Towards an understanding of the biopsychosocial determinants of CVD in SLE: a scoping review

Abstract

Objective

Systemic lupus erythematosus (SLE) is a chronic autoimmune condition with significant physical, mental, psychosocial and economic impacts. A main driver of SLE morbidity and mortality is cardiovascular disease (CVD). Both SLE and CVD exhibit disparities related to gender, race and other social dimensions linked with biological outcomes and health trajectories. However, the biospsychosocial dimensions of CVD in SLE populations remain poorly understood. The objective of this study was to systematically investigate the existing literature around known social factors influencing the development of CVD in SLE.

Methods

A scoping review protocol was developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping reviews guidelines. The search strategy encompassed three main concepts: SLE, CVD and social factors. Four databases were searched (PubMed, SCOPUS, PsychINFO and CINAHL). 682 studies were identified for screening. Articles were screened in two phases (title/abstract and full text) to determine whether they fulfilled the selection criteria.

Results

Nine studies were included after screening. All were conducted in the USA between 2009 and 2017. Six studies (67%) were cross-sectional and three (33%) were longitudinal. Most employed SLE cohorts (n=7, 78%) and two drew from healthcare databases (n=2; 22%). We identified five main themes encompassing social factors: socioeconomic status and education (n=5; 56%), race and/or ethnicity (n=7; 78%), mental health (n=2; 22%), gender (n=3; 33%) and healthcare quality and/or insurance (n=2; 22%). Overall, low income, fewer years of education, black race and/or ethnicity, depression, male gender, lack of insurance and healthcare fragmentation were all associated with CVD risk factors and outcomes in SLE.

Conclusions

While several social factors contribute to CVD in SLE populations, considerable gaps remain as many social determinants remain un(der)explored. There is rich opportunity to integrate social theory, advance conceptualisations of race and/or ethnicity and gender, expand investigations of mental health and explore novel geographical contexts. In healthcare policy and practice, identified social factors should be considered for SLE populations during decision-making and treatment, and education resources should be targeted for these groups.

Correspondence to Dr Emily Shantz; [email protected]

WHAT IS ALREADY KNOWN ON THIS TOPIC

• Cardiovascular disease (CVD) is a primary driver of morbidity and mortality in systemic lupus erythematosus (SLE), and both conditions are associated with social determinants and disparities.

WHAT THIS STUDY ADDS

• This study provides a knowledge synthesis of the known social factors driving CVD in SLE populations. The current literature centres around five themes associated with the development of CVD risk and outcomes—socioeconomic status/education, race and/or ethnicity, mental health, gender and healthcare quality and/or insurance—but gaps remain as other social determinants remain un(der)explored.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• The identified social factors should be considered by healthcare practitioners in the assessment of CVD risk and/or associated treatment, and patient education initiatives should be targeted for these groups. Future research should consider un(der)explored social determinants and social theory, more nuanced conceptualisations of race and/or ethnicity and gender and novel geographical contexts.

Introduction

This paper explores the interconnections between a chronic illness and the risk of cardiovascular disease, as mediated by factors in the social environment. Systemic lupus erythematosus (SLE) is a chronic autoimmune condition resulting in autoantibodies that attack normally healthy organs and tissues. This ongoing inflammation results in a variety of clinical signs and symptoms such as muscle and joint pain, extreme fatigue, UV sensitivity and/or a characteristic butterfly-shaped rash. These symptoms are highly variable from person to person¹ and are often invisible, that is, an observer may not recognise that the individual is ill.² It is well known that SLE may be triggered by stressors, which may be environmental (eg, ultraviolet light)³ or psychosocial (eg, post-traumatic stress disorder) in nature.⁴ In addition to these debilitating and unpredictable physical impacts, patients with SLE also face social limitations,^{2 5} mental health challenges^{6 7} and a variety of direct and indirect economic ‘lifecosts’ related to altered career trajectories, increased healthcare and treatment and decreased quality of life.⁸ SLE affects predominantly young women,⁹ as well as women of colour, who are disproportionately represented,¹⁰ with these patients often experiencing poorer clinical outcomes.^{11 12} Taken together, we characterise SLE as gendered, racialised, invisible, episodic and idiosyncratic. As such, recent literature has begun to view SLE through a bio(psycho)social lens, an approach that considers the intersections of biology, psychology and social systems in the production of health and illness.¹³

A leading cause of morbidity and mortality for patients with SLE is cardiovascular disease (CVD)¹⁴; an estimated 27%–52% of SLE-related deaths are due to CVD.¹⁵ A recent meta-analysis indicates that patients with SLE have at least a twofold greater risk of CVD than populations without SLE, including significantly increased risks of atherosclerosis, myocardial infarction, peripheral vascular disease and heart failure.¹⁶ The increased incidence of CVD in SLE populations has been attributed in part to a number of inflammatory pathways promoting endothelial dysfunction¹⁷ and vascular stiffness¹⁸ including elevated levels of type I interferons,¹⁹ low-density granulocytes,²⁰ autoantibodies²¹ and dyslipidaemia,²² however, the specific aetiology remains unclear.

