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Higher Levels of Cardiovascular Biomarkers Following Hypertensive Compared to Normotensive Pregnancy
Austin M Gabel1, Lindsay Cheu2, Mindy Pike2
1Medical Scientist Training Program, University of Washington, Seattle, Washington, USA.
Insights
Hypertensive disorder of pregnancy (HDP) elevates cardiovascular disease (CVD) protein markers years later. Early identification of these biomarkers post-HDP can guide interventions for high-risk individuals.
Area of Science:
- Cardiovascular Science
- Reproductive Health
- Biomarker Discovery
Background:
- Hypertensive disorder of pregnancy (HDP) is linked to increased later-life cardiovascular disease (CVD) risk.
- The specific role of the HDP pregnancy itself in conferring future CVD risk requires further investigation.
- Identifying early CVD markers post-HDP is crucial for risk stratification and intervention.
Purpose of the Study:
- To investigate whether CVD-associated protein markers differ in individuals with a history of HDP compared to those with normotensive pregnancies.
- To explore potential differences in inflammatory markers between these groups.
- To assess the association of HDP history with CVD protein levels years after pregnancy.
Main Methods:
- Measured 77 proteins (CVD-associated and inflammatory markers) in 22 individuals with HDP history and 42 controls.
- Analysis conducted a median of 4 years post-pregnancy.
- Utilized multivariable linear regression and sample clustering based on 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 protein levels after controlling for confounders (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 CVD-associated protein markers years after pregnancy.
- These findings highlight the potential for using specific protein biomarkers for early CVD risk assessment in women with HDP history.
- Targeted interventions informed by these biomarkers may help mitigate future cardiovascular events in this high-risk 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 toward 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 = 42 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 those 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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