Christopher E. Aston

Blueberries Decrease Cardiovascular Risk Factors in Obese Men and Women with Metabolic Syndrome

Among all fruits, berries have shown substantial cardio-protective benefits due to their high polyphenol content. However, investigation of their efficacy in improving features of metabolic syndrome and related cardiovascular risk factors in obesity is limited. We examined the effects of blueberry supplementation on features of metabolic syndrome, lipid peroxidation, and inflammation in obese men and women. Forty-eight participants with metabolic syndrome [4 males and 44 females; BMI: 37.8 +/- 2.3 kg/m(2); age: 50.0 +/- 3.0 y (mean +/- SE)] consumed freeze-dried blueberry beverage (50 g freeze-dried blueberries, approximately 350 g fresh blueberries) or equivalent amounts of fluids (controls, 960 mL water) daily for 8 wk in a randomized controlled trial. Anthropometric and blood pressure measurements, assessment of dietary intakes, and fasting blood draws were conducted at screening and at wk 4 and 8 of the study. The decreases in systolic and diastolic blood pressures were greater in the blueberry-supplemented group (- 6 and - 4%, respectively) than in controls (- 1.5 and - 1.2%) (P lt 0.05), whereas the serum glucose concentration and lipid profiles were not affected. The decreases in plasma oxidized LDL and serum malondialdehyde and hydroxynonenal concentrations were greater in the blueberry group (- 28 and - 17%, respectively) than in the control group (- 9 and - 9%) (P lt 0.01). Our study shows blueberries may improve selected features of metabolic syndrome and related cardiovascular risk factors at dietary achievable doses.

Green tea supplementation affects body weight, lipids, and lipid peroxidation in obese subjects with metabolic syndrome

Objective: To compare the effects of supplementation of green tea beverage or green tea extracts with controls on body weight, glucose and lipid profile, biomarkers of oxidative stress, and safety parameters in obese subjects with metabolic syndrome. Design: Randomized, controlled prospective trial. Setting: General Clinical Research Center (GCRC) at University of Oklahoma Health Sciences Center (OUHSC). Subjects: Thirty-five subjects with obesity and metabolic syndrome were recruited in age- and gender-matched trios and were randomly assigned to the control (4 cups water/d), green tea (4 cups/d), or green tea extract (2 capsules and 4 cups water/d) group for 8 weeks. The tea and extract groups had similar dosing of epiogallocatechin-3-gallate (EGCG), the active compound in green tea. Methods: Anthropometrics, blood pressure, fasting glucose and lipids, nuclear magnetic resonance (NMR)-based lipid particle size, safety parameters, biomarkers of oxidative stress (oxidized low-density lipoprotein [LDL], myeloperoxidase [MPO], malondialdehyde and hydroxynonenals [MDA and HNE]), and free catechins were analyzed at screen and at 4 and 8 weeks of the study. Results: Pairwise comparisons showed green tea beverage and green tea extracts caused a significant decrease in body weight and body mass index (BMI) versus controls at 8 weeks (−2.5 ± 0.7 kg, p < 0.01, and −1.9 ± 0.6, p < 0.05, respectively). Green tea beverage showed a decreasing trend in LDL-cholesterol and LDL/high-density lipoprotein (HDL) versus controls (p < 0.1). Green tea beverage also significantly decreased MDA and HNE (−0.39 ± 0.06 µM, p < 0.0001) versus controls. Plasma free catechins were detectable in both beverage and extract groups versus controls at screen and at 8 weeks, indicating compliance and bioavailability of green tea catechins. Conclusions: Green tea beverage consumption (4 cups/d) or extract supplementation (2 capsules/d) for 8 weeks significantly decreased body weight and BMI. Green tea beverage further lowered lipid peroxidation versus age- and gender-matched controls, suggesting the role of green tea flavonoids in improving features of metabolic syndrome in obese patients.