In the general population, CVD is linked to social and structural determinants (eg, poverty, education, neighbourhood, racism/discrimination).^23–25 These determinants have been shown to drive health behaviours and individual risk that lead to CVD but are also increasingly recognised for direct biological impact as mediated by chronic stress.²⁶ Although SLE populations have significantly elevated risk of CVD events, the contributions of the socioenvironmental context remain poorly understood. Recognising this gap, the objective of this study was to explore and characterise how different social factors influence risk and outcomes of CVD in patients with SLE using a scoping review approach.

Methods

A scoping review was used for this broad research question that has yet to receive extensive attention in the literature. In contrast to other types of reviews, scoping reviews are useful for identifying the types of available evidence, how existing research was conducted, what key factors have been examined and any outstanding knowledge gaps.²⁷ We were guided by Arksey & O’Malley’s methodological framework²⁸ for conducting scoping reviews in conjunction with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping reviews (PRISMA-ScR) guidelines²⁹ to ensure transparency and rigour. A protocol for this review has not been registered or previously published.

Patient

Our research team includes a trained patient partner (CS) with lived experience with SLE. A previously validated integrated knowledge translation (iKT) approach^{30 31} was used in which our patient partner and other members of our multidisciplinary research team provided input and feedback on all stages of design, measurement and evaluation of this research, including the interpretation of results and manuscript preparation.

Search strategy

A search strategy was developed in collaboration with a university librarian (Jackie Stapleton) with extensive experience in conducting and publishing scoping reviews. The search string was developed based on three concepts: SLE, CVD and social factors. For each main concept, a list of relevant search terms was established (table 1). The search terms for CVD were developed in collaboration with one of the authors (MYC), a rheumatologist specialising in SLE. The search terms for social factors were developed based on the social determinants of health framework³² supplemented by key references in the biopsychosocial literature,^{33 34} or biopsychosocial studies focusing on SLE¹³ or CVD.²³ The search strategy was iteratively reviewed by the research team.

Table 1

Search concepts and keywords

Lupus	Social factors	Cardiovascular disease
	General terms
Lupus SLE Systemic lupus erythematosus	Social factors Social determinants Social environment Social conditions Social gradient(s) Social inequities/inequalities	Coronary heart disease Coronary death Coronary insufficiency Coronary artery bypass graft Coronary procedure (eg, bypass, stent) Percutaneous coronary intervention Angina Cerebral infarction Myocardial infarction Transient ischaemic attack (TIA) Ischaemic stroke Ischaemic heart disease Cerebrovascular events Cerebrovascular accidents Stroke Peripheral artery disease Peripheral vascular disease Heart failure Congestive heart failure ST elevation Non-ST elevation Occlusion and stenosis of carotid artery Claudication
	Social determinants of health
	Income Social protection Finances Financial need (Socio)economic status Education School* Degree* College/University Unemployment/Non-employment Job (in)security Work/job/career Food (in)security Nutrition† Diet† Housing/House/Dwelling Environment* Neighbourhood Early childhood/life Social inclusion/exclusion Discrimination Social capital Racism/Race Stigma Social support/cohesion Structural conflict Crime Violence War Health services Health access Health affordability Quality of health services Insurance Hospital* Healthcare* Gender
	Biopsychosocial literature
	Stress Trauma Allostatic load Risk conditions Infrastructure Social services Poverty Social disorder Psychosocial/mental health Occupation Capital (social, economic, human, cultural) Exercise† Physical activity† Obesity† Overweight† Abdominal liposity† Wellbeing†

The table lists the three primary concepts and keywords used to develop the search strategy and resulting search string.

*Indicates keywords excluded from the search to increase sensitivity.

†Indicates keywords included in the search but excluded from later stages of analysis.

Four databases were chosen based on their relevance to the biopsychosocial literature (eg, subject matter is biology, health or social sciences): PubMed, Scopus, PsychINFO, and CINAHL. The four databases were searched from 2000 to 2022 to correspond with the initial publication of the social determinants of health framework³² and the time of searching. Articles were searched in English only due to the language proficiency limitations of the team. The search was limited to peer-reviewed journal articles only. Test searches were performed in conjunction with the librarian to identify and adjust or remove search terms generating non-specific results. A sample search strategy is detailed in figure 1. Searches were conducted in July 2022. Studies identified by the search strategy were imported into Covidence software (www.covidence.org) and duplicate records were removed. A copy of the scoping protocol is available on request.

