Pirjo Valtonen

Subtle changes in ADMA and l-arginine concentrations in normal pregnancies are unlikely to account for pregnancy-related increased flow-mediated dilatation.

Background:  Our objective was to investigate whether serum concentrations of asymmetric dimethylarginine (ADMA) or l‐arginine correlate to hyperlipidemia or endothelial function in normal pregnancy compared with the non‐pregnant subjects.

Flow mediated vasodilation and circulating concentrations of high sensitive C-reactive protein, interleukin-6 and tumor necrosis factor-α in normal pregnancy – The Cardiovascular Risk in Young Finns Study

Background:  Traditional risk factors such as hyperlipidemia induce a state of inflammation that impairs vascular function. Despite marked maternal hyperlipidemia, endothelial function improves during pregnancy. In non‐pregnant state increased circulating levels of pro‐inflammatory cytokines and high sensitive C‐reactive protein (hsCRP) lead to attenuated flow mediated vasodilation. Relation between endothelial function and pro‐inflammatory cytokines has not been studied thoroughly in pregnancy. The aim of this study was to evaluate the effect of pregnancy on hsCRP and pro‐inflammatory cytokines and their associations with vascular endothelial function.

Blood pressure and heart rate variability analysis of orthostatic challenge in normal human pregnancies.

The aim of the present study was to evaluate pregnancy‐related changes in autonomic regulatory functions in healthy subjects. We studied cardiovascular autonomic responses to head‐up tilt (HUT) in 28 pregnant women during the third trimester of pregnancy and 3 months after parturition. The maternal ECG and non‐invasive beat‐to‐beat blood pressure were recorded in the horizontal position (left‐lateral position) and during HUT in the upright position. Stroke volume was assessed from blood pressure signal by using the arterial pulse contour method. Heart rate variability (HRV) was analysed in frequency domain, and baroreflex sensitivity by the cross‐spectral and the sequence methods. In the horizontal position, all frequency components of HRV were lower during pregnancy than 3 months after parturition (P < 0·01 to <0·001), while pregnancy had no influence on normalized low frequency and high frequency powers. During pregnancy haemodynamics was well balanced with only minor changes in response to postural change while haemodynamic responses to HUT were more remarkable after parturition. In pregnant women HRV and especially its very low frequency component increased in response to HUT, whereas at 3 months after parturition the direction of these changes was opposite. Parasympathetic deactivation towards term is likely to contribute to increased heart rate and cardiac output at rest, whereas restored sympathetic modulation with modest responses may contribute stable peripheral resistance and sufficient placental blood supply under stimulated conditions. It is important to understand cardiovascular autonomic nervous system and haemodynamic control in normal pregnancy before being able to judge whether they are dysregulated in complicated pregnancies.

Need for insulin to control gestational diabetes is reflected in the ambulatory arterial stiffness index

BackgroundThe aim was to evaluate the metabolic profile in conjunction with vascular function using the ambulatory arterial stiffness index (AASI) in women with uncomplicated pregnancies and in women with gestational diabetes mellitus (GDM).MethodsPlasma glucose, lipids, HOMA –IR (homeostasis model assessment of insulin resistance) and AASI, as obtained from 24-hour ambulatory blood pressure monitoring in third trimester pregnancy and at three months postpartum, were measured in three groups of women: controls (N = 32), women with GDM on diet (N = 42) and women with GDM requiring insulin treatment (N = 10).ResultsWomen with GDM had poorer glycemic control and higher HOMA-IR during and after pregnancy and their total and LDL (low density lipoprotein) cholesterol levels were significantly higher after pregnancy than in the controls. After delivery, there was an improvement in AASI from 0.26 ± 0.10 to 0.17 ± 0.09 (P = 0.002) in women with GDM on diet, but not in women with GDM receiving insulin whose AASI tended to worsen after delivery from 0.30 ± 0.23 to 0.33 ± 0.09 (NS), then being significantly higher than in the other groups (P = 0.001-0.047).ConclusionsWomen with GDM had more unfavorable lipid profile and higher blood glucose values at three months after delivery, the metabolic profile being worst in women requiring insulin. Interestingly, the metabolic disturbances at three months postpartum were accompanied by a tendency towards arterial stiffness to increase in women requiring insulin.

