Melissa C. Caughey

Relation between Digital Peripheral Arterial Tonometry and Brachial Artery Ultrasound Measures of Vascular Function in Patients with Coronary Artery Disease and in Healthy Volunteers

Digital peripheral arterial tonometry (PAT) is an emerging, noninvasive method to assess vascular function. The physiology underlying this phenotype, however, remains unclear. Therefore, we evaluated the relation between digital PAT and established brachial artery ultrasound measures of vascular function under basal conditions and after reactive hyperemia. Using a cross-sectional study design, digital PAT and brachial artery ultrasonography with pulsed wave Doppler were simultaneously completed at baseline and after reactive hyperemia in both those with established coronary artery disease (n = 99) and healthy volunteers with low cardiovascular disease risk (n = 40). Under basal conditions, the digital pulse volume amplitude demonstrated a significant positive correlation with the brachial artery velocity-time integral that was independent of the arterial diameter, in both the healthy volunteer (r(s) = 0.64, p <0.001) and coronary artery disease (r(s) = 0.63, p <0.001) cohorts. Similar positive relations were observed with the baseline brachial artery blood flow velocity and blood flow. In contrast, no relation between the reactive hyperemia-evoked digital PAT ratio and either brachial artery flow-mediated dilation or shear stress was observed in either cohort (p = NS). In conclusion, these findings demonstrate that the digital PAT measures of vascular function more closely reflect basal blood flow in the brachial artery than reactive hyperemia-induced changes in the arterial diameter or flow velocity, and the presence of vascular disease does not modify the physiology underlying the digital PAT phenotype.

Non-invasive in vivo characterization of human carotid plaques with acoustic radiation force impulse ultrasound: comparison with histology after endarterectomy.

Ischemic stroke from thromboembolic sources is linked to carotid artery atherosclerotic disease with a trend toward medical management in asymptomatic patients. Extent of disease is currently diagnosed by non-invasive imaging techniques that measure luminal stenosis, but it has been suggested that a better biomarker for determining risk of future thromboembolic events is plaque morphology and composition. Specifically, plaques that are composed of mechanically soft lipid/necrotic regions covered by thin fibrous caps are the most vulnerable to rupture. An ultrasound technique that non-invasively interrogates the mechanical properties of soft tissue, called acoustic radiation force impulse (ARFI) imaging, has been developed as a new modality for atherosclerotic plaque characterization using phantoms and atherosclerotic pigs, but the technique has yet to be validated in vivo in humans. In this preliminary study, in vivo ARFI imaging is presented in a case study format for four patients undergoing clinically indicated carotid endarterectomy and compared with histology. In two type Va plaques, characterized by lipid/necrotic cores covered by fibrous caps, mean ARFI displacements in focal regions were high relative to the surrounding plaque material, suggesting soft features were covered by stiffer layers within the plaques. In two type Vb plaques, characterized by heavy calcification, mean ARFI peak displacements were low relative to the surrounding plaque and arterial wall, suggesting stiff tissue. This pilot study illustrates the feasibility and challenges of transcutaneous ARFI for characterizing the material and structural composition of carotid atherosclerotic plaques via mechanical properties, in humans, in vivo.

Sickle Cell Trait and Incident Ischemic Stroke in the Atherosclerosis Risk in Communities Study

Background and Purpose— Numerous case reports describe stroke in individuals with sickle cell trait (SCT) in the absence of traditional risk factors for cerebrovascular disease. To date, no prospective epidemiological studies have investigated this association. Methods— A population-based sample of blacks (n=3497; mean age=54 years; female=62%) was followed from 1987 to 2011 in the Atherosclerosis Risk in Communities (ARIC) study, contributing a total of 65 371 person-years. Hazard ratios and incidence rate differences for ischemic stroke were estimated, contrasting SCT to homozygous hemoglobin A. Models were adjusted for age, sex, smoking, diabetes mellitus, hypertension, total cholesterol, atrial fibrillation, and coronary heart disease. Results— SCT was identified in 223 (6.4%) participants. During a median follow-up of 22 years, 401 subjects experienced incident stroke (89% ischemic). Incident ischemic stroke was more frequent among those with SCT (13%) than those with homozygous hemoglobin A (10%). SCT was associated with an ischemic stroke hazard ratio of 1.4 (1.0–2.0) and an incidence rate difference amounting to 1.9 (0.4–3.8) extra strokes per 1000 person-years. Conclusions— We observed an increased risk of ischemic stroke in blacks with SCT. Further investigation of the incidence and pathophysiology of stroke in patients with SCT is warranted.

