Endothelial function is well preserved in obese patients with mild obstructive sleep apnea.

PURPOSE: Endothelial dysfunction is one of the early markers of cardiovascular complications in obstructive sleep apnea (OSA). The aim of our study was to evaluate whether overweight patients with mild OSA displayed endothelial dysfunction, and to assess the effect of 1-year lifestyle intervention with an early very low calorie diet in endothelial function. METHODS: At baseline, the study population consisted of 83 overweight patients with mild OSA and 46 weight-matched non-OSA subjects. OSA patients were further randomized into a 1-year supervised lifestyle intervention group or control group which received routine lifestyle counselling. Endothelial function measured by brachial artery flow-mediated dilatation (FMD), apnea-hypopnea index (AHI), body mass index (BMI), and metabolic parameters were assessed at baseline and 12 months. RESULTS: No correlations between endothelial function and mild OSA were detected. However, patients with impaired endothelial function had lower mean saturation and impaired endothelial function correlated significantly with glucose intolerance and dyslipidemia. After the lifestyle intervention and successful weight reduction, AHI, BMI, serum triglycerides and insulin improved significantly; however, no improvement in FMD was detected. CONCLUSIONS: Mild OSA was not observed to be associated with endothelial dysfunction. Although in mild OSA endothelial function is still preserved, lifestyle intervention with weight reduction did achieve an improvement in other obesity-related risk factors for cardiovascular diseases, thus highlighting the importance of early intervention.

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

BACKGROUND: The 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). METHODS: Plasma 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). RESULTS: Women 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). CONCLUSIONS: Women 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.

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.

Estimation of arterial baroreflex sensitivity in relation to carotid artery stiffness.

Arterial baroreflex has a significant role in regulating blood pressure. It is known that increased stiffness of the carotid sinus affects mecanotransduction of baroreceptors and therefore limits baroreceptors capability to detect changes in blood pressure. By using high resolution ultrasound video signal and continuous measurement of electrocardiogram (ECG) and blood pressure, it is possible to define elastic properties of artery simultaneously with baroreflex sensitivity parameters. In this paper dataset which consist 38 subjects, 11 diabetics and 27 healthy controls was analyzed. Use of diabetic and healthy test subjects gives wide scale of arteries with different elasticity properties, which provide opportunity to validate baroreflex and artery stiffness estimation methods.

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.

Cardiovascular autonomic responses to head-up tilt in gestational hypertension and normal pregnancy.

AIMS: The aim of the present study was to evaluate the influence of gestational hypertension on hemodynamics and cardiovascular autonomic regulation at rest and their responses to head-up tilt (HUT). We prospectively studied 56 pregnant women (28 with gestational hypertension and 28 healthy pregnant women) during the third trimester of pregnancy and 3 months after pregnancy. MAJOR FINDINGS: In women with pregnancy-induced hypertension, compared with control women, there were significant differences in hemodynamics and in markers of cardiovascular regulation (p < 0.05 to p < 0.001). Postural change from the supine to the upright position was associated with significant changes in hemodynamic responses in both groups during pregnancy (from p < 0.05 to p < 0.001). Regulatory response to HUT in both groups was characterized with a decrease in HF power and increase in LF/HF ratio (from p < 0.01 to p < 0.001). Responses to HUT in total power and VLF power were attenuated in hypertensive pregnancies (p < 0.001 to p < 0.01, respectively, vs control group). CONCLUSIONS: Our results suggest that autonomic cardiovascular regulation may not play a major role in women with gestational hypertension . The lack of irreversible changes in autonomic nervous function in hypertensive women appeared to be a feature of gestational-induced hypertension.

Tracking serum lipid levels and the association of cholesterol concentrations, blood pressure and cigarette smoking with carotid artery intima-media thickness in young adults born small for gestational age.

BACKGROUND: Small birth size is associated with increased cardiovascular disease risk, but the mediating factors are poorly understood. METHODS AND RESULTS: Serum lipids, blood pressure (BP), carotid artery intima-media thickness (CA-IMT), and brachial artery flow-mediated dilatation (BA-FMD) were studied in 70 20-year-old subjects [35 sex- and age-matched pairs born small (SGA) and appropriate for gestational age (AGA)]. The SGA subjects had higher serum levels of low-density lipoprotein (LDL) cholesterol, total/high-density lipoprotein (HDL) and LDL/HDL cholesterol ratios, and lower HDL cholesterol levels than the AGA subjects (2.71 vs 2.37 mmol/L, P<0.05; 3.12 vs 2.80, P<0.01; 1.98 vs 1.61, P=0.002; 1.43 vs 1.56 mmol/L, P<0.05, respectively). In the SGA group, total and LDL cholesterol levels correlated inversely with adult height SD score (r=0.463, P=0.006 and r=0.413, P=0.015, respectively). CA-IMT or BA-FMD did not differ between the groups, but cigarette smoking, higher diastolic BP, and shorter birth length associated with higher CA-IMT in the whole study population. A clear tracking of cholesterol levels was found from 12 to 20 years. CONCLUSIONS: SGA subjects had more unfavorable lipid profiles than the controls, the shortest having the highest LDL cholesterol. Cigarette smoking, higher diastolic BP, and shorter birth length associated with higher CA-IMT in the whole study population. A clear tracking of cholesterol levels through adolescence enables early targeting of lifestyle counseling for reducing cardiovascular disease risk.

