Article Text

Original research
Prevalence of major adverse cardiovascular events among Saudi patients with systemic lupus erythematosus compared with the general population: updates from the national SLE and PURE cohorts
  1. Ibrahim Almaghlouth1,
  2. Kawther Ghassan Bohuliga1,
  3. Boshra Alanazi1,
  4. Bushra Khaled Alhawsa1,
  5. Abdulaziz Mohammed Alabdulkareem1,
  6. Wael Alqarawi2,
  7. Kazi Nur Asfina3,
  8. Najma Khalil3,
  9. Hebatallah Hamed Ali3,
  10. Mohammed Bedaiwi1,
  11. Aos Aboabat1,
  12. Jiandong Su4,
  13. Tariq Asef Alam5,
  14. Fehaid Ghali Alanazi1,
  15. Mohammed A Omair1,
  16. Abdurhman S Alarfaj1,
  17. Haya M Almalag6,
  18. Mostafa Al Shamiri2 and
  19. Khalid F Alhabib2
  1. 1Rheumatology Unit, Department of Medicine, King Saud University, Riyadh, Saudi Arabia
  2. 2Department of Cardiac Sciences, King Fahad Cardiac Center, College of Medicine, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
  3. 3College of Medicine Research Centre, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  4. 4University Health Network, University of Toronto, Toronto, Ontario, Canada
  5. 5Emergency Medicine, Norfolk and Norwich University Hospital, Norwich, UK
  6. 6Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
  1. Correspondence to Dr Haya M Almalag; halmalaq{at}


Objective This study examined the prevalence of major adverse cardiovascular events (MACE) among Saudi patients with SLE and the general population and considered factors associated with such outcomes were taken into consideration.

Methods This is a cohort study evaluating the period prevalence of MACE from 2020 to 2023. The study used two datasets, namely the Saudi national prospective cohort for SLE patients and the Prospective Urban-Rural Epidemiology Study Saudi subcohort (PURE-Saudi) for the general population. Participants in both studies were monitored using a standardised protocol. MACE was defined as myocardial infarction (MI), stroke or angina. The analysis was adjusted for demographics, traditional cardiovascular risk factors and SLE diagnosis through logistic regression models.

Results The PURE and national SLE cohorts comprised 488 and 746 patients, respectively. Patients with SLE from the SLE cohort were younger (40.7±12.5 vs 49.5±8.6 years) and predominantly female (90.6% vs 41.6%). The prevalence of traditional risk factors was greater in the PURE cohort compared with the SLE cohort. These factors included dyslipidaemia (28.9% vs 49.4%), obesity (63% vs 85%) and diabetes (7.8% vs 27.2%), but not hypertension (19.3% vs 18.8%). MACE (defined as MI or stroke or venous thromboembolism or heart failure) occurred more frequently in patients with SLE (4.3% vs 1.6%, p=0.004). Older age and lupus diagnosis were independently associated with MACE after adjusting for conventional risk factors. The odds of MACE were significantly related to age and lupus diagnosis (p=0.00 and p=0.00, respectively), but not cardiovascular disease (CVD) risk factors (p=0.83).

Conclusion Patients with SLE have a significantly higher risk of developing MACE than the general population. This risk is not well explained by traditional risk factors, which may explain the failure of CVD risk scores to stratify patients with SLE adequately. Further studies are needed to understand CVD risk’s pathogenesis in SLE and mitigate it.

  • Prevalence
  • Cardiovascular Diseases
  • Lupus Erythematosus, Systemic

Data availability statement

Data are available upon reasonable request.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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  • Patients with inflammatory and autoimmune disorders have a higher risk of cardiovascular disease (CVD), warranting preventive measures. All genetically linked populations should be studied to understand the variations in prevalence, thus modifying prevention and management accordingly.


  • It provides baseline information and documentation of the prevalence of CVD in an understudied population.


  • This study could inform the customisation of preventive measures against the development of CVD in the Saudi population with SLE.


