Women with prepregnancy biomarkers for lipids in the higher end of the “normal” range faced higher odds of developing hypertensive disorders of pregnancy, according to a study published in JAMA Network Open.

The risk was most acute for apolipoprotein B (ApoB), low-density lipoprotein (LDL) cholesterol, and triglycerides, suggesting that current clinical “safety zones” may mask significant cardiovascular risks prior to gestation. Researchers also showed some markers of inflammation and glucose metabolism were associated with higher odds of developing gestational hypertension and superimposed preeclampsia.

“What we are raising now as a novelty is risk at these lower values,” said Karin Leander, PhD, cardiovascular epidemiologist at the Karolinska Institutet in Stockholm, Sweden, who led the study. “Established lipidemia and diabetes are associated with higher risk; we already know that.”

While blood pressure is closely monitored during doctor’s visits once a person is pregnant, the new research suggests that testing lipid and glucose levels before conception and counseling about lifestyle changes could prevent some cardiovascular issues during pregnancy and labor.

Hypertensive disorders, such as high blood pressure and preeclampsia, are the leading cause of maternal mortality worldwide. As many as 10% of pregnancies in the US have a hypertensive disorder, a 25% rise in the past two decades, according to the CDC.

Leander and her team analyzed prepregnancy blood samples from 35,189 women in a population-based study linked to the Swedish Medical Birth Register that included people in the Stockholm area.

They measured blood sugar, blood lipids, and markers of low-grade inflammation. When the women later became pregnant (average age, 30 years), Leander and her colleagues followed up using national health registers and defined hypertensive disorders as preeclampsia, superimposed preeclampsia, or a dispensed antihypertensive drug used for pregnancy-induced hypertension from 20 weeks of gestation to 1 week postpartum, excluding isolated chronic hypertension.

Nearly 6% (n = 1938) of women developed hypertensive disorders of pregnancy, about the same rate as the US. Those who had hypertensive disorders were slightly older and more frequently had obesity or a chronic condition such as diabetes, chronic hypertension, kidney disease, dyslipidemia, polycystic ovarian syndrome, and cardiovascular disease.

The study showed that having lipid levels in the 75th percentile of normal ranges could increase the odds of developing hypertensive disorders during pregnancy, especially for LDL cholesterol (adjusted odds ratio [aOR], 1.41; 95% CI, 1.05-1.89), ApoB (aOR, 1.90; 95% CI, 1.36-2.65), and fasting triglycerides (aOR, 1.19; 95% CI, 1.03-1.37). Higher-than-normal levels of non-high-density lipoprotein cholesterol and ApoB/ApoA1 ratios also showed a higher risk than lipid levels that were considered clinically normal.

When it came to markers of inflammation, elevated haptoglobin was linked to an increased odds of developing the conditions (aOR, 1.20; 95% CI, 1.02-1.42). That was surprising because clinicians typically no longer test for haptoglobin, Leander said. An elevated triglyceride-glucose index, a measure of impaired glucose metabolism, was also linked to increased odds (aOR, 1.21; 95% CI, 1.04-1.40).

Elevated fasting glucose levels alone were not associated with a statistically significant increased risk, and neither was elevated C-reactive protein or leukocyte counts.

Paying attention to risk factors for cardiovascular disease in people who plan to become pregnant is “a welcome pursuit,” especially in first-time parents, said Cande Ananth, PhD, MPH, distinguished professor of obstetrics, gynecology, and reproductive sciences at the Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey.

“If the metabolic lipid profiles are off in any woman, she potentially becomes a candidate for follow-up pre-conception,” said Ananth, who was not involved in the study. “She is already at higher risk for preeclampsia.”

Lifestyle changes such as diet, exercise, and smoking cessation can decrease metabolic risk factors.

“If they can get the risk factors down before conception, that would be the best approach,” Ananth said.

Currently, the American College of Obstetricians and Gynecologists and the American Heart Association do not have screening guidelines for people who have not yet become pregnant.

If additional studies support the findings, future guidelines may include prevention for hypertensive disorders of pregnancy rather than just treatment for the disorders once they occur, Leander said.

“It’s one study, so we have to be careful to go directly to guidelines,” she said. But “doctors who meet women when they stop contraceptives could maybe test for these biomarkers.”

The study was funded by the Swedish Heart Lung Foundation and the Karolinska Institutet. Various authors reported receiving grants and personal fees, holding stock and clinical research appointments, and receiving other support from the Stockholm County Council (Region Stockholm), Roche Diagnostics, Thermo Fisher Scientific, and AstraZeneca, among others.