Marker Of Vascular Disease Research Articles

Association of circulating Robo4 with obesity, hypertension and atherosclerotic plaque burden.

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Type 2 diabetes mellitus (T2DM) is a major risk factor for ASCVD development, being associated with endothelial dysfunction and accelerated atherosclerosis. In the current study we aimed to explore the potential value of circulating Robo4 (soluble Robo4, sRobo4), an endothelial-specific receptor that regulates endothelial cell (EC) junctional integrity, vascular permeability, EC-mediated inflammatory responses and angiogenesis, as a marker of vascular disease in individuals with or without T2DM. Thirty-four individuals with T2DM and 15 non-diabetic individuals (control) of similar age and sex were included in the study. sROBO4 was comparable between individuals with T2DM and control (T2DM: 1.54±1.19 vs control: 1.59±0.77 ng/mL, P=0.46). Of interest, sRobo4 positively correlated with body mass index (BMI) (rs=0.384, P=0.006), and negatively correlated with renal function as determined by estimated glomerular filtration rate (rs= -0.429, P=0.003). Moreover, individuals with arterial hypertension had higher sRobo4 compared to normotensive individuals (P=0.03). More importantly, we observed that individuals with 2 or more atherosclerotic plaques (n=28) in their femoral and/or carotid arteries had significantly higher sRobo4 levels compared to individuals with a total of none or 1 atherosclerotic plaque (n=20) (P=0.008). The association of sRobo4 with higher atherosclerotic burden remained significant when separately controlling for the effect of age, sex, presence of T2DM, total cholesterol, or BMI levels. In vivo studies utilizing models of atherosclerosis as well as larger prospective cohort studies are warranted to delineate causality and prognostic value of sRobo4 in atherosclerotic cardiovascular disease.

A quantitative MRI comparative study of imaging markers for cerebral small vessel disease in the middle-aged and elderly patients with and without hypertension

Objective: To explore the difference of MRI markers of small cerebral vascular disease in middle-aged and elderly patients with hypertension and non-hypertension. Methods: A cross-sectional study. The clinical data of 316 patients who underwent head MRI with susceptibility weighted imaging scans at the Affiliated Zhongda Hospital of Southeast University from November 2013 to August 2022 were retrospectively analyzed, including 190 males and 126 females, with the age of (71.6±8.9)years. According to the history of hypertension, the patients were divided into hypertension group(n=259) and the non-hypertension group(n=57). The patients in the non-hypertension group were further divided into abnormal blood pressure group on admission (n=19) and normal blood pressure group on admission (n=38). The imaging features of different CSVD dimensions in the patient's images were quantified or graded and compared between hypertensive and non-hypertensive patient groups. Deep learning methods were employed to segment white matter lesions, and voxel-wise analysis was conducted to investigate the differences in whole-brain white matter lesion probability between patients in both groups. Spearman correlation analysis was used to analyze the correlation between hypertension and small cerebral vascular disease. Results: Compared with the non-hypertensive group, the cerebral microhemorrhage count, deep microhemorrhage count, basal ganglia level lacunae count, perivascular space (EPVS) grade of hemioval center level and EPVS grade of basal ganglia level were higher in the hypertensive group (all P<0.05). The cerebral microhemorrhage count [3.0(1.0, 15.0) vs 1.0 (0, 4.2)], deep microhemorrhage count [1.0 (0, 7.0) vs 1.0 (0, 4.2)] and EPVS classification at basal ganglium level [2.0(1.0, 3.0) vs 1.0(1.0, 2.0)] in the group with history of hypertension were higher than those in the group with normal blood pressure at admission (all P<0.05). The EPVS grade at the central level of the semiovale in the hypertension group was higher than that of the group with normal blood pressure at admission [2.0(1.0, 2.0) vs 1.0 (1.0, 2.0)], and also higher than that of the group with abnormal blood pressure at admission [2.0(1.0, 2.0) vs 1.0(1.0, 2.0)](both P<0.05). Voxel-by-voxel analysis showed no significant difference in the probability of white matter lesions in the whole brain between patients with and without a history of hypertension, but patients with a history of hypertension showed more extensive para-ventricular white matter hypersignaling than those without a history of hypertension. Spearman correlation analysis showed that hypertension grade was correlated with the number of microbleeding lesions in depth (r=0.149), the number of lacunae lesions in the center of the hemioval (r=0.209), and the number of lacunae lesions in the basal ganglia (r=0.204) (all P<0.05). Conclusions: Chronic hypertension can affect different dimensions of small vessel disease imaging, primarily manifested in the increases of deep microbleed counts and the EPVS grade.

