Oxidative stress markers in hypertensive states of pregnancy: preterm and term disease

Abstract

Discussion continues as to whether de novo hypertension in pregnancy with significant proteinuria (pre-eclampsia; PE) and non-proteinuric new hypertension (gestational hypertension; GH) are parts of the same disease spectrum or represent different conditions. Non-pregnant hypertension, pregnancy and PE are all associated with oxidative stress. We have established a 6 weeks postpartum clinic for women who experienced a hypertensive pregnancy. We hypothesized that PE and GH could be distinguished by markers of oxidative stress; thiobarbituric acid reactive substances (TBARS) and antioxidants (ferric ion reducing ability of plasma; FRAP). Since the severity of PE and GH is greater pre-term, we also compared pre-term and term disease. Fifty-eight women had term PE, 23 pre-term PE, 60 had term GH and 6 pre-term GH, 11 pre-existing (essential) hypertension (EH) without PE. Limited data were available from normotensive pregnancies (n = 7) and non-pregnant controls (n = 14). There were no differences in postpartum TBARS or FRAP between hypertensive states; TBARS (P = 0.001) and FRAP (P = 0.009) were lower in plasma of non-pregnant controls compared to recently-pregnant women. Interestingly FRAP was higher in preterm than term GH (P = 0.013). In PE and GH, TBARS correlated with low density lipoprotein (LDL)-cholesterol (P = 0.036); this association strengthened with inclusion of EH (P = 0.011). The 10 year Framingham index for cardiovascular risk was positively associated with TBARS (P = 0.003). Oxidative stress profiles do not differ between hypertensive states but appear to distinguish between recently-pregnant and non-pregnant states. This suggests that pregnancy may alter vascular integrity with changes remaining 6 weeks postpartum. LDL-cholesterol is a known determinant of oxidative stress in cardiovascular disease and we have shown this association to be present in hypertensive pregnancy further emphasizing that such a pregnancy may be revealing a pre-existing cardiovascular risk.

Keywords: hypertension; oxidative stress; pre-eclampsia; pregnancy; preterm; term.

Figure 1

Lipid peroxidation, measured in units of MDA, shown by prematurity status in the PE and GH diagnostic groups. No differences were observed between hypertensive diagnostic groups or between term and preterm status. The dotted line is the median reference value for non-pregnant females within this assay.

Figure 2

Antioxidant status, measured as FRAP, shown by prematurity status in the PE and GH diagnostic groups. Note the log₁₀ scale. Significantly higher antioxidant status in the GH preterm than the GH term group (P = 0.013). The dotted line is the median reference value for non-pregnant females within this assay.

Figure 3

The relationship between oxidative lipid peroxidation (TBARS-MDA) and LDL-cholesterol at 6 weeks postpartum. A significant positive association was found (R² = 0.053, r = 0.23, P = 0.011).

Figure 4

The relationship between lipid peroxidation, measured by TBARS-MDA, at 6 weeks postpartum, and a cardiovascular disease risk score, the Framingham 10 year index (R² = 0.061, r = 0.248, P = 0.003).