Effect of hawthorn standardized extract on flow mediated dilation in prehypertensive and mildly hypertensive adults: a randomized, controlled cross-over trial

BackgroundHawthorn extract has been used for cardiovascular diseases for centuries. Recent trials have demonstrated its efficacy for the treatment of heart failure, and the results of several small trials suggest it may lower blood pressure. However, there is little published evidence to guide its dosing. The blood pressure lowering effect of hawthorn has been linked to nitric oxide-mediated vasodilation. The aim of this study was to investigate the relationship between hawthorn extract dose and brachial artery flow mediated dilation (FMD), an indirect measure of nitric oxide release.MethodsWe used a four-period cross-over design to evaluate brachial artery FMD in response to placebo or hawthorn extract (standardized to 50 mg oligomeric procyanidin per 250 mg extract). Randomly sequenced doses of hawthorn extract (1000 mg, 1500 mg, and 2500 mg) and placebo were assigned to each participant. Doses were taken twice daily for 3 1/2 days followed by FMD and a 4-day washout before proceeding to the next dosing period.ResultsTwenty-one prehypertensive or mildly hypertensive adults completed the study. There was no evidence of a dose-response effect for our main outcome (FMD percent) or any of our secondary outcomes (absolute change in brachial artery diameter and blood pressure). Most participants indicated that if given evidence that hawthorn could lower their blood pressure, they would be likely to use it either in conjunction with or instead of lifestyle modification or anti-hypertensive medications.ConclusionWe found no evidence of a dose-response effect of hawthorn extract on FMD. If hawthorn has a blood pressure lowering effect, it is likely to be mediated via an NO-independent mechanism.Trial RegistrationThis trial has been registered with ClinicalTrials.gov, a service of the U.S. National Institutes of Health: NCT01331486.

What characteristics of nutrition and physical activity interventions are key to effectively reducing weight gain in obese or overweight pregnant women? A systematic review and meta-analysis

Lifestyle interventions targeting gestational weight gain (GWG) report varying degrees of success. To better understand factors influencing efficacy, we reviewed randomized trials specifically among obese and overweight pregnant women.

Dietary Supplementation with Olive Oil or Fish Oil and Vascular Effects of Concentrated Ambient Particulate Matter Exposure in Human Volunteers.

Background Exposure to ambient particulate matter (PM) induces endothelial dysfunction, a risk factor for cardiovascular disease. Olive oil (OO) and fish oil (FO) supplements have beneficial effects on endothelial function. Objective In this study we evaluated the potential efficacy of OO and FO in mitigating endothelial dysfunction and disruption of hemostasis caused by exposure to particulate matter (PM). Methods and Results Forty-two participants (58 ± 1 years of age) received either 3 g/day of OO or FO, or no supplements (naive) for 4 weeks prior to undergoing 2-hr exposures to filtered air and concentrated ambient particulate matter (CAP; mean, 253 ± 16 μg/m3). Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery preexposure, immediately postexposure, and 20 hr postexposure. Levels of endothelin-1 and markers of fibrinolysis and inflammation were also measured. The FMD was significantly lower after CAP exposure in the naive (–19.4%; 95% CI: –36.4, –2.3 per 100 μg/m3 CAP relative to baseline; p = 0.03) and FO groups (–13.7%; 95% CI: –24.5, –2.9; p = 0.01), but not in the OO group (–7.6%; 95% CI: –21.5, 6.3; p = 0.27). Tissue plasminogen activator levels were significantly increased immediately after (11.6%; 95% CI: 0.8, 22.2; p = 0.04) and 20 hr after CAP exposure in the OO group. Endothelin-1 levels were significantly increased 20 hr after CAP exposure in the naive group only (17.1%; 95% CI: 2.2, 32.0; p = 0.03). Conclusions Short-term exposure to CAP induced vascular endothelial dysfunction. OO supplementation attenuated CAP-induced reduction of FMD and changes in blood markers associated with vasoconstriction and fibrinolysis, suggesting that OO supplementation may be an efficacious intervention to protect against vascular effects of exposure to PM. Citation Tong H, Rappold AG, Caughey M, Hinderliter AL, Bassett M, Montilla T, Case MW, Berntsen J, Bromberg PA, Cascio WE, Diaz-Sanchez D, Devlin RB, Samet JM. 2015. Dietary supplementation with olive oil or fish oil and vascular effects of concentrated ambient particulate matter exposure in human volunteers. Environ Health Perspect 123:1173–1179; http://dx.doi.org/10.1289/ehp.1408988

Estimated pulmonary artery systolic pressure and sickle cell disease: a meta-analysis and systematic review.

Many studies report estimated pulmonary artery systolic pressure (ePASP) in patients with sickle cell disease (SCD) screened by echocardiography. To better understand the prevalence and outcomes of elevated ePASP in clinically stable SCD patients, we conducted a random‐effects meta‐analysis. A total of 45 studies, representing 15 countries and including 6109 individuals, met our inclusion criteria. In most (70%) studies, elevated ePASP was defined by a tricuspid regurgitant velocity of 2·5 m/s. The prevalence of elevated ePASP was 21% (17–26%) in children and 30% (26–35%) in adults. After adjustment for sex, SCD genotype, haemoglobin, hydroxycarbamide (hydroxyurea) treatment, country and publication year, age remained associated with elevated ePASP, yielding a 12% (0·4–23%) higher adjusted prevalence in adults. Few studies reported 6‐min walk tests or mortality outcomes, and estimates were highly heterogeneous. In random effects meta‐analyses, patients with elevated ePASP walked an estimated 30·4 (6·9–53·9) metres less than those without elevated ePASP and had an associated mortality hazard ratio of 4·9 (2·4–9·7).

