Carotid total plaque area as a marker of asymptomatic lower extremity arterial disease

Objective: to examine the prognostic value of ultrasound markers of carotid atherosclerosis in relation to the presence of asymptomatic lower extremity peripheral artery disease (PAD). Materials and Methods: the study included 193 patients with carotid atherosclerosis. All patients underwent duplex ultrasound scanning (DUS) of carotid and lower limb arteries. The carotid plaque score (cPS) was determined as the total height of all plaques in the carotid arteries. The carotid total plaque area (cTPA) was estimated in the longitudinal position, the area of plaque was measured in the manual trace mode.Results: asymptomatic lower extremity PAD was diagnosed in 31.6% of patients. The increase in cTPA, in contrast to cPS and the degree of carotid stenosis, was independent predictor of lower extremity PAD and was associated with an increase in the relative risk of its presence by 6.78 times (95% CI 2.48-18.5; p <0.0001). cTPA ≥42.5 mm2 made it possible to diagnose asymptomatic lower extremity PAD with a sensitivity of 70.2% and specificity of 73.0%. Conclusion: In patients with carotid atherosclerosis among carotid atherosclerosis markers only cTPA, in contrast to cPS and the degree of carotid stenosis, had an independent predictive value regarding the presence of asymptomatic lower extremity PAD.

A comparative study of the effects of Aducanumab and scanning ultrasound on amyloid plaques and behavior in the APP23 mouse model of Alzheimer disease

Background Aducanumab is an anti-amyloid-β (Aβ) antibody that achieved reduced amyloid pathology in Alzheimer’s disease (AD) trials; however, it is controversial whether it also improved cognition, which has been suggested would require a sufficiently high cumulative dose of the antibody in the brain. Therapeutic ultrasound, in contrast, has only begun to be investigated in human AD clinical trials. We have previously shown that scanning ultrasound in combination with intravenously injected microbubbles (SUS), which temporarily and safely opens the blood-brain barrier (BBB), removes amyloid and restores cognition in APP23 mice. However, there has been no direct testing of how the effects of SUS compare to immunotherapy or whether a combination therapy is more effective. Methods In a study comprising four treatment arms, we tested the efficacy of an Aducanumab analog, Adu, both in comparison to SUS, and as a combination therapy, in APP23 mice (aged 13–22 months), using sham as a control. The active place avoidance (APA) test was used to test spatial memory, and histology and ELISA were used to measure amyloid. Brain antibody levels were also determined. Results We found that both Adu and SUS reduced the total plaque area in the hippocampus with no additive effect observed with the combination treatment (SUS + Adu). Whereas in the cortex where there was a trend towards reducing the total plaque area from either Adu or SUS, only the combination treatment yielded a statistically significant decrease in total plaque area compared to sham. Only the SUS and SUS + Adu groups included animals that had their plaque load reduced to below 1% from above 10%. There was a robust improvement in spatial memory for the SUS + Adu group only, and in this group the level of Adu, when measured 3 days post-treatment, was 5-fold higher compared to those mice that received Adu on its own. Together, these findings suggest that SUS should be considered as a treatment option for AD. Alternatively, a combination trial using Aducanumab together with ultrasound to increase brain levels of the antibody may be warranted.

Comparative Analysis of Arterial Stiffness Between Patients with Chronic Obstructive Pulmonary Disease and Healthy People

