The left ventricular (LV) end-systolic (ES) pressure volume relationship (ESPVR) is the cornerstone of systolic LV function analysis. We describe a 2D real-time (RT) MRI-based method (RTPVR) with ...separate software tools for 1) semi-automatic level set-based shape prior method (LSSPM) of the LV, 2) generation of synchronized pressure area loops and 3) calculation of the ESPVR. We used the RTPVR method to measure ventricular geometry, ES pressure area relationship (ESPAR) and ESPVR during vena cava occlusion (VCO) in normal sheep. 14 adult sheep were anesthetized and underwent measurement of LV systolic function. Ten of the 14 sheep underwent RTMRI and eight of the 14 underwent measurement with conductance catheter; 4 had both RTMRI and conductance measurements. 2D cross sectional RTMRI were performed at apex, mid-ventricle and base levels during separate VCOs. The Dice similarity coefficient was used to compare LSSPM and manual image segmentation and thus determine LSSPM accuracy. LV cross-sectional area, major and minor axis length, axis ratio, major axis orientation angle and ESPAR were measured at each LV level. ESPVR was calculated with a trapezoidal rule. The Dice similarity coefficient between LSSPM and manual segmentation by two readers was 87.31#177;2.51% and 88.13#177;3.43%. All cross sections became more elliptical during VCO. The major axis orientation shifted during VCO but remained in the septo-lateral direction. LV chamber obliteration at the apical level occurred during VCO in 7 of 10 sheep that underwent RTMRI. ESPAR was non-linear at all levels. Finally, ESPVR was non-linear because of apical collapse. ESPVR measured by conductance catheter (E.sub.ES,Index = 2.23#177;0.66 mmHg/ml/m.sup.2) and RT (E.sub.ES,Index = 2.31#177;0.31 mmHg/ml/m.sup.2) was not significantly different. LSSPM segmentation of 2D RT MRI images is accurate and allows calculation of LV geometry, ESPAR and ESPVR during VCO. In the future, RTPVR will facilitate determination of regional systolic material parameters underlying ESPVR.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Arterial stiffness and peripheral artery disease (PAD) are both associated with an elevated risk of major adverse cardiac events; however, the association between arterial stiffness and PAD is less ...well characterized. The goal of this study was to examine the association between parameters of radial artery tonometry, a noninvasive measure of arterial stiffness, and PAD.
We conducted a cross-sectional study of 134 vascular surgery outpatients (controls, 33; PAD, 101) using arterial applanation tonometry. Central augmentation index (AIX) normalized to 75 beats/min and peripheral AIX were measured using radial artery pulse wave analysis. Pulse wave velocity was recorded at the carotid and femoral arteries. PAD was defined as symptomatic claudication with an ankle-brachial index of <0.9 or a history of peripheral revascularization. Controls had no history of atherosclerotic vascular disease and an ankle-brachial index ≥0.9.
Among the 126 participants with high-quality tonometry data, compared with controls (n = 33), patients with PAD (n = 93) were older, with higher rates of hypertension, hyperlipidemia, diabetes, and smoking (P < .05). Patients with PAD also had greater arterial stiffness as measured by central AIX, peripheral AIX, and pulse wave velocity (P < .05). In a multivariable model, a significantly increased odds of PAD was associated with each 10-unit increase in central AIX (odds ratio, 2.1; 95% confidence interval, 1.1-3.9; P = .03) and peripheral AIX (odds ratio, 1.9; 95% confidence interval, 1.2-3.2; P = .01). In addition, central and peripheral AIX were highly correlated (r120 = 0.76; P < .001).
In a cross-sectional analysis, arterial stiffness as measured by the AIX is independently associated with PAD, even when adjusting for several atherosclerotic risk factors. Further prospective data are needed to establish whether radial artery tonometry could be a tool for risk stratification in the PAD population.