A principal component regression approach for estimation of ventricular repolarization characteristics.

The time interval between Q-wave onset and T-wave offset, i.e., QT interval, in an ECG corresponds to the total ventricular activity, including both depolarization and repolarization times. It has been suggested that abnormal QT variability could be a marker of cardiac diseases such as ventricular arrhythmias, and QT-interval has also been observed to lengthen during hypoglycemia. In this paper, we propose a robust method for estimating ventricular repolarization characteristics such as QT interval and T-wave amplitude. The method is based on principal component regression. In the method, QT epochs are first extracted from ECG in respect of R-waves. Then, correlation matrix of the extracted epochs is formed and its eigenvectors computed. The most significant eigenvectors are then fitted to the data to obtain noise-free estimates of QT epochs. Nonstationarities in QT-epoch characteristics can also be modeled by updating the eigenvectors dynamically. The main benefit of the proposed method is robustness to noise, i.e., it works also when using ECGs that have low SNR, for example, signals measured during normal-life environments. One application of the proposed method could be the detection of the hypoglycemia.

Women with hypertensive pregnancies have difficulties in regaining pre-pregnancy weight and show metabolic disturbances.

The aim was to determine maternal weight gain and body composition during pregnancy and 3 months postpartum in women with uncomplicated singleton and twin pregnancies and in women with gestational diabetes (GDM) and gestational hypertension (GH). This prospective study includes four groups of subjects: those with an uncomplicated pregnancy (n = 32), those with a diagnosis of GH (n = 28), those with a diagnosis of GDM (n = 52), and those with twin pregnancy (n = 11). Their body compositions were estimated by a bioimpedance analysis and fasting lipids and glucose levels were determined during the pregnancy and 3 months after pregnancy. Women with GDM were 11.7 kg heavier than the reference group before pregnancy, whereas weight before pregnancy was not different in other investigated groups. Weight loss after delivery was attenuated in GH group. Percentage body fat remained elevated in women with GDM (34.1 +/- 7.0%) and hypertension (31.5 +/- 6.4%) at 3 months after pregnancy. Also their total cholesterol and low-density lipoprotein (LDL)-cholesterol levels as well as fasting glucose remained elevated in comparison to values of the reference group. In conclusion, women with hypertensive pregnancies, though not overweight before pregnancy, gain and retain excess gestational weight and this leads to metabolic abnormalities similar to those seen in women GDM. Thus, postpartum period appears to be critical for weight management and interventional programs are called for.

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.

Flow mediated vasodilation and circulating concentrations of high sensitive C-reactive protein, interleukin-6 and tumor necrosis factor-alpha 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. METHODS: As part of population-based, prospective cohort Cardiovascular Risk in Young Finns study conducted in Finland we measured brachial artery flow mediated dilation (FMD) and serum concentrations of hsCRP, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in 57 pregnant Finnish women throughout gestation and 62 control women matched for age and smoking. RESULTS: HsCRP-concentration was greater in pregnancy compared to non-pregnant controls (median hsCRP 2.52 mg l(-1) versus 1.21 mg l(-1), P<0.001). IL-6-concentration was slightly increased in pregnancy compared with the non-pregnant controls (median 1.66 versus 1.32 mg l(-1), non-significant [NS]) and TNF-alpha-concentration was slightly decreased in pregnant group (2.11 versus 2.38 pg ml(-1), NS). FMD increased during pregnancy and IL-6 had a positive correlation to the FMD in pregnancy (R = 0.288, P = 0.031). CONCLUSIONS: Improvement of FMD in normal pregnancy was not affected by increase in hsCRP concentration. We found an association with IL-6 and FMD but we believe that improvement in endothelial function during normal pregnancy is not caused by variation in hsCRP, IL-6 or TNF-alpha.

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.

