Identifying peripheral arterial disease in the elderly patients using machine-learning algorithms.

BACKGROUND: Peripheral artery disease (PAD) is a common syndrome in elderly people. Recently, artificial intelligence (AI) algorithms, in particular machine-learning algorithms, have been increasingly used in disease diagnosis. AIM: In this study, we designed an effective diagnostic model of PAD in the elderly patients using artificial intelligence. METHODS: The study was performed with 539 participants, all over 80 years in age, who underwent the measurements of Doppler ultrasonography and ankle-brachial pressure index (ABI). Blood samples were collected. ABI and two machine-learning algorithms (MLAs)-logistic regression and a random forest (RF) model-were established to diagnose PAD. The sensitivity and specificity of the models were analyzed. An additional RF model was designed based on the most significant features of the original RF model and a prospective study was conducted to demonstrate its external validity. RESULTS: Thirteen of the 28 features introduced to the MLAs differed significantly between PAD and non-PAD participants. The respective sensitivities and specificities of logistic regression, RF, and ABI were as follows: logistic regression (81.5%, 83.8%), RF (89.3%, 91.6%) and ABI (85.1%, 84.5%). In the prospective study, the newly designed RF model based on the most significant seven features exhibited an acceptable performance rate for the diagnosis of PAD with 100.0% sensitivity and 90.3% specificity. CONCLUSIONS: An RF model was a more effective method than the logistic regression and ABI for the diagnosis of PAD in an elderly cohort.

Carotid plague formation is associated with ankle-brachial index in elderly people.

AIMS: This study aimed at examining whether ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) were independently associated with carotid Intima-media thickness (CIMT) or carotid artery plaque (CAP) in elderly people. METHODS: A cross-sectional analysis was performed in 155 individuals aged over 75 years who underwent the measurements of ABI and baPWV. Low ABI was defined as ABI ≤ 1.0. High baPWV was defined as baPWV > 2000 cm/s. The CIMT and CAP were measured with a B-mode tomographic ultrasound system. RESULTS: Neither ABI nor baPWV was associated with CIMT in this elderly population. The group with low ABI (≤ 1.0) was significantly associated with a higher prevalence of carotid plaque (P = 0.001), while the relationship between baPWV and prevalence of carotid plaque was not found. Linear regression analysis showed that the value of ABI was significantly associated with the thickness of carotid plaque. Even in the full adjusted model, each 0.01unit ABI decreasing still increased 0.1663 mm of carotid plaque thickness (P = 0.004). Logistic Regression Analysis demonstrated that ABI lower than 1.0 had predictive value in the formation of carotid plaque with top quartile thickness (OR 2.834, 95% CI 1.131-7.099, P = 0.026). Furthermore, individuals with low ABI (≤ 1.0) were more likely to form hypoechoic carotid plaques according to ultrasonography. CONCLUSION: Low ABI but not high baPWV was associated with the formation of carotid plaque. Furthermore, ABI was significantly associated with the thickness and morphology of carotid plaque in elderly people.

Erythrocyte rheological properties but not whole blood and plasma viscosity are associated with severity of hypertension in older people.

OBJECTIVE: This study was carried out to determine whether changes in hemorheological parameters parallel the severity of essential hypertension. METHODS: A total of 198 older hypertensive patients were recruited and classified into 3 stages of hypertension according to the grading standard of hypertension. The whole blood viscosity (WBV) at various shear rates, plasma viscosity and erythrocyte rheology (including erythrocyte rigidity index, erythrocyte aggregation index and erythrocyte deformation index) were examined. RESULTS: Erythrocyte rheology paralleled the severity of essential hypertension and was significantly correlated to the average 24 h systolic blood pressure and diastolic blood pressure. Logistic analysis revealed that erythrocyte rigidity and the erythrocyte aggregation index were positively correlated with the severity of hypertension, while the erythrocyte deformation index was negatively correlated. No association was found between WBV, plasma viscosity and the severity of hypertension. CONCLUSION: The rheological properties of erythrocyte viscosity were correlated with the severity of hypertension in older people but the WBV and plasma viscosity were not.

Serum levels of cathepsin D, sirtuin1, and endothelial nitric oxide synthase are correlatively reduced in elderly healthy people.

