Cardiometabolic disease (CMD) is a complex pathophysiological syndrome characterized by progressive abdominal adiposity, dyslipidemia, hypertension, and insulin resistance [1,2]. It is well established that CMD heightens the risk for cardiovascular disease (CVD) [3]. Individuals with CMD have a 2-fold risk of mortality from coronary artery disease and a twice greater risk of stroke [4]. In recent years, the prevalence of CMD in women has risen drastically in comparison to men [3], and the risk increases with age [5]. Studies demonstrate that females experience more sex-specific risk factors that increase adiposity [6], resulting in greater risk for CMD [7,8]. Furthermore, CMD is disturbingly prevalent in African American women; for example, 55% of non-Hispanic Black women in the United States are obese [9], 43% have hypertension [10], and 13% have been diagnosed with diabetes mellitus [11]. While CVD mortality has declined in the United States, these same reductions have not been seen in African American women who continue to experience a disproportionate CVD burden compared to their White counterparts, even after controlling for traditional risk factors, such as smoking and weight [12].

Numerous studies link higher levels of psychosocial stress to both CMD and CVD [13-17]. Recent evidence demonstrates that stressful life events, including experiencing racism and perceived discrimination, play a substantial role in contributing to inflammatory diseases, such as CMD [18,19]. African Americans who reported a history of experiencing racism had a significantly greater incidence of carotid artery plaque [20] and hypertension [21] than those who did not. African American women experience greater social stress from exposure to both racism and sexism [22,23]. Furthermore, low socioeconomic status may contribute to chronic stress in African American women, thereby increasing the risk of CMD [24]. Adaptive coping (seeking social support, problem-solving, and resistance to racism) may reduce stress-related symptoms (current perceived stress, depressive symptoms, fatigue, and sleep disturbance) and inflammatory burden [25-27] and moderate the impact of racism on well-being and health [28-30]. Furthermore, evidence demonstrates that there are sex differences in the types of coping strategies used, particularly in response to racial discrimination; for example, while men tend to use suppression and distraction, women are more prone to rumination [31]. Importantly, individuals can learn adaptive coping strategies that result in decreased stress-related symptoms [32], inflammatory burden (ie, proinflammatory cytokines) [33], and CVD [34].

Despite evidence that chronic stress associated with experiencing racism, discrimination, and sexism increases the inflammatory response, few evidence-based interventions are available to assist individuals from minoritized communities in coping with the chronic stress related to their racial or ethnic identity. Interventions to assist individuals in managing chronic stress, such as mindfulness-based stress reduction (MBSR) and cognitive behavioral therapy (CBT) do not address trauma related to experiencing racism and discrimination [35]. Furthermore, MBSR and CBT do not specifically address race-based stressors. To date, only 3 published interventions address coping with discrimination; 2 interventions focus on coping related to discrimination experienced by individuals positive for HIV [36], and the other addresses racial socialization within Black families [37]. However, none of these interventions specifically address racism and discrimination experienced by African American women at risk for CMD. As research related to discrimination grows, there is a significant need for evidence-based interventions to address the psychobiological and health consequences of discrimination at the individual level [38].

Our proposed randomized controlled trial (RCT) will test a race-based intervention tailored to African American women, called Resilience, Stress, and Ethnicity (RiSE) [35] (Motley D, unpublished data, November 2017). In this group-based, 8-week intervention, cognitive behavioral and stress reduction strategies will be integrated [39] focusing on the biopsychosocial effect of racism [40,41], racial identity development [42-44], and empowerment [45]. Table 1 presents the schedule of enrollment, interventions, and assessments for the study.

Our previous pilot study found that RiSE improved the ability of African American women to cope with racism and increased the use of adaptive coping strategies through emotional validation and cognitive restructuring of the response to racism and discrimination [35]. However, no research has examined RiSE as an intervention for the reduction of stress-related symptoms and inflammation in African American women at risk for CMD. The psychobiological impact of RiSE and its potential to reduce health risks may improve the health of many minoritized groups who endure chronic discrimination and racism [35]. Importantly, our study addresses the impact of racism on the individual that has not previously been addressed by other interventions.

On the basis of our preliminary data as well as evidence from other stress reduction interventions [46,47], we propose that RiSE will improve stress-related symptoms by providing access to coping strategies that may decrease inflammation (as indicated by biomarkers such as C-reactive protein [CRP], interleukin-6 [IL-6], tumor necrosis factor–alpha [TNF-α], interleukin-1beta [IL-1β], and interferon-gamma [IFN-γ]). Our pilot data indicate that RiSE attenuates maladaptive coping [48]. Adaptive coping, such as seeking social support and active coping, has been found to lessen the harmful effects of perceived discrimination and racism on the health of minoritized groups [49,50]. Furthermore, adaptive coping is related to well-being and lower levels of inflammation [51].

