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Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension.

BACKGROUND Olive oil polyphenols have been associated with several cardiovascular health benefits. This study aims to examine the influence of a polyphenol-rich olive oil on blood pressure (BP) and endothelial function in 24 young women with high-normal BP or stage 1 essential hypertension. METHODS We conducted a double-blind, randomized, crossover dietary-intervention study. After a run-in period of 4 months (baseline values), two diets were used, one with polyphenol-rich olive oil (∼30 mg/day), the other with polyphenol-free olive oil. Each dietary period lasted 2 months with a 4-week washout between diets. Systolic and diastolic BP, serum or plasma biomarkers of endothelial function, oxidative stress, and inflammation, and ischemia-induced hyperemia in the forearm were measured. RESULTS When compared to baseline values, only the polyphenol-rich olive oil diet led to a significant (P < 0.01) decrease of 7.91 mm Hg in systolic and 6.65 mm Hg of diastolic BP. A similar finding was found for serum asymmetric dimethylarginine (ADMA) (-0.09 ± 0.01 µmol/l, P < 0.01), oxidized low-density lipoprotein (ox-LDL) (-28.2 ± 28.5 µg/l, P < 0.01), and plasma C-reactive protein (CRP) (-1.9 ± 1.3 mg/l, P < 0.001). The polyphenol-rich olive oil diet also elicited an increase in plasma nitrites/nitrates (+4.7 ± 6.6 µmol/l, P < 0.001) and hyperemic area after ischemia (+345 ± 386 perfusion units (PU)/sec, P < 0.001). CONCLUSIONS We concluded that the consumption of a diet containing polyphenol-rich olive oil can decrease BP and improve endothelial function in young women with high-normal BP or stage 1 essential hypertension.

Simvastatin improves endothelial function in spontaneously hypertensive rats through a superoxide dismutase mediated antioxidant effect.

Background Hydroxymethylglutaryl coenzyme A (HMGCoA) reductase inhibitors have beneficial effects beyond their cholesterol-lowering properties. The antioxidant mechanism of HMGCoA reductase inhibitors is not completely understood. Objectives To elucidate the antioxidant effect of simvastatin. Methods We studied the influence of simvastatin treatment on the development of hypertension, modification of antioxidant systems, and reactivity of aortic rings in Wistar–Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Results Simvastatin had no effect on blood pressure (BP). Simvastatin treatment (either 1 or 2 mg/kg body weight for 12 or 20 weeks) increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in SHR rats compared with untreated control SHR rats. Carbachol-induced relaxation of aortic rings was impaired in control SHR rats and was restored by simvastatin treatment. Addition of SOD improved the response in control SHR rats and did not have any effect in treated SHR rats. Addition of diethyldithiocarbamic acid, a selective inhibitor of SOD, produced a mild non-significant impairment in carbachol-induced relaxation in control SHR rats, suggesting a deficient antioxidant system in these animals. However, in treated SHR and in WKY rats, impairment of the relaxation was marked, implying that SOD activity in these animals was important to maintain endothelial function. In aortic rings without endothelium from SHR rats, contraction induced by free radicals was substantially higher than in WKY rats. This effect was attenuated in 1-mg-treated rats and abolished in 2-mg-treated rats. Conclusions Simvastatin promotes intracellular antioxidant systems, fundamentally SOD, restoring endothelial function but not having any effect on blood pressure.

Decreased Level of Cord Blood Circulating Endothelial Colony–Forming Cells in Preeclampsia