AIM: Nowadays, cathepsins have been reported to be related to aging. The aim of this study is to evaluate the association between serum levels of cathepsin D (CTSD) and human aging. METHODS: In the present study, we analyzed the serum levels of CTSD and its relation with levels of sirtuin1 (SIRT1) and endothelial nitric oxide synthase (eNOS) activity, which were known having an important role in aging. This study recruited 90 healthy subjects (62 men and 28 women), which were subdivided into three groups with respect to age: young (about 19 years old, n = 30), middle-age (about 40 years old, n = 30), and aged (above 65 years old, n = 30). Altered serum levels of CTSD and SIRT1 were measured by enzyme-linked immunosorbent assay, and eNOS activity was assessed by the conversion of 14(C)-L-arginine to 14(C)-L-citrulline. RESULTS: Elderly subjects had significantly lower CTSD, SIRT1, and eNOS than younger ones. Serum levels of CTSD were negatively correlated with age. There was a statistically significant positive correlation between serum levels of CTSD, eNOS, and SIRT1. CONCLUSIONS: This study shows lower serum CTSD values in elderly subjects than in younger subjects. This is the first to demonstrate age-related changes in cathepsin D levels in humans and the association between SIRT1 and eNOS.

Decreased serum level of HMGB1 and MyD88 during human aging progress in healthy individuals.

AIMS: Previous studies have suggested that high mobility group box-1 protein (HMGB1) binds to the toll-like receptor 4 (TLR4) signaling mediates the progression of various inflammatory diseases. But the roles of HMGB1 and TLR4 in aging remain poorly unknown. In this study, we aimed to investigate the serum levels of HMGB1 and myeloid differentiation factor 88 (MyD88), which is one of TLR4's intracellular adaptor proteins during human aging process and their relevance with cathepsin B (CTSB). METHODS: This research was conducted using the blood samples provided by healthy people (n = 90, 63 men and 27 women). Subjects were subdivided into groups with respect to age: young (about 25 years old, n = 30), middle age (about 40 years old, n = 30), and aged (above 65 years old, n = 30). Altered serum levels of HMGB1, MyD88 and CTSB were measured using an enzyme-linked immunosorbent assay. RESULTS: The serum levels of HMGB1 and MyD88 were significantly decreased in the aged group compared with those in the young group. Linear regression analysis showed that HMGB1 and MyD88 positively correlated with CTSB among the whole healthy people. A negative correlation was determined between MyD88 and age. CONCLUSIONS: The serum levels of HMGB1 and MyD88 significantly decreased with age. MyD88, but not HMGB1, was negatively correlated with age.

GA to HbA1C ratio, but not HbA1C is associated with cognition in Chinese nondiabetic old adults.

OBJECTIVES: To investigate the relationship between glycated albumin (GA) to glycated hemoglobin (HbA1c) ratio and cognitive impairment in old age. Diabetes is associated with cognitive impairment in older people. However, the link between elevated GA/HbA1c levels and the risk of cognitive impairment in nondiabetic individuals is unclear. METHODS: A cross-sectional study of 474 old, nondiabetic adults (192 women, mean age 73.8 years ± 6.9 SD) who had been admitted to our hospital was conducted. Glycemic measures included fasting plasma glucose (FPG), 2-hour post-prandial plasmic glucose (2hPPG), GA and HbA1c. Cognitive function was assessed using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at the same examination visit in which the glycemic measures were determined. RESULTS: When the individuals were divided into two groups according to the median of GA/HbA1c ratio, old adults with GA/HbA1c ratio ≥ 2.53 showed lower MMSE and MoCA scores compared to those with GA/HbA1c ratio < 2.53. Univariate regression analysis showed that MMSE and MoCA scores were not correlated with HbA1c, but were inversely correlated with GA and GA/HbA1c ratio. Linear regression analysis revealed that there was a significant negative correlation between GA/HbA1c and cognitive function (ß = -0.77, P < 0.01 for MoCA and ß = -0.69, P < 0.05 for MMSE) even after adjustment for age, body mass index, systolic blood pressure, lipoprotein(a) and sex. CONCLUSION: Our results indicate that even in the absence of manifest type 2 diabetes mellitus, GA/HbA1c ratio levels exert a negative influence on cognition and it may be a better predictor for cognitive impairment in the older population.

Correlation between ankle-brachial index and subtle cognitive decline.