Carotid artery elasticity decreases during pregnancy - the Cardiovascular Risk in Young Finns study

BackgroundThe aims were to evaluate the effect of pregnancy on carotid artery elasticity and determine the associations between maternal lipids, endothelial function and arterial elasticity during pregnancy.MethodsWe examined 99 pregnant and 99 matched non-pregnant control women as part of a population-based prospective cohort study. Carotid artery elasticity indexes; carotid artery distensibility (CAD), Young’s elastic modulus (YEM) and stiffness index (SI) as well as brachial artery flow-mediated dilation (FMD) were assessed using ultrasound; serum lipid levels were also determined.ResultsSI was 57% and YEM 75% higher and CAD 36% lower in the third trimester group than the corresponding values in the first trimester group. Serum cholesterol and triglyceride levels were significantly higher in women at the end of the pregnancy than at the beginning of pregnancy (P < 0.001) and in controls (P < 0.001). In multivariate analysis, gestational age was the only independent correlate of arterial elasticity in pregnant women. In controls, age (P ≤ 0.001) and common carotid diameter (P = 0.001-0.029) were associated with SI, YEM and CAD.ConclusionsThe present study revealed that carotid artery elasticity declined towards the end of the pregnancy; this neither is straight correlating with maternal hyperlipidemia or the diameter of the carotid artery nor is it associated with changes in endothelial function.

Flow-Mediated Vasodilation Is Not Attenuated in Hypertensive Pregnancies Despite Biochemical Signs of Inflammation

Background. Our objective was to evaluate endothelial function and markers of inflammation during and after pregnancy in normal pregnancies compared to pregnancies complicated with hypertension or preeclampsia (PE). Methods and Results. We measured endothelium-dependent brachial artery flow-mediated vasodilation (FMD) and high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) in 32 women with normal pregnancy and in 28 women whose pregnancy was complicated with hypertensive disorder in the second half of pregnancy and minimum 3-month postpartum. Enhancement of endothelial function was greater in hypertensive than normal pregnancies, the mean FMD% being 11.0% versus 8.8% during pregnancy (P = 0.194) and 8.0% versus 7.9% postpartum (P = 0.978). Concentrations of markers of inflammation were markedly increased in pregnant hypertensive group compared to those after delivery (hsCRP 4.5 versus 0.80 mg/L, P = 0.023, IL-6 2.1 versus 1.2 pg/mL, P = 0.006; TNF-α 1.9 versus 1.5 pg/mL, P = 0.030). There were no statistically significant associations between the markers of inflammation and FMD. Conclusions. Brachial artery FMD was not attenuated in the third trimester hypertensive pregnancies compared to normal pregnancies, whereas circulating concentrations of hsCRP and IL-6 and TNF-α reacted to hypertensive complications.

Ambulatory arterial stiffness index is unchanged in uncomplicated third-trimester singleton and twin pregnancies

Objective. To document the ambulatory arterial stiffness index (AASI) during pregnancy compared to three months after delivery in singleton and twin pregnancies. Design. Descriptive study with a follow‐up design. Setting. University hospital in Eastern Finland. Population. 43 childbearing women; 32 with singleton and 11 with twin pregnancies. Methods. Ambulatory blood pressure measurements were conducted using a digital ambulatory blood pressure system. AASI was calculated as 1 minus the regression slope of diastolic on systolic blood pressures obtained from 24‐hour monitoring. Main Outcome Measures. Arterial stiffness measured by AASI. Results. In normotensive pregnant women, the 95th percentiles of AASI were 0.40 in singleton and 0.46 in twin pregnancies, respectively, implying arterial normality and high elasticity. There were no differences in AASI values between singleton and twin pregnancies and no changes were observed postpartum. After delivery, but not during pregnancy, AASI correlated negatively with nocturnal systolic and diastolic blood pressure reduction (dipping) (r=−0.536, p=0.001; r=−0.674, p<0.001) and with maternal HDL (r=−0.363, p=0.038) and positively with maternal age (r=0.440, p=0.009), whereas maternal BMI had a significant impact on AASI both during and after pregnancy (r=0.366, p=0.016; r=0.377, p=0.028). Conclusions. Normal singleton or twin pregnancies had no detectable effects on AASI. However, pregnancy appeared to overcome the negative effects of low high‐density lipoproteins, unfavorable dipping status and advanced maternal age on arterial stiffness, but not the effect caused by maternal body mass index.

