Faculty Bibliography

AIM/OBJECTIVE:To investigate how psychosocial stress contributes to accelerated thrombosis, focusing on platelet activation and hyperreactivity. The specific objective was to identify novel platelet regulators involved in stress-mediated thrombosis, with a particular emphasis on the tetraspanin CD37. METHODS AND RESULTS/RESULTS:To explore how stress contributes to platelet hyperreactivity, platelets were isolated from (1) mice that experienced chronic variable stress and stress-free controls (n=8/group) and (2) human subjects with self-reported high and no stress levels (n=18/group), followed by RNA-sequencing. By comparing mutually expressed transcripts, a subset of genes differentially expressed following psychosocial stress was identified in both human and mouse platelets. In both mice and humans, platelet CD37 positively associates with platelet aggregation responses that underlie thrombosis, with Cd37-/- platelets exhibiting impaired integrin αIIbβ3 signaling, characterized by reduced platelet fibrinogen spreading and decreased agonist-induced αIIbβ3 activation. Consistent with a role for CD37 in regulating platelet activation responses, chimeric mice that received Cd37-/- bone marrow experienced a significantly increased time to vessel occlusion in the carotid artery FeCl3 model compared to mice reconstituted with wild-type bone marrow. CD37 deficiency did not alter hemostasis, as platelet count, coagulation metrics, prothrombin time, and partial thromboplastin time did not differ in Cd37-/- mice relative to wild-type mice. Consistent with this, bleeding time did not differ between wild-type and Cd37-/- mice following tail tip transection. CONCLUSIONS:This study provides new insights into the platelet-associated mechanisms underlying stress-mediated thrombosis. Identifying CD37 as a novel regulator of platelet activation responses offers potential therapeutic targets for reducing the thrombotic risk associated with psychosocial stress. The findings also contribute to understanding how psychosocial stress accelerates thrombotic events and underscore the importance of platelet activation in this process.

BACKGROUND:Women with chronic coronary disease have more frequent angina and worse health status than men, despite having less coronary artery disease (CAD). We examined whether perceived stress and depressive symptoms mediate sex differences in angina, and whether this relationship differs in the setting of obstructive CAD or ischemia with no obstructive coronary artery disease (INOCA). METHODS:We analyzed the association between sex, stress (Perceived Stress Scale-4) and depressive symptoms (Patient Health Questionnaire-8) on angina-related health status (Seattle Angina Questionnaire [SAQ]) at enrollment in the ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial and CIAO-ISCHEMIA (Changes in Ischemia and Angina Over 1 Year Among ISCHEMIA Trial Screen Failures With No Obstructive CAD on Coronary CT [Computed Tomography] Angiography) ancillary study. RESULTS:=0.012). Higher stress and depressive symptoms were associated with worse angina in both cohorts. Female sex, Perceived Stress Scale-4 score, and Patient Health Questionnaire-8 score were each independently associated with lower SAQ summary score, but CAD versus INOCA cohort was not. There was no interaction between sex and stress (-0.39 [95% CI, -1.01 to 0.23]) or sex and depression (-0.00 [95% CI, -0.53 to 0.53]) on SAQ summary score. CONCLUSIONS:High stress and depressive symptoms were independently associated with worse angina and poorer health status, without interaction with sex with or without obstructive CAD. Factors other than stress or depression contribute to worse health status in women with obstructive CAD or INOCA. REGISTRATION/BACKGROUND:URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02347215, NCT01471522.

BACKGROUND/UNASSIGNED:Elevated perceived stress is associated with adverse outcomes following myocardial infarction (MI) and may account for poorer recovery among women vs men. OBJECTIVES/UNASSIGNED:This randomized controlled trial tested effects of a mindfulness-based intervention on stress levels among women with MI. METHODS/UNASSIGNED:Women with elevated stress (Perceived Stress Scale [PSS-4]≥6) at least 2 months after MI were enrolled from 12 hospitals in the United States and Canada and via community advertising. Participants were randomized to a remotely delivered mindfulness intervention (MBCT-Brief) or heart disease education, both 8 weeks long. Follow-up was 6 months. Changes in stress (PSS-10; primary outcome) and secondary outcomes (depressive symptoms, anxiety, quality of life, disease-specific health status, actigraphy-assessed sleep) were compared between groups. RESULTS/UNASSIGNED: = 0.036). CONCLUSIONS/UNASSIGNED:MBCT-Brief was associated with greater 6-month reductions in stress than an active control among adherent participants. More frequent mindfulness practice was associated with greater improvements in psychological outcomes. Strategies to engage women with MI in mindfulness training and support regular home practice may enhance these effects.