Preeclampsia is a pregnancy-related disorder associated with increased cardiovascular risk for the offspring. Endothelial colony–forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that participate in the formation of vasculature during development. However, the effect of preeclampsia on fetal levels of ECFCs is largely unknown. In this study, we sought to determine whether cord blood ECFC abundance and function are altered in preeclampsia. We conducted a prospective cohort study that included women with normal (n=35) and preeclamptic (n=15) pregnancies. We measured ECFC levels in the umbilical cord blood of neonates and characterized ECFC phenotype, cloning-forming ability, proliferation, and migration toward vascular endothelial growth factor-A and fibroblast growth factor-2, in vitro formation of capillary-like structures, and in vivo vasculogenic ability in immunodeficient mice. We found that the level of cord blood ECFCs was statistically lower in preeclampsia than in control pregnancies (P=0.04), a reduction that was independent of other obstetric factors. In addition, cord blood ECFCs from preeclamptic pregnancies required more time to emerge in culture than control ECFCs. However, once derived in culture, ECFC function was deemed normal and highly similar between preeclampsia and control, including the ability to form vascular networks in vivo. This study demonstrates that preeclampsia affects ECFC abundance in neonates. A reduced level of ECFCs during preeclamptic pregnancies may contribute to an increased risk of developing future cardiovascular events.

Role of Circulating Cell-free DNA Levels in Patients With Severe Preeclampsia and HELLP Syndrome

BACKGROUND Increased plasma levels of circulating cell-free DNA (c-f DNA) have been recently described in diseases related to ischemia and/or hypoxia. Preeclampsia (PCL) is a hypertensive disorder of pregnancy, of unknown origin, where a defective placentation resulting in placental ischemia plays an important role. HELLP syndrome (haemolysis, elevated liver enzymes, and low platelet count) is the most serious form of PCL. The origin of the disease is unknown, and there are no markers to help us to make an early diagnosis of disease or to predict patients who are at risk of suffering serious complications. METHODS We measured circulating c-f DNA levels in a group of control pregnant women (n = 20), patients with mild PCL (n = 9), patients with severe PCL (n = 24), and patients with HELLP syndrome (n = 8). RESULTS Values of circulating c-f DNA were 333.59 ± 64.3 ng/ml in control subjects; 635.11 ± 111.7 ng/ml in patients with mild PCL; 1,264.63 ± 127.1 ng/ml in patients with severe PCL, and 1,595.95 ± 269.8 ng/ml in patients with HELPP syndrome. (P < 0.0001). Values of c-f DNA >950 ng/ml had a sensitivity and specificity for detecting severe PCL and/or HELLLP syndrome of 0.71 and 0.93, respectively. CONCLUSIONS As far as we know, this is the first report of increased c-f DNA levels in HELLP syndrome. In this preliminary report, we have observed a gradual and strong relation between c-f DNA levels and range of severity of PCL, with it the highest in patients with HELLP syndrome. Further studies are needed for evaluating the utility of this technique in hypertensive disorders of pregnancy and, particularly, in HELLP syndrome.

Erythrocyte Na(+)-Li+ countertransport in essential hypertension: correlation with membrane lipids levels.

Objective To examine whether Na+-Li+ countertransport (SLC) activity is linked to erythrocyte membrane lipid content. Design An observational case-control study. The maximal efflux rate of SLC, plasma cholesterol, triglycerides, phospholipids, low- and high-density lipoprotein cholesterol levels and the erythrocyte membrane cholesterol, phospholipids and fatty acids contents were determined both in fasting normolipaemic normotensive subjects and in hypertensive patients. Methods The Li+-stimulated Na+ efflux was measured in Li+-preloaded erythrocytes. Membrane cholesterol and phospholipids levels were determined by the latroscan technique. Membrane fatty acids were identificated by gas chromatography. Several derived indices were also obtained. Results Erythrocyte membranes of hypertensive patients showed an increase in cholesterol:phospholipid ratio and a decrease in the total amount of polyunsaturated fatty acids, mainly at the expense of arachidonic acid and docosatetraenoic acid. SLC activity was higher in hypertensive patients and correlated positively with the plasma triglycerides level and negatively with the ratio of C20:4 to C20:3. Conclusion Our data from untreated normolipaemic hypertensive patients show that a higher SLC activity was accompained by parameters that indicate a lower membrane fluidity.

Genotype of the CYBA promoter -930A/G, polymorphism C677T of the MTHFR and APOE genotype in patients with hypertensive disorders of pregnancy: an observational study.