BACKGROUND: Subtle cognitive decline (SCD) is considered the early stage of Alzheimer's disease (AD) and is of great clinical significance for the prevention and treatment of AD. The ankle-brachial index (ABI) has been reported to be associated with cognitive impairment; however, there are few studies on the relationship between ABI and SCD. METHODS: From August 2019 to April 2021, subjects were recruited to participate in a cognitive function test at the Shanghai Sixth People's Hospital. Based on the test results, 217 patients with SCD were selected as the experimental group and 259 patients with normal cognitive function were selected as the control group. The data of the two groups were compared, and the correlation between the ABI and cognitive decline was analyzed. RESULTS: There were significant differences in age, sex, smoking status, hypertension, diabetes, triglycerides, serum creatinine, and ABI (p < .05)between the two groups. Logistic regression analysis showed that age, hypertension, diabetes, and ABI influenced cognitive decline(p < .05). After correcting for other factors, ABI was independently related to cognitive decline. Pearson's correlation analysis showed that a low ABI (<0.9) had a significant effect on memory and visual space of the cognitive domain (p < . 05). CONCLUSIONS: ABI is significantly associated with SCD and may be a critical tool to predict early cognitive decline.

Common carotid flow velocity is associated with cognition in older adults.

AIMS: To assess the relationship between carotid flow velocity and cognitive impairment in patients with mild-moderate (<50%) carotid artery disease. METHODS: We studied 407 participants with available carotid ultrasound and cognitive measures. We related peak systolic velocity (PSV) and end diastolic velocity (EDV) of internal carotid artery (ICA) and common carotid artery (CCA) and intimal medial thickness (IMT) to Mini Mental State Examination (MMSE), Clock Draw Test (CDT), Activities of Daily Living Scale (ADL)and Montreal Cognitive Assessment (MoCA). RESULTS: EDV of CCA was significantly different in higher and lower MoCA (MMSE) groups. Multiple regression analysis demonstrated that lower EDV was significantly associated with lower MoCA (+0.459 per standard deviation (SD), p<0. 01 for the left; +0.539 per SD, p<0. 01 for the right) and CDT (odds ratio (OR) 0.093, p< 0.05 for the left; OR) 0.120, p<0. 01 for the right) scores. PSV of left CCA (-0.205 per SD, p<0.05) and IMT (+42.536 per SD, p< 0.001) were associated with ADL. PSV of right CCA was associated with MMSE (+0.081 per SD, p<0.001). No significant relationship between ICA flow velocity and cognitive performance was observed. CONCLUSIONS: Our preliminary data show that common carotid artery flow velocity was associated with cognitive performance.

Inflammatory myofibroblastic tumor: A demographic, clinical and therapeutic study of 92 cases.

PURPOSE: Inflammatory myofibroblastic tumors (IMT) was a rare kind of tumor defined by WHO since 2012. Little was known about this disease. There were controversies about IMT's behavior, predilection site, age distribution, and the best treatment methods. Here we provided a systematic overview on tumor demographical, clinical, biological features as well as treatment efficacy based on real cases from Surveillance, Epidemiology, and End Results (SEER) database. METHODS: 92 patients diagnosed with IMT by histopathology were drawn from SEER database between 2002 and 2014. Patient demographics, clinical features and treatment information were analyzed. RESULTS: The mean age of onset was 47.4 ± 22.4 years (0 to 83y) and the ages prone to this disease are middle-aged (from 41y to 64y), accounting for 1/3 of all patients. Three peak ages of onsets were 0-4y, 36-40y and more than 50y. 42% of the tumors were located in the soft tissues of limbs, hip, shoulder, head, face and neck. The average tumor sizes were 6.5 ± 5.3cm (1cm to 25cm). Survival in the group of tumor size smaller than 6.5cm was better compared to group of tumor size larger than 6.5cm (P < 0.05). Most of the tumors were malignant or malignant potential (89%), though local and distant metastasis rate were low (5%). Surgery was the most common treatment. However, the survival benefit was still uncertain compared to adjuvant chemotherapy or radiotherapy. Multivariate regression analysis demonstrated that young patients had better survival than old ones. CONCLUSIONS: IMT was a malignant tumor with low risk of local and distant metastasis. The peak ages were 0-4y, 36-40y and more than 50y. The prone sites were the soft tissues of the limbs, hip, shoulder, head, face and neck. Tumor sizes and ages were the factors correlated with survival time.

Cathepsin L deficiency results in reactive oxygen species (ROS) accumulation and vascular cells activation.