The decrease in contractility in myocardium adjacent (border zone; BZ) to a myocardial infarction (MI) is correlated with an increase in reactive oxygen species (ROS). We hypothesized that injection ...of a thermoresponsive hydrogel, with ROS scavenging properties, into the MI would decrease ROS and improve BZ function. Fourteen sheep underwent antero‐apical MI. Seven sheep had a comb‐like copolymer synthesized from N‐isopropyl acrylamide (NIPAAm) and 1500 MW methoxy poly(ethylene glycol) methacrylate, (NIPAAm‐PEG1500), injected (20 × 0.5 mL) into the MI zone 40 min after MI (MI + NIPAAm‐PEG1500) and seven sheep were MI controls. Cardiac MRI was performed 2 weeks before and 6 weeks after MI + NIPAAm‐PEG1500. BZ wall thickness at end systole was significantly higher for MI + NIPAAm‐PEG1500 (12.32 ± 0.51 mm/m2 MI + NIPAAm‐PEG1500 vs. 9.88 ± 0.30 MI; p = .023). Demembranated muscle force development for BZ myocardium 6 weeks after MI was significantly higher for MI + NIPAAm‐PEG1500 (67.67 ± 2.61 mN/m2 MI + NIPAAm‐PEG1500 vs. 40.53 ± 1.04 MI; p < .0001) but not significantly different from remote myocardium or BZ or non‐operated controls. Levels of ROS in BZ tissue were significantly lower in the MI + NIPAAm‐PEG1500 treatment group (hydroxyl p = .0031; superoxide p = .0182). We conclude that infarct injection of the NIPAAm‐PEG1500 hydrogel with ROS scavenging properties decreased ROS and improved contractile protein function in the border zone 6 weeks after MI.
OBJECTIVE:To evaluate the effects of HIV preexposure prophylaxis (PrEP) with tenofovir disoproxial fumurate (TDF)/emtricitabine (FTC) on kidney function and kidney tubular health.
DESIGN:The ...Iniciativa Profilaxis Pre-Exposicion open-label extension (iPrEx-OLE) study enrolled former PrEP trial participants to receive open-label TDF/FTC. This study included 123 iPrEx-OLE participants who demonstrated PrEP adherence.
METHODS:We compared estimated glomerular filtration rate calculated using serum creatinine (eGFRcr), serum cystatin C (eGFRcys), and in combination (eGFRcr-cys), and a panel of 14 urine biomarkers reflecting kidney tubular health before and 6 months after PrEP initiation.
RESULTS:At baseline, mean eGFRcr, eGFRcys, and eGFRcr-cys were 108.3, 107.0, and 111.1 ml/min per 1.73 m, respectively. Six months after PrEP initiation, eGFRcr declined by −4% (95% CI−5.7 to −2.4%), eGFRcys declined by −3.3% (95% CI−8.3 to 1.9%), and eGFRcr-cys declined by −4.1% (95% CI−7.5 to −0.7%). From the urine biomarker panel, α1-microglobulin and β2-microglobulin increased by 22.7% (95% CI11.8--34.7%) and 14.1% (95% CI−6.1 to 38.6%), whereas chitinase-3-like 1 protein and monocyte chemoattractant protein-1 decreased by −37.7% (95% CI−53.0 to −17.3%) and −15.6% (95% CI−31.6 to 4.2%), respectively. Ten of the 14 urine biomarkers, including albumin, had estimated changes of less than 12% with wide confidence intervals.
CONCLUSION:Six months of PrEP with TDF/FTC was associated with decreases in eGFRcr and eGFRcys. We also observed for the first time changes in flour of 14 urine biomarkers reflecting kidney tubular health. These findings demonstrate that PrEP has direct effects on eGFR and the proximal tubule.
Resistin is a hormone that has been associated with metabolic syndrome and cardiovascular disease. The role of resistin in patients with peripheral artery disease (PAD) has not been fully explored. ...This study seeks to understand the relationship between serum resistin, vascular function, and cardiovascular outcomes in patients with PAD.
There were 106 patients with PAD who were recruited between 2011 and 2016. Patients attended a baseline visit during which a comprehensive vascular physiology assessment including medical and surgical history, radial artery tonometry, and flow mediated-vasodilation (FMD) was completed. A blood sample was drawn, and serum resistin was assayed using enzyme-linked immunosorbent assay kits. Using the time of study enrollment as the time of origin, incident major adverse cardiac events (MACEs) were identified by subsequent chart review and defined as a composite end point of myocardial infarction, coronary revascularization, transient ischemic attack, stroke, or death from a cardiac cause.
Patients had a mean age of 68 ± 8 years, were largely white (75%), and had comorbidities commonly associated with PAD including hypertension (92%), hyperlipidemia (87%), coronary artery disease (37%), and diabetes mellitus (38%). After stratification by resistin quartile, higher resistin quartiles were significantly associated with an older age, a greater number of pack-years smoked, and a lower estimated glomerular filtration rate. Despite similar comorbidities and medication use, endothelial function, as measured by FMD, was significantly lower with increasing resistin quartile (I, 9.1% ± 3.3%; II, 7.1% ± 3.5%; III, 5.8% ± 4.0%; IV, 5.6% ± 3.5%; P = .002). In multivariable linear regression, higher resistin quartiles (III and IV) were associated with lower FMD relative to quartile I after adjusting for several patient characteristics, medications, and comorbidities (III, −2.26 95% confidence interval (CI), −4.51 to −0.01; P = .05; IV, −2.53 95% CI, −4.87 to −0.20; P = .03). During a median follow-up period of 36 months (interquartile range, 29-45 months), 21 patients experienced the primary end point. In a Cox proportional hazards model adjusted for smoking status, coronary artery disease, and age, each 1 ng/mL increase in resistin was associated with a 10% increased risk of MACEs (hazard ratio, 1.10; 95% CI, 1.00-1.20; P = .04).