BACKGROUND/UNASSIGNED:Caregiving has been associated with high blood pressure in middle-aged and older women, but this relationship is understudied among younger Black women, a population at high risk for hypertension. We examined the associations of caregiving stress and caregiving for high-needs dependents with incident hypertension among reproductive-age women in the JHS (Jackson Heart Study), a cohort of community-dwelling Black adults. METHODS/UNASSIGNED:We included 453 participants, aged 21 to 44 years, with blood pressure <140/90 mm Hg, and not taking antihypertensive medication at baseline (2000-2004). Caregiving stress over the past 12 months was assessed via a single item in the global perceived stress scale. Caregiving for a high-needs dependent status was assessed via a question on hours per week spent caregiving for children (≤5 years or disabled) or older adults. Incident hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or self-report of taking antihypertensive medication at follow-up exams in 2005 to 2008 and 2009 to 2013. RESULTS/UNASSIGNED:Over a median follow-up of 7.4 years, 43.5% of participants developed hypertension. Participants with moderate/high versus no/low caregiving stress had a higher incidence of hypertension (51.7% versus 40.6%). Higher caregiving stress was associated with incident hypertension after adjustment for sociodemographic and clinical factors, health behaviors, and depressive symptoms (hazard ratio, 1.39 [95% CI, 1.01-1.94]). Being a caregiver for a high-needs dependent was not associated with incident hypertension (adjusted hazard ratio, 0.88 [95% CI, 0.64-1.21]). CONCLUSIONS/UNASSIGNED:Higher caregiving stress among reproductive-age Black women was associated with incident hypertension. Hypertension prevention approaches for this high-risk population may include caregiving stress management strategies.

OBJECTIVE:Residents of Puerto Rico are disproportionately exposed to social and environmental stressors (e.g., Hurricane María and the 2020 sequence of tremors) known to be associated with psychological distress. Shift-and-persist (SP), or the ability to adapt the self to stressors while preserving focus on the future, has been linked with lower psychological distress, but no study has evaluated this in Puerto Rico. This study examined the association between SP and psychological distress (including that from natural disasters) in a sample of young adults in Puerto Rico. METHODS:Data from the Puerto Rico-OUTLOOK study (18-29 y) were used. Participants (n = 1497) completed assessments between September 2020 and September 2022. SP was measured with the Chen scale and categorized into quartiles (SPQ1-SPQ4). Psychological distress included symptoms of depression (CESD-10), anxiety (STAI-10), post-traumatic stress disorder (Civilian Abbreviated Scale PTSD checklist), and ataque de nervios (an idiom of distress used by Latinx groups). Outcomes were dichotomized according to clinical cutoffs when available, otherwise used sample-based cutoffs. Two additional items assessed the perceived mental health impact of Hurricane María and the 2020 sequence of tremors (categorized as no/little impact vs. some/a lot). Adjusted prevalence ratios (PR) and their 95% confidence intervals (CI) were estimated. RESULTS:The most commonly reported psychological distress outcome was PTSD (77%). In adjusted models, compared to SP Q1, persons in SP Q2-Q4 were less likely to have elevated symptoms of depression (PR Q2 = 0.79, 95% CI = 0.72-0.85; PR Q3 = 0.65, 95% CI = 0.58-0.73; and PR Q4 = 0.41, 95% CI = 0.35-0.48), PTSD (PR Q2 = 0.92, 95% CI = 0.87-0.98; PR Q3 = 0.86, 95% CI = 0.80-0.93; and PR Q4 = 0.76, 95% CI = 0.70-0.83), anxiety (PR Q2 = 0.39, 95% CI = 0.31-0.48; PR Q3 = 0.27, 95% CI = 0.20-0.37; and PR Q4 = 0.11, 95% CI = 0.07-0.17) and experiences of ataque de nervios (PR Q2 = 0.85, 95% CI = 0.76-0.94; PR Q3 = 0.79, 95% CI = 0.70-0.90; and PR Q4 = 0.68, 95% CI = 0.60-0.78). Compared to persons in SP Q1, persons in SP Q3-Q4 were less likely to report adverse mental health impacts from Hurricane María (PR Q3 = 0.66, 95% CI = 0.55-0.79; and PR Q4 = 0.53, 95% CI = 0.44-0.65) and the 2020 sequence of tremors (PR Q3 = 0.77, 95% CI = 0.61-0.98; and PR Q4 = 0.74, 95% CI = 0.59-0.94). CONCLUSION/CONCLUSIONS:SP was associated with lower psychological distress. Studies are needed to confirm our findings and evaluate potential mechanisms of action.

