A large Swedish cohort study shows that subtle changes in cholesterol, glucose, and inflammation years before pregnancy may signal future risk of hypertensive complications, highlighting the potential for earlier risk assessment and targeted prevention.
Study: Pregestational Cardiometabolic Biomarkers and Future Hypertensive Disorders of Pregnancy. Image credit: MVelishchuk/Shutterstock.com
A simple blood test years before pregnancy may help improve early risk assessment for dangerous pregnancy-related hypertension (hypertensive disorders of pregnancy, HDP), according to a study published in JAMA Network Open.
Cardiometabolic changes may underlie pregnancy hypertension risk
HDP affects up to 15 % of pregnancies, causing complications and deaths in both mothers and infants. In addition, it increases the long-term risks of cardiovascular disease. HDP rates are going up, probably because women are older at first delivery and more likely to be obese.
HDP includes chronic hypertension, gestational hypertension, preeclampsia, and superimposed preeclampsia. These seem to arise from impaired adaptive responses to the increased cardiovascular burden of pregnancy. Moreover, such women often have higher blood cholesterol and glucose levels, as well as inflammatory markers, during pregnancy.
Existing literature shows conflicting findings as to whether these markers are elevated before pregnancy, prompting the current study.
This underscores the need for identifying early risk factors. Those that are already known include advanced age at pregnancy, obesity, diabetes, and hypertension. However, most of these were established using data collected during or after pregnancy, mostly past the potential intervention points.
Tracing preconceptional risk markers forward into pregnancy
In the current study, Swedish researchers used data from the Apolipoprotein-Related Mortality Risk (AMORIS) cohort set in Stockholm. Birth registry data were used for 35,189 first-time mothers aged 18 years or above. The mean age at delivery was 31 years
Blood samples were analyzed for a range of cardiometabolic health and inflammation biomarkers. This data predated the first completed pregnancy by a median of 4-6 years.
The HDP cohort
Approximately 5.5 % of participants (1938 women) had HDP. About 13 % of the HDP cases had gestational hypertension, while the rest had pre-eclampsia, mostly arising after 37 weeks of gestation. More mothers with HDP had conceived via assisted reproduction. The HDP group also had higher rates of twins or other multiple births and a shorter pregnancy duration.
Clinical cutoffs were used where relevant: for dyslipidemia, prediabetes, and diabetes, as well as age-specific thresholds for different categories of lipids. In addition, researchers compared women with the highest and lowest levels of these markers to assess associations between HDP and subclinical rises in these markers. Risk associations were analyzed after adjusting for early-pregnancy body mass index, maternal age at delivery, calendar year of pregnancy, and chronic hypertension, with additional adjustment for diabetes or dyslipidemia depending on biomarker type.
Approximately 5.5 % to 12.8 % of women with elevations in any of these markers developed HDP, compared to 4.1 % to 5.3 % of women with normal markers. Among women with clinically elevated values, 9.8 % to 12.8 % developed HDP. For lipid markers, clinical dyslipidemia cutoffs were associated with a higher risk of HDP except for LDL, which narrowly missed statistical significance.
Subtle metabolic changes years earlier predict pregnancy hypertension
Among women with the highest levels of these markers, 5.5 % to 7.3 % developed HDP. The odds of HDP were 23 % higher among women with the highest serum cholesterol. Similarly, the highest quartile of low-density lipoprotein (LDL) cholesterol and of triglycerides was associated with 41 % and 19 % higher odds of HDP compared to the lowest, even though clinically elevated LDL did not show such an association.
The odds of HDP increased by approximately 20 % in statistical models using these biomarkers as continuous variables for fasting triglycerides, total cholesterol, LDL, and non-HDL cholesterol. A nonlinear pattern was observed for HDL, with some indications of higher risk at both low and high levels, but a nonlinear association was found between fasting glucose and HDP risk.
Apo B, a major marker of cardiometabolic disease, showed the strongest association with HDP risk (90 % higher odds). At the same time, the ApoB/ApoA1 ratio was associated with a 59 % higher risk.
Other markers associated with an increased HDP risk were haptoglobin and the triglyceride-glucose index, with about 20 % higher odds for each. No association was observed for C-reactive protein or leukocyte count.
An existing diagnosis of diabetes or fasting glucose of 126 mg/dL or above was associated with nearly double the risk of HDP. Prediabetes categories were not significantly associated with HDP, and the highest quartile of fasting glucose did not show a statistically significant increase in risk. For most associations, the difference in HDP rates was small. However, some markers were associated with HDP at subclinical levels: fasting triglycerides, TC, and LDL.
Study limitations
Only first-time mothers were included, limiting the generalizability. Residual confounding could have affected the results despite adjusting for multiple risk factors. Multiple biomarkers were analyzed, allowing for hypothesis generation but not for definitive findings, and no adjustment was made for multiple testing, meaning the results should be considered exploratory.
Pre-pregnancy metabolic health may guide preventive strategies
Despite the preliminary nature of these results, they support the idea that both cardiovascular disease and HDP share a common pathway, involving vascular maladaptation. The associations of HDP with subclinical rises in several biomarkers also raise the question of “whether HDP guidelines should be revisited.”
If confirmed in future studies, these findings could potentially provide very early identification of HDP risk through cardiometabolic biomarkers measured in routine blood tests, allowing counseling on lifestyle changes and risk assessment before pregnancy.
Download your PDF copy by clicking here.