Trends in Acute Coronary Syndromes in Systemic Lupus Erythematosus: Are We Moving in the Right Direction?

Cardiovascular (CV) disease (CVD) in systemic lupus erythematosus (SLE) is driven by chronic inflammation, traditional risk factors, and SLE-specific immunological processes that likely begin before clinical diagnosis. Multiple study designs, including population-based registries, case-control studies, and systematic reviews and metaanalyses, consistently show a 2- to 3-fold increased risk of CVD in patients with SLE.^1-4

Given this well-established excess risk, the relevant question is whether increased awareness over recent decades has translated into improvements in CVD morbidity. Tektonidou et al used the Nationwide Inpatient Sample (NIS; now the National Inpatient Sample), part of the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project, to estimate trends in hospitalization for myocardial infarction (MI), unstable angina, and ischemic stroke in patients with SLE in the United States from 1996 to 2012.⁵ They reported rising rates of hospitalization for acute MI and ischemic stroke in SLE over that period, while hospitalizations for unstable angina declined. In contrast, rates for all 3 conditions declined in the general population during the same interval, with a faster decline in unstable angina among non-SLE patients. Tektonidou et al concluded that increased awareness had not yet improved outcomes over their study period.⁵

In this issue of The Journal of Rheumatology, Parperis and colleagues also used the NIS to assess whether rates of hospitalization for acute coronary syndrome (ACS) in SLE changed over a more recent interval (2006-2019), and whether outcomes and healthcare utilization differed between patients with and without SLE.⁶ ACS typically results from rupture or erosion of an atherosclerotic plaque followed by thrombus formation, producing unstable angina, ST-elevation MI (STEMI), or non-STEMI (NSTEMI).⁷

Parperis et al found that ACS hospitalization rates in SLE rose gradually from 2006 to 2014 and then declined by nearly 40% over the next 5 years, although rates remained higher than in the general population.⁶ The pre-2014 rise is concordant with the earlier report by Tektonidou et al.⁵ The cause of the more recent decline shown in the study by Parperis et al is uncertain. The authors suggest improved SLE therapies and treat-to-target strategies as possible contributors; belimumab’s approval in 2011 and subsequent long-term data supporting glucocorticoid tapering and less accrual of organ damage (including CV damage) could be relevant. Broader factors such as greater emphasis on heart-healthy lifestyle changes may also have contributed, though ACS hospitalizations in the general population show a more steady decline from 2006 onward and did not display the same pre-2014 rise followed by a rapid fall as seen in SLE. Expansion of health insurance after implementation of provisions of the Affordable Care Act in 2014 may also have improved access to preventive care. In the current study,⁶ patients with SLE were more likely to be covered by Medicaid than by commercial insurance compared with non-SLE patients.

The NIS is the largest publicly available all-payer inpatient database in the US and is well suited for studying rare conditions and uncommon events. However, it has limitations. In 2012, the NIS was redesigned to improve national estimates; this produced a one-time disruption of historical trends (an estimated ~4.3% decline in discharge counts).⁸ Although this redesign could affect trend analyses spanning 2012, it would not plausibly explain a sustained ~40% decline in ACS through 2019. Importantly, the NIS tracks hospitalizations rather than unique patients; repeated admissions by the same individual can be counted more than once, potentially overestimating the number of affected patients.

Demographically, in the study by Parperis et al,⁶ patients with SLE hospitalized for ACS were more often younger women and more frequently African American than non-SLE ACS patients. A higher proportion of SLE patients with ACS lived in the South and in zip codes in the lowest quartile of median household income. These findings align with prior observations suggesting that overall hospitalization rates may mask important subgroup differences.^9,10 For example, using 2016-2019 NIS data, investigators found that rural residence doubled the risk of hospitalization for MI in people with SLE, independent of demographics, payer status, social determinants of health, and hospital characteristics.¹⁰

The contribution of traditional CV risk factors to ACS in SLE remains incompletely defined. The current study suggests that hypertension, hyperlipidemia, and diabetes were less common among SLE patients with ACS than in non-SLE ACS patients, whereas antiphospholipid antibodies (aPL), prior thrombotic events, and end-stage renal disease were more frequent.⁶ Traditional risk factors are important and should be aggressively managed in SLE, but SLE-specific mechanisms must also be considered. One relevant entity is MI with nonobstructive coronary arteries (MINOCA), which disproportionately affects young Black women and often presents with MI in the absence of obstructive coronary lesions. Patients with MINOCA typically have fewer conventional risk factors, and the condition may have distinct causes, such as coronary spasm, plaque erosion/rupture without obstructive stenosis, spontaneous coronary artery dissection, or thrombophilia (including aPL), thereby requiring different diagnostic and therapeutic approaches.^11,12 Although understudied in SLE, MINOCA appears associated with an SLE phenotype characterized by thrombophilia and younger age.

Other limitations of the NIS include reliance on coded diagnoses, which can miss comorbidities or clinical detail; lack of imaging, laboratory, and medication data; and absence of unique patient identifiers to distinguish index from repeat events. Despite these limitations, inpatient mortality for ACS appears similar between patients with and without SLE. Singh and Cleveland also reported a narrowing in-hospital mortality gap between SLE and non-SLE hospitalizations.¹³ By contrast, hospital charges and length of stay are higher for ACS admissions in SLE in the current study.⁶ Note that the NIS reports hospital charges, not the actual costs or payments; without claims data and a cost-to-charge ratio, charges serve only as a crude proxy for resource utilization.

In summary, the NIS remains a valuable resource for longitudinal trend analyses, especially for rare conditions that require large sample sizes to enable subgroup comparisons and assessments of payer, hospital, rural-urban, and demographic disparities. Using the NIS, Parperis and colleagues⁶ report favorable recent trends in ACS hospitalizations in both patients with and without SLE, though rates remain elevated in those with SLE. The data suggest that higher-than-expected rates of ACS in SLE may be driven by specific subgroups, particularly young women, racial minorities, residents of certain regions, those with lower socioeconomic status, and patients with SLE-related risk factors such as aPL and renal disease. Despite limitations, including a lack of unique patient identifiers, limited clinical detail, and absence of out-of-hospital events, this study provides important insights. Policymakers and payers should support quality measures that incentivize CV screening and treatment in SLE, expand access to preventive medications, and fund implementation studies to close equity gaps. Research must move beyond descriptive studies to test interventions targeting SLE-specific atherogenic mechanisms and to evaluate the effectiveness of intensive risk factor modification in this population.

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