C-reactive protein and later preeclampsia

Rebelo, Fernanda; Schlüssel, Michael Maia; Vaz, Juliana dos Santos; Franco‐Sena, Ana Beatriz; Pinto, Thatiana de Jesus Pereira; Bastos, Francisco I.; Adegboye, Amanda Rodrigues Amorim; Kac, Gilberto

doi:10.1097/hjh.0b013e32835b0556

Cited by 66 publications

(37 citation statements)

References 56 publications

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“…The apparent discrepancy can be explained by differences in the timing of venipuncture, or methodological differences (including variation in study population and laboratory methods). The observation that CRP concentrations are higher in women with PE than in those with uncomplicated pregnancies at the time of diagnosis is consistent with previous studies (60, 149–158), and may partly explain prior observations that patients with PE are at an increased risk of cardiovascular events in later life (102–112). …”

Section: Discussionsupporting

confidence: 90%

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Maternal plasma soluble TRAIL is decreased in preeclampsia

Chaemsaithong¹,

Chaiworapongsa²,

Romero³

et al. 2013

The Journal of Maternal-Fetal & Neonatal Medicine

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Objective Preeclampsia (PE) is characterized by systemic intravascular inflammation. Women who develop PE are at an increased risk for cardiovascular disease in later life. Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) has anti-atherosclerotic effects in endothelial cells and can mediate neutrophil apoptosis. Low soluble TRAIL (sTRAIL) and high C-reactive protein (CRP) concentrations are associated with an increased risk of future cardiovascular disease in non-pregnant individuals. The aim of this study was to determine whether maternal plasma concentrations of sTRAIL and CRP differ between women with PE and those with uncomplicated pregnancies. Methods This cross-sectional study included women with an uncomplicated pregnancy (n=93) and those with PE (n=52). Maternal plasma concentrations of sTRAIL and CRP concentrations were determined by ELISA. Results 1) The median plasma sTRAIL concentration (pg/mL) was significantly lower and the median plasma CRP concentration was significantly higher in women with PE than in those with an uncomplicated pregnancy (25.55 vs. 29.17; p = 0.03 and 8.0 vs. 4.1; p=0.001, respectively); 2) the median plasma concentration sTRAIL/CRP ratio was twofold lower in women with PE than in those with an uncomplicated pregnancy (p<0.001); and 3) women with plasma sTRAIL and CRP ratio in the lowest quartile were eight times more likely to have PE than women with concentrations in the upper three quartiles (OR 8.9; 95% CI: 2.8–27.8). Conclusion Maternal plasma sTRAIL concentrations are lower (while those of CRP are higher) in women with PE than in those with uncomplicated pregnancies. These findings are consistent with the evidence of intravascular inflammation in this disorder.

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Section: Discussionsupporting

confidence: 90%

“…A solid body of evidence has shown that CRP is a major predictor of the subsequent risk of cardiovascular disease in non-pregnant subjects (135–148). CRP is also known to be elevated in women with PE before (60, 149–153) and at the time of diagnosis (154–158). …”

Section: Introductionmentioning

confidence: 99%

Maternal plasma soluble TRAIL is decreased in preeclampsia

Chaemsaithong¹,

Chaiworapongsa²,

Romero³

et al. 2013

The Journal of Maternal-Fetal & Neonatal Medicine

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“…The extent to which changes in this largely IL-6 and TNFα driven biomarker of inflammation are due to activation of classical innate immune responses or other cells (i.e. adipocytes or necrotic processes associated with placenta ageing) is under active investigation [83, 87, 88]. Interestingly, several groups have found undetectable changes or decreases in CRP over the course of healthy pregnancy [83, 89–92].…”

Section: Discussionmentioning

confidence: 99%

In vivo immune signatures of healthy human pregnancy: Inherently inflammatory or anti-inflammatory?