Our conceptual model (Figure 1) is based on allostatic load theory [52], which posits that chronic stressors produce wear and tear on the body through prolonged hyperactivity or hypoactivity of adaptive physiological systems.

There are 3 types of responses to stressors: frequent activation of the stress response (eg, responding to the frequency and severity of a stressor), failed response (eg, chronic response where the body is unable to stop reacting to the stressor), and inadequate response (eg, the body has little to no response to the stressor) [52]. Our model proposes that psychosocial stressors, such as discrimination, racism, and social context (eg, socioeconomic precarity) when chronic, repeated, and overbearing, may heighten inflammation [53-55].

In this paper, we present a research protocol for the primary aim: to investigate the impact of RiSE on the response to chronic psychosocial stressors and inflammation. The subaim is to explore the impact of RiSE on adaptive coping (ie, problem- and emotion-focused coping strategies, such as positive mindset reframing and venting) versus maladaptive coping strategies) [55]. We hypothesize that women who participate in the RiSE intervention will exhibit decreases in stress-related symptoms (current perceived stress, depressive symptoms, fatigue, and sleep disturbance) as well as decreases in inflammatory burden (as indicated by biomarkers such as IL-6, TNF-α, IL-1β, IFN-γ, and CRP) compared to women in the health education program (HEP), which is the active control arm. For the subaim, we anticipate that women who participate in the RiSE intervention will report an increase in the use of adaptive coping strategies (seeking social support, problem-solving, and resistance to racism) and a decrease in the use of maladaptive coping strategies (avoidance and internalizing racism). This work is innovative because we are working to add resources to the toolbox of minoritized groups to increase resiliency in the face of racism at the interpersonal level. Although successful in some populations and types of stress-related conditions, CBT and MBSR were not specifically developed to reduce the impact of racism and discrimination [35]. RiSE has the potential to reduce the psychobiological consequences of racism and discrimination. This research study should aid in the continuing efforts of researchers to provide tools, which can be implemented as necessary, to groups considered marginalized.

This study was approved by the Loyola University Chicago Health Sciences Institutional Review Board (LU214133) and the WCG Institutional Review Board (20230283). Eligible and willing participants will provide written informed consent. Participants can choose to opt out at any point during the study. All data are deidentified. Given the extent of participant involvement, we ensured fairness in the compensation process. The participants can be compensated up to US $500 in electronic Amazon gift cards. Compensation transparency is ensured. The recruitment flyers, telephone screen, and consent form all contain the mode of compensation and the amount. The study has been registered at ClinicalTrials.gov (NCT05902741).

In this RCT (stage II [traditional efficacy testing] of the National Institutes of Health Stage Model for Behavioral Intervention Development [56,57]), we will determine the effectiveness of the 8-week, group-based RiSE program (intervention) in improving stress-related symptoms (current perceived stress, depressive symptoms, fatigue, and sleep disturbance), reducing inflammatory burden, and improving coping strategies from baseline to after the intervention in African American women aged 50 to 75 years at risk for CMD. This age range was chosen because women develop a higher risk for CMD [58] during perimenopause [59]. We are excluding women aged >75 years to control for the effects of older age on inflammation and DNA methylation [60,61]. Outcomes from the intervention group (RiSE) will be compared to those from the active control group (HEP). Figure 2 presents the overview of the study design.

We will recruit 300 African American women at risk for CMD from 2 large metropolitan cities in the United States (Chicago and New York City). Both communities are ethnically and racially diverse with relatively large African American populations [62,63].

We will use several recruitment strategies. First, we will work closely with key trusted community leaders (eg, church leaders) to promote the study. This strategy is particularly effective in recruiting people from minoritized communities in clinical trials [64,65]. In addition, we will meet regularly with our community advisory board, made up of individuals from the surrounding community, for suggestions on how best to recruit potential participants. We will send recruitment letters describing the study to African American women (aged 50-75 y) who broadly meet eligibility criteria (eg, no history of myocardial infarction or ischemic stroke) from our respective hospital databases. In addition, we will recruit women through community clinics, churches, health fairs, hair salons, social media, newspaper advertisements, and word of mouth. The use of proven recruitment and retention strategies for research participants from minoritized communities [64,66,67] will also be advantageous for this study. These efforts include sharing health information about CMD, engaging community representatives through the sharing of health information, and providing cultural sensitivity training for the study team [68-70]. Potential study participants will be prescreened for eligibility over the telephone. An appointment will be scheduled for further screening for those meeting the study eligibility criteria. Textbox 1 presents detailed inclusion and exclusion criteria.

Participants will be assessed for CMD risk. They will also be assessed for cognitive impairment using the 3-item Brief Screen for Cognitive Impairment [71]: a total score of ≥8, which suggests cognitive impairment, will lead to the exclusion of the participant from the study. All ineligible participants will receive a gift card (US $10) after the screening. Baseline measures will be collected after the screening.

