Person:

Sorond, Farzaneh A.

Background: Recombinant factor VIIa (rFVIIa) may be used for rapid hemostasis in life-threatening hemorrhage. In warfarin-associated intracerebral hemorrhage (wICH), FVIIa use is controversial and may carry significant thromboembolic risks. We compared incidence of baseline thromboembolic risk factors and thromboembolism rates in wICH patients treated with additional rFVIIa to those treated with standard therapy of fresh frozen plasma (FFP) and vitamin K alone. Methods: We identified 45 consecutive wICH patients treated with additional rFVIIa over 5-year period, and 34 consecutive wICH patients treated with standard therapy alone as comparison group. We compared the incidence of post-hemorrhage cardiac and extra-cardiac thromboembolic complications between two treatment groups, and used logistic regression to adjust for significant confounders such as baseline thromboembolic risk factors. We performed secondary analysis comparing the quantity of FFP transfused between two treatment cohorts. Results: Both rFVIIa-treated and standard therapy-treated wICH patients had a high prevalence of pre-existing thromboembolic diseases including atrial fibrillation (73% vs 68%), deep venous thrombosis (DVT) or pulmonary embolism (PE) (22% vs 18%), coronary artery disease (CAD) (38% vs 32%), and abnormal electrocardiogram (EKG) (78% vs 85%). Troponin elevation following wICH was prevalent in both groups (47% vs 41%). Clinically significant myocardial infarction (MI), defined as troponin > 1.0 ng/dL, occurred in 13% of rFVIIa-treated and 6% of standard therapy-treated patients (p=0.52). Past history of CAD (p=0.0061) and baseline abnormal EKG (p=0.02) were independently associated with clinically significant MI following wICH while rFVIIa use was not. The incidences of DVT/PE (2% vs 9%; p=0.18) and ischemic stroke (2% vs 0%; p=0.38) were similar between two treatment groups. Recombinant FVIIa-treated patients had lower mean INR at 3 (p=0.0001) and 6 hours (p<0.0001) and received fewer units of FFP transfusion (3 vs 5; p=0.003). Conclusions: Pre-existing thromboembolic risk factors as well as post-hemorrhage troponin elevation are prevalent in wICH patients. Clinically significant MI occurs in up to 13% of wICH patients. rFVIIa use was not associated with increased incidence of clinically significant MI or other venous or arterial thromboembolic events in this wICH cohort.

Background: Circulating vascular adhesion molecule-1 (sVCAM-1) is a presumed marker of endothelial activation and dysfunction, but little is known about its association with mood. We hypothesized that elevated plasma concentrations of sVCAM-1 may be a marker of depressive symptoms due to cerebral vascular disease. Methods: We studied 680 community-dwelling participants in the MOBILIZE Boston Study, aged 65 years and older. sICAM-1 and sVCAM-1 were measured by ELISA assay and depressive symptoms were assessed during home interviews using the Revised Center for Epidemiological Studies Depression Scale (CESD-R). Cerebral White Matter Hyperintensities (WMHs) were quantified by MRI in a subgroup of 25 participants. Results: One hundred seventy nine (27 %) subjects had a CESD-R Score ≥ 16, indicative of depressive symptoms. The mean sVCAM-1 concentration (±SD) was 1176 ± 417 ng/mL in a group with CESD-R Scores <16 and 1239 ± 451 ng/mL in those with CESD-R Scores ≥16 (p = 0.036). CESD-R Score was positively associated with sVCAM-1 (r = 0.11, p = 0.004). The highest quintile of sVCAM-1, which is indicative of endothelial dysfunction, was significantly associated with depressive symptoms compared to the lowest quintile (OR = 1.97 (1.14-3.57) p = 0.015). In a subset of subjects, sVCAM-1 concentration was positively correlated with cerebral WMHs volume (p = 0.018). Conclusions: The association between high levels of sVCAM-1 and depressive symptoms may be due to endothelial dysfunction from cerebral microvascular damage. Future longitudinal studies are needed to determine whether sVCAM-1 can serve as a biomarker for cerebrovascular causes of depression.

Background: Falls are the sixth leading cause of death in elderly people in the U.S. Despite progress in understanding risk factors for falls, many suspected risk factors have not been adequately studied. Putative risk factors for falls such as pain, reductions in cerebral blood flow, somatosensory deficits, and foot disorders are poorly understood, in part because they pose measurement challenges, particularly for large observational studies. Methods: The MOBILIZE Boston Study (MBS), an NIA-funded Program Project, is a prospective cohort study of a unique set of risk factors for falls in seniors in the Boston area. Using a door-to-door population-based recruitment, we have enrolled 765 persons aged 70 and older. The baseline assessment was conducted in 2 segments: a 3-hour home interview followed within 4 weeks by a 3-hour clinic examination. Measures included pain, cerebral hemodynamics, and foot disorders as well as established fall risk factors. For the falls follow-up, participants return fall calendar postcards to the research center at the end of each month. Reports of falls are followed-up with a telephone interview to assess circumstances and consequences of each fall. A second assessment is performed 18 months following baseline. Results: Of the 2382 who met all eligibility criteria at the door, 1616 (67.8%) agreed to participate and were referred to the research center for further screening. The primary reason for ineligibility was inability to communicate in English. Results from the first 600 participants showed that participants are largely representative of seniors in the Boston area in terms of age, sex, race and Hispanic ethnicity. The average age of study participants was 77.9 years (s.d. 5.5) and nearly two-thirds were women. The study cohort was 78% white and 17% black. Many participants (39%) reported having fallen at least once in the year before baseline. Conclusion: Our results demonstrate the feasibility of conducting comprehensive assessments, including rigorous physiologic measurements, in a diverse population of older adults to study non-traditional risk factors for falls and disability. The MBS will provide an important new data resource for examining novel risk factors for falls and mobility problems in the older population.