Background: Analyze and compare the difference in arterial stiffness between patients with chronic obstructive pulmonary disease (COPD) and healthy people. Methods: A retrospective analysis of 83 patients with COPD who were treated the observation group; 80 healthy people were selected as the control group during the same period. Pearson correlation analysis software was used to analyze the correlation between arterial stiffness and ultrasound index in COPD patients. Results: The ultrasound RI and PI level of observation group were lower than those of control group and PI level (t=6.326, 8.321, P=0.000). Observation group IMT (1.36±0.13) mm, total plaque area (19.75±2.19) cm2, plaque number (1.67±0.64) were higher than control group IMT (0.94±0.10) mm, total plaque area (5.84±1.32) cm2, number of plaques (0.82±0.30) (t=4.574, 7.493, 5.093, P=0.000). The arterial stiffness (1585.49±14.36) cm/s and ABI level (1.63±0.24) of the observation group were higher than the arterial stiffness (1142.45±10.77) cm/s and ABI level (1.12±0.16) of the control group (t=6.392, 5.109, P=0.000). Arterial stiffness in COPD patients was negatively correlated with ABI, RI, PI levels (P<0.05); positively correlated with IMT, total plaque area, and plaque number (P<0.05). Conclusion The arterial stiffness of COPD patients is higher than that of healthy people; the ultrasound index can be used as an auxiliary indicator for clinical prediction of arterial stiffness, which is helpful to improve the accuracy of prediction and thus better guide clinical intervention in high-risk groups of COPD in time.

A comparative study of the effects of Aducanumab and scanning ultrasound on amyloid plaques and behavior in the APP23 mouse model of Alzheimer disease

BackgroundAducanumab is an anti-amyloid-β (Aβ) antibody that achieved reduced amyloid pathology in Alzheimer’s disease (AD) trials, but it is controversial whether it also improved cognition. It has been claimed that this would require a sufficiently high cumulative dose of the antibody in the brain. Therapeutic ultrasound, in contrast, has only begun to be investigated in human AD clinical trials. We have previously shown that scanning ultrasound in combination with intravenously injected microbubbles (SUS), that temporarily and safely opens the blood-brain barrier (BBB), removes amyloid and restores cognition in APP23 mice. It has not been directly tested how the effects of SUS compare to immunotherapy or whether a combination therapy is more effective.MethodsIn a study comprising four treatment arms, we tested the efficacy of an Aducanumab analogue, Adu, in comparison to SUS, as well as a combination therapy in APP23 mice, using sham as a control (aged 13-22 months). The active place avoidance (APA) test was used to test spatial memory, and histology and ELISA were used to measure amyloid. Brain antibody levels were also determined.ResultsWe found that both Adu and SUS reduced the total plaque area in the hippocampus to a similar degree, with no additive effect in the combination treatment (SUS+Adu). Whereas there was only a trend towards a reduction for both Adu and SUS in the cortex, the combination trial yielded a statistically significant reduction compared to sham. Only the SUS and SUS+Adu groups included animals that had their plaque load reduced to below 1% from above 10%. There was a robust improvement in spatial memory for SUS+Adu only. In this group, when measured three days post-treatment, Adu levels were still 5-fold increased in the combination therapy compared to delivery of Adu on its own.Together, these findings suggest that SUS should be seriously considered as a treatment option for AD. Alternatively, a combination trial using Aducanumab together with ultrasound to increase brain levels of Aducanumab may be warranted, as the two approaches may engage different (albeit shared) clearance mechanisms.

Abstract P245: Therapeutic Effects Of Mir-29b-Chitosan On Hypertension And Diabetic Complications