Gestational diabetic patients with adequate management have normal cardiovascular autonomic regulation during the third trimester of pregnancy and 3 months after delivery

OBJECTIVE The aim of the present study was to evaluate the influence of gestational diabetes mellitus (GDM) on hemodynamics and cardiovascular autonomic regulation at rest and their responses to head-up tilt (HUT). RESEARCH DESIGN AND METHODS We prospectively studied 79 pregnant women (51 with GDM, 28 without GDM) during the third trimester of pregnancy and after parturition. The maternal electrocardiogram and arterial blood pressure were noninvasively measured. Heart rate and blood pressure were measured in the supine position and in the upright position. Stroke volume was assessed from noninvasive blood pressure signals, heart rate variability (HRV) was analyzed in frequency domain, and baroreflex sensitivity by the cross-spectral and sequence methods. RESULTS Between the GDM group and control pregnant women there were no significant differences in hemodynamics and cardiovascular autonomic regulation throughout the protocol. Increased normalized low-frequency component and low-frequency to high-frequency ratio suggested a change in sympathovagal balance towards sympathetic predominance during pregnancy in both groups. The response to head-up tilt (HUT) was similar in both GDM and control pregnant women. The pregnancy modulated the response to HUT in systolic and diastolic blood pressure, stroke volume, cardiac index, peripheral resistance, total power of HRV, and its low- and high-frequency components. CONCLUSIONS Our results suggest that pregnancy modulates cardiovascular autonomic regulation and hemodynamics equally in subjects with GDM and without GDM, suggesting that metabolic disorder during pregnancy does not result in cardiovascular dysfunction when GDM is in good balance.

ADMA concentration changes across the menstrual cycle and during oral contraceptive use: the Cardiovascular Risk in Young Finns Study

OBJECTIVE The aim of this study was to evaluate changes in the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) levels during different menstrual cycle phases in young adult women with or without oral contraceptive (OC) use. DESIGN AND METHODS The subjects (n=1079) originated from a large population-based, prospective cohort study conducted in Finland. Plasma ADMA, symmetric dimethylarginine (SDMA), L-arginine, C-reactive protein, creatinine, and brachial artery flow-mediated dilatation (FMD) were measured. The use of OCs and menstrual cycle phase were determined from a questionnaire. RESULTS In non-OC users, ADMA (P=0.017), L-arginine (P=0.002), and ADMA/SDMA ratio (P<0.001) were significantly lower in the luteal phase than in the follicular phase of the menstrual cycle. Non-OC users also had significantly higher ADMA and SDMA concentrations (P<0.001) and lower L-arginine concentrations (P<0.001) compared to OC users of estrogen-containing pills. Progestin-only contraceptive pills (POPs) did not lower the ADMA level, but maintained it at the same level as in non-OC users. In OC users, there were no significant differences found in ADMA, FMD, or FMD% across menstrual cycle, whereas brachial artery diameter was significantly more decreased in the luteal phase (P=0.013) than in the follicular phase. CONCLUSION We observed that the circulating ADMA concentration varies across the menstrual cycle in young women not using OCs, and women on OCs displayed significantly lower circulating ADMA concentrations than non-OC users, though this was not the case with POP contraception.

Maternal serum ADMA is not associated with proinflammatory cytokines or C-reactive protein during normal pregnancy

Normal pregnancy is associated with changes in the immune system. We studied whether asymmetrical dimethylarginine (ADMA) is associated with this immune system change by assaying high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). The cytokine and dimethylarginine serum concentrations were determined from women with normal pregnancy (n=77) and healthy non-pregnant controls (n=61) matched for age and smoking status as a part of a large population-based, prospective cohort study conducted in Finland. The hsCRP levels were significantly elevated in the second (P=0.016) and third trimesters (P=0.001) of pregnancy compared to the levels of non-pregnant women. IL-6 levels were significantly higher in the third trimester (P=0.029) of pregnancy than in non-pregnant state. TNF-alpha concentrations did not change significantly during pregnancy. ADMA and SDMA concentrations were significantly lower during pregnancy compared to the levels of non-pregnant women (P<0.001). There was no significant association between ADMA and inflammation markers regardless of the elevated serum concentrations of hsCRP and IL-6 in the third trimester of normal pregnancy. These results suggest that maternal systemic ADMA and SDMA concentrations are more likely to become decreased due to the hemodilution and increased renal clearance than being directly influenced by the change of cytokines during pregnancy.