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A recent study in The Journal of Rheumatology sheds light on the importance of preconceptional cardiovascular health in women with systemic lupus erythematosus. Although many questions remain, improved cardiovascular health measures seem to positively affect pregnancy outcomes, suggesting a potential role for preconception cardiovascular interventions.1
Women with lupus now have healthier pregnancies than in the past, but pregnancy still poses an increased risk for certain problems for mother and child, including preeclampsia, postpartum infection, thromboembolic disease, spontaneous abortion and issues resulting from preterm delivery and small-for-gestational-age infants.2 Estimates of the prevalence of infants born preterm or small-for-gestational age put the risk at two to six times higher in lupus patients than in the general population.1
Women with lupus are also at a fivefold increased risk of significant cardiovascular events than those without the disease.3 The cardiovascular risk factors of hypertension, dyslipidemia and obesity appear to be relatively common comorbidities in lupus patients and may be more common than in the population at large.1,3 Yet these factors alone may not fully account for the increased risk in these patients, because often, younger patients without traditional risk factors seem to be at the greater risk of such events.3 Moreover, previous studies have shown that pregnancy complications, such as those resulting in a small-for-gestational-age infants, may increase the later risk of cardiovascular mortality in lupus patients.4
Amanda Eudy, PhD, is an assistant professor of medicine at Duke University, Durham, N.C., and first author of the recent study. “It’s an important topic for the health of the infant and the impact of the pregnancy,” she explains, noting the impetus for the study.
“It also has long-term implications for the overall health of the mother. Since cardiovascular events are more prevalent in lupus patients compared to the general population anyway, perhaps improving cardiovascular health at an earlier age—during those reproductive years, could have a long-term impact on improving their health overall.”
Study Design
For the study, Dr. Eudy and colleagues used data from the Hopkins Lupus Pregnancy Cohort, which began to study pregnant lupus patients as a prospective cohort in 1987. Ultimately, 309 lupus pregnancies were analyzed (from 261 lupus patients). The research team focused its efforts on the cardiovascular health impact goals elucidated by the American Heart Association (AHA).5 Data for three of these factors were available: total cholesterol, blood pressure and body mass index (BMI). Data were collected from the year prior to conception or from the first trimester if preconception data were not available.
Poor cholesterol health was defined as greater than or equal to 240 mg/dL; intermediate health as 200–239 mg/dL or treated to goal; ideal health as less than 200 mg/dL. For blood pressure, poor health was defined as systolic greater than or equal to 140 mmHg or diastolic greater than or equal to 90 mmHg; intermediate health as between 120 and 139 mmHg systolic or between 80 and 89 mmHg diastolic or treated to goal; ideal health as less than 120 mmHg systolic and less than 80 mmHg diastolic. For BMI, obese was defined as greater than or equal to 30 kg/m2; overweight as between 25 and 30 kg/m2; ideal as less than 25 kg/m2.
To account for confounding variables, Dr. Eudy and colleagues included covariates in their analysis, including race, age, education, disease duration, medication use, renal involvement and organ damage at conception. Using ANOVA, Fisher’s exact test and regression models, the researchers analyzed differences in the prevalence of preterm birth, small-for-gestational-age infants, mean gestational age and mean birth weight for gestational age z-score.
Findings
Using these criteria, 51% of patients were found to be in the ideal blood pressure category, 85% had ideal total cholesterol, and 56% had ideal BMI.
Blood pressure
“We found that when we analyzed gestational age as a continuous variable, patients with intermediate or poor blood pressure delivered earlier,” says Dr. Eudy. “Having poor blood pressure meant a patient delivered about a week earlier than patients who did not meet the ideal blood pressure marker” (β –0.96, 95% confidence interval [CI] –1.62 to –0.29). Blood pressure did not appear to have an impact on the risk of having a small-for-gestational-age infant. Dr. Eudy notes that increased blood pressure is associated with an increased risk of preterm birth in the general population, “so that was similar in our study as well.”
