Cindy E McCrea

Test–retest reliability of pulse amplitude tonometry measures of vascular endothelial function: Implications for clinical trial design

Endothelial dysfunction is an important outcome for assessing vascular health in intervention studies. However, reliability of the standard non-invasive method (flow-mediated dilation) is a significant challenge for clinical applications and multicenter trials. We evaluated the repeatability of pulse amplitude tonometry (PAT) to measure change in pulse wave amplitude during reactive hyperemia (Itamar Medical Ltd, Caesarea, Israel). Twenty healthy adults completed two PAT tests (mean interval = 19.5 days) under standardized conditions. PAT-derived measures of endothelial function (reactive hyperemia index, RHI) and arterial stiffness (augmentation index, AI) showed strong repeatability (intra-class correlations = 0.74 and 0.83, respectively). To guide future research, we also analyzed sample size requirements for a range of effect sizes. A crossover design powered at 0.90 requires 28 participants to detect a 15% change in RHI. Our study is the first to show that PAT measurements are repeatable in adults over an interval greater than 1 week.

DHA-enriched high–oleic acid canola oil improves lipid profile and lowers predicted cardiovascular disease risk in the canola oil multicenter randomized controlled trial

BACKGROUND It is well recognized that amounts of trans and saturated fats should be minimized in Western diets; however, considerable debate remains regarding optimal amounts of dietary n-9, n-6, and n-3 fatty acids. OBJECTIVE The objective was to examine the effects of varying n-9, n-6, and longer-chain n-3 fatty acid composition on markers of coronary heart disease (CHD) risk. DESIGN A randomized, double-blind, 5-period, crossover design was used. Each 4-wk treatment period was separated by 4-wk washout intervals. Volunteers with abdominal obesity consumed each of 5 identical weight-maintaining, fixed-composition diets with one of the following treatment oils (60 g/3000 kcal) in beverages: 1) conventional canola oil (Canola; n-9 rich), 2) high-oleic acid canola oil with docosahexaenoic acid (CanolaDHA; n-9 and n-3 rich), 3) a blend of corn and safflower oil (25:75) (CornSaff; n-6 rich), 4) a blend of flax and safflower oils (60:40) (FlaxSaff; n-6 and short-chain n-3 rich), or 5) high-oleic acid canola oil (CanolaOleic; highest in n-9). RESULTS One hundred thirty individuals completed the trial. At endpoint, total cholesterol (TC) was lowest after the FlaxSaff phase (P < 0.05 compared with Canola and CanolaDHA) and highest after the CanolaDHA phase (P < 0.05 compared with CornSaff, FlaxSaff, and CanolaOleic). Low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were highest, and triglycerides were lowest, after CanolaDHA (P < 0.05 compared with the other diets). All diets decreased TC and LDL cholesterol from baseline to treatment endpoint (P < 0.05). CanolaDHA was the only diet that increased HDL cholesterol from baseline (3.5 ± 1.8%; P < 0.05) and produced the greatest reduction in triglycerides (-20.7 ± 3.8%; P < 0.001) and in systolic blood pressure (-3.3 ± 0.8%; P < 0.001) compared with the other diets (P < 0.05). Percentage reductions in Framingham 10-y CHD risk scores (FRS) from baseline were greatest after CanolaDHA (-19.0 ± 3.1%; P < 0.001) than after other treatments (P < 0.05). CONCLUSION Consumption of CanolaDHA, a novel DHA-rich canola oil, improves HDL cholesterol, triglycerides, and blood pressure, thereby reducing FRS compared with other oils varying in unsaturated fatty acid composition. This trial was registered at www.clinicaltrials.gov as NCT01351012.

Effects of pistachios on the lipid/lipoprotein profile, glycemic control, inflammation, and endothelial function in type 2 diabetes: A randomized trial.