Figure 1. Sample search strategy. *Multiple character searching. SLE, systemic lupus erythematosus; TIA, transient ischaemic attack.

Study selection

A two-phase screening process was employed: (1) title and abstract screening and (2) full-text screening. Title and abstract screening was conducted in duplicate by the first author and a research assistant using predetermined selection criteria. Included studies were required to address all three of SLE, CVD and social factors and use an adult (>18 years) study population. Paediatric studies were excluded due to differences from adult SLE in aetiology, experiences and health trajectories.^35–37 Animal studies were excluded due to a lack of transferability with respect to social dimensions. Other studies were excluded due to unsuitable study type (eg, clinical case reports, review articles, conference reports, commentaries); wrong population (eg, did not address SLE and CVD), desired outcomes were not measured (eg, outcomes not related to CVD), or desired variables were not measured (eg, variables not related to social factors). The references of relevant reviews were screened for any additional studies not obtained from the initial search.

Screening was performed independently using Covidence and any conflicts were resolved by discussion with the research team. Full-text screening was conducted in duplicate by the first author and at least one other researcher from the team, with each researcher screening a minimum of two studies. Our patient partner participated in the process as a third screener with support from the first author.

A decision was made to modify the selection criteria during full-text screening to focus on ‘first-order’ social determinants (ie, a social aspect of being), rather than ‘second-order’ determinants (ie, a behaviour or state driven by social aspects of being). At this point, we developed a conceptual framework to clearly delineate these terms (figure 2). This framework is informed by and adapted from the socioecological model³⁸ and differentiates between biological factors (eg, age, sex, genetics, hormones, etc), lifestyle and behavioural factors (eg, physical activity, smoking, alcohol and drug use) and social factors (eg, socioeconomic status (SES), race, gender, etc) related to health. While we recognise the complex interconnectedness of these types of factors in constructing health and ill-health, and the various ways that these types of factors influence one another, this scoping review focuses on the broader social determinants as detailed in table 1. As a result of this decision, some previously included concepts (see table 1) were excluded from the final analysis. This process is represented in the PRISMA chart shown in figure 3.

Figure 2. Conceptual framework for the biological, lifestyle and behavioural and social factors influencing health.

Figure 3. PRISMA flowchart of the study selection process. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Data extraction

The data were charted using an extraction template from Covidence. The data were charted independently by the first author (ES) and reviewed by the research team. The following variables were sought during the charting process: country/region in which the study was conducted, theory/framework used, purpose/aim, study design, start/end dates, social variable(s) studied, operational definition(s) of social variable(s) studied, cardiovascular outcomes measured, population description, participant base/affiliation (eg, universities, hospitals, other), participant inclusion/exclusion criteria, total number of participants, key findings, study limitations, study strengths, knowledge translation (KT) plan and coproduction of knowledge (ie, whether knowledge users were included in the research process). Critical appraisal of individual sources of evidence was not performed²⁷ as this was a scoping review.

Data synthesis

The extracted data were analysed thematically and grouped according to the social factors addressed in each article (see table 2). The most salient findings were taken from each study in line with: (1) the article’s original objective and (2) our research objective. The findings from all selected papers were compared, contrasted and synthesised according to theme, and overall results within each theme are presented below.