In patients with PAD, higher levels of resistin were associated with impaired endothelial function and an increased rate of MACEs. These results suggest that resistin may be a marker or effector of impaired vascular physiology and adverse cardiac outcomes in patients with PAD. Further research is needed to determine the potential mechanisms by which resistin may impair endothelial function and increase MACEs in this population.
Novel urine biomarkers have enabled the characterization of kidney tubular dysfunction and injury among persons living with HIV, a population at an increased risk of kidney disease. Even though ...several urine biomarkers predict progressive kidney function decline, antiretroviral toxicity, and mortality in the setting of HIV infection, the relationships among the risk factors for chronic kidney disease (CKD) and urine biomarkers are unclear.
We assessed traditional and infection-related CKD risk factors and measured 14 urine biomarkers at baseline and at follow-up among women living with HIV in the Women's Interagency Health Study (WIHS). We then used simultaneously adjusted multivariable linear regression models to evaluate the associations of CKD risk factors with longitudinal changes in biomarker levels.
Of the 647 women living with HIV in this analysis, the majority (67%) were Black, the median age was 45 years and median follow-up time was 2.5 years. Each traditional and infection-related CKD risk factor was associated with a unique set of changes in urine biomarkers. For example, baseline hemoglobin a1c was associated with worse tubular injury (higher interleukin IL-18), proximal tubular reabsorptive dysfunction (higher α1-microglobulin), tubular reserve (lower uromodulin) and immune response to injury (higher chitinase-3-like protein-1 YKL-40). Furthermore, increasing hemoglobin a1c at follow-up was associated with further worsening of tubular injury (higher kidney injury molecule-1 KIM-1 and IL-18), as well as higher YKL-40. HCV co-infection was associated with worsening proximal tubular reabsorptive dysfunction (higher β2-microglobulin β2m), and higher YKL-40, whereas HIV viremia was associated with worsening markers of tubular and glomerular injury (higher KIM-1 and albuminuria, respectively).
CKD risk factors are associated with unique patterns of biomarker changes among women living with HIV, suggesting that serial measurements of multiple biomarkers may help in detecting and monitoring kidney disease in this setting.
Contact author: Tammie J. Spaulding, Department of Speech, Language, and Hearing Sciences, P.O. Box 210071, The University of Arizona, Tucson, AZ 85721-0071. Email: spauld20{at}email.arizona.edu
...PURPOSE: The assumption that children with language impairment will receive low scores on standardized tests, and therefore that low scores will accurately identify these children, is examined through a review of data in the manuals of tests that are intended for use in identifying such children.
METHOD: Data from 43 commercially available tests of child language were compiled to identify whether evidence exists to support their use in identifying language impairment in children.
RESULTS: A review of data concerning the performance of children with impaired language failed to support the assumption that these children will routinely score at the low end of a test's normative distribution. A majority of tests reported that such children scored above 1.5 SD below the mean, and scores were within 1 SD of the mean for more than a quarter (27%) of the tests. The primary evidence needed to support the purpose of identification, test sensitivity and specificity, was available for 9 of the 43 tests, and acceptable accuracy (80% or better) was reported for 5 of these tests.
IMPLICATIONS: Specific data supporting the application of "low score" criteria for the identification of language impairment is not supported by the majority of current commercially available tests. However, alternate sources of data (sensitivity and specificity rates) that support accurate identification are available for a subset of the available tests.