Age-associated gadolinium leakage into ocular structures in patients with acute traumatic brain injury

BackgroundGadolinium Leakage into Ocular Structures (GLOS) is common following acute cerebrovascular events. The objective of this study was to investigate the occurrence of GLOS in an acute traumatic brain injury (TBI) cohort without acute cerebrovascular injury and to explore associated factors. MethodsEnrolled acute TBI patients had a baseline MRI ≤48 h of injury (TP1) and follow-up MRI ≤72 h after baseline (TP2). Vitreous chamber enhancement and signal intensity ratios (SIRs) were calculated using pre- and post-contrast Fluid Attenuated Inversion Recovery (FLAIR). White matter hyperintensities (WMHs) were assessed using the Fazekas scale. ResultsOf the 128 TBI patients included, median age was 47 years, 70% male, and 66% presented with Glasgow Coma Scale of 15. No GLOS was detected at TP1 but was present in 23% of patients at TP2. GLOS+ patients were older (68 years [56–76] vs 39 years [27–53], p < 0.001), more likely to report falls as injury mechanism (62% vs 36%, p = 0.006), report history of hypertension (41% vs 19%, p = 0.025), and had a higher burden of WMHs (59% vs 14% with a total Fazekas ≥2, p < 0.001). Quantitative SIRs confirmed qualitative assessments: GLOS+ patients had higher SIRs at TP2 (0.43 vs 0.22, p < 0.001). Age (OR 3.28, 95%CI [1.88–5.71], p < 0.001) and prior TBI history (OR 4.99, 95%CI [1.46–17.06], p = 0.010) were independent predictors of GLOS. When age was removed, total Fazekas score (OR 2.53, 95%CI [1.60–4.00], p < 0.001) was an independent predictor of GLOS. ConclusionsGLOS is primarily associated with age and may serve as another imaging marker of chronic vascular disease.

Deep Diving Into the Cardiovascular Health Paradox: A Journey Towards Personalized Prevention.

The Life's Simple 7 score (LS7) promotes cardiovascular health (CVH). Despite this, some with optimal LS7 develop cardiovascular disease (CVD), while others with poor CVH do not, termed the "CVH paradox." This paper explores pathways explaining this paradox. We examined methodological aspects: 1) misclassification bias in self-reported lifestyle factors (smoking, physical activity, diet); 2) cumulative exposure to risk factors over a lifetime, impacting the CVH paradox. Punctual risk factor assessments are suboptimal for predicting outcomes. We proposed personalized prevention using "novel" elements to refine CVH assessment: 1) subclinical vascular disease markers, 2) metabolic biomarkers in blood and urine, 3) emerging risk factors, 4) polygenic risk scores (PRS), 5) epigenetics, and 6) the exposome. Addressing the CVH paradox requires a multifaceted approach, reducing misclassification bias, considering cumulative risk exposure, and incorporating novel personalized prevention elements. A holistic, individualized approach to CVH assessment and CVD prevention can better reduce cardiovascular outcomes and improve population health. Collaboration among researchers, healthcare providers, policymakers, and communities is essential for effective implementation and realization of these strategies.