BACKGROUND AND OBJECTIVE Hypertensive disorders of pregnancy could be favoured by polymorphisms in genes affecting vascular physiology. The aim of our work was to study several variants in the genes regulating oxidative stress, plasma lipids metabolism and endothelial function (observational study). MATERIAL AND METHODS We studied the -930A/G polymorphism of the CYBA gene promoter, the apolipoprotein E (APOE) genotype and the methylene-tetrahydrofolate reductase (MTHFR) gene C677T polymorphism in 134 healthy pregnant women, 266 pregnant with non-proteinuric hypertension (NPH) and 184 patients with preeclampsia (PE). RESULTS The GG genotype of the CYBA gene promoter was present in 32.1% of the control population, 38.7% of patients with NPH (P=0.19) and 21.2% of the women with PE (P=0.03). A higher frequency of epsilon 3/epsilon 4 and epsilon 4/epsilon 4 genotypes of APOE was observed in patients with PE or NPH compared with controls (P<0.01). There were no significant differences detected in genotype or allele distribution of the MTHFR, C677T polymorphism. APOE epsilon 3/epsilon 4 and epsilon 4/epsilon 4 genotypes had a worse lipoprotein profile characterized by higher plasma values of total cholesterol (P<0.05) and triglycerides (P<0.005). Despite no differences in MTHFR C677T polymorphism distribution, higher levels of plasma homocysteine were observed in patients with PE than in patients with NPH or controls. CONCLUSIONS CYBA and APOE polymorphism showed a different distribution in the groups studied, while no differences were observed in MTHFR C677T polymorphism. APOE genotype was associated with changes in lipid and lipoprotein profiles in pregnant women.

Which parameter is better to define endothelial dysfunction in a test of postocclusive hyperemia measured by laser-Doppler flowmetry?

Background and objectiveEndothelial function can be measured by the level of reactive vasodilation due to a transient ischemia caused by a blood pressure cuff on the arm, measured using Laser-Doppler flowmetry. This device has software that provides various parameters that can measure the magnitude of this response, but there are no general agreements with regard to which of them is the best to use. In this study, we analyze which of the parameters obtained using this technique is better to discriminate between patients with coronary artery disease (CAD) and healthy controls. MethodsWe analyzed 40 patients with proven CAD and 60 healthy controls. We studied the hyperemic response to the ischemia in the forearm using a Laser-Doppler flowmeter. ResultsThe most important differences between patients and controls were determined considering the area of hyperemia, which was 2.6 times higher in healthy controls than that in patients (754.9±566.4 vs 1981.3±1156.3 perfusion units per second, P<0.001). To diagnose the disease, a cutoff point of 860 perfusion units per second had a sensitivity of 0.82 and a specificity of 0.97. This is probably because the area of hyperemia measures at the same time speed, intensity, and duration of the hyperemic response. ConclusionThe area of hyperemia was the parameter with a higher sensitivity and specificity for identification of patients with CAD. Nevertheless, further studies are needed to confirm the usefulness of this parameter, obtained using a noninvasive test, to assess the presence of subclinical coronary heart disease.

Sodium Transport Kinetics, Cell Membrane Lipid Composition, Neural Conduction and Metabolic Control in Type 1 Diabetic Patients

