Plasma homocysteine concentration is increased in preeclampsia and is associated with evidence of endothelial activation☆,☆☆,★

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Abstract

Objective: We tested the hypothesis that the independent risk factor for atherosclerosis of increased plasma homocysteine concentration is associated with the pregnancy syndrome of preeclampsia. We further hypothesized that increased plasma homocysteine concentration during pregnancy may advance endothelial dysfunction in preeclampsia by promoting oxidative stress. Study Design: Antepartum blood samples were collected ≥6 hours after the last meal from 33 women with normal, uncomplicated pregnancies and from 21 women with preeclampsia. These plasma samples were analyzed for concentrations of total homocysteine; folate; triglycerides; creatinine; a marker of endothelial activation, cellular fibronectin; and a marker of oxidative stress, malondialdehyde. Results: The mean value of total plasma homocysteine in preeclampsia was significantly higher than that observed in normal pregnancy (P < .04). Similarly, plasma malondialdehyde (P < .001), triglyceride (P < .001), and cellular fibronectin (P < .006) concentrations were also greater in women with preeclampsia than in control subjects. However, no differences were observed between women with preeclampsia and control subjects in folate (P = .97) or creatinine (P = .28) concentrations. Homocysteine concentration did not correlate with plasma creatinine (P = .61), malondialdehyde (P = .32), or triglyceride (P = .89) concentrations. However, cellular fibronectin concentration correlated positively with homocysteine concentration in both women with preeclampsia and control subjects (r = 0.87, P < .0001, and r = 0.50, P < .004, respectively), and folate concentrations were weakly but negatively correlated with homocysteine values (P = .03, r = 0.32). Conclusions: Total plasma homocysteine concentration is increased in preeclampsia and is significantly correlated with cellular fibronectin concentration, suggesting that homocysteine plays a role in promoting endothelial dysfunction in preeclampsia. Furthermore, despite the use of pregnancy multivitamins and no indications of overt folate deficiency in this subject population, homocysteine concentration weakly and negatively correlates with plasma folate concentration. (Am J Obstet Gynecol 1998;179:1605-11.)

Section snippets

Subjects

Fifty-four nulliparous subjects were recruited at admission to labor and delivery at Magee-Womens Hospital as part of an ongoing investigation of preeclampsia. This study was approved by the institutional review board. Twenty-one of the subjects had preeclampsia according to the criteria of hypertension, proteinuria, hyperuricemia, and the reversal of hypertension and proteinuria after pregnancy.7 Hypertension was defined as an increase with respect to values obtained before 20 weeks’ gestation

Results

The clinical characteristics of the patient groups in this study are summarized in Table I.

. Clinical characteristics of the patient groups

Empty CellControl (n = 33)Preeclampsia (n = 21)Significance
Maternal age (y)21.3 ± 3.127.8 ± 6.9P < .0001
Prepregnancy body mass index (kg/m2 )24.6 ± 6.024.7 ± 4.1P = NS
Blood pressure at registration (mm Hg)112/67 ± 11/8116/71 ± 13/9P = NS
Blood pressure at term (mm Hg)117/71 ± 11/5153/95 ± 13/9P < .0001
Gestational age at delivery (wk)37.5 ± 3.333.3 ± 4.2P < .001
Infant

Comment

Increased plasma homocysteine concentration has been recognized as an independent risk factor for coronary artery and peripheral vascular disease for >25 years.2 This risk is proposed to include the modification of endothelial function as a result of homocysteine exposure. The exact mechanism through which homocysteine promotes endothelial dysfunction remains unclear, but it appears to involve both cytotoxic and oxidative stress mechanisms similar to those postulated to promote endothelial

Acknowledgements

We thank Beth Hauth and Marcia Gallaher for their technical assistance, Kirk Conrad, MD, for his helpful discussions regarding metabolic clearance rates, the Clinical Data Core of Program Project Grant, and the nurses and physicians of Magee-Womens Hospital for sample collection.

References (25)

  • RN Taylor et al.

    High plasma cellular fibronectin levels correlate with biochemical and clinical features of preeclampsia but cannot be attributed to hypertension alone

    Am J Obstet Gynecol

    (1991)
  • G Frauscher et al.

    Oral administration of homocysteine leads to increased plasma triglycerides and homocysteic acid: additional mechanisms in homocysteine-induced endothelial damage

    Life Sci

    (1995)

    • Cited by (0)

    ☆

    Supported by National Institutes of Health grants PO1 HD 30367 and NRSA 1 F32 HD08310-01.

    ☆☆

    Reprint requests: Robert Powers, PhD, Magee-Womens Research Institute, 204 Craft Ave, Room 620, Pittsburgh, PA 15213.

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    0002-9378/98 $5.00 + 06/1/92332

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