Leptin Is Associated with Testosterone, Nutritional Markers, and Vascular Muscular Dysfunction in Chronic Kidney Disease.

Chronic kidney disease (CKD) causes specific hormonal disturbances, such as variations in leptin and testosterone levels and function. These disturbances can promote errors in signaling interaction and cellular information processing and can be implicated in the pathogenesis of atherosclerosis. This study investigates the factors that affect leptin in CKD patients and examines how leptin is related to markers of vascular disease. We conducted a cross-sectional study of 162 patients with CKD in pre-dialysis and dialysis stages. We recorded clinical and laboratory data, including leptin, testosterone, and subclinical atherosclerosis markers like brachial-ankle pulse wave velocity (ba PWV) in pre-dialysis CKD patients and flow-mediated vasodilation (FMD) and nitroglycerin-mediated vasodilation (NMD) in hemodialysis (HD) patients. Leptin was significantly correlated with testosterone in CKD pre-dialysis stages (p < 0.001) and also in HD (p = 0.026), with adipose tissue mass in pre-dialysis stages (p < 0.001), and also in HD (p < 0.001). In women HD patients, leptin correlated with NMD (p = 0.039; r = -0.379); in all HD patients, leptin correlated with C reactive protein (p = 0.007; r = 0.28) and parathormone (p = 0.039; r = -0.220). Our research emphasizes the connection between leptin, adipose tissue, and testosterone in all stages of CKD. Leptin was associated with NMD in HD women and correlated with inflammatory syndrome and parathyroid hormone in all HD patients.

Lung Function and Brain MRI Outcomes in the Atherosclerosis Risk in Communities Neurocognitive Study.

Brain imaging studies may provide etiologic insight into observed links between lung function and dementia and stroke. We evaluated associations of lung function measures with brain MRI markers of vascular and neurodegenerative disease in the ARIC Neurocognitive Study, as few studies have examined the associations. Lung function was measured at participants' midlife in 1990-1992 (mean age = 56±5 years) and later-life in 2011-2013 (mean age = 76±5 years), and brain MRI was performed in 2011-2013. Linear regression models were used to examine the associations of lung function with brain and white matter hyperintensity (WMH) volumes, and logistic regression models were used for cerebral infarcts and microbleeds, adjusting for potential confounders. In cross-sectional analysis (i.e., examining later-life lung function and MRI markers, n = 1,223), higher forced-expiratory volume in one second (FEV1) and forced vital capacity (FVC) were associated with larger brain and lower WMH volumes [e.g., 8.62 (95% CI:2.54-14.71) cm3 greater total brain volume per one-liter higher FEV1]. No association was seen with microbleeds in the overall sample, but higher FVC was associated with lower odds of microbleeds in never-smokers and higher odds in ever-smokers. In the cross-temporal analysis (i.e., associations with midlife lung function, n = 1,787), higher FVC levels were significantly associated with lower later-life brain volumes. Our results support modest associations of better lung function with less neurodegenerative and cerebrovascular pathology, although findings for microbleeds were unexpected in ever-smokers.

Distinct effects of blood pressure parameters on Alzheimer’s and vascular markers in 1,952 Asian individuals without dementia