SLE is a chronic, multisystem disease associated with an increased risk of organ damage and mortality.1 Cardiovascular diseases (CVDs) are a major cause of death.1–3 The impact of CVDs on lupus mortality appears to follow the late peak of the bimodal distribution of mortality, as described by Urowitz et al.4 However, the odds of CVD events appear to be much higher in younger individuals than in the general population. This finding supports the hypothesis that the pathogenesis of CVD in SLE is heterogeneous.5 6 Both accelerated atherosclerosis and thrombosis are well-known contributors to the development of CVDs among patients with SLE.7 8 Furthermore, racial background may influence the risk of CVDs.9 For example, in a population-based cohort study using the Georgia Lupus Registry, patients with SLE were found to have a sevenfold higher risk of developing CVD within the lupus population if they were of black ethnicity compared with non-black ethnicity.9 These findings reflect the interplay between the genetic predisposition to CVD and SLE-related racial disparities in disease severity and remission patterns.10

However, little is known about the risk of major adverse cardiovascular events (MACE) in Saudi patients with lupus. The Saudi population is unique because it has a high level of inbreeding and a high prevalence of diabetes and obesity.11 12 Furthermore, the population is largely homogenous with a unique Arab ethnic background.13 All these factors could increase the risk of CVD in the general population and may have an adjusting effect in the SLE population. This study aimed to compare the prevalence of MACE in Saudi patients with SLE with that in the general population and to examine the factors associated with such outcomes.


Study design and setting

This study was the result of two prospective cohorts that assessed the period prevalence of any MACE in patients with SLE enrolled in a national prospective cohort of SLE in Saudi Arabia since its initiation in 2020.14 For comparison, the Prospective Urban-Rural Epidemiology Study Saudi subcohort (PURE-Saudi) was used, comprising participants registered during the same follow-up period. This observational study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines.15 The follow-up period for this study was 3 years (the recruitment period of the time-matched groups extended from January 2020 to November 2023).

Participants, variables and data sources

Two prospective cohorts were used for the comparison. The first was a national prospective cohort study of patients with SLE in Saudi Arabia that enrolled patients using an open cohort design until the end of October 2020.14 In this prevalence cohort, adult patients who fulfilled the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria were enrolled and followed up every 3–6 months using a standardised protocol to collect demographic, clinical and biochemical data, including disease activity and damage index based on the Systemic Lupus Erythematosus Disease Activity Index 200016 and SLICC/American College of Rheumatology Damage Index,17 respectively.

The second cohort was the PURE-Saudi, a part of an international epidemiological cohort that aims to examine CVD’s social and environmental determinants globally (in 17 countries).18 In the Saudi subgroup, participants without SLE were recruited in 2012 using a random sampling approach from both urban and rural areas of Riyadh and have been followed regularly since then according to standardised protocols, including demographics, medications and clinical and biochemical data .19

Exposure and outcome

The primary outcome was the prevalence of MACE (patients reported with MACE for those followed up over the last 3 years). MACE was defined as ‘any history of angina, myocardial infarction (MI), or stroke’. Two other definitions were also examined for sensitivity analysis: MACE 2, defined as ‘any angina, MI, heart failure, or stroke’, and MACE 3: ‘MI, deep venous thrombosis, stroke, or any CVD-related deaths’.

Exposures included age, sex and traditional CVD risk factors, including history of smoking, hypertension defined as ‘blood pressure more than 140/90 mm Hg as well as more than 130/80 mm Hg in sensitivity analysis’, diabetes mellitus ‘HbA1c more than 7% or being on hyperglycaemic medications’, dyslipidaemia ‘defined as any abnormality in the following: total cholesterol more than 5.2 mmol/L, low-density lipoprotein [LDL] more than 3.4 mmol/L, high-density lipoprotein [HDL] less than 0.77 mmol/L’18 and obesity defined as ‘BMI≥25 kg/m2’. Traditional CVD risk factors were initially treated as categorical (presence of any risk factor) or individually in the sensitivity analysis.