Serum L-homoarginine concentration is elevated during normal pregnancy and is related to flow-mediated vasodilatation.

BACKGROUND: Normal pregnancy is associated with enhanced vasodilatation because of the increased nitric oxide (NO) production. Because L-homoarginine can act as a substrate for NO production, concentrations of L-homoarginine in normal pregnancy were assessed in the present study to test whether L-homoarginine is associated with endothelial function. METHODS AND RESULTS: Healthy non-pregnant (n=61) and pregnant women (n=58) were studied in a cross-sectional study. L-homoarginine, L-arginine, asymmetric dimethylarginine and symmetric dimethylarginine concentrations were determined simultaneously by high-performance liquid chromatography. Endothelium-dependent brachial artery flow-mediated dilation (FMD) was measured by ultrasound. The serum L-homoarginine concentration was significantly higher during the second and the third trimesters compared with the levels in the non-pregnant women (4.8+/-1.7 and 5.3+/-1.5 vs 2.7+/-1.0 micromol/L, p<0.001, respectively). In line with this, FMD increased in response to pregnancy (p<0.05). Three months after delivery, the L-homoarginine concentrations and FMD were comparable to those recorded in the non-pregnant females. The concentration of L-homoarginine correlated significantly with gestational age (r=0.426, p=0.001) and brachial artery diameter and FMD (r=0.362, p=0.006 and r=0.306, p=0.022, respectively) in pregnancy. CONCLUSIONS: L-homoarginine appears to be increased during the second and third trimesters of pregnancy and may contribute to the enhanced endothelial function in normal pregnancies.

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.

Electrocardiographic alterations during hyperinsulinemic hypoglycemia in healthy subjects.

BACKGROUND: We evaluated the arrhythmogenic potential of hypoglycemia by studying electrocardiographic (ECG) changes in response to hyperinsulinemic hypoglycemia and associated sympathoadrenal counterregulatory responses in healthy subjects. METHODS: The study population consisted of 18 subjects, aged 30-40 years. Five-minute ECG recordings and blood samplings were performed at baseline and during the euglycemic and hypoglycemic hyperinsulinemic clamp studies. PR, QT, and QTc intervals of electrocardiogram and ECG morphology were assessed from signal-averaged ECG. RESULTS: Although cardiac beat interval remained unchanged, PR interval decreased (P < 0.01) and QTc interval (P < 0.001) increased in response to hyperinsulinemic hypoglycemia. Concomitant morphological alterations consisted of slight increases in R-wave amplitude and area (P < 0.01 for both), significant decreases in T-wave amplitude and area (P < 0.001 for both), and moderate ST depression (P < 0.001). Counterregulatory norepinephrine response correlated with amplification of the R wave (r =-0.620, P < 0.05) and epinephrine response correlated with flattening of the T wave (r =-0.508, P < 0.05). CONCLUSIONS: Hyperinsulinemic hypoglycemia with consequent sympathetic humoral activation is associated with several ECG alterations in atrioventricular conduction, ventricular depolarization, and ventricular repolarization. Such alterations in cardiac electrical function may be of importance in provoking severe arrhythmias and "dead-in-bed" syndrome in diabetic patients with unrecognized hypoglycemic episodes.

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. METHODS AND RESULTS: As a part of population-based, prospective cohort Cardiovascular Risk in Young Finns study conducted in Finland we examined 57 pregnant Finnish women throughout gestation and 62 control women matched for age and smoking. Serum glucose, triglycerides (TG), total cholesterol (TC), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C) and ADMA, symmetric dimethylarginine (SDMA) and l-arginine were determined concomitantly with endothelium-dependent brachial artery flow-mediated dilation (FMD), measured by ultrasound. All serum lipid concentrations were significantly higher in pregnant women than in non-pregnant women (P < 0.001 for each). The mean serum ADMA concentration in pregnant women was significantly lower compared with the non-pregnant controls (0.513 micromol l(-1) +/- 0.0593 versus 0.577 micromol l(-1) +/- 0.0710, P < 0.001). Lowered ADMA concentrations did not correlate statistically to FMD in these healthy pregnant women but FMD was enhanced towards the end of pregnancy. CONCLUSIONS: ADMA and l-arginine concentrations fall in normal pregnancy despite marked hypercholesterolemia. Endothelium-dependent vasodilation is enhanced in normal pregnancy but is not statistically correlated to maternal serum ADMA or l-arginine concentrations.

Effects of plant stanol esters on serum cholesterol concentrations, relative markers of cholesterol metabolism and endothelial function in type 1 diabetes.