BackgroundRisk factors for cardiovascular disease, including elevated blood pressure, are known to increase risk of Alzheimer’s disease. There has been increasing awareness of the relationship between long-term blood pressure (BP) patterns and their effects on the brain. We aimed to investigate the association of repeated BP measurements with Alzheimer’s and vascular disease markers.MethodsWe recruited 1,952 participants without dementia between August 2015 and February 2022. During serial clinic visits, we assessed both systolic BP (SBP) and diastolic BP (DBP), and visit-to-visit BP variability (BPV) was quantified from repeated measurements. In order to investigate the relationship of mean SBP (or DBP) with Alzheimer’s and vascular markers and cognition, we performed multiple linear and logistic regression analyses after controlling for potential confounders (Model 1). Next, we investigated the relationship of with variation of SBP (or DBP) with the aforementioned variables by adding it into Model 1 (Model 2). In addition, mediation analyses were conducted to determine mediation effects of Alzheimer’s and vascular makers on the relationship between BP parameters and cognitive impairment.ResultsHigh Aβ uptake was associated with greater mean SBP (β = 1.049, 95% confidence interval 1.016–1.083). High vascular burden was positively associated with mean SBP (odds ratio = 1.293, 95% CI 1.015–1.647) and mean DBP (1.390, 1.098–1.757). High tau uptake was related to greater systolic BPV (0.094, 0.001–0.187) and diastolic BPV (0.096, 0.007–0.184). High Aβ uptake partially mediated the relationship between mean SBP and the Mini-Mental State Examination (MMSE) scores. Hippocampal atrophy mediated the relationship between diastolic BPV and MMSE scores.ConclusionsEach BP parameter affects Alzheimer’s and vascular disease markers differently, which in turn leads to cognitive impairment. Therefore, it is necessary to appropriately control specific BP parameters to prevent the development of dementia. Furthermore, a better understanding of pathways from specific BP parameters to cognitive impairments might enable us to select the managements targeting the specific BP parameters to prevent dementia effectively.

Evaluation of feline heartworm disease based on gross necropsy, serology, pulmonary histopathology, and radiographic evidence in adult shelter cats in northeastern Alabama

Background: Veterinary knowledge regarding feline heartworm has been increasing significantly over the past two decades. Necropsy surveys of shelter cats have shown feline adult heartworm infection prevalence to be 5–20% of the rate in unprotected dogs; however, other studies have shown feline heartworm antibody prevalence up to 33%, reflecting higher exposure rates and potential immature adult infections. Thus, the true prevalence of feline heartworm infection is likely underestimated due to the limitations of current diagnostic techniques, inadequate testing protocols, and the high likelihood of cats exhibiting transient clinical signs or dying without confirmation of infection. Diagnosing Feline Heartworm Disease (FHWD), also referred to as Heartworm Associated Respiratory Disease (HARD), is one of the conundrums of veterinary medicine. The purpose of this study was to evaluate and characterize the occurrence of Heartworm Associated Respiratory Disease [HARD] in shelter cats, naturally-infected with D.immitis.MethodsFifty shelter cats slated for euthanasia between December 2009 and June 2010 were investigated by gross necropsy, radiography, serology, and lung histopathology using techniques that have been established in experimental models of cat heartworm infection. The relationship between pulmonary vascular disease and serological markers for heartworm was also examined using correlations and statistical modeling. Serology included standard heartworm antigen test and a commonly used heartworm antibody test. Also included were heat-treated heartworm antigen test and two additional heartworm antibody tests previously evaluated on experimentally-infected cats.ResultsNone of the cats were heartworm antibody (HW Ab) positive on a commonly used HW Ab test used by many reference laboratories even though 20% of the study cats were heartworm antigen (HW Ag) positive on heat-treated samples. Two additional HW Ab test were positive on 26% and 22% of the study cats. The combination of heat-treated HW Ag, HW Ab tests, and histopathology indicated 34% of the study cats had HARD.ConclusionsUtilizing both, the above tests, and thoracic radiographs, enhanced the ability to predict vascular disease, possibly caused by infection with immature and adult heartworms and supported the premise that cats develop heartworm disease at the same rate as dogs.Graphical

Single-cell RNA sequencing reveals critical modulators of extracellular matrix of penile cavernous cells in erectile dysfunction