Statistical analysis and modelling

We combined the two cohorts to increase the outcomes, thus strengthening the study’s statistical power. Being a patient with SLE or not was used as the principal independent variable of interest. Logistic regression was used to model all MACE definitions. Univariable and multivariable analyses were conducted, and all multivariable models were adjusted for patient sex and age. Three incremental multivariate logistic models were built, with adjustments for age and sex. Second, we adjusted for age, sex and other traditional risk factors. Third, we adjusted for age, sex and traditional and lupus diagnoses (full adjustment). Analysis was performed for the complete case. We conducted sensitivity analysis employing inverse probability of treatment weighting (IPTW) analysis to further refine adjustments for potential confounding factors associated with the diagnosis of SLE. Detailed information regarding the construction of the IPTW model is provided in online supplemental material 2.20

Supplemental material

Patient and public involvement

None of the patients or members of the public were involved in the design, conduct, reporting or dissemination of our research plans.


Descriptive analysis

Demographic features of the study participants, such as age and sex, were compared between the two cohorts (table 1). The average age of a Lupus patient was 40.7±12.5 years compared with that of the PURE cohort (49.5±8.6 years). Females comprised 90.6% of the Lupus cohort and 41.6% of the PURE cohort (table 1). We found that 8.9% of the PURE cohort were smokers compared with 2.4% of the Lupus cohort (2.4%). The prevalences of dyslipidaemia (49.4%), obesity (85%) and diabetes (27.2%) were also higher in the PURE cohort (p<0.001, p<0.001 and p<0.001, respectively). The breakdown of the lipid profile demonstrated that the average total cholesterol and LDL levels were lower in the Lupus cohort than in the PURE cohort (p<0.001 and p<0.001, respectively). The mean HDL level was higher in the Lupus cohort than in the PURE cohort (p=0.005) (table 1). In contrast, the prevalence of hypertension, either conventional (19.3%) or American College of Cardiology/American Heart Association (27.7 in SLE and 28.4% in PURE), was significantly higher among the Lupus patients (p<0.001 and p<0.001, respectively). The primary outcome occurred in 4.3% of the Lupus group compared with 1.6% of the PURE group (1.6%) in the unadjusted analysis (p=0.004). Stroke was found in five (1%) patients in the Lupus group compared with one (0.1%) in the PURE group (p=0.028) (table 2).

Table 1

Baseline characteristics of Lupus and PURE cohorts

Table 2

Outcomes of Lupus and PURE cohorts

Associated factors of MACE

In the multivariate regression model, age and lupus diagnosis were associated with greater odds of having MACE 1 (OR 1.06, 95% CI 1.02 to 1.11, p=0.003; OR 11.65, 95% CI 3.49 to 38.94, p=0.000, correspondingly). Similar results were observed for other MACE (see online supplemental material 1 for regression models). CVD risk factors (dyslipidaemia, hypertension, obesity, diabetes and statin treatment) did not significantly change the odds of MACE in the regression model (table 3). These results were consistent when these variables were included separately in the regression model or grouped into one variable, which was also true for IPTW sensitivity analysis (online supplemental material 2).

Supplemental material

Table 3

Regression models of outcome variables (MACE 1 including MI, stroke or angina, n=13) of the Lupus cohort compared with PURE cohort

Two regression models were constructed using conceptual models to examine the factors associated with MACE in each study cohort (PURE and Lupus). MACE 1, 2 and 3 in the PURE cohort were associated with demographic and CVD risk factors. Age and diabetes increased the odds of MACE (OR 1.15, 95% CI 1.08 to 1.23, p<0.001; OR 11.04, 95% CI 1.87 to 65.22, p<0.009, respectively). The results were consistent in the multivariate exploration for age (OR 1.11, 95% CI 1.03 to 1.20, p=0.006). Age was also associated with increased odds of MACE in the Lupus cohort (OR 1.75, 95% CI 1.14 to 2.68, p=0.011), along with SLICC (OR 1.75, 95% CI 1.14 to 2.68, p=0.011) (tables 4 and 5).

