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Elevated Cardiovascular Biomarkers Following Hypertensive Disorder of Pregnancy
Insights
Hypertensive disorder of pregnancy (HDP) is linked to higher levels of cardiovascular disease (CVD) proteins years later. Identifying these biomarkers aids in early risk stratification and targeted interventions for women with HDP history.
Area of Science:
- Obstetrics and Gynecology
- Cardiovascular Medicine
- Biomarker Discovery
Background:
- Hypertensive disorder of pregnancy (HDP) is a known risk factor for later-life cardiovascular disease (CVD).
- The specific mechanisms linking HDP to long-term CVD risk are not fully understood.
- Investigating intermediate biomarkers post-pregnancy may clarify HDP's impact on cardiovascular health.
Purpose of the Study:
- To determine if cardiovascular risk-associated protein levels differ between women with and without a history of HDP.
- To identify specific protein biomarkers that may indicate elevated CVD risk in the years following HDP.
- To explore the relationship between HDP history and circulating CVD-associated proteins and inflammatory markers.
Main Methods:
- Measured 77 proteins, including CVD-associated and inflammatory markers, in 22 individuals with HDP history and 43 controls.
- Collected samples at a median of 4 years after pregnancy.
- Utilized multivariable linear regression and sample clustering to analyze protein expression patterns.
Main Results:
- Several CVD-associated proteins (fibrinogen, fetuin-A, L-selectin, alpha-1-acid glycoprotein) were significantly elevated in the HDP group (p<0.0001).
- HDP history remained associated with higher CVD-associated protein levels after controlling for covariates (p<0.0001).
- Distinct CVD protein expression patterns were observed between post-HDP and post-normotensive pregnancy groups; inflammatory markers showed less significant differences.
Conclusions:
- A history of HDP is associated with significantly elevated levels of specific CVD-associated proteins years after pregnancy.
- These protein biomarkers may aid in identifying individuals at higher risk for future cardiovascular events post-HDP.
- Further research into these biomarkers can inform targeted interventions to mitigate cardiovascular risk in this population.
Abstract:
Hypertensive disorder of pregnancy (HDP) is associated with an increased risk for later-life cardiovascular disease (CVD). Whether the HDP pregnancy itself confers risk towards CVD later in life is suggested in several epidemiologic studies. Given this connection and that the HDP exposure itself may play a role, understanding whether markers associated with cardiovascular risk vary based on HDP history in the years following pregnancy may assist with risk stratification and development of targeted interventions. We measured 77 proteins (CVD-associated and inflammatory markers) in n=22 individuals with a history of HDP and n=43 matched controls with no HDP history at a median of 4 years after pregnancy. Several CVD-associated proteins (fibrinogen, fetuin-A, L-selectin, and alpha-1-acid glycoprotein) were significantly elevated, by orders of magnitude, in individuals with a history of HDP compared to normotensive pregnancies (all p<0.0001). In multivariable linear regression models controlling for age, body mass index, chronic hypertension, and diabetes, a history of HDP remained associated with higher levels of CVD-associated proteins (all p<0.0001). We clustered samples based on global patterns of CVD protein expression and found a significant difference in CVD protein expression patterns between post-Normal and post-HDP samples. Conversely, differences in circulating inflammatory markers were largely insignificant or more subtle than that observed with the CVD-associated proteins. Identification of biomarkers associated with CVD in the intervening years after HDP but before evident CVD is critical to understanding post-HDP cardiovascular risk to provide insight for the development of therapeutic interventions that mitigate CVD event risk in this high-risk population.
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