Erectile dysfunction (ED) is a common and difficult to treat disease, and has a high incidence rate worldwide. As a marker of vascular disease, ED usually occurs in cardiovascular disease, 2–5 years prior to cardiovascular disease events. The extracellular matrix (ECM) network plays a crucial role in maintaining cardiac homeostasis, not only by providing structural support, but also by promoting force transmission, and by transducing key signals to intracardiac cells. However, the relationship between ECM and ED remains unclear. To help fill this gap, we profiled single-cell RNA-seq (scRNA-seq) to obtain transcriptome maps of 82,554 cavernous single cells from ED and non-ED samples. Cellular composition of cavernous tissues was explored by uniform manifold approximation and projection. Pseudo-time cell trajectory combined with gene enrichment analysis were performed to unveil the molecular pathways of cell fate determination. The relationship between cavernous cells and the ECM, and the changes in related genes were elucidated. The CellChat identified ligand-receptor pairs (e.g., PTN-SDC2, PTN-NCL, and MDK-SDC2) among the major cell types in the cavernous tissue microenvironment. Differential analysis revealed that the cell type-specific transcriptomic changes in ED are related to ECM and extracellular structure organization, external encapsulating structure organization, and regulation of vasculature development. Trajectory analysis predicted the underlying target genes to modulate ECM (e.g., COL3A1, MDK, MMP2, and POSTN). Together, this study highlights potential cell–cell interactions and the main regulatory factors of ECM, and reveals that genes may represent potential marker features of ED progression.

Associations of galectin-3 levels with measures of vascular disease in patients with rheumatoid arthritis

ObjectivesGalectin-3 is a beta-galactoside-binding lectin and is a marker of cardiovascular disease (CVD) in the general population. It may also play a role in joint inflammation. We asked whether serum galectin-3 is a useful marker of subclinical vascular disease in patients with rheumatoid arthritis (RA). MethodsRA patients without clinical CVD underwent assessment of coronary artery calcium (CAC) score, aortic inflammation (using 18Fluorodeoxyglucose positron emission-computed tomography [FDG PET/CT]), and myocardial flow reserve (MFR). Aorta FDG uptake was measured as standardized uptake values (SUV). Generalized linear models were constructed to explore the associations of galectin-3 levels with CAC score, aortic SUV, and MFR. ResultsA total of 124 RA patients (mean age 57; 82 % women, 45 % Hispanic; median RA duration 6.8 years; 75 % seropositive; median CDAI 16; 33 % on prednisone; 89 % on DMARDs; median CAC score 0; median aorta SUV 2.59; mean MFR 2.86; median galectin-3 level 8.54 ng/mL) were analyzed. In univariable analysis, higher galectin-3 levels were associated with higher aortic SUV (p = 0.007) but CAC score and MFR were not. In multivariable analysis, higher galectin-3 level remained significantly associated with higher aortic SUV (ß Coefficient=0.1786, p value=0.002). ConclusionIn our cohort of RA patients without clinical CVD, higher serum galectin-3 levels were independently associated with higher levels of aortic inflammation, but not CAC score or MFR. This suggests that galectin-3 may be a biomarker for an inflammatory and potentially reversible stage, but not a later (calcified) stage, of atherosclerosis in patients with RA.

How does atherosclerotic plaque become calcified, and why?

&lt;p&gt;Vascular calcification involves the crystallization of calcium/phosphate in the form of hydroxyapatoite in the extracellular matrix of the arterial wall. Vascular calcification is categorized into 3 main etiologies: (1) inflammatory/atherosclerotic (mostly intimal), (2) metabolic (mostly medial), and (3) genetic background (mostly medial). Several overlapping mechanisms trigger all three types of calcifications. Intimal coronary artery calcification simultaneously develops with the progression of atherosclerosis and has been recognized as a surrogate marker of atherosclerotic inflammatory vascular disease. Pathologically, atherosclerotic calcification initially occurs as microcalcifications (0.5 to 15 µm) and results in larger dense calcification, eventually forming sheet calcifications (&amp;gt;3 mm). Among the plaque types, the degree of calcification is the highest in fibrocalcific plaques, followed by healed plaque ruptures, and is the lowest in pathologic intimal thickening. Recent pathologic and imaging-based studies suggest that massive dense calcifications are usually associated with stable plaques, whereas microcalcifications are indicative of vulnerable plaques which may cause acute thrombotic events. Although the mechanisms of calcification are not fully elucidated, apoptotic inflammatory cells and smooth muscle cells, along with the induction of bone formation, play crucial roles in its initiation and progression. A deeper understanding of vascular calcification will improve the risk stratification and patient outcomes through the development of new therapies.&lt;/p&gt;