Fluvastatin Inhibits Hepatitis C Replication in Humans

BACKGROUNDHepatitis C viral (HCV) infection is the leading cause of death due to liver disease in the United States. Currently, pegylated interferon and ribavirin produce sustained viral remission in only 50% of patients. Additional agents are needed to increase the cure rate. In vitro experiments show strong antiviral effects of fluvastatin against HCV.OBJECTIVES:To assess the safety and antiviral effects of fluvastatin in chronic HCV carriers.METHODS:31 veterans with chronic HCV were prospectively given oral doses of fluvastatin, 20 to 320 mg/day, for 2–12 weeks with weekly monitoring of HCV RNA and liver tests. Reductions of viral load (P < 0.01) versus a control group were considered suppressive.RESULTS:With 80 mg a day or less, 11/22 (50%) patients responded by lowering HCV RNA. The first lowering occurred within 4 weeks (9/11, 82%). The greatest weekly change in HCV RNA level was a 1.75 log10 reduction. When lowered in responders, the viral load remained relatively constant for 2–5 weeks (7/9, 78%), or on the next test rebounded immediately to a non-significant change from, baseline (n = 2). Continued lowering of virus was seen in 2/19 (22 %) patients when the study ended. We found no evidence of liver tests worsening.CONCLUSIONS:FLV used as monotherapy in vivo showed suppressive effects of HCV clinically that are modest, variable, and often short-lived. These findings support “proof-of-concept” for pilot trials combining fluvastatin with standard therapy. Statins and fluvastatin, in particular, appear to be safe for use in hepatitis C.

Real-time ultrasound guidance facilitates femoral arterial access and reduces vascular complications: FAUST (Femoral Arterial Access With Ultrasound Trial).

OBJECTIVES The aim of this study was to compare the procedural and clinical outcomes of femoral arterial access with ultrasound (US) guidance with standard fluoroscopic guidance. BACKGROUND Real-time US guidance reduces time to access, number of attempts, and complications in central venous access but has not been adequately assessed in femoral artery cannulation. METHODS Patients (n = 1,004) undergoing retrograde femoral arterial access were randomized 1:1 to either fluoroscopic or US guidance. The primary end point was successful common femoral artery (CFA) cannulation by femoral angiography. Secondary end points included time to sheath insertion, number of forward needle advancements, first pass success, accidental venipunctures, and vascular access complications at 30 days. RESULTS Compared with fluoroscopic guidance, US guidance produced no difference in CFA cannulation rates (86.4% vs. 83.3%, p = 0.17), except in the subgroup of patients with CFA bifurcations occurring over the femoral head (82.6% vs. 69.8%, p < 0.01). US guidance resulted in an improved first-pass success rate (83% vs. 46%, p < 0.0001), reduced number of attempts (1.3 vs. 3.0, p < 0.0001), reduced risk of venipuncture (2.4% vs. 15.8%, p < 0.0001), and reduced median time to access (136 s vs. 148 s, p = 0.003). Vascular complications occurred in 7 of 503 and 17 of 501 in the US and fluoroscopy groups, respectively (1.4% vs. 3.4% p = 0.04). CONCLUSIONS In this multicenter randomized controlled trial, routine real-time US guidance improved CFA cannulation only in patients with high CFA bifurcations but reduced the number of attempts, time to access, risk of venipunctures, and vascular complications in femoral arterial access. (Femoral Arterial Access With Ultrasound Trial [FAUST]; NCT00667381).

Green Tea minimally affects Biomarkers of Inflammation in Obese Subjects with Metabolic Syndrome