Background: A decreased content of n–3 fatty acids in erythrocyte membrane of type 1 diabetic patients, which is inversely related to plasma levels of HbA1c, has been reported previously. Our aim in this study was to observe the changes after a low-dose n–3 fatty acid (330 mg/day docosahexaenoic acid and 630 mg/day eicosapentanoic acid) dietary intervention in the lipid composition of cell membrane and metabolic control (measured according to plasma HbA1c levels). Since changes in both parameters may alter transmembrane sodium transport or influence parameters measuring target organ damage, we also studied the neural conduction quality and activity of four sodium transporters. Methods: Eighteen type 1 diabetic patients were randomly assigned to continue their usual diet (control group) or to supplement their diet with a daily low dose of n–3 fatty acids (supplemented group). The changes between baseline and end values of the following parameters were compared: HbA1c, lipid and phospholipid composition of cell membrane, activity of four ion carriers and neural conduction quality. Results: The dietary supplementation caused statistically significant changes in membrane lipid composition, particularly an increase of C22:6 (n–3) and the total n–3 fatty acid (respectively +0.90 ± 1.14% vs. –0.44 ± 1.23% and +1.36 ± 1.62% vs. –0.5 ± 1.80%, p < 0.05). After the dietary supplementation, we also observed a significant decrease of HbA1c (–2.00 ± 1.9% vs. –0.13 ± 0.48%, p < 0.05), without significant changes in the dose of insulin required, an increase in the motor conduction velocity by the median nerve (+2.12 ± 1.35 m/s vs. –0.8 ± 2.34 m/s, p < 0.05) and a decrease of the Vmax of the Na+-Li+ countertransport (–96.6 ± 111.2 vs. +58.1 ± 81.3 μmol/l cell/h–1, p < 0.01). Conclusion: A low-dose omega–3 fatty acid dietary supplementation may change the fatty acid composition of the cell membrane and improve the metabolic control of diabetes. Using this dose, we also observed a decrease of the maximal rate of Na+-Li+ countertransport and a slight improvement of neural conduction.

Obstructive sleep apnoea syndrome, endothelial function and markers of endothelialization. Changes after CPAP.

Study objectives This study tries to assess the endothelial function in vivo using flow-mediated dilatation (FMD) and several biomarkers of endothelium formation/restoration and damage in patients with obstructive sleep apnoea (OSA) syndrome at baseline and after three months with CPAP therapy. Design Observational study, before and after CPAP therapy. Setting and Patients We studied 30 patients with apnoea/hypopnoea index (AHI) >15/h that were compared with themselves after three months of CPAP therapy. FMD was assessed non-invasively in vivo using the Laser-Doppler flowmetry. Circulating cell-free DNA (cf-DNA) and microparticles (MPs) were measured as markers of endothelial damage and the vascular endothelial growth factor (VEGF) was determined as a marker of endothelial restoration process. Measurements and results After three month with CPAP, FMD significantly increased (1072.26 ± 483.21 vs. 1604.38 ± 915.69 PU, p< 0.005) cf-DNA and MPs significantly decreased (187.93 ± 115.81 vs. 121.28 ± 78.98 pg/ml, p<0.01, and 69.60 ± 62.60 vs. 39.82 ± 22.14 U/μL, p<0.05, respectively) and VEGF levels increased (585.02 ± 246.06 vs. 641.11 ± 212.69 pg/ml, p<0.05). These changes were higher in patients with more severe disease. There was a relationship between markers of damage (r = -0.53, p<0.005) but not between markers of damage and restoration, thus suggesting that both types of markers should be measured together. Conclusions CPAP therapy improves FMD. This improvement may be related to an increase of endothelial restoration process and a decrease of endothelial damage.

Obstructive Sleep Apnea Syndrome, Vascular Pathology, Endothelial Function and Endothelial Cells and Circulating Microparticles

Accelerated atherosclerosis and increased cardiovascular risk are frequently reported in patients with obstructive sleep apnea (OSA) syndrome. In this article the authors attempt a review of the current understanding of the relationship between vascular risk and OSA syndrome based on large cohort studies that related the disease to several cardiovascular risk factors and vascular pathologies. We also discuss the pathophysiological mechanisms that may be involved in this relationship, starting with endothelial dysfunction and its mediators. These include an increased oxidative stress and inflammation as well as several disorders of coagulation and lipid metabolism. Moreover, circulating microparticles from activated leukocytes (CD62L_MPs) are higher in patients with OSA and there is a positive correlation between circulating levels of CD62L_MPs and nocturnal hypoxemia severity. Finally, circulating level of endothelial microparticles and circulating endothelial cells seem to be increased in patients with OSA. Also, endothelial progenitor cells are reduced and plasma levels of the vascular endothelial growth factor are increased.