We investigated the effect of plant stanol esters (STAEST) on serum total and LDL cholesterol concentrations and endothelial function in subjects with type 1 diabetes (T1D). In addition, the changes in the relative serum markers of cholesterol metabolism were recorded. In a parallel, randomized, double-blind study the intervention group (n = 11) consumed STAEST spread (2g/day stanols) and the control group (n=8) the same spread containing no added stanols for 12 weeks. At baseline, brachial artery diameter was negatively correlated with serum HDL cholesterol concentration (r = -0.476, P < 0.05), but not with total or LDL cholesterol concentrations or serum non-cholesterol sterol ratios to cholesterol. Flow-mediated dilatation was positively associated with serum absorption marker ratios to cholesterol, significantly so with the sitosterol ratio (r = 0.467, P < 0.05). During the intervention, serum total and LDL cholesterol concentrations were reduced by 4.9 and 6.9% from baseline in the STAEST group, and by 10.8 and 16.1% from controls, respectively (P < 0.05 for all). No significant changes in HDL cholesterol and serum triglyceride concentrations were found. The STAEST consumption reduced serum campesterol and sitosterol ratios by 17-21% (P<0.05) from baseline, but the relative serum synthesis markers were not changed. Brachial artery diameter and flow-mediated dilatation did not change during the investigation. In conclusion, STAEST significantly reduced serum total and LDL cholesterol concentrations and serum plant sterol ratios without affecting HDL and triglyceride concentrations in subjects with T1D. STAEST had no effect on endothelial function.

Pregnancy-related hyperlipidemia and endothelial function in healthy women.

BACKGROUND: The purpose of the present study was to investigate pregnancy-related changes in the maternal serum lipid profile and endothelial function. METHODS AND RESULTS: As part of the population-based, prospective cohort Cardiovascular Risk in Young Finns study conducted in Finland, 57 pregnant Finnish women and 62 control women matched for age and smoking were examined throughout gestation. Serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined and concomitantly endothelium-dependent brachial artery flow mediated dilation (FMD) was measured by ultrasound. During pregnancy serum TC, LDL-C, HDL-C, TG and very-low-density lipoprotein cholesterol increased significantly when compared with the non-pregnant state (p<0.001 for each) and towards the end of pregnancy (p<0.001, p<0.001, p=0.007, p<0.001, p<0.001). FMD increased towards the end of pregnancy and there was a statistically significant direct correlation between gestational age and FMD% (r=0.345, p=0.010). Brachial artery diameter at rest and FMD% were negatively correlated in pregnant (r=-0.280, p=0.035) and non-pregnant women (r=-0.360, p<0.004). The univariate correlation analysis showed a direct correlation between maternal serum TC (r=0.333, p=0.012) and TG (r=0.366, p=0.006) and FMD%, whereas a negative non-significant correlation was found in non-pregnant women. In a multivariate model, vessel size (beta=-0.436, p=0.001) and TG (beta=0.502, p<0.001) were the most powerful predictors for FMD% in pregnancy, the influence of other lipids was non-significant. CONCLUSIONS: In healthy pregnant women increased gestational age is associated with improved endothelium-dependent vasodilation responses regardless of concurrently appearing lipid changes.

Endothelial function in hypercholesterolemic subjects: Effects of plant stanol and sterol esters.

We investigated the effects of stanol (STAEST) and sterol esters (STEEST) on endothelial function in hypercholesterolemic subjects. In addition, associations of variables of cholesterol metabolism with endothelial function were investigated. In a double-blind randomized cross-over study (n=39) with age-matched parallel control group (n=37) the subjects consumed STAEST or STEEST spread (total plant sterols and stanols 1.93-1.98g/day) for 10 weeks each. Controls consumed the spread without sterols or stanols for 20 weeks. At baseline, brachial artery diameter was positively correlated with serum triglycerides (r=0.375, p=0.001) and glucose (r=0.420, p<0.001) and with cholesterol synthesis marker ratios to cholesterol (e.g. desmosterol r=0.540, p<0.001) and negatively with HDL cholesterol (r=-0.309, p=0.008) and absorption marker ratios (e.g. campesterol r=-0.332, p=0.004). During the intervention, LDL cholesterol was reduced by 6-9% from baseline with STAEST and STEEST spreads (p<0.05), and by 9-12%, respectively, from controls (p<0.05). Flow-mediated dilatation did not change during the investigation. Brachial artery diameter was unchanged in controls and during STAEST periods, but it was reduced during STEEST by 2.2% (p=0.012) from STAEST. In conclusion, variables of cholesterol metabolism are associated with brachial artery diameter at baseline. STEEST diminishes brachial artery diameter, but its clinical relevance remains unclear.