Incidence and determinants of hypertensive retinopathy in hypertension patients at a teaching hospital in North Western Karnataka

Persistently raised blood pressure not only leads to retinal vascular damage but also leads to systemic diseases. The retinal vasculature observation by fundoscopy offers a great opportunity to explore the association of systemic microvascular disease caused by hypertension. Hypertensive retinopathy (HR) is considered to be a marker for vascular disease and death. The aim of the present study was to find out the prevalence of hypertensive retinopathy among hypertensive subjects and assess the pattern of retinopathy and associated risk factors. This was a hospital based cross-sectional study conducted among hypertensive patients at a teaching hospital, for a period of 3 months.A total of 300 hypertensive patients formed the study population. The prevalence of the hypertensive retinopathy in the present study was 49.33%. Hypertensive retinopathy was more prevalent in men 62% than women 38%. The prevalence of grade 1 and grade 2 hypertensive retinopathies was 43.24% and 33.11% respectively and 20.95% and 2.7% had grade 3 and 4 respectively. The prevalence of retinopathy was found to be statistically higher in patients who had h/o hypertension for more than 5 years. The prevalence of hypertensive retinopathy was more common in age group &amp;#62;60yrs. The prevalence of target organ damage was higher in those having retinopathy.The prevalence of hypertensive retinopathy is high in the present study which reflects lack of awareness, patient compliance, sub optimal measures to control blood pressure and even lack of prompt follow up with ophthalmologists. There is need to spread awareness and take adequate measures to reduce the burden of hypertensive retinopathy.

Lifetime influences on imaging markers of adverse brain health and vascular disease

Cerebral small vessel disease (cSVD) is highly prevalent in the general population, increases with age and vascular risk factor exposure, and is a common cause of stroke and dementia. There is great variation in cSVD burden experienced in older age, and maintaining brain health across the life course requires looking beyond an individual's current clinical status and traditional vascular risk factors. Of particular importance are social determinants of health which can be more important than healthcare or lifestyle choices in influencing later life health outcomes, including brain health. In this paper we discuss the social determinants of cerebrovascular disease, focusing on the impact of socioeconomic status on markers of cSVD. We outline the potential mechanisms behind these associations, including early life exposures, health behaviours and brain reserve and maintenance, and we highlight the importance of public health interventions to address the key determinants and risk factors for cSVD from early life stages.

Extent of Abdominal Aortic Calcification Is Associated With Incident Rapid Weight Loss Over 5 Years: The Perth Longitudinal Study of Ageing Women.

