Higher levels of several cardiometabolic biomarkers measured years prior to pregnancy were associated with increased odds of hypertensive disorders of pregnancy in a large Swedish cohort study.

Among 35,189 nulliparous women, 1,938 (5.5%) developed hypertensive disorders of pregnancy (HDP), defined as gestational hypertension, preeclampsia, or superimposed preeclampsia occurring from 20 weeks’ gestation through 1 week postpartum. Most cases (about 87%) were preeclampsia rather than gestational hypertension.

Researchers linked data from the Apolipoprotein-Related Mortality Risk cohort with national Swedish registers. Biomarkers were measured a median of 4 to 6 years prior to pregnancy, with a range of up to three decades.

Lipids showed the most consistent associations

Lipid-related biomarkers demonstrated the strongest and most consistent associations with HDP risk. Compared with women in the lowest quartile, those in the highest quartile of apolipoprotein B had 1.9 times the odds of HDP. Elevated levels of low-density lipoprotein cholesterol and total cholesterol were also associated with increased odds, along with triglycerides and the apolipoprotein B to apolipoprotein A1 ratio (1.6 times the odds).

Non–high-density lipoprotein cholesterol showed one of the strongest associations at clinically defined levels, with more than twice the odds of HDP among women meeting dyslipidemia thresholds.

For several lipid markers—including triglycerides, total cholesterol, low-density lipoprotein cholesterol, and non–high-density lipoprotein cholesterol—risk increases were observed even at levels below standard clinical cutoffs. Modeling suggested largely linear relationships across the biomarker range, with approximately 20% higher odds of HDP per unit increase in these measures.

Notably, the association for low-density lipoprotein cholesterol at clinical cutoff levels did not clearly exclude no difference, underscoring some uncertainty in threshold-based interpretations.

Glucose and insulin resistance findings were mixed

Glucose-related findings were less consistent. Diagnosed diabetes or fasting glucose of at least 126 mg/dL was associated with nearly twice the odds of HDP. Prediabetes categories were not associated with increased risk.

Quartile analyses showed a non-linear pattern: mid-range fasting glucose levels were associated with higher odds of HDP, whereas the highest quartile was not clearly associated after adjustment.

The triglyceride-glucose index—a surrogate marker of insulin resistance—was associated with modestly increased odds of HDP.

Inflammation markers showed selective signals

Among inflammatory biomarkers, higher haptoglobin levels were associated with increased odds of HDP, with similar estimates in the upper two quartiles rather than a clear dose-response pattern. C-reactive protein and leukocyte count were not associated with HDP risk.

HDL-C findings varied by analysis

High-density lipoprotein cholesterol was not associated with HDP risk in the primary analysis. However, clinically low HDL-C levels were associated with increased risk in all sensitivity analyses, including restricted subgroups, suggesting potential instability in the primary estimate.

Interpretation requires caution

The study adjusted for early pregnancy body mass index, maternal age, calendar year, chronic hypertension, and relevant metabolic conditions. Additional sensitivity analyses accounting for smoking, polycystic ovarian syndrome, and alternative body mass index modeling yielded similar results.

However, the findings should be interpreted cautiously. The study was observational and cannot establish causality. Biomarkers were measured years prior to pregnancy and may not reflect levels at conception. Analyses included multiple biomarkers and exploratory categorizations without adjustment for multiple comparisons.

Generalizability may also be limited to nulliparous women with available pregestational laboratory testing.

“Assessment of cardiometabolic biomarkers may improve identification of women at risk of HDP, both in preconceptional counseling settings and at enrollment in antenatal health care,” wrote lead researcher Angelika Qvick, MD, of Karolinska Institutet, and colleagues.

Clinical context

The findings support the concept that cardiometabolic risk factors associated with cardiovascular disease may precede and contribute to HDP risk. The observation that risk extends into subclinical ranges suggests that current diagnostic thresholds may not fully capture risk in women of reproductive age.

At the same time, the absence of formal risk prediction modeling and the exploratory nature of the analyses limit immediate clinical application.

Disclosures can be found in the published study.

Source: JAMA Network Open