Table 4

Regression models of outcome variables (MACE 2 including MI, VTE or stroke, n=21) of Lupus cohort compared with PURE cohort

Table 5

Regression models of outcome variables (MACE 3 including MI, VTE, or stroke or CVD death, n=24) of Lupus cohort compared with PURE cohort


This study is the first to examine the prevalence of MACE in patients with SLE in Saudi Arabia compared with that in the general population. In addition, although participants with SLE were younger and had fewer risk factors than the general population, they still had a greater risk of developing MACE. The two subpopulations were compared with demographics, comorbidities and SLE-specific factors to assess the prevalence of MACE and better understand the factors driving this difference. The two study groups originated from the same population (Saudi nationals living predominantly in the central region). There was an expected significant imbalance between groups in terms of demographics. The Lupus cohort was relatively younger and predominantly female and were both consistent with the nature of disease epidemiology. Interestingly, the Lupus cohort demonstrated fewer traditional cardiovascular risk factors than the general population with PURE. The smoking prevalence was lower among patients with SLE, similar to the prevalence of diabetes mellitus and obesity. Furthermore, the Lupus cohort had a much more favourable lipid profile than the PURE cohort. Particularly, patients with SLE had higher HDL levels but lower LDL levels than those in the PURE cohort. This difference could not be attributed to statin therapy, given the minimal use of statins in both study groups. Differences in lipid profiles may be related to Lupus patients receiving more attentive care from their rheumatologists, with special emphasis on CVD risk factor modification, compared with the general population. Another potential factor is the influence of inflammation on lipid profiles in patients with lupus. In a study by Chung et al, patients with lupus were found to have elevated triglyceride, LDL, total cholesterol and low HDL levels.21 These findings were compared with those of age and sex-matched healthy controls. Interestingly, this difference was associated with a higher degree of inflammation and the use of higher doses of steroids. Several other factors may explain these findings, including other treatments like hydroxychloroquine. The effects of hydroxychloroquine on lipid metabolism in patients with SLE have been demonstrated in two clinical trials and observational studies. In a pilot study by Kavanaugh et al, total cholesterol was reduced using a 400 mg dose of hydroxychloroquine.22 Other lipid profile parameters, including triglyceride and LDL levels, require significantly higher doses. These findings are consistent with our finding that patients with lupus, most of whom were taking hydroxychloroquine, had a more favourable lipid profile than the healthy cohort.

In this study, patients with lupus had more MACE than the general population despite being younger.

Multiple studies have examined the relationship between MACE and cardiac surgery and confirmed that patients are at greater risk.23–25 However, no studies evaluated patients with SLE and compared them to the general population. A comparison of patients with SLE to the general population is of particular importance in this study. Additionally, modifiable cardiovascular risk factors are highly prevalent among patients in Saudi Arabia.26 These findings confirm the global association between SLE and the risk of MACE in the Saudi population. Falasinnu et al examined the effect of racial differences on CVD outcomes between patients with SLE and controls in a community-based case–control study that included approximately 9000 participants.27 They found a significant increase in the odds of CVD among patients with SLE, but an insignificant difference was observed in participants across different racial backgrounds. However, significant disparities in CVD risk based on racial background have been observed in several studies. For example, in a population-based cohort study using the Georgia Lupus Registry, it was found that patients with lupus had a sevenfold higher risk of CVD if they were of black ethnicity compared with non-black ethnicity.9 These findings could be related to the inherited risk of CVD in the black population of the US population or SLE-related racial factors, such as the severity of the disease, likelihood of disease remission or issues related to access or coverage of care.10 In contrast, our study population had universal coverage and access to care as part of the existing Saudi healthcare, which reduced unmeasured social disparity impact on MACE development in our population.