OBJECTIVE The health benefits of regular nut consumption have been well-documented; however, effects on cardiovascular risk in diabetes are emerging. This study examined the effects of daily pistachio consumption on the lipid/lipoprotein profile, glycemic control, markers of inflammation, and endothelial function in adults with type 2 diabetes. MATERIALS/METHODS We enrolled 30 adults (40-74 years) with well-controlled type 2 diabetes (mean glycated hemoglobin 6.2%) in a randomized, crossover, controlled feeding study. After a 2-week run-in period, participants consumed nutritionally-adequate diets with pistachios (contributing 20% of total energy) or without pistachios for 4 weeks each, separated by a 2-week washout. We assessed fasting lipids/lipoproteins, glycemic measures (while fasted and during a 75 g oral glucose tolerance test), inflammatory markers, and endothelial function after each diet period. RESULTS Total cholesterol and the ratio of total to HDL cholesterol were significantly lower (p<0.05) following the pistachio diet (4.00 mmol/L and 4.06 mmol/L, respectively) compared to the control diet (4.15 mmol/L and 4.37 mmol/L, respectively). Triglycerides were significantly lower (p=0.003) following the pistachio diet (1.56 mmol/L) compared to the control diet (1.84 mmol/L). There were no treatment differences in fasting glucose and insulin, but fructosamine was significantly lower (p=0.03) following the pistachio diet (228.5 μmol/l) compared to the control diet (233.5 μmol/l). Inflammatory markers and endothelial function were unchanged. CONCLUSION Daily pistachio consumption can improve some cardiometabolic risk factors in adults with well-controlled type 2 diabetes. Our findings support recommendations that individuals with diabetes follow healthy dietary patterns that include nuts.

Plasma fatty acid changes following consumption of dietary oils containing n-3, n-6, and n-9 fatty acids at different proportions: preliminary findings of the Canola Oil Multicenter Intervention Trial (COMIT)

BackgroundThe Canola Oil Multicenter Intervention Trial (COMIT) was a randomized controlled crossover study designed to evaluate the effects of five diets that provided different oils and/or oil blends on cardiovascular disease (CVD) risk factors in individuals with abdominal obesity. The present objective is to report preliminary findings on plasma fatty acid profiles in volunteers with abdominal obesity, following the consumption of diets enriched with n-3, n-6 and n-9 fatty acids.MethodsCOMIT was conducted at three clinical sites, Winnipeg, Manitoba, Canada, Québec City, Québec, Canada and University Park, Pennsylvania, United States. Inclusion criteria were at least one of the followings: waist circumference (≥90 cm for males and ≥84 cm for females), and at least one other criterion: triglycerides ≥1.7 mmol/L, high density lipoprotein cholesterol <1 mmol/L (males) or <1.3 mmol/L (females), blood pressure ≥130 mmHg (systolic) and/or ≥85 mmHg (diastolic), and glucose ≥5.5 mmol/L. Weight-maintaining diets that included shakes with one of the dietary oil blends were provided during each of the five 30-day dietary phases. Dietary phases were separated by four-week washout periods. Treatment oils were canola oil, high oleic canola oil, high oleic canola oil enriched with docosahexaenoic acid (DHA), flax oil and safflower oil blend, and corn oil and safflower oil blend. A per protocol approach with a mixed model analysis was decided to be appropriate for data analysis.ResultsOne hundred and seventy volunteers were randomized and 130 completed the study with a dropout rate of 23.5%. The mean plasma total DHA concentrations, which were analyzed among all participants as a measure of adherence, increased by more than 100% in the DHA-enriched phase, compared to other phases, demonstrating excellent dietary adherence.ConclusionsRecruitment and retention strategies were effective in achieving a sufficient number of participants who completed the study protocol to enable sufficient statistical power to resolve small differences in outcome measures. It is expected that the study will generate important data thereby enhancing our understanding of the effects of n-3, n-6, and n-9 fatty acid-containing oils on CVD risks.Trial registrationClinicalTrials.gov NCT01351012.