KEY WORDS: language disorder, assessment, evidence-based practice, school-age children
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Population‐based data suggest that individuals who consume large dietary amounts of n‐3 polyunsaturated fatty acids (PUFA) have lower odds of peripheral artery disease (PAD); however, clinical ...studies examining n‐3 PUFA levels in patients with PAD are sparse. The objective of this study is to compare erythrocyte membrane fatty acid (FA) content between patients with PAD and controls. We conducted a cross‐sectional study of 179 vascular surgery outpatients (controls, 34; PAD, 145). A blood sample was drawn and the erythrocyte FA content was assayed using capillary gas chromatography. We calculated the ratio of the n‐3 PUFA eicosapentaenoic acid (EPA) to the n‐6 PUFA arachidonic acid (ARA) as well as the omega‐3 index (O3I), a measure of erythrocyte content of the n‐3 PUFA, EPA, and docosahexaenoic acid (DHA), expressed as a percentage of total erythrocyte FA. Compared with controls, patients with PAD smoked more and were more likely to have hypertension and hyperlipidemia (p < 0.05). Patients with PAD had a lower mean O3I (5.0 ± 1.7% vs 6.0 ± 1.6%, p < 0.001) and EPA:ARA ratio (0.04 ± 0.02 vs 0.05 ± 0.05, p < 0.001), but greater mean total saturated fats (39.5 ± 2.5% vs 38.5 ± 2.6%, p = 0.01). After adjusting for several patient characteristics, comorbidities, and medications, an absolute decrease of 1% in the O3I was associated with 39% greater odds of PAD (odds ratio OR 1.39, 95% confidence interval CI 1.03–1.86, and p = 0.03). PAD was associated with a deficiency of erythrocyte n‐3 PUFA, a lower EPA:ARA ratio, and greater mean total saturated fats. These alterations in FA content may be involved in the pathogenesis or development of poor outcomes in PAD.
Leptin, adiponectin, and resistin are in a class of hormones called adipokines that are produced by adipocytes and have been implicated in the causal pathway of atherosclerosis. We examined the ...association between adipokine levels and peripheral artery disease (PAD), hypothesizing that after adjusting for fat mass, leptin and resistin would be higher, whereas adiponectin would be lower, in patients with PAD.
A cross-sectional sample of 179 predominately male (97%) vascular surgery outpatients was recruited from the San Francisco Veterans Affairs Medical Center (SFVAMC). PAD was defined as either an ankle-brachial index < 0.9 plus symptoms of claudication or prior revascularization for symptomatic PAD (n = 141). Controls had an ankle-brachial index ≥0.9 and no history of atherosclerotic disease (n = 38). Adipokines were assayed using commercially available ELISA kits and values were log-transformed. Fat mass was measured using bioelectrical impedance.
In an analysis adjusting for body mass index (BMI) and atherosclerotic risk factors, higher serum leptin was associated with PAD (OR 2.54, 95% CI 1.07-6.01, P = 0.03), whereas high molecular weight adiponectin was inversely associated, though not significantly (OR 0.60, 95% CI 0.33-1.08, P = 0.09). Resistin was not associated with PAD. Sensitivity analyses using fat mass/height2 rather than BMI yielded similar results.
These results indicate that after adjusting for BMI or fat mass, serum leptin levels are positively and independently associated with PAD, whereas high molecular weight adiponectin might be inversely associated. Using a more representative, nonveteran sample, further investigations should focus on the potential role of adipokines in the pathophysiology of PAD as well as determine whether leptin levels have clinical utility in predicting PAD outcomes.
Peripheral artery disease (PAD) is associated with increased arterial stiffness, as measured by an increasing radial artery augmentation index (AIX). However, it has not yet been clearly demonstrated ...whether AIX is associated with adverse cardiovascular outcomes in a PAD population.
Seventy-two patients with PAD were recruited between 2011 and 2016. Radial artery applanation tonometry was performed at a baseline visit, and the central AIX, normalized to 75 beats/min, and the peripheral AIX were calculated using pulse wave analysis. Incident major adverse cardiac events (MACEs) were identified by subsequent chart review.
Study subjects had comorbidities commonly associated with PAD including a high prevalence of hypertension (93%), hyperlipidemia (85%), coronary artery disease (39%), and diabetes mellitus (39%). During a median follow-up period of 34 mo (interquartile range 29-38), 14 patients experienced a MACE. In a univariate Cox proportional hazards model, a 10-unit increase in the peripheral AIX was significantly associated with a 54% increased rate of MACE (hazard ratio HR 1.54, 95% confidence interval CI 1.06-2.22, P = 0.02), but central AIX, normalized to 75 beats/min, was not (HR 1.33, 95% CI 0.71-2.47, P = 0.37). In a multivariable model adjusted for coronary artery disease, age, and Rutherford category the peripheral AIX remained significantly associated with MACE (HR 1.70, 95% CI 1.10-2.62, P = 0.02).
Increased arterial stiffness, as measured by the peripheral AIX, was independently associated with an increased rate of MACE in patients with PAD. The use of radial artery tonometry should be contemplated as a tool for risk stratification in patients with PAD.
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