The finding of more MACE among patients with SLE than among the general population, despite a more favourable traditional cardiovascular risk profile among the Lupus cohort, was predominantly driven by lupus diagnosis and not by traditional CVD risk factors. These findings are consistent with those of the primary and sensitivity analyses. These findings raise important questions regarding the mechanisms of these events and whether they are metabolic or inflammatory. Roman et al examined, in 2003, the correlation between SLE and atherosclerosis using a case–control design.8 This finding supports the correlation between the presence of carotid plaques and lupus. This correlation was prominent in the younger population and appeared to diminish with age after controlling for traditional CVD risk factors. The mechanism that drives plaque formation or MACE in patients with SLE may be inflammatory in younger populations, whereas traditional atherosclerotic factors contribute more with age. These insights could explain the mixed findings regarding the effect of statins on atherosclerosis prevention in patients with SLE. They should be considered in CVD risk score development among the SLE population, especially with the current performance of general lupus-specific CVD risk scores.

Finally, this study was subject to the usual issues of observational studies, including selection, information and confounding biases. We mitigated this by ensuring that both study groups were from the same location. We then used data from prospective cohort studies to minimise information-related biases and applied regression models to account for systematic differences between study groups. We also conducted several sensitivity analyses to ensure that various definitions of study outcomes were examined. We believe our findings shed light on MACE in Saudi patients with SLE for the first time. We also examine an important assumption related to the association between traditional CVD risk factors and MACE development among the SLE population. Further studies are needed to explore the pathogenesis of MACE in SLE and the contributing factors.


Patients with SLE are at a significant risk of MACE compared with the general population. This risk is not well explained by traditional risk factors, which may explain the failure of CVD risk scores to stratify patients with SLE adequately. Further studies are needed to understand the pathogenesis of CVD risk in patients with SLE and subsequently mitigate it.

Data availability statement

Data are available upon reasonable request.

Ethics statements

Patient consent for publication

Ethics approval

The institutional review board of King Saud University and King Saud University Medical City approved both cohorts (PURE E-11-428 and SLE E-19-3955/58), and participants provided written informed consent.


The authors thank the Saudi Heart Association, Dr Mohammad Alfagih Hospital, the Deanship of Scientific Research at King Saud University (research group number: RG-1436-013), Riyadh and Saleh Hamza Serafi Chair for Research on Coronary Heart Disease and Mr AlQura University, Makkah, Saudi Arabia. The authors also thank Hani Altaradi, Monther Abdulrahaman and Rehab Alnoree for their help with data collection from the PURE cohort.


Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.


  • IA and KGB are joint first authors.

  • IA and KGB contributed equally.

  • Presented at The works were presented at the European League Against Rheumatism 2023 Annual Meeting: Ghassan Bohuliga K, Alhawsa B, Omair MA, et al. AB0639 prevalence of MACE among Saudi with SLE. Annals of Rheumatic Diseases 2023;82:1522.

  • Contributors IA: conceptualisation, data curation, methodology, data collection, data analysis, writing original draft, revision of final daft and is also the guarantor and accepts full responsibility for the work and/or the conduct of the study, had access to the data, controlled the decision to publish; KGB: conceptualisation, data curation, methodology, data collection, writing original draft, revision of final daft; BA, BKA and AMA: methodology, data collection, revision of final daft; KNA and NK: data collection, writing original draft, revision of final daft; HHA: data collection, writing original draft, revision of daft; MB, HMA and MAS: methodology, data curation, writing original draft, revision of final daft; AA, TAA, FGA, MAO and ASA: methodology, data curation, writing original draft, revision of daft; JS: methodology, data curation, software, formal analysis, writing original draft, revision of final daft; KFA: methodology, data curation, supervision, writing original draft, revision of final daft.

  • Funding The project is funded by the College of Medicine Research Centre.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.