Test–retest reliability of peripheral arterial tonometry in the metabolic syndrome

Endothelial dysfunction is an important contributor to atherosclerosis and cardiovascular disease. However, routine assessment via angiography or flow-mediated dilation is difficult due to technical limitations. Peripheral arterial tonometry (PAT) is a promising alternative method for non-invasive assessment of endothelial dysfunction. This study assessed the test–retest reliability of PAT in adults with the metabolic syndrome (n = 20) and provides sample size and power estimates for study design. Participants completed five PAT tests each separated by 1 week. The PAT-derived reactive hyperaemia index (RHI) showed robust repeatability (intra-class correlation = 0.74). A parallel-arm study powered at 0.90 would require 22 participants to detect an absolute change in RHI of 0.40 units (equal to ~25% change in this sample), whereas a crossover study would require 12 participants. In conclusion, we have demonstrated that PAT can be used to assess endothelial dysfunction in adults with the metabolic syndrome as reliably as in healthy samples.

Pistachio Nut Consumption Modifies Systemic Hemodynamics, Increases Heart Rate Variability, and Reduces Ambulatory Blood Pressure in Well‐Controlled Type 2 Diabetes: a Randomized Trial

Background Managing cardiovascular risk factors is important for reducing vascular complications in type 2 diabetes, even in individuals who have achieved glycemic control. Nut consumption is associated with reduced cardiovascular risk; however, there is mixed evidence about the effect of nuts on blood pressure (BP), and limited research on the underlying hemodynamics. This study assessed the effect of pistachio consumption on BP, systemic hemodynamics, and heart rate variability in adults with well‐controlled type 2 diabetes. Methods and Results We enrolled 30 adults (40 to 74 years) with type 2 diabetes in a randomized, crossover, controlled feeding study. After a 2‐week run‐in period, participants consumed a low‐fat control diet (27% fat) containing low‐fat/high‐carbohydrate snacks and a moderate‐fat diet (33% fat) containing pistachios (20% of total energy) for 4 weeks each, separated by a 2‐week washout. Following each diet period, we assessed BP, systemic hemodynamics, and heart rate variability at rest and during acute mental stress, and, in a subset of participants (n=21), 24‐hour ambulatory BP. BP at rest and during stress did not differ between treatments. The pistachio diet significantly reduced total peripheral resistance (−3.7±2.9%, P=0.004), increased cardiac output (3.1±2.3%, P=0.002), and improved some measures of heart rate variability (all P<0.05). Systolic ambulatory BP was significantly reduced by 3.5±2.2 mm Hg (P=0.046) following the pistachio diet, with the greatest reduction observed during sleep (−5.7±2.6 mm Hg, P=0.052). Conclusions A moderate‐fat diet containing pistachios modestly improves some cardiovascular risk factors in adults with well‐controlled type 2 diabetes. Clinical Trial Registration URL: www.clinicaltrials.gov. Unique identifier: NCT00956735.

Effects of canola and high‐oleic‐acid canola oils on abdominal fat mass in individuals with central obesity

To determine the effect of diets low in saturated fatty acids and high in monounsaturated fatty acids (MUFA) or polyunsaturated fatty acids on body composition in participants at risk for metabolic syndrome (MetS).

Acute Peanut Consumption Alters Postprandial Lipids and Vascular Responses in Healthy Overweight or Obese Men

