Are Adverse Pregnancy Outcomes Associated With Accelerated Cardiovascular Events in SLE?

Systemic lupus erythematosus (SLE) increases the risk for pregnancy-related complications, affecting both the mother and the fetus.¹ As the survival of patients with SLE improves, cardiovascular (CV) causes, including ischemic heart disease and stroke, have emerged as the main cause of death. A meta-analysis found that compared with the general population, SLE is associated with a 3-, 2.3-, and 1.7-fold increase in the risk for death from CV causes, ischemic heart disease, and stroke, respectively.^2,3 Compared with pregnant women without SLE, up to 25% of those with SLE have preeclampsia (compared with less than 4% in the general population), 20% to 31% have preterm delivery (compared with 4.3% to 8.7% in the general population), and these women are more likely to die from a CV event. Preeclampsia is associated with approximately a 4.5-fold increased rate of stroke in patients with SLE compared with those without SLE. Similar findings have been reported in other studies.^4-6 

Although maternal placental syndrome (MPS) is associated with increased risk for death from CV-related causes, a direct correlation between pregnancy complications and cardiovascular disease (CVD) has not been established, and the underlying pathophysiologic mechanisms have not been defined. A meta-analysis that evaluated outcomes of more than 3 million pregnancies in patients with SLE found approximately a 4-fold increase in the risk for hypertension and a 2-fold increase in the risk for stroke and ischemic heart disease occurring a decade after the pregnancy.⁷ It has also been shown that patients with SLE who have a history of preeclampsia have almost 4-fold increase in the rate of subclinical CVD.⁸

Although traditional risk factors for CVD, including obesity, cigarette smoking, hypertension, diabetes, and lipid abnormalities, are also evident in pregnancy complications such as preeclampsia, low birth weight, and preterm delivery, a relationship linking traditional CV and SLE-specific risks for adverse pregnancy outcomes has not been established.⁸ It is possible that in the absence of traditional CV risk factors in pregnant women with SLE, the premature CV morbidity may be associated with MPS.² The speculation is that the elevated risk for CV events in pregnant women with SLE is multifactorial, perhaps triggered by an underlying active inflammatory disease, vasculitis, atherosclerotic process, or a combination of these processes. Placental-related secretions leading to vascular insufficiency and hypoxia are thought to play a role. Hypertension, vascular damage, and increased arterial stiffness are factors associated with preeclampsia and endothelial dysfunction.⁴

It is thought that autoantibodies and damaging antiangiogenic factors associated with MPS complicate the pregnancies of women with SLE. Indeed, pregnant women with SLE have higher levels of the soluble fms-tyrosine-like kinase-1 (sFlt-1); higher circulating levels of sFlt-1 and soluble endoglin, lower levels of placenta-like growth factor (PIGF), and s high sFlt-1/PIGF ratio can be used to predict preeclampsia in patients with SLE.² The association between placental secretions and adverse pregnancy outcome was demonstrated in the multicenter Predictors of Pregnancy Outcome: Biomarkers in APL Syndrome and SLE (PROMISSE) study.⁹ The study found that in patients with sFlt-1 level <1872 pg/mL and PIGF >70.3 pg/mL, the rate of severe adverse pregnancy outcomes was <5%.

Currently, there is no algorithm to stratify patients to accurately predict those who are at greatest risk for CV events, and who may benefit most from early screening. “Management should include both SLE-specific treatment that can be used during pregnancy for at least 6 months prior to conceiving,” said Rosalind Ramsey-Goldman, MD, DrPH, Solovy Arthritis Research Society professor of medicine and medical director in the Clinical Research Unit at Northwestern University.

Dr Ramsey-Goldman also stressed the importance of supportive care to prevent CV events and other complications. “Supportive treatment includes not smoking, controlling blood pressure if needed with medications that can be used during pregnancy, taking aspirin or a blood thinner medication if the woman has an increased risk of blood clots (has antiphospholipid antibodies), monitoring for diabetes, and maintaining a healthy weight for pregnancy.”

For women who want to become pregnant, a proactive approach of patient management is recommended. “When women with SLE are considering pregnancy, they should have a consultation with their rheumatologist concerning the risks of pregnancy for themselves and their baby,” said Dr Ramsey-Goldman, adding, “the rheumatologist may recommend seeing other specialists including but not limited to high-risk obstetrician, cardiologist, nephrologist, or hematologist.”

The multisystem nature of SLE calls for well-designed multidisciplinary collaborative research that may include cardiologists, obstetrician, and rheumatologists to better understand the underlying cause of the increased risk for CV events and various adverse pregnancy outcomes. In the absence of therapeutic interventions to prevent or treat MPS, patient education, counseling, and preventive strategies are essential so that women understand that a child born prematurely as a result of complications from SLE will also be at risk for CV events in the future.

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References

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8. Lin P, Rhew E, Ness RB, et al. Adverse pregnancy outcomes and subsequent risk of cardiovascular disease in women with systemic lupus erythematosus. Lupus Sci Med. 2014;1:e000024.
9. Kim MY, Buyon JP, Guerra MM, et al. Angiogenic factor imbalance early in pregnancy predicts adverse outcomes in patients with lupus and antiphospholipid antibodies: results of the PROMISSE study. Am J Obstet Gynecol. 2016;214(1):108.e1-08.e14.