Cardiovascular effects caused by increasing concentrations of diesel exhaust in middle-aged healthy GSTM1 null human volunteers

Abstract Context: Epidemiological studies have shown an association between the incidence of adverse cardiovascular effects and exposure to ambient particulate matter (PM). Diesel exhaust (DE) is a major contributor to ambient PM and gaseous emissions in urban areas. Objective: This was a pilot study designed to evaluate concentration-dependent effects of short-term exposure to whole DE on the cardiovascular system in order to identify a threshold concentration that can elicit biological responses in healthy human volunteers. Materials and methods: Six healthy middle-aged participants with glutathione-S-transferase-Mu 1 (GSTM1) null genotype underwent sequential exposures to 100 µg/m3, 200 µg/m3, and 300 µg/m3 whole DE generated in real time using an idling diesel truck engine. Exposures were separated by 14 d and each was 2 h in duration. Results: We report concentration-dependent effects of exposure to DE, with 100 µg/m3 concentration causing minimal cardiovascular effects, while exposure to 300 µg/m3 DE for 2 h resulted in a borderline significant reduction of baseline brachial artery diameter (3.34 ± 0.27 mm pre- versus 3.23 ± 0.25 mm post-exposure; p = 0.08). Exposure to the highest concentration of DE also resulted in increases of 5 mmHg in diastolic blood pressure as well as a decrease in indices of the frequency domain of heart rate variability (HRV). Discussion and conclusions: These findings demonstrate that acute exposure to relatively high concentrations of DE produces cardiovascular changes in middle-aged GSTM1 null individuals. This study therefore suggests that arterial vasoconstriction and changes in HRV are responses through which traffic-related air pollution increases the risk of adverse cardiovascular outcomes.

Transcatheter versus surgical aortic valve replacement in intermediate risk patients: a meta-analysis

BACKGROUND Transcatheter aortic valve replacement (TAVR) has been approved in patients with high or prohibited surgical risk for surgery for treatment of severe symptomatic aortic stenosis. Prospective studies examining the benefits of TAVR in intermediate risk patients are ongoing. Other smaller studies including lower risk patients have been conducted, but further meta-analysis of these studies is required to draw more broad comparisons. METHODS A Medline search was conducted using standard methodology to search for clinical trials and observational studies including intermediate risk patients. We limited our meta-analysis to studies matching patient populations by propensity scores or randomization and examined clinical outcomes between TAVR and surgical aortic valve replacement (SAVR). RESULTS Analysis of the TAVR and SAVR cohorts revealed no significant differences in the outcomes of 30-day [OR (95% CI): 0.85 (0.57, 1.26)] or 1-year mortality [OR (95% CI): 0.96 (0.75, 1.23)]. A trend towards benefit with TAVR was noted in terms of neurological events and myocardial infarction (MI) without statistical significance. A statistically significant decrease in risk of post-procedural acute renal failure in the TAVR group [OR (95% CI): 0.52 (0.27, 0.99)] was observed, but so was a significantly higher rate of pacemaker implantations for the TAVR group [OR (95% CI): 6.51 (3.23, 13.12)]. CONCLUSIONS We conclude that in intermediate risk patients undergoing aortic valve replacement, the risk of mortality, neurological outcomes, and MI do not appear to be significantly different between TAVR and SAVR. However, there appears to be a significant reduction in risk of acute renal failure at the expense of an increased risk of requiring a permanent pacemaker in low and intermediate risk patients undergoing TAVR compared to SAVR.

Risk factors for mortality in adult patients with sickle cell disease: a meta-analysis of studies in North America and Europe.

Although recent studies show an improved survival of children with sickle cell disease in the US and Europe, for adult patients mortality remains high. This study was conducted to evaluate the factors associated with mortality in adult patients following the approval of hydroxyurea. We first evaluated the association between selected variables and mortality at an academic center (University of North Carolina). Data sources were then searched for publications from 1998 to June 2016, with meta-analysis of eligible studies conducted in North America and Europe to evaluate the associations of selected variables with mortality in adult patients. Nine studies, combined with the UNC cohort (total n=3257 patients) met the eligibility criteria. Mortality was significantly associated with age (per 10-year increase in age) [7 studies, 2306 participants; hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.10–1.50], tricuspid regurgitant jet velocity 2.5 m/s or more (5 studies, 1577 participants; HR: 3.03; 95%CI: 2.0–4.60), reticulocyte count (3 studies, 1050 participants; HR: 1.05; 95%CI: 1.01–1.10), log(N-terminal-pro-brain natriuretic peptide) (3 studies, 800 participants; HR: 1.68; 95%CI: 1.48–1.90), and fetal hemoglobin (7 studies, 2477 participants; HR: 0.97; 95%CI: 0.94–1.0). This study identifies variables associated with mortality in adult patients with sickle cell disease in the hydroxyurea era.