Table 2

Summary of findings from selected studies

Author(s), year	Themes explored	Study objective	Study population	Methodology	Key findings
Pons-Estel et al, 200944	Socioeconomic status; education; race; gender; other: marital status	To determine the features predictive of atherosclerotic damage in patients with SLE (using SLICC damage index: cardiovascular domain)	LUMINA (Lupus in MInorities, NAture vs nurture) cohort comprised of 637 Hispanic, African-American and white patients who meet at least 4 ACR criteria for SLE, are>16 years, and have disease duration<5 years.	Longitudinal—logistic regression	Male gender was associated with CV damage in univariate and multivariate analyses. Years of education was negatively associated with CV damage.
Scalzi et al, 201050	Race and/or ethnicity	To determine whether racial disparities exist with regard to the age at which patients with SLE experience CVD and CVD-associated death	Clinical records for all adult patients>18 years identified as having SLE by ICD-9 classification were obtained from the Nationwide Inpatient Sample (NIS) database.	Cross-sectional—logistic regression	Black women with SLE were the youngest to experience CVD, while white patients were significantly younger than racialized groups. Black patients were 9.6 years younger than white patients at the time of first CVD hospitalisation. Black women were the youngest to have in-hospital CVD-associated death and had a consistent decline in mortality with age.
Maynard et al, 201246	Socioeconomic status; education; race	To investigate whether education or income levels are associated with cardiovascular risk factors and outcomes in SLE	1752 patients from the Hopkins Lupus Cohort with SLE as diagnosed by the principal investigator who were either white or African American.	Longitudinal—logistic regression	Both income and education were associated with cardiovascular risk factors and outcomes, but these relationships differed for African American and white groups.
Rhew et al, 200949	Socioeconomic status; education; race	To compare traditional and SLE-related risk factors for CVD, and to compare the various measures of subclinical CVD in African American and white women with SLE	309 women from the Chicago Lupus Database and Pittsburgh Lupus Registry who met at least 4 ACR criteria for SLE, were>18 years, and had no history of CVD events. Only African American and white patients included.	Cross-sectional—logistic regression	African American women with SLE are twice as likely to have carotid plaque, and more frequently exhibited traditional risk factors for CVD than white women with SLE.
Tan et al, 201251	Race and/or ethnicity; gender	To compare key clinical characteristics of SLE among male and female patients in a multiethnic population	1979 patients with SLE from the Hopkins Lupus Cohort who were white or African American.	Cross-sectional—comparative	African American men with SLE were more likely than white men with SLE to have CV damage and hypertension.
Jorge et al, 201752	Race; mental health	To evaluate the relationship between depression and progression of subclinical atherosclerosis in women with SLE	149 women with SLE from the SOLVABLE cohort who met at least 4 ACR criteria for SLE and were>18 years. 126 healthy controls were matched by age, ethnicity and zip code.	Longitudinal—logistic and linear regression, multivariate analyses	Patients with SLE had significantly higher depression at baseline than those without. Baseline depression was associated with increased progression of carotid intima-media thickness (CIMT), but not carotid plaque, in the SLE group, and this was independent of traditional risk factors.
Greco et al, 201245	Education; mental health	To evaluate the association between depression and vascular disease in SLE	161 women with SLE from the Pittsburgh Lupus Registry that met at least 4 ACR criteria for SLE, were>18 years, and had no history of CVD.	Cross-sectional – logistic regression	Years of education was associated with vascular disease. Depression was more prevalent among women with SLE who had vascular disease, compared with those without. Patients with depression had nearly 4-fold increased odds of developing vascular disease independent of traditional risk factors.
Lee et al, 200847	Socioeconomic status; education; ethnicity; gender; insurance; other: marital status	To evaluate the effects of treatment and demographic, anthropometric and socioeconomic variables on high sensitivity C-reactive protein (hsCRP) levels as an indicator of cardiovascular risk in SLE	610 patients with SLE from the Hopkins Lupus Cohort who met at least four ACR criteria for SLE.	Cross-sectional—logistic regression	Levels of hsCRP were associated with ethnicity and education level. African-American patients had significantly higher hsCRP levels than other ethnic groups. Patients with high hsCRP levels were more often African American, less educated, lower income and publicly or not insured.
Walunas et al, 201753	Healthcare fragmentation; race; insurance	To examine the impact of healthcare fragmentation (healthcare received from multiple healthcare institutions/ providers) on disease outcomes in patients with SLE.	Clinical records for 4, 276 patients aged 18–69 years that were identified as having SLE by ICD-9 classification, as obtained from the Chicago HealthLNK Data Repository.	Cross-sectional—logistic regression	SLE patients with fragmented care had increased odds of CVD outcomes. African American patients with public insurance and fragmented care were over seven times more likely to develop CVD than the general population, suggesting a relationship between care fragmentation, race and health insurance.

ACR, American College of Rheumatology; CVD, cardiovascular disease; ICD-9, International Classification of Diseases, Ninth Revision; SLE, systemic lupus erythematosus; SLICC, Systemic Lupus Erythematosus International Collaborating Clinics.

Results

The search resulted in 826 records, of which 144 duplicates were removed, leaving 682 studies for screening. After the first phase of title and abstract screening, 13 studies were eligible for full-text screening. Studies were excluded due to irrelevant variables measured (n=3) or ineligible study design (eg, intervention studies) (n=1). A total of nine studies were included for analysis. A summary of the charted data is included in table 2.

Study descriptions

All studies included were conducted in the US between 2008 and 2017. Figure 4 illustrates the trend in publication of included articles over time: most in 2012 (n=3; 33%), 2009 (n=2; 22%) and 2017 (n=2; 22%), with one each (11%) in 2008 and 2010, respectively.