IMPORTANCE/UNASSIGNED:Black and Hispanic patients have high rates of recurrent stroke and uncontrolled hypertension in the US. The effectiveness of home blood pressure telemonitoring (HBPTM) and telephonic nurse case management (NCM) among low-income Black and Hispanic patients with stroke is unknown. OBJECTIVE/UNASSIGNED:To determine whether NCM plus HBPTM results in greater systolic blood pressure (SBP) reduction at 12 months and lower rate of stroke recurrence at 24 months than HBPTM alone among Black and Hispanic stroke survivors with uncontrolled hypertension. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Practice-based, multicenter, randomized clinical trial in 8 stroke centers and ambulatory practices in New York City. Black and Hispanic study participants were enrolled between April 18, 2014, and December 19, 2017, with a final follow-up visit on December 31, 2019. INTERVENTIONS/UNASSIGNED:Participants were randomly assigned to receive either HBPTM alone (12 home BP measurements/week for 12 months, with results transmitted to a clinician; n = 226) or NCM plus HBPTM (20 counseling calls over 12 months; n = 224). MAIN OUTCOMES AND MEASURES/UNASSIGNED:Primary outcomes were change in SBP at 12 months and rate of recurrent stroke at 24 months. Final statistical analyses were completed March 14, 2024. RESULTS/UNASSIGNED:Among 450 participants who were enrolled and randomized (mean [SD] age, 61.7 [11.0] years; 51% were Black [n = 231]; 44% were women [n = 200]; 31% had ≥3 comorbid conditions [n = 137]; 72% had household income <$25 000/y [n = 234/324]), 358 (80%) completed the trial. Those in the NCM plus HBPTM group had a significantly greater SBP reduction than those in the HBPTM alone group at 12 months (-15.1 mm Hg [95% CI, -17.2 to -13.0] vs -5.8 mm Hg [95% CI, -7.9 to -3.7], respectively; P < .001). The between-group difference in SBP reduction at 12 months, adjusted for primary care physician clustering, was -8.1 mm Hg (95% CI, -11.2 to -5.0; P < .001) at 12 months. The rate of recurrent stroke was similar between both groups at 24 months (4.0% in the NCM plus HBPTM group vs 4.0% in the HBPTM alone group, P > .99). CONCLUSIONS AND RELEVANCE/UNASSIGNED:Among predominantly low-income Black and Hispanic stroke survivors with uncontrolled hypertension, addition of NCM to HBPTM led to greater SBP reduction than HBPTM alone. Additional studies are needed to understand the long-term clinical outcomes, cost-effectiveness, and generalizability of NCM-enhanced telehealth programs among low-income Black and Hispanic stroke survivors with significant comorbidity. TRIAL REGISTRATION/UNASSIGNED:Clinical Trials.gov Identifier: NCT02011685.