Cholesterol
The team also found an association between cholesterol and preterm births, although not a link with small-for-gestational-age infants. “Patients who had intermediate or poor total cholesterol preconceptionally had an increased risk of preterm birth,” explains Dr. Eudy (odds ratio [OR] 2.21, 95% CI 1.06–4.62). She adds, “Among general population women with or without lupus, we’ve also seen that association.” Previous limited research suggests this link with spontaneous preterm birth may be potentially mediated via maternal inflammation.1
BMI
The group’s findings surrounding BMI were perhaps the most surprising. No real association was seen for patients who were overweight in terms of preterm birth. Explains Dr. Eudy, “We did see almost a decreased risk for patients who were obese, which was inverse from what we were expecting.” She and her team speculate that one potential mechanism may have been increased care and more targeted interventions provided to such patients.
The team lacked the data to identify whether preterm births were spontaneous or medically indicated, situations with different risk factors. As Dr. Eudy explains, “Indicated preterm birth could be due to such factors as preeclampsia, which goes along with high blood pressure, whereas spontaneous preterm birth can be caused by other risk factors. Unfortunately, we weren’t able to stratify by the indication for preterm birth, which I think could be insightful in understanding this outcome.”
Having an intermediate (overweight) BMI was associated with decreased odds of having a small-for-gestational-age infant (OR 0.26, 95% CI 0.11–0.63, adjusted for race and prednisone use).
Dr. Eudy notes the risk of having a small-for-gestational-age infant may decrease with increasing BMI, because large-for-gestational-age infants are more common with increasing BMI. “I think more work is needed in that particular aspect to see if that association is seen in other cohorts,” she says.
Other potential metrics
In the future, Dr. Eudy would like to see a composite risk score that includes the other four factors highlighted by the AHA: smoking status, fasting glucose, physical activity level and dietary information.5 Dr. Eudy notes that having a poor metric on any of these variables may also increase the risk of preterm birth or small-for-gestational-age infants, given existing data gathered from the general population.
Preconception Counseling
The bottom line is that these cardiovascular factors are worth bringing up with lupus patients considering pregnancy. Rheumatologists can play an important role checking in with patients who may intentionally or accidentally become pregnant to ensure they are as healthy as possible before conception. Although a rheumatologist is unlikely to have primary management of these specific cardiac risk factors, they can play an important role in co-management. Consider introducing a preconception exercise program or other intervention that may improve pregnancy and overall health outcomes.
“When you are counseling a lupus patient prior to becoming pregnant, in addition to thinking about their lupus activity—Is it well controlled? Has it been controlled for the past six months? What medications are they taking?—we also need to think outside lupus for a little bit as well,” says Dr. Eudy. “We need to take into consideration these more traditional risk factors of poor pregnancy outcomes and cardiovascular health to help give a complete idea of their risk factors during pregnancy.”
Ruth Jessen Hickman, MD, is a graduate of the Indiana University School of Medicine. She is a freelance medical and science writer living in Bloomington, Ind.
References
- Eudy AM, Siega-Riz AM, Engel SM, et al. Preconceptional cardiovascular health and pregnancy outcomes in women with systemic lupus erythematosus. J Rheumatol. 2019 Jan;46(1):70–77.
- Bundhun PK, Soogund MZ, Huang F. Impact of systemic lupus erythematosus on maternal and fetal outcomes following pregnancy: A meta-analysis of studies published between years 2001–2016. J Autoimmun. 2017 May;79:17–27.
- Soh MC, Nelson-Piercy C, Westgren M, et al. Do adverse pregnancy outcomes contribute to accelerated cardiovascular events seen in young women with systemic lupus erythematosus? Lupus. 2017 Nov;26(13):1351–1367.
- Soh MC, Nelson-Piercy C, Dib F, et al. Brief report: Association between pregnancy outcomes and death from cardiovascular causes in parous women with systemic lupus erythematosus: a study using Swedish population registries. Arthritis Rheumatol. 2015 Sep;67(9):2376–2382.
- Lloyd-Jones DM, Hong Y, Labarthe D, et al. Defining and setting national goals for cardiovascular health promotion and disease reduction: The American Heart Association’s strategic impact goal through 2020 and beyond. Circulation. 2010;121(4):586–613.
