Pregnancy in Rheumatic Disease Quadruples CVE Risk

SAN DIEGO, California — Pregnant individuals with autoimmune rheumatic diseases (ARDs) are at least four times more likely to experience an acute cardiovascular event (CVE) than are pregnant individuals without these conditions, according to new research presented at the American College of Rheumatology (ACR) 2023 Annual Meeting. Pregnant individuals with primary antiphospholipid syndrome (APS) had a 15-fold increase in CVE risk.

Patients who experienced CVEs were also more likely to experience preterm birth and other adverse pregnancy outcomes (APOs).

Rashmi Dhital, MD, a rheumatology fellow at the University of California, San Diego, and colleagues examined the medical records of pregnant individuals in California who had delivered singleton live-born infants from 2005 to 2020. Using data from the Study of Outcomes in Mothers and Infants (SOMI) database, an administrative population-based birth cohort in California, they identified more than 7 million individuals, 19,340 with ARDs and 7758 with APS.

They then analyzed how many patients experienced an acute CVE during pregnancy and up to 6 weeks after giving birth.

CVEs occurred in 2.0% of patients with ARDs, 6.9% of individuals with APS, and 0.4% of women without these conditions. CVE risk was four times higher in the ARDs group (adjusted relative risk [aRR], 4.1; 95% CI, 3.7 – 4.5) and nearly 15 times higher in the APS group (aRR, 14.7; 95% CI, 13.5 – 16.0) than in the comparison group. Patients with systemic lupus erythematosus (SLE) had a sixfold higher risk of CVE, which was further exacerbated by concomitant APS (18-fold higher risk) or lupus nephritis (15-fold higher risk).

Dhital also classified CVEs as either venous thromboembolism (VTE) and non-VTE events. Pregnant patients with APS had a high risk for VTE-only CVE (40-fold greater) and a 3.7-fold higher risk of non-VTE events, compared with pregnant patients without these conditions. Patients with SLE along with lupus nephritis had a 20-fold increased risk of VTE-only CVE and an 11-fold higher risk of non-VTE CVE.

Although the study grouped rheumatic diseases together, “lupus is generally driving these results,” Sharon Kolasinski, MD, of the University of Pennsylvania in Philadelphia noted in an interview with Medscape Medical News. She moderated the plenary session where the research was presented. “If you take out lupus, then what is the risk? That would be an interesting question.”

Between 25% to 30% of all CVEs occurred in the postpartum period, highlighting the importance of close monitoring of cardiovascular risks and events in women with ARDs or APS both during pregnancy and postpartum, Dhital noted.

Recognizing these risks “can sometimes be challenging due to a lower suspicion of CVE in younger patients, and also symptoms overlap with normal pregnancy,” Dhital said during her plenary presentation. Working with other clinical teams could help physicians detect these risks in patients, she noted.

“It’s important for us to remember that there’s increased risk of cardiovascular events in pregnancy in our patients. It’s uncommon, but it’s not zero,” added Kolasinski, and this study highlighted when physicians should be more focused about that risk.

Dhital noted there were some limitations to the study that are inherent in using administrative databases for research that relies on ICD codes, including “the availability of information on disease activity, medications, and labs, which may restrict clinical interpretation.”

SOMI Data Reinforced by National Inpatient Sample Study

The findings were complemented by a study using the National Inpatient Sample (NIS) database to explore CVE risk in pregnant individuals with various rheumatic diseases. Lead author Karun Shrestha, MD, a resident physician at St. Barnabas Hospital in the Bronx, New York City, and colleagues identified delivery hospitalizations from 2016 to 2019 for individuals with SLE, rheumatoid arthritis (RA), and systemic vasculitis and looked for CVEs including preeclampsia, peripartum cardiomyopathy (PPCM), heart failure, stroke, cardiac arrhythmias, and VTE.

Out of over 3.4 million delivery hospitalizations, researchers identified 5900 individuals with SLE, 4895 with RA, and 325 with vasculitis. After adjusting for confounding factors such as race, age, insurance, and other comorbidities, SLE was identified as an independent risk factor for preeclampsia (odds ratio [OR], 1.5; 95% CI, 1.1 – 2.1), arrhythmia (OR, 3.17; 95% CI, 1.73 – 5.79), and venous thrombosis (OR, 8.4; 95% CI, 2.9 – 22.1). Vasculitis was tied to increased risk for preeclampsia (OR, 4.7; 95% CI, 2 – 11.3), stroke (OR, 513.3; 95% CI, 114 – 2284), heart failure (OR, 24.17; 95% CI, 4.68 – 124.6), and PPCM (OR, 66.7; 95% CI, 8.7 – 509.4). RA was tied to an increased risk for preeclampsia (OR, 1.5; 95% CI, 1.05 – 2.1).

Patients with SLE or vasculitis had longer, more costly hospital stays, compared with those without these conditions, and they experienced higher rates of in-hospital mortality. While previous research has demonstrated that patients with SLE have higher risk of cardiac events, there is less literature on CVE risk in pregnancies for vasculitis, Shrestha told Medscape.

“It’s something to work on,” he said.

Adverse Pregnancy Outcomes Higher With ARDs, APS

In a second abstract also led by Dhital using SOMI data, researchers found that pregnant individuals with ARDs or APS had a higher risk of experiencing an APO — preterm birth or small-for-gestational age — than individuals without these conditions. CVEs exacerbated that risk, regardless of underlying chronic health conditions.

Patients Experiencing Adverse Pregnancy Outcomes
  With Acute CVE Without Acute CVE
NO ARD or APS (n = 7,004,334) 28.2% (n = 4838) 15.2% (n = 1,063,115)
Any ARD (n = 19,340) 53.4% (n = 143) 26.6% (n = 5063)
Primary APS (n = 7758) 30.6% (n = 132) 20.7% (n = 1516)

Over half of patients with an ARD and a CVE during pregnancy experienced an APO — most commonly preterm birth. More than 1 in 4 pregnant individuals without ARD or APS who experienced a CVE also had an APO.

After differentiating CVEs as either VTE and non-VTE events, patients with ARD and a non-VTE CVE had a fivefold greater risk of early preterm birth (< 32 weeks) and a threefold higher risk of moderate preterm birth (32 to < 34 weeks).

“These findings highlight the need for close monitoring and management of pregnant women, not only for adverse outcomes, but also for cardiovascular risks and events, in order to identify those at the highest risk for adverse outcomes,” the authors write. “This need is particularly significant for individuals with ARDs, as 53.4% of our population with an ARD and CVE in pregnancy experienced an APO.”

Dhital, Kolasinski, and Shrestha have disclosed no relevant financial relationships.

American College of Rheumatology (ACR) 2023 Annual Meeting: Abstracts 0722, 0467. Presented November 12, 2023.

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