adults are incompletely understood, but platelet activation and immune activation leading to a prothrombotic state have been proposed as significant contributors. Aspirin has antiplatelet and immunomodulatory properties. We explored whether 1 week of low-dose aspirin attenuates platelet activation and immune activation in HIV-1-infected and virologically suppressed adults on antiretroviral therapy. Methods: Platelet activation and immune activation were measured in HIV-1-infected subjects virologically suppressed on antiretroviral therapy and controls before and after 1 week of low-dose aspirin. Results: Compared with control subjects, HIV-1-infected subjects had increased platelet activation, as measured by spontaneous platelet aggregation and aggregation in response to adenosine diphosphate, collagen, and arachidonic acid. After aspirin therapy, percent aggregation decreased similarly in both HIV-1-infected and control subjects to all platelet agonists tested except aggregation in response to arachidonic acid, which remained elevated in the HIV-1-infected group. HIV-1-infected subjects exhibited increased markers of T-cell activation (CD38 and HLA-DR) and monocyte activation (sCD14), which decreased after 1 week of aspirin therapy. Moreover, leukocyte responses to Toll-like receptor stimulation were enhanced after 1 week of aspirin therapy. In vitro studies showed that HIV-1 plasma could activate healthy platelets, which in turn activated monocytes, implicating a direct role for activated platelets in immune activation. Conclusions: Our data demonstrate that heightened platelet activation and immune activation in treated HIV-1 disease are attenuated by 1 week of aspirin therapy. Aspirin should be further studied for its antithrombotic and immunomodulatory benefits in treated HIV-1 disease.

Some studies suggest that mean platelet volume (MPV) correlates with increased risk for cardiovascular morbidity and mortality. In this study, we aim to assess reproducibility, need for standardized measurements, effect of aspirin, and association with other established markers of platelet activity. Following an overnight fast, 48 healthy volunteers had weekly assessment of platelet activity and were administered aspirin 81 mg daily for 7 d between weeks 3 and 4. We investigated the influence of time between phlebotomy and MPV measurement (n = 10). Reproducibility was assessed by coefficient of variation (CV) and intraclass correlation coefficient (ICC). MPV measurements were reproducible (Week 1: 10.6 fL [9.9–11], Week 2: 10.6 fL [10.0–10.9], Week 3: 10.6 fL [9.8–11]). CV was ≤4% and ICC > 0.85 (p < 0.001) for each comparison, indicating excellent reproducibility. There was no effect of aspirin on MPV (10.6 fL [9.8–11] versus 10.5 fL [9.9–11]; p = 0.81). MPV significantly increased as time between phlebotomy and MPV measurement increased (Spearman’s rho = 0.94, p = 0.001). Increasing MPV tertiles was associated with collagen- and thrombin receptor-activated peptide-induced platelet aggregation but not with ADP- or arachidonic acid-induced or spontaneous platelet aggregation. In conclusion, when standardized, MPV is a reproducible marker of platelet size and not affected by low-dose aspirin. MPV is modestly associated with some, but not all, markers of platelet activity.