The 24-hour day consists of physical activity (PA), sedentary behavior, and sleep, and changing the time spent on one activity affects the others. Little is known about the impact of such changes on cardiovascular risk, particularly in Asian American immigrant (AAI) women, who not only have a higher cardiovascular risk but also place greater cultural value on family and domestic responsibilities compared to other racial/ethnic groups. The purpose of this study was to evaluate the effects of reallocating 30 minutes of each 24-hour activity component for another on BMI, waist circumference, and blood pressure in AAI women. Seventy-five AAI women completed 7 days of hip and wrist actigraphy monitoring and were included in the analysis (age = 61.5±8.0 years, BMI = 25.5±3.6 kg/m2, waist circumference = 85.9±10.2 cm). Sleep was identified from wrist actigraphy data, and moderate-to-vigorous PA (MVPA), light PA, and sedentary behavior identified from hip actigraphy data. On average, the women spent 0.5 hours in MVPA, 6.2 hours in light PA, 10 hours in sedentary activities, and 5.3 hours sleeping within a 24-hour day. According to the isotemporal substitution models, replacing 30 minutes of sedentary behavior with MVPA reduced BMI by 1.4 kg/m2 and waist circumference by 4.0 cm. Replacing that same sedentary time with sleep reduced BMI by 0.5 kg/m2 and waist circumference by 1.4 cm. Replacing 30 minutes of light PA with MVPA decreased BMI by 1.6 kg/m2 and waist circumference by 4.3 cm. Replacing 30 minutes of light PA with sleep also reduced BMI by 0.8 kg/m2 and waist circumference by 1.7 cm. However, none of the behavioral substitutions affected blood pressure. Considering AAI women's short sleep duration, replacing their sedentary time with sleep might be a feasible strategy to reduce their BMI and waist circumference.

BACKGROUND:Women with myocardial infarction (MI) are more likely to have elevated stress levels and depression than men with MI. OBJECTIVES:We investigated psychosocial factors in women with myocardial infarction with nonobstructive coronary arteries (MINOCA) and those with MI and obstructive coronary artery disease (CAD). METHODS:Women with MI enrolled in a multicenter study and completed measures of perceived stress (Perceived Stress Scale-4) and depressive symptoms (Patient Health Questionnaire-2) at the time of MI (baseline) and 2 months later. Stress, depression, and changes over time were compared between MI subtypes. RESULTS:We included 172 MINOCA and 314 MI-CAD patients. Women with MINOCA were younger (age 59.4 years vs 64.2 years; P < 0.001) and more diverse than those with MI-CAD. Women with MINOCA were less likely to have high stress (Perceived Stress Scale-4 ≥6) at the time of MI (51.0% vs 63.0%; P = 0.021) and at 2 months post-MI (32.5% vs 46.3%; P = 0.019) than women with MI-CAD. There was no difference in elevated depressive symptoms (Patient Health Questionnaire-2 ≥2) at the time of MI (36% vs 43%; P = 0.229) or at 2 months post-MI (39% vs 40%; P = 0.999). No differences in the rate of 2-month decline in stress and depression scores were observed between groups. CONCLUSIONS:Stress and depression are common among women at the time of and 2 months after MI. MINOCA patients were less likely to report high stress compared with MI-CAD patients, but the frequency of elevated depressive symptoms did not differ between the 2 groups. Stress and depressive symptoms decreased in both MI-CAD and MINOCA patients over time.

BACKGROUND:Negative emotional eating (EE) is associated with unfavorable behavioral and health outcomes. Understanding its association with positive factors, such as optimism, may shed light into novel interventions. We examined the association between optimism and negative EE in US Caribbean Latinx adults, a population disproportionately exposed to adversity. METHOD/METHODS:This cross-sectional analysis used data from the Latino Health and Well-being Study (21-84 years; n = 579). Optimism was measured with the Life Orientation Test-Revised version. EE was measured with the Three-Factor Eating Questionnaire R18-V2. Adjusted Poisson models with robust error variance estimated prevalence ratios (PR). RESULTS:The proportion of individuals reporting high EE was greater in the low (39.0%) and moderate (36.8%) optimism groups than that in the high optimism group (24.8%; p = 0.011). Individuals with high optimism (vs. low) were less likely to report high EE over no EE (PR = 0.68; 95% CI = 0.53-0.88). CONCLUSION/CONCLUSIONS:High optimism was negatively associated with high EE. Future studies are needed to confirm our findings and test interventions promoting optimism for preventing negative EE in US Caribbean Latinx adults.