et al. 2017

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Changes in maternal innate immunity during healthy human pregnancy are not well understood. Whether basal immune status in vivo is largely unaffected by pregnancy, is constitutively biased towards an inflammatory phenotype (transiently enhancing host defense) or exhibits anti-inflammatory bias (reducing potential responsiveness to the fetus) is unclear. Here, in a longitudinal study of healthy women who gave birth to healthy infants following uncomplicated pregnancies within the Canadian Healthy Infant Longitudinal Development (CHILD) cohort, we test the hypothesis that a progressively altered bias in resting innate immune status develops. Women were examined during pregnancy and again, one and/or three years postpartum. Most pro-inflammatory cytokine expression, including CCL2, CXCL10, IL-18 and TNFα, was reduced in vivo during pregnancy (20–57%, p<0.0001). Anti-inflammatory biomarkers (sTNF-RI, sTNF-RII, and IL-1Ra) were elevated by ~50–100% (p<0.0001). Systemic IL-10 levels were unaltered during vs. post-pregnancy. Kinetic studies demonstrate that while decreased pro-inflammatory biomarker expression (CCL2, CXCL10, IL-18, and TNFα) was constant, anti-inflammatory expression increased progressively with increasing gestational age (p<0.0001). We conclude that healthy resting maternal immune status is characterized by an increasingly pronounced bias towards a systemic anti-inflammatory innate phenotype during the last two trimesters of pregnancy. This is resolved by one year postpartum in the absence of repeat pregnancy. The findings provide enhanced understanding of immunological changes that occur in vivo during healthy human pregnancy.

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“…Levels of CRP are significantly elevated in women who go on to develop preeclampsia compared to those who remain normotensive throughout pregnancy (14, 15). Additionally, variants in the CRP gene have been found to be associated with an increased risk for preeclampsia development (16, 17).…”

Section: Introductionmentioning

confidence: 99%

Genetic predisposition to elevated levels of C-reactive protein is associated with a decreased risk for preeclampsia

Spracklen

Smith

Saftlas

et al. 2016

Hypertension in Pregnancy

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Objective To examine the association between genetic predisposition to elevated C-reactive protein and risk for preeclampsia using validated genetic loci for C-reactive protein. Methods Preeclampsia cases (n=177) and normotensive controls (n=116) were selected from live birth certificates to nulliparous Iowa women during the period August 2002–May 2005. Disease status was verified by medical chart review. Genetic predisposition to CRP was estimated by a genetic risk score on the basis of established loci for CRP levels. Logistic regression analyses were used to evaluate the relationships between the genotype score and preeclampsia. Replication analyses were performed in an independent, US population of preeclampsia cases (n=516) and controls (n=1,097) of European ancestry. Results The GRS related to higher levels of CRP demonstrated a significantly decreased risk of preeclampsia (OR 0.89, 95% CI 0.82–0.96). When the GRS was analyzed by quartile, an inverse linear trend was observed (p=0.0006). Results were similar after adjustments for body mass index (BMI), smoking, and leisure-time physical activity. In the independent replication population, the association with the CRP GRS was also marginally significant (OR 0.97, 95% CI 0.92, 1.02). Meta-analysis of the two studies was statistically significant (OR 0.95, 95% CI 0.90, 0.99). Conclusion Our data suggest an inverse, counterintuitive association between the genetic predisposition to elevated levels of CRP and a decreased risk of preeclampsia. This suggests blood CRP level is a marker of preeclampsia but it does not appear to be a factor on the causal pathway.

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C-reactive protein and later preeclampsia

Abstract: The pooled WMD suggest that women with higher levels of CRP may have an increased risk of developing preeclampsia. This association seems to be modified by confounders, such as BMI. Further studies of high methodological quality are needed.

Cited by 66 publications

References 56 publications

Maternal plasma soluble TRAIL is decreased in preeclampsia

Maternal plasma soluble TRAIL is decreased in preeclampsia

In vivo immune signatures of healthy human pregnancy: Inherently inflammatory or anti-inflammatory?

Genetic predisposition to elevated levels of C-reactive protein is associated with a decreased risk for preeclampsia

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