Recent evidence suggests a link between cathepsin L (CTSL) and vascular diseases. However, its contribution to reactive oxygen species (ROS) homeostasis in the vasculature remains unknown. p66shc is a redox enzyme implicated in mitochondrial ROS generation and translation of oxidative signals. In this study, we explored the relationship between CTSL and oxidative damage in vasculature and whether the oxidative damage is mediated by p66shc.Carotid arteries from aged mice (24 months old) showed a reduction in CTSL expression compared with young wild-type mice (4 months old). Local knockdown of CTSL in carotid arteries of young mice by adenoviral vector encoding the short hairpin RNA targeting CTSL leading to premature vascular aging, as shown by mitochondrial disruption, increased ß-galactosidase-positive cells, reduced telomerase activity, and up-regulation of p66shc. Knockdown of CTSL decreased the expression of mitochondrial oxidative phosphorylation (OXPHOS) complexes I, III, and IV, leading to increased mitochondrial ROS and hyperpolarization of the mitochondrial membrane in vitro. Furthermore, knockdown of CTSL also stimulated ROS production and senescence in vascular cells, accompanied by the up-regulation of p66shc.However, p66shc knockdown blunted the alteration in ROS production, and senescence in CTSL knockdown vascular cells. This study suggests that CTSL knockdown partially induces vascular cells damage via increased ROS production and up-regulation of p66shc.

Differential levels of cathepsin B and L in serum between young and aged healthy people and their association with matrix metalloproteinase 2.

OBJECTIVE: Most publications describe cathepsin B and L as tumor and metastasis factors. These proteases also play a very important role in aging process. The aim of this study was to evaluate the serum level of cathepsin B and L with aging and their association with matrix metalloproteinase 2 (MMP2), which was reported to associate with age-related diseases. METHODS: This research was conducted using blood samples provided by healthy people (n=90, 63 men and 27 women). Subjects were subdivided into groups with respect to age: young (about 18-30 years old, n=30), middle age (about 36-50 years old, n=30), and aged (above 56 years old, n=30). Altered serum level of cathepsin B, cathepsin L, and MMP2 with aging was studied by enzyme-linked immunosorbent assay (ELISA) and Western blotting using discriminative antibodies specific for each factor. RESULTS: ELISA and Western blotting revealed that the serum level of cathepsin L and MMP2, but not cathepsin B significantly decreased in aged group compared with young group. Cathepsin L positively correlates with MMP2 among the whole healthy people (r(2)=0.869, p<0.0001). CONCLUSION: The serum level of cathepsin L decreased with age, while cathepsin B remained no significant difference between young and aged individuals. In addition, cathepsin L positively correlates with MMP2. PRACTICE: The cathepsin L may be used as a monitoring index in age-related diseases. IMPLICATIONS: In addition to cathepsin B, cathepsin L may be also involved in the aging process.

Aldosterone-induced osteopontin expression in vascular smooth muscle cells involves MR, ERK, and p38 MAPK.

Osteopontin (OPN) is known to be one of the cytokines that is involved in the vascular inflammation caused by aldosterone (Ald). Previous reports have shown that Ald increases OPN expression, and the mechanisms for this remain to be clarified. In this study, we investigated how Ald increases OPN expression in the vascular smooth muscle cells (VSMCs) of rats. Ald increased OPN expression time dependently as well as dose dependently. This increase was diminished by spironolactone, a mineralocorticoid receptor (MR) antagonist. PD98059, an inhibitor of p42/44 MAPK pathway, and SB203580, an inhibitor of p38 MAPK pathway, suppressed Ald-induced OPN expression and secretion in VSMCs. VSMCs migration stimulated by aldosterone required OPN expression. In conclusion, these data suggest that Ald-induced OPN expression in VSMC is mediated by MR and signaling cascades involving ERK and p38 MAPK. These molecules may represent therapeutic targets for the prevention of pathological vascular remodeling.

Expression and function of osteopontin in vascular adventitial fibroblasts and pathological vascular remodeling.

Osteopontin is known to play important roles in various diseases including vascular disorders. However, little is known about its expression and function in vascular adventitial fibroblasts. Adventitial fibroblasts have been shown to play a key role in pathological vascular remodeling associating with various vascular disorders. In this study, we measured activation of Osteopontin and its biological functions in cultured adventitial fibroblasts and injured rat carotid injury arteries induced by balloon angioplasty. Our results showed that angiotensin II and aldosterone increased Osteopontin expression in adventitial fibroblasts in a time- and concentration-dependent manner. MAPKs and AP-1 pathways were involved in Osteopontin upregulation. In addition, Adventitial fibroblast migration stimulated by Angiotensin II and aldosterone required OPN expression. Perivascular delivery of antisense oligonucleotide for Osteopontin suppressed neointimal formation post-injury. We concluded that upregulation of Osteopontin expression in adventitial fibroblasts might be important in the pathogenesis of vascular remodeling after arterial injury.