OBJECTIVE Green tea (Camellia sinensis) has shown to exert cardioprotective benefits in observational studies. The objective of this clinical trial was to assess the effects of green tea on features of metabolic syndrome and inflammation in obese subjects. METHODS We conducted a randomized controlled trial in obese subjects with metabolic syndrome. Thirty-five subjects [(mean ± SE) age 42.5 ± 1.7 y, body mass index 36.1 ± 1.3 kg/m(2)] completed the 8-wk study and were randomly assigned to receive green tea (4 cups/d), green tea extract (2 capsules and 4 cups water/d), or no treatment (4 cups water/d). Both the beverage and extract groups had similar dosing of epigallocatechin-3-gallate, the active green tea polyphenol. Fasting blood samples were collected at screening, 4 and 8 wk of the study. RESULTS Green tea beverage or extract supplementation did not significantly alter features of metabolic syndrome or biomarkers of inflammation including adiponectin, C-reactive protein, interleukin-6, interleukin-1β, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, leptin, or leptin:adiponectin ratio. However, both green tea beverage and extracts significantly reduced plasma serum amyloid alpha versus no treatment (P < 0.005). CONCLUSION This study suggests that the daily consumption of green tea beverage or extracts for 8 wk was well tolerated but did not affect the features of metabolic syndrome. However, green tea significantly reduced plasma serum amyloid alpha, an independent cardiovascular disease risk factor, in obese subjects with metabolic syndrome.

Reduced Body Weight and Increased Postimplantation Fetal Death in Tyrosylprotein Sulfotransferase-1-deficient Mice

Tyrosine sulfation is mediated by one of two Golgi isoenzymes, called tyrosylprotein sulfotransferases (TPST-1 and TPST-2). A relatively small number of proteins are known to undergo tyrosine sulfation, including certain adhesion molecules, G-protein-coupled receptors, coagulation factors, serpins, extracellular matrix proteins, and hormones. As one approach to explore the role of these enzymes in vivo and how they might interact in biological systems, we have generated TPST-1-deficient mice by targeted disruption of the Tpst1 gene.Tpst1 +/− mice appear normal and, when interbred, yield litters of normal size with a Mendelian genetic distribution and an equal sex distribution.Tpst1 −/− mice appear healthy but have ≈5% lower average body weight than Tpst1 +/+controls. In addition, we show that although fertility ofTpst1 −/− males and females per seis normal, Tpst1 −/− females have significantly smaller litters because of fetal death between 8.5 and 15.5 days postcoitum. These findings suggest that there are proteins involved in regulation of body weight and reproductive physiology, which require tyrosine sulfation for optimal function that are yet to be described. Our findings also strongly support the conclusion that TPST-1 and TPST-2 have distinct biological roles that may reflect differences in their macromolecular substrate specificity.

Autoimmune Basis for Postural Tachycardia Syndrome

Background Patients with postural tachycardia syndrome (POTS) have exaggerated orthostatic tachycardia often following a viral illness, suggesting autoimmunity may play a pathophysiological role in POTS. We tested the hypothesis that they harbor functional autoantibodies to adrenergic receptors (AR). Methods and Results Fourteen POTS patients (7 each from 2 institutions) and 10 healthy subjects were examined for α1AR autoantibody‐mediated contractility using a perfused rat cremaster arteriole assay. A receptor‐transfected cell‐based assay was used to detect the presence of β1AR and β2AR autoantibodies. Data were normalized and expressed as a percentage of baseline. The sera of all 14 POTS patients demonstrated significant arteriolar contractile activity (69±3% compared to 91±1% of baseline for healthy controls, P<0.001) when coexisting β2AR dilative activity was blocked; and this was suppressed by α1AR blockade with prazosin. POTS sera acted as a partial α1AR antagonist significantly shifting phenylephrine contractility curves to the right. All POTS sera increased β1AR activation (130±3% of baseline, P<0.01) and a subset had increased β2AR activity versus healthy subjects. POTS sera shifted isoproterenol cAMP response curves to the left, consistent with enhanced β1AR and β2AR agonist activity. Autoantibody‐positive POTS sera demonstrated specific binding to β1AR, β2AR, and α1AR in transfected cells. Conclusions POTS patients have elevated α1AR autoantibodies exerting a partial peripheral antagonist effect resulting in a compensatory sympathoneural activation of α1AR for vasoconstriction and concurrent βAR‐mediated tachycardia. Coexisting β1AR and β2AR agonistic autoantibodies facilitate this tachycardia. These findings may explain the increased standing plasma norepinephrine and excessive tachycardia observed in many POTS patients.