MicroRNA miR-29 promotes endothelial function in human arterioles in part by targeting LYPLA1 and increasing nitric oxide production. Endothelial dysfunction is common in cardiovascular diseases such as hypertension and diabetic microvascular complications. In addition, miR-29 is a master inhibitor of extracellular matrix gene expression, which may attenuate fibrosis but could also weaken tissue structure. The goal of this study was to develop an effective miR-29 therapeutic for multiple cardiovascular diseases using mouse models. Substantial accumulation of miR-29b and effective knockdown of Lypla1 in mouse tissues were achieved using a chitosan-packaged, chemically modified miR-29b mimic (miR-29b-CH) injected systemically at 200 μg/kg body weight. miR-29b-CH, injected once every three days, significantly attenuated angiotensin II-induced hypertension over two weeks (mean arterial pressure of 128 ± 5 vs 149 ± 5 mmHg, N = 7 Scr-CH, 8 miR-29b-CH p<0.05). In db/db mice, miR-29b-CH treatment for 12 weeks decreased cardiac (0.98 ± 0.13 vs 1.55 ± 0.17 % fibrosis) and renal (2.85 ± 0.28 vs 4.85 ± 0.47 % fibrosis) fibrosis and urinary albuminuria 0.0051 ± 0.0004 vs 0.0069 ± 0.0005 albumin/creatinine, N = 12 Scr-CH, 9 miR-29b-CH, p<0.05). In uninephrectomized db/db mice, the miR-29b-CH treatment for 20 weeks significantly improved myocardial performance index (0.36 ± 0.02 vs 0.57 ± 0.05) in addition to attenuating proteinuria (0.015 ± 0.004 vs 0.033 ± 0.005 protein/creatinine) (N = 8 Scr-CH, 8 miR-29b-CH, p<0.05). miR-29b-CH did not worsen abdominal aortic aneurysm in ApoE knockout mice treated with angiotensin II (33.7 ± 8.2 vs 29.8 ± 6.7% increase in suprarenal abdominal aorta diameter from baseline, N = 8 Scr-CH and 7 miR-29b-CH). miR-29b-CH caused aortic root fibrotic cap thinning (13.8 ± 2.5 vs 20.8 ± 1.8 % of total plaque area) in ApoE knockout mice fed a high cholesterol and high fat diet but did not worsen the necrotic zone (15.2 ± 1.4 vs 12.5 ± 1.0 % of total plaque area) or the mortality (11/12 control mice survived until end of study vs 10/12 miR-29b-CH treated, N = 8 Scr-CH, 7 miR-29b-CH). In conclusion, systemic delivery of low dose miR-29b-CH is an effective therapeutic for several forms of hypertension and diabetic complications in mice.

P173 Progression of subclinical cardiovascular disease in SLE: a five year follow up study

Background Patients with SLE have 5-10-fold increased risk of developing CVD compared to age and sex-matched controls. The average age of developing a first CVD event in patients with SLE is only 49. In this study we aimed to describe the rate and determinants of carotid plaque progression in a cohort of SLE patients who were asymptomatic of CVD at baseline. Methods We carried out vascular ultrasound studies of 100 patients with SLE asymptomatic of CVD at baseline. Sixty-nine patients were rescanned over a median of 5 years of follow up. Ninety-four percent who were re-scanned were women and the mean overall age was 46 years (SD 11). Clinical and CVD risk was assessed at baseline and follow up. The same protocol for assessment at baseline using B-mode Doppler ultrasound to measure intimal media thickness and plaque was used at follow up to assess progression. We also assessed total plaque area (TPA), a more sensitive measure of plaque, and echolucency expressed as gray scale median (GSM) which is linked to plaque lipid content. Results Of the 100 patients with a baseline scan, 69 patients had a second scan at a median of 5 years follow up. New plaque developed in 9% and 26% had an increase in plaque number. The mean overall IMT (0.111 vs 0.064, p &lt; 0.01) and common carotid IMT (0.065 vs 0.055, p &lt; 0.01) were significantly raised in plaque vs non-plaque patients. In a multi -variable analysis CIMT at follow-up was independently associated with age (beta 0.415, p &lt; 0.001) and diastolic blood pressure (beta 0.285, p &lt; 0.021). Independent predictors of plaque at follow-up scan on multi-variable analysis were age at scan&gt;52 years (OR 10.41, CI 2.66-40.80) and systolic BP &gt; 133 (OR 5.26, CI 1.396 - 19.862). In contrast, total cholesterol was negatively correlated with TPA (beta = -1.167, p = 0.002) and with GSM (beta = -0.513, p = 0.012). Conclusion Amongst these 69 patients, 26% had increased plaque and none had decreased plaque over a median of five years follow-up. Measurement of novel ultrasound variables such as TPA and echolucency may identify more modifiable risk factors that can be used to improve CVD outcomes in patients with SLE. Disclosures J. Bakshi: None. M. Griffin: None. S. Croca: None. F. Farhina: None. D. Isenberg: None. A. Nicolaides: None. A. Rahman: None.