The Relationship of Plasma Volume, Sympathetic Tone, and Proinflammatory Cytokines in Young Healthy Nonpregnant Women

Objective. Preeclampsia has been associated with elevated proinflammatory markers, increased sympathetic activity, and decreased plasma volume (PV). We hypothesized that these associations would be identified in women prior to a first pregnancy. Methods. We studied 76 healthy nulligravid participants measuring the proinflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha). Plasma volume was measured in supine position and corrected for body mass index (BMI). We examined supine plasma levels of epinephrine and norepinephrine and blood pressure response to Valsalva maneuver to quantify sympathetic activation. We then examined the association of PV and sympathetic activity with proinflammatory cytokines with P < .05 accepted for significance. Results. CRP was significantly increased in participants with lowest PV/BMI quartile when compared to middle 2 quartiles and highest quartile (analysis of variance [ANOVA], P = .037). We found no significant association of PV/BMI with either IL-6 or TNF-alpha. Both plasma epinephrine concentration (r = .29, P = .02) and the late phase II ( phase II_L) blood pressure response to Valsalva maneuver (r = .44, P < .0001) were associated with serum IL-6 concentrations. Conclusions. Low PV is associated with increased CRP levels and increased sympathetic tone is linked to elevated IL-6 concentration in young nonpregnant women. These findings represent elements of a nonpregnancy phenotype that parallels the findings observed in preeclampsia and in women at risk for ischemic cardiovascular disease. This suggests that the relationships observed during preeclampsia, which have been associated with placental pathology, may predate pregnancy and be independent of placental activity.