Figure 4. Trends in publication of selected studies over time.

Six studies (67%) employed a cross-sectional design, while the remaining three (33%) were longitudinal. Nearly all used existing SLE cohort populations (n=7; 78%) that were based in universities (n=4; 44%), hospitals (n=1;11%) or regional/city settings (n=2; 22%). One study drew from a regional/city healthcare database (n=1; 11%), while the remaining study drew from national-level insurance database (n=1;11%), reflecting a broader scale.

Study populations

Our selection criteria intentionally selected for study populations of adults >18 years of age living with SLE. Confirmation of SLE diagnosis for participants was described by most studies (n=8; 89%), either by meeting at least four of the American College of Rheumatology criteria for SLE (n=5; 56%),^{39 40} meeting ICD-9 criteria for SLE (n=2; 22%)⁴¹ or diagnosis by a cohort principal investigator (n=1; 11%). Six studies included both men and women (67%), while three were restricted to women only (33%). Other exclusions included patients with rheumatoid arthritis or scleroderma (n=1;11%), patients with a history of CVD (n=2; 22%) and patients who did not identify as either white or African American (n=3; 33%).

Social factors influencing CVD in SLE

We identified five themes encompassing social factors: SES and education, race and/or ethnicity, mental health, gender and healthcare quality and/or insurance. Race and/or ethnicity (n=7; 78%) and SES/education (n=5; 56%) were the most frequently addressed in the context of CVD and SLE, followed by gender (n=3; 33%), mental health (n=2; 22%) and healthcare quality and/or insurance (n=2; 22%). As this was a scoping review, please note that all population labels used below are taken directly from the published manuscripts and reflect the language used in each original study. (The exception to this is articles that used the language “Caucasian”, which has been change to “white” in recognition that the aforementioned term has been discontinued.)

Socioeconomic status and education

SES is an important indicator of health, defined as the sum of an individual’s combined economic and social status.⁴² Thus, SES comprises a number of factors including income, education, occupation/work, social class, relative poverty, etc.⁴³

In a multivariate analysis of a multiethnic cohort by Pons-Estel et al,⁴⁴ patients with SLE with fewer total years of education were more likely to have cumulative cardiovascular damage defined as one or more of: (1) angina or coronary artery bypass surgery, (2) heart failure and (3) myocardial infarction lasting more than 6 months (OR=0.85). Similar results were reported by Greco et al,⁴⁵ who found that total years of education (≤12 years or ≥12 years) were negatively associated with vascular disease (OR=0.80) assessed by the presence of subclinical coronary artery calcification and/or carotid artery plaque.

In an analysis by Maynard et al,⁴⁶ both education and combined household income were associated with cardiovascular risk factors and outcomes in individuals with SLE, although this relationship was different for the racial/ethnic groups studied. Overall, the lowest income group (<US$25 000 per year) were more likely to smoke tobacco (OR=2.31 for white; OR=3.64 for African American) and experience cerebrovascular incident (OR=2.85 for white; OR=1.66 for African American) compared with the middle (US$25 000–60 000 per year) and upper (>US$60 000 per year) income tertiles. The lowest income group of white background was more likely to be obese (body mass index (BMI) >27.8 kg/m² for men; >27.3 kg/m² for women) (OR=1.65) and/or experience myocardial infarction (defined using Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) damage index) (OR=3.24), while the lowest income African Americans had a higher frequency of hyperlipidaemia (cholesterol >200 mg/dL) (p=0.04) when compared. When multivariate analysis was performed for the white patients with SLE, a significant graded relationship was observed between income and risk factors such as smoking, hypertension, hyperlipidaemia and diabetes (according to American Diabetes Association criteria) as well cardiovascular outcomes such as myocardial infarction and cerebrovascular incidents. While this relationship was not seen in the African American patients with SLE, lower income was associated with diabetes and smoking in this population.

Lee et al⁴⁷ investigated the relationship between socioeconomic factors and levels of highly sensitive C reactive protein (hsCRP), which this study considers to be indicator for CVD risk.⁴⁸ Median hsCRP levels were significantly higher in patients with less education (high school or less, compared with college and above) and lower income (<US$25 000 per year) and individuals with high hsCRP (>3.0 mg/L) were more often from these groups. Taken together, these findings indicate that individuals with SLE who are lower income and lower education are at overall higher risk for developing CVD.