After the baseline interview (T0), eligible participants will be randomized 1:1 to RiSE or HEP, with each wave of enrollment treated as a block. The randomization plan (PROC PLAN) generated in SAS 9.4 (SAS Institute Inc) includes the site as a stratifying variable, and we plan for each site to have at least 6 RiSE and 6 control participants per wave. Patient registration data, group assignment, and self-report survey data will be managed via a single REDCap (Research Electronic Data Capture; Vanderbilt University) server with access for both sites.

Assessments are completed face-to-face in a private room of our research building. At each of the 4 assessment points (T0: baseline, T1: midintervention; 4 wk, T2: intervention completion; 8 wk, and T3: 6 mo after intervention completion), trained interviewers will collect the following anthropometric measurements: 3 blood pressure readings, waist and hip circumference, weight, height, body fat percentage, and body water percentage. Data on psychosocial factors, health behaviors, and medical history will be collected using an audio computer-assisted self-interview system [72] and REDCap surveys. In addition, we will collect saliva samples using a passive drool kit to measure participants’ inflammatory burden (as indicated by biomarkers such as CRP, IL-6, TNF-α, IL-1β, and IFN-γ) [46,51,73-82]. At T0 and T3 (ie, baseline and final assessment; 6 mo after intervention completion, respectively), we will collect participants’ saliva samples using the Oragene DNA kit (DNA Genotek) to measure DNA methylation [68]. Study participants will receive a gift card (US $50) after the completion of each interview (T0-T3).

The outcome variables for the trial include stress-related symptoms (current perceived stress, depressive symptoms, fatigue, and sleep disturbance) and inflammatory burden (as indicated by biomarkers such as IL-6, TNF-α, IL-1β, IFN-γ, and salivary CRP; Table 3). Each of these variables will be collected at 4 time points: T0, T1, T2, and T3.

We will enroll 300 participants and anticipate that at least 250 (n=125, 50% per arm) will have the 6-month postintervention follow-up data. For the primary end point of the Perceived Stress Scale (PSS), this sample size has >80% power to detect a 3-point difference in mean PSS scores at follow-up using an F test in an analysis of covariance. This assumes the R-squared value of 5 covariates, including baseline PSS, to be 0.3 and uses a significance level of α=.05. This calculation conservatively estimates the SD of PSS to be 10 points. Initial psychometric studies and norm groups analysis of the PSS reported SDs of 7.2 points in African Americans; relevant to the RiSE study, group SDs ranged from 6 to 10 points from a pilot trial involving African Americans with hypertension [127]. At this sample size and with similar design assumptions, effect sizes were estimated using the RiSE pilot study for the hypothesized mediator of coping as well as biomarkers [48]. The estimates from the analysis of covariance (Table 4) represent the lower limits for power because the mixed model approach that incorporates all time points may be more powerful in detecting meaningful differences.

This study proposes to examine the effect of a race-based stress reduction intervention, called RiSE, on stress-related symptoms, coping, and inflammation in older African American women at risk for CMD. We anticipate that participants completing the RiSE program will have decreased stress-related symptoms, improved adaptive coping, and decreased inflammatory burden compared to those randomized to the active control group (HEP).

Racism is dangerous, pervasive, and unfortunately a growing problem in the United States. A third of African Americans report experiencing a race-related incident in the past year [128]. Undeniably, racism needs to be addressed at the interpersonal, community, and societal levels. However, until such time, ways to reduce the impact of racism on psychological and physical health at the individual level must be developed and tested. The RiSE intervention may accomplish this goal. It reduces stress and has the potential to reduce the psychobiological consequences of racism and discrimination, leading to decreased inflammation and ultimately contributing to lowered CMD and CVD risk in African American women. In sum, despite evidence that experiencing racism and perceived discrimination heightens the inflammatory response and CMD [19,53], few evidence-based interventions are available to help individuals from minoritized communities cope with unique stressors related to their racial or ethnic identity. There is evidence that health behaviors [129], early life adversity [130,131], and ethnic identity [132-134] may impact the relationships among chronic stressors (perceived discrimination, racism, and subjective social status) and the psychological and inflammatory response to stress.

The proposed study has some limitations that should be recognized. As with most RCTs, challenges related to recruitment and retention are anticipated. In response, we have developed a detailed recruitment plan supported by our community advisory board as well as strategies to minimize attrition, including immediately contacting participants who miss program classes or data collection visits as well as providing fair compensation. In addition, generalizability is a potential limitation of this study. Future work will examine RiSE in additional populations. Despite these challenges, this study will be one of the first to examine a race-based stress reduction intervention in African American women and has the potential to improve the health of minoritized groups faced with the chronic stress associated with experiencing racism and discrimination [35,39-45,48,55] (Motley D, unpublished data, November 2017). In addition, RiSE is being offered via Zoom, which may allow participants who cannot travel or have caregiving responsibilities the opportunity to participate in the program. If RiSE is found to be effective in older African American women, future research may consider evaluating RiSE in other populations, such as younger African American women as well as men.