Increased serum pigment epithelium derived factor levels in Type 2 diabetes patients

Serum PEDF levels (mean (S.D.)) were increased in 96 Type 2 diabetic vs. 54 non-diabetic subjects; 5.3 (2.8) vs. 3.2 (2.0)mug/ml, p<0.001. In diabetes, PEDF correlated with BMI, serum creatinine and LDL-cholesterol, but not with other lipids, HbA1c or CRP. PEDF did not differ by drugs, complications, or gender.

Fluoroscopy vs. Traditional guided femoral arterial access and the use of closure devices: A randomized controlled trial†

Objective: To compare the effectiveness of accessing the common femoral artery (CFA) using fluoroscopic guidance (FG) versus traditional anatomic landmark guidance (TALG) during cardiac catheterization and to determine the effect of the two modalities on the appropriateness for use of vascular closure devices (VCDs). Background: Previous studies have shown a consistent relationship between the head of the femur and the CFA, yet there is no prospective data validating the superiority of fluoroscopy‐assisted CFA access. Methods: A total of 972 patients were randomized to either FG or TALG access. The primary endpoint of the study was the angiographic suitability of the puncture site for VCD use. Secondary endpoints included arteriotomy location, time and number of attempts needed to obtain access, and the incidence of vascular complications. Results: Of these, 474 patients were randomized into the FG arm and 498 patients into the TALG arm. A total of 79.5% of patients in the fluoroscopy arm and 80.7% in the traditional arm (P = 0.7) were deemed angiographically suitable for VCD based on the arteriotomy. The fluoroscopy group had significantly less arteriotomies below the inferior border of the head of the femur (P = 0.03). Total time for sheath insertion (105.7 ± 130.7 vs. 106.5 ± 152.6 sec) and number of arterial punctures (1.1 ± 0.4 vs. 1.1 ± 0.5) did not differ among the FG and TALG, respectively. The rates of vascular complications were not different. Conclusion: The angiographic suitability for VCD was not different between FG and TALG groups. Fluoroscopy decreased the number of low arteriotomies. The time to sheath insertion, number of arterial punctures needed to obtain access, and the incidence of complications were also similar.

Serum Carotenoids and Fat-Soluble Vitamins in Women With Type 1 Diabetes and Preeclampsia: A longitudinal study

OBJECTIVE Increased oxidative stress and immune dysfunction are implicated in preeclampsia (PE) and may contribute to the two- to fourfold increase in PE prevalence among women with type 1 diabetes. Prospective measures of fat-soluble vitamins in diabetic pregnancy are therefore of interest. RESEARCH DESIGN AND METHODS Maternal serum carotenoids (α- and β-carotene, lycopene, and lutein) and vitamins A, D, and E (α- and γ-tocopherols) were measured at first (12.2 ± 1.9 weeks [mean ± SD], visit 1), second (21.6 ± 1.5 weeks, visit 2), and third (31.5 ± 1.7 weeks, visit 3) trimesters of pregnancy in 23 women with type 1 diabetes who subsequently developed PE (DM PE+) and 24 women with type 1 diabetes, matched for age, diabetes duration, HbA1c, and parity, who did not develop PE (DM PE−). Data were analyzed without and with adjustment for baseline differences in BMI, HDL cholesterol, and prandial status. RESULTS In unadjusted analysis, in DM PE+ versus DM PE−, α-carotene and β-carotene were 45 and 53% lower, respectively, at visit 3 (P < 0.05), before PE onset. In adjusted analyses, the difference in β-carotene at visit 3 remained significant. Most participants were vitamin D deficient (<20 ng/mL), and vitamin D levels were lower in DM PE+ versus DM PE− throughout the pregnancy, although this did not reach statistical significance. CONCLUSIONS In pregnant women with type 1 diabetes, low serum α- and β-carotene were associated with subsequent development of PE, and vitamin D deficiency may also be implicated.