Race and/or ethnicity

The findings by Maynard et al⁴⁶ described above found that while SES was indeed associated with CVD in SLE, this relationship was altered when stratified by racial/ethnic groups. Specifically, while the lowest income white group had an increased frequency of obesity, the lowest income African American group exhibited higher rates of hyperlipidaemia. Building on these results, four additional studies examined such relationships.

In a study cross-sectional study of African American and white women with SLE, Rhew et al⁴⁹ found that African American women with SLE were more than two times as likely to have subclinical carotid plaque than their white counterparts and had significantly higher levels of lipoprotein A and C reactive protein in the blood. Furthermore, they had higher blood pressure, corticosteroid use, disease damage (measured by SLICC Damage Index) and disease activity (measured by SLEDAI), all of which increase overall risk for CVD.

Scalzi et al⁵⁰ found similar results in their cross-sectional study of racial disparities in age at cardiovascular events and/or CVD-associated hospital death. White patients with SLE were significantly older than black, Hispanic and other racial groups at the time of cardiovascular events and/or related deaths, although this relationship was not significantly different between the white and Asian groups (mean age at CVD-related death=67.1 years for white; 52.8 for black; 62.0 for Hispanic; 63.8 for Asian; 63.5 for other). The greatest disparity was between white and black SLE populations, as black patients with SLE were, on average, 9.6 years younger at the time of hospitalisation for CVD. When categorised by age group, 55% of black women with SLE were admitted to hospital for CVD in the youngest age group (<55 years), compared with 41% Hispanic women, 33% Asian women and 26% white women with SLE. Overall, black race was independently associated with poorer health trajectories and outcomes in the context of SLE and CVD.

In a cross-sectional study of both men and women with SLE, Tan et al⁵¹ found that African American men were more likely to have cardiovascular damage, as assessed by both laboratory and clinical features, than white men. Lee et al⁴⁷ further found that levels of hsCRP were elevated in African American patients with SLE (median 3.70 mg/L) relative to white (median 1.70 mg/L), Asian (median 1.30 mg/L) and Hispanic (median 0.90 mg/L) ethnic groups, indicating increased CVD risk.

Only one study found no association between Hispanic, African American or white populations and cardiovascular damage in a longitudinal SLE cohort.⁴⁴

Mental health

Two studies investigated the relationship between mental health, specifically depression, and the progression of subclinical vascular disease among individuals with SLE.

In a cross-sectional study, depression was more prevalent among women with SLE and vascular disease as compared with those without vascular disease.⁴⁵ Those patients with SLE with depression had nearly fourfold greater odds of vascular disease and this was independent of traditional risk factors. Given that these relationships remained relatively unaltered after adjusting for other covariates, the authors concluded that depression has an independent role in the development of CVD in SLE.

A similar study revealed that depression was associated with increased progression of carotid intima-media thickness over the next 5 years in the SLE group, independent of traditional risk factors.⁵²

Gender

Three studies referenced gender as a variable; both found that men with SLE experienced more frequent and severe CVD outcomes than women. While Pons-Estel et al⁴⁴ found that male gender was independently associated with cardiovascular damage (p<0.0006), Tan et al⁵¹ found that men were more likely to have hypertension as a risk factor (OR=1.8) as well as cardiovascular outcomes such as angina (OR=2.2), myocardial infarction (OR=2.5) and venous thrombosis (OR=2.9). Lee et al⁴⁷ did not observe significant differences between hsCRP levels according to gender.

Two studies explored the impacts of healthcare quality and/or health insurance on CVD risk and outcomes in SLE. Walunas et al⁵³ investigated how healthcare fragmentation—receiving care at multiple institutions or from multiple providers—impacts disease outcomes in SLE. Healthcare fragmentation is thought to put patients at greater risk for poor health outcomes due to the obstruction of information exchange, communication and coordinated decision-making by healthcare teams, thereby exacerbating existing inequalities or disparities in care quality. Indeed, patients with SLE who experienced care fragmentation more frequently developed SLE than those who did not. This was further compounded by issues of race and health insurance, as African American patients with public insurance and fragmented care were over seven times more likely to develop CVD than the general population.

This notion was reflected by findings from Lee et al⁴⁷ that patients with SLE with public or no insurance tended to have elevated levels of hsCRP compared with those with private insurance.

Discussion

Summary of key findings

Five broad social themes emerged from this scoping review in connection to CVD in SLE: SES/education, race and/or ethnicity, mental health, gender and healthcare quality and/or insurance. Specifically, low income, fewer years of education, black race and/or ethnicity, depression, male gender, lack of insurance and healthcare fragmentation were all associated with the development of cardiovascular risk factors and outcomes. Other social determinants of health found in the Marmot framework³²—including stress, early life, social exclusion, work, unemployment, social support, substance use, food security, transport, housing, political conflict, and health services access—though interconnected with the identified themes—were not directly addressed in the literature in the context of SLE and CVD.