Background: Postprandial hyperlipidemia is associated with impaired endothelial function. Peanut consumption favorably affects the lipid and lipoprotein profile; however, the effects on endothelial function remain unclear. Objective: The purpose of the study was to evaluate the effects of acute peanut consumption as part of a high-fat meal on postprandial endothelial function. Methods: We conducted a randomized, controlled, crossover postprandial study to evaluate the effect of acute peanut consumption on postprandial lipids and endothelial function as assessed by flow-mediated dilatation (FMD) of the brachial artery in 15 healthy overweight or obese men [mean age: 26.7 y; mean body mass index (in kg/m2): 31.4]. Participants consumed, in a randomized order, a peanut meal containing 3 ounces (85 g) ground peanuts (1198 kcal; 40.0% carbohydrate, 47.7% fat, 19.4% saturated fat, 13.2% protein) and a control meal matched for energy and macronutrient content. Meals were in the form of a shake, scheduled ≥1 wk apart. Lipids, lipoproteins, glucose, and insulin were measured at baseline (0 min) and at 30, 60, 120, and 240 min after shake consumption. FMD was measured at baseline and at 240 min. Results: Acute peanut consumption blunted the serum triglyceride (TG) response 120 and 240 min after consumption compared with the control meal (means ± SEMs—120 min: 188.9 ± 19.4 compared with 197.5 ± 20.7 mg/dL; 240 min: 189.9 ± 24.3 compared with 197.3 ± 18.4 mg/dL; P < 0.05 for both). Total, LDL, and HDL cholesterol and glucose and insulin responses were similar between the test meals. Compared with baseline, only the control meal significantly decreased FMD at 240 min (control: −1.2% ± 0.5%; P = 0.029; peanut: −0.6% ± 0.5%; P = 0.3). Participants with higher baseline total (>150 mg/dL) and LDL (>100 mg/dL)-cholesterol concentrations showed a significant decrease in FMD after the control meal (−1.8%, P = 0.017; −2.0%, P = 0.038), whereas the peanut meal maintained endothelial function in all participants irrespective of total- and LDL-cholesterol concentrations. Conclusion: The inclusion of 85 g peanuts (3 ounces) as part of a high-fat meal improved the postprandial TG response and preserved endothelial function in healthy overweight or obese men. This trial was registered at clinicaltrials.gov as NCT01405300.

Concurrent herb-prescription medication use and health care provider disclosure among university students

OBJECTIVES To determine the extent to which college students are intermixing mood-altering herbs with prescription medications and whether they are disclosing this information to their health care providers. DESIGN AND SETTING A nonrandom sample was drawn from the student body of a Northwestern state university (n=305). METHODS In November 2008 participants completed an online survey detailing herb use, disclosure to health care providers and herb/medicinal intermixing. RESULTS There were no demographic differences between herb users and non-users. Most herb usage was self-prescribed (60%) and undisclosed to healthcare providers (only 25% of herb users disclosed to a healthcare provider). 34% of herb users used them to treat a mood disorder. Of herb users, 13% had simultaneously used herbs and prescription medication in the last year. In addition, herb users who intermixed herbs with prescription medications had higher depression and anxiety scores than those who did not intermix. CONCLUSIONS College student herb use is primarily self prescribed and undisclosed to healthcare professionals, who may prescribe pharmaceuticals that interact negatively with herbals. Physician awareness and query is invaluable for the prevention of adverse herb and drug interactions.

Noninvasive assessment of hemodynamics: a comparative analysis of fingertip pulse contour analysis and impedance cardiography.

ObjectiveSystemic hemodynamic assessment is useful for characterizing the underlying physiology of hypertension, selecting individualized treatment approaches, and understanding the underlying mechanisms of action of interventions. Invasive methods are not suitable for routine clinic or research use, and noninvasive methods such as impedance cardiography have technical and practical limitations. Fingertip pulse contour analysis using the Nexfin device is a novel alternative to noninvasive assessment of blood pressure and hemodynamics. Although both impedance cardiography and the Nexfin have been validated against invasive methods, the extent to which they are correlated with each other is unknown. This study is a comparative analysis of data simultaneously obtained by impedance cardiography and using the Nexfin device. MethodsAs part of a larger clinical trial, 13 adults with type 2 diabetes completed cardiovascular reactivity testing on three occasions: at study baseline and after two 4-week dietary treatment periods. Blood pressure, hemodynamics, and heart rate variability were assessed at rest and during acute mental stress. ResultsBlood pressure, heart rate, and heart rate variability data were significantly correlated between the two devices, but hemodynamic data (stroke volume, cardiac output, total peripheral resistance) were not significantly correlated. Both techniques detected treatment-related changes in blood pressure and total peripheral resistance, but significantly differed in the magnitude and/or direction of treatment effects. ConclusionWe conclude that Nexfin is not an appropriate alternative to impedance cardiography for measurement of underlying hemodynamics in psychophysiological research, but may be useful for beat-to-beat monitoring of blood pressure and heart rate variability.