All studies employed a quantitative methodology. None described a theoretical framework, inclusion of knowledge users or other KT approaches, although all did address the clinical implications stemming from their results. There is clear opportunity for future studies to expand this line of inquiry by first integrating social theory. As Nancy Krieger reminds us, without theory observation is blind and explanation is impossible.⁵⁴ In addition, a more comprehensive story of CVD and SLE could be told using qualitative and/or mixed methods. Innovative qualitative methodologies such as oral histories and photovoice are unique lenses into the complex web of factors shaping chronic illness.^{55 56} Such methodologies have the potential to not only describe what happens but also how it happens: in the case of CVD for patients with SLE, qualitative methods may provide additional insight into the historical and ongoing experiences of racism, gender discrimination, poverty and mental illness, for example, and how these social processes literally ‘get under the skin’ with biological repercussions.⁵⁷ Furthermore, the involvement of knowledge users in the production of knowledge has been shown to effect greater change—and better science—given regular input into the research process.^{31 58} This is indeed the strategy used by the research team undertaking this scoping review.

Social factors in SLE and CVD

Four studies examined the relationships between SES, SLE and CVD, and three of these studies were in accord that low SES increases risk of CVD. Notably, all four studies used education as an indicator of SES, and only one used measures of income. These findings are unsurprising, given the associations of low SES with poorer SLE outcomes over the disease course⁵⁹ and similar relationships demonstrated among other chronic conditions.^60–62

Race and/or ethnicity was the most widely studied theme and while racialised individuals with SLE were all at higher risk of CVD than white SLE groups, African American and black populations consistently fared worst. This is in line with similar investigations of racial inequities morbidity and mortality in pregnancy,⁶³ cancer⁶⁴ and COVID-19,⁶⁵ among others, in the general population. In SLE, these results may be in part due to these individuals experiencing greater SLE-related organ and tissue damage,⁶⁶ but likely also reflect the systemic racism experienced by these groups both in healthcare systems⁶⁷ and societally.^{68 69} In contrast to its widespread investigation, there was little clarity in how race and/or ethnicity was defined and operationalised, nor was there discussion of both race and ethnicity as social constructs ‘without scientific or biological meaning’.⁷⁰ The exploration of racial/ethnic identities was also limited: of the studies that included race and/or ethnicity as a variable, three restricted their analyses to African American and white participants only.^{46 49 51} Three additional studies expanded this to include Hispanic populations^{44 50} and only two included categories for Asian/Pacific Islander and ‘other’.⁴⁴ A notable gap was representation of Indigenous Native American populations, for whom SLE is more common and more severe,⁷¹ and whose experiences are further compounded by the intergenerational impacts of colonisation and resulting barriers to healthcare access.^{72 73} Future studies should address these gaps, and endeavour to (1) adopt more nuanced definitions of race and ethnicity⁷⁰; (2) broaden analyses to additional racialised groups, including individuals identifying across multiple minority groups⁷⁴; and to this end, (3) engage with theories of intersectionality.^{75 76}

Although two studies reported gender differences in the development of CVD in SLE, the results remain somewhat inconclusive as it is unclear whether the variables studied were, in fact, self-identified or self-reported gender—a social construct—or biological sex. Given the established links between SLE and female hormones,⁷⁷ there are likely to be sex-based differences; however, the role of gender is more convoluted. Future studies could address this through adopting broader views of gender outside of the gender binary, and how this influences SLE and/or CVD experiences and health trajectories. As outlined above, future socially rooted studies should draw on feminist theorisations of intersectionality⁷⁸ to better account for the effects of gender in conjunction with other concomitant identities. Nonetheless, these study findings report that, importantly, men with SLE are at particular risk for CVD, delineating important implications for clinical practice.

It has been well established that patients with SLE face a number of mental health challenges, which may reflect neuropsychiatric manifestations of the condition⁷⁹ or psychosocial stress.⁸⁰ Although two studies explored this theme, the only mental condition examined was depression. Patients with SLE are indeed at higher risk of developing depression than the general population,⁸¹ and the literature has established links between depression and CVD in other contexts.^{82 83} However, individuals living with SLE are also particularly vulnerable to developing anxiety,⁸⁴ cognitive impairment and other mental disorders, which are associated with heightened morbidity and mortality from CVD. These relationships should additionally be explored to support better prediction of risk as well as to inform screening, intervention and treatment.

Expanding geographical analysis

All of the studies included for the analysis were based on the USA and used American populations. There was some geographic variation across the country, as studies drew on SLE cohorts primarily from the northeast,^{45–47 49 51–53} with some representation from southern states⁴⁴ as well as a national sample from an insurance database.⁵⁰ Taken together, this set of studies provides some insight into how these effects pervade distinct environments with their own social structures, geo-political influences and cultural norms; in particular, the organisation of healthcare systems and health insurance appears to play a particular role in SLE/CVD trajectories. However, such social systems and influences are necessarily shaped by place and as such may have differential effects based on the context. Furthermore, SLE is a demonstrated global health issue, affecting individuals worldwide.^{85 86} Thus, the expansion of similar research into novel geographical settings is needed.

Inferring causal mechanisms

A notable limitation of the selected studies is that while important connections are made between the social environment, SLE and CVD, insight into the causal mechanisms of this interplay remains to be elucidated. There is growing interest in social epigenetics, chronic stress and allostatic load as possible mediators of these processes.^{13 87 88} While current evidence demonstrates how acute and chronic stress promote inflammatory atherosclerotic processes,²⁶ these processes are not yet well understood, and additional work is required to disentangle these systems in the context of SLE.

This scoping review has several strengths. First, the search string developed captures not only the established social determinants of health³² but also other important CVD determinants reported in the bio(psycho)social literature.^{23 33 34} Given our iKT approach, a transdisciplinary team of experts—including an SLE physician and patient partner—provided input and feedback at all stages of the research process, including identifying other contributing factors to add to the search strategy. Including knowledge users on our research team was effective in both developing a robust study design, but perhaps more importantly, ensuring that our research results were useful, useable and meaningful.³¹ As our review was guided by an established framework²⁸ and PRISMA-ScR guidelines,²⁹ we have ensured rigour and reproducibility.

There are some limitations as well. First, due to the language abilities of the research team, our search was limited to articles in English only; therefore, it is possible that additional articles in other languages and contexts were not accessible. Due to the timing of data collection and analysis, any articles published past 2022 were not included. Studies examining paediatric SLE were also excluded from the dataset as these conditions exhibit different aetiologies³⁶; therefore, these patients are not represented in the analysis. Finally, although every effort was made to ensure the robustness of our search, some relevant articles may not have been captured due to the keywords and/or filters used.

Conclusions

As CVD is the leading cause of death for patients with SLE, there are important implications for policy and practice. Those with SLE who are men, belong to racialized groups, have low SES/education or live in low SES regions and/or have a history of depression are at particular risk of CVD and should be targeted by healthcare professionals for early preventative therapy and risk monitoring. In line with the most recent guidelines from the American College of Cardiology, these characteristics should be considered as ‘risk enhancing factors’ in clinical practice and inform decisions about treatment for at-risk individuals.⁸⁹ Moreover, patient education initiatives about the risks of CVD and evidence-informed management strategies should be developed and tailored towards these groups. Identifying at-risk SLE populations may also be an effective step towards developing social interventions, in line with recent advances in social prescriptions^{90 91} to reduce morbidity and mortality and increase quality of life for those living with SLE.

This review underscores that there is much work to be done in this area; particularly, work that employs alternative epistemologies, is theoretically informed, and in partnership with knowledge users.

We gratefully acknowledge Jackie Stapleton, Librarian at the University of Waterloo for her expertise and guidance on developing the scoping review search strategy, and Annabel Jefferies for her assistance in screening.

Data availability statement

Data are available upon reasonable request. The scoping review protocol and associated data including records retrieved, records excluded and all charted data are available upon reasonable request from the first author ([email protected]).

Ethics statements

Patient consent for publication

Not applicable.

Ethics approval

Not applicable.

Footnote

Contributors All authors contributed to conceptualising the study and its methodology. Funding was acquired by MYC and SJE. The project was administered by ES including data collection and analysis. MYC, SJE, KB and CS all assisted in full-text screening and decision-making related to inclusion and exclusion criteria. SJE and MYC supervised the study. ES was responsible for writing the original draft of the manuscript, and all authors contributed to processes related to review, revising and editing. All authors approved the final draft of the manuscript. ES is the guarantor.

Funding Financial support of this study was provided by the Canadian Institutes for Health Research (CIHR) (Funding reference number: PJT-17836) and the National Institutes of Health (Funding reference number: K24AR066109). ES was supported by a Social Sciences and Humanities Research Council (SSHRC) Doctoral Fellowship. This work is based on the first author’s doctoral thesis.

Competing interests None declared.

Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

Provenance and peer review Not commissioned; externally peer-reviewed.

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