Abdominal aortic calcification (AAC), a marker of vascular disease, is associated with disease in other vascular beds including gastrointestinal arteries. We investigated whether AAC is related to rapid weight loss over 5 years and whether rapid weight loss is associated with 9.5-year all-cause mortality in community-dwelling older women. Lateral spine images from dual-energy x-ray absorptiometry (1998/1999) were used to assess AAC (24-point AAC scoring method) in 929 older women. Over 5 years, body weight was assessed at 12-month intervals. Rapid weight loss was defined as >5% decrease in body weight within any 12-month interval. Multivariable-adjusted logistic regression was used to assess AAC and rapid weight loss and Cox regression to assess the relationship between rapid weight loss and 9.5-year all-cause mortality. Mean±SD age of women was 75.0±2.6 years. During the initial 5 years, 366 (39%) women presented with rapid weight loss. Compared with women with low AAC (24-point AAC score 0-1), those with moderate (24-point AAC score 2-5: odds ratio, 1.36 [95% CI, 1.00-1.85]) and extensive (24-point AAC score 6+: odds ratio, 1.59 [95% CI, 1.10-2.31]) AAC had higher odds for presenting with rapid weight loss. Results remained similar after further adjustment for dietary factors (alcohol, protein, fat, and carbohydrates), diet quality, blood pressure, and cholesterol measures. The estimates were similar in subgroups of women who met protein intake (n=599) and physical activity (n=735) recommendations (extensive AAC: odds ratios, 1.81 [95% CI, 1.12-2.92] and 1.58 [95% CI, 1.02-2.44], respectively). Rapid weight loss was associated with all-cause mortality over the next 9.5 years (hazard ratio, 1.49 [95% CI, 1.17-1.89]; P=0.001). AAC extent was associated with greater risk for rapid weight loss over 5 years in older women, a risk for all-cause mortality. Since the association was unchanged after taking nutritional intakes into account, these data support the possibility that vascular disease may play a role in the maintenance of body weight.

Accumulation of advanced glycation end products in skin and increased vascular ageing in the general population: the Malmö Offspring Study.

Advanced glycation end product (AGE) is an established risk marker for diabetic vascular disease, and associated with the degree of diabetes complications, renal failure, and atherosclerosis in middle-aged and older individuals. The relationship between AGEs and aortic stiffness has not been thoroughly examined in the younger general population. We aimed to evaluate the association between AGEs and aortic stiffness in the general population of young and middle-aged adults. We analysed cross-sectionally 2518 participants from a Swedish population-based cohort, the Malmö Offspring Study (mean age 41.8 ± 14.5 years, 52.2%). Advanced glycation end-products (AGEs) were measured by a well validated, noninvasive method using skin autofluorescence with AGE-Reader. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV) and augmentation index (Aix) was calibrated to a standard heart rate of 75 bpm at the arteria radialis using SphygmoCor. Multivariable linear regression was performed stratified by age to analyse the association between skin AGE and aortic stiffness. Increased levels of AGEs were significantly associated with higher direct measurements of aortic stiffness (vascular ageing) in younger individuals (PWV β 0.55 m/s, P < 0.001) after adjustment for traditional cardiometabolic risk factors, however, not in older individuals (PWV β 0.23 m/s, P = 0.10). Indirect vascular ageing was also significantly associated with higher levels of AGEs in both younger (Aix β 7.78, P < 0.001) and older individuals (Aix β 3.69, P < 0.001). Higher levels of skin autofluorescence-AGEs are positively associated with increased vascular ageing in younger adults from the general population, independent of cardiometabolic risk factors.

Depression in patients with cerebral microangiopathy

Cerebral microangiopathy (CMA) is one of the significant causes of depression in the elderly. Close associations of the risk of developing depression with white matter hyperintensity, the presence of lacunar infarcts, and other markers of vascular disease are shown. The available data suggest that various vascular mechanisms, in particular, involvement of small vessels of the brain, generalized microvascular and endothelial dysfunction, metabolic risk factors, – are risk factors for the development of depression. Pathogenetic mechanisms include cerebral hypoperfusion and immune dysregulation. Depression is also a common complication of coronavirus infection, occurring both in the acute and postCOVID periods. The same mechanisms as in vascular depression are involved in the pathogenesis of the development of post-COVID depressive disorders. Given the complexity of the mechanisms of development of depressive disorders in patients with CMA, the presence of severe comorbid vascular pathology, antidepressants with an optimal ratio of efficacy and safety should be preferred. Agomelatine (Valdoxan) is one of such drugs.

Changes in Cardiovascular Health Across Midlife and Late-Life and Magnetic Resonance Imaging Markers of Cerebral Vascular Disease in Late-Life.

Cardiovascular health may be used for prevention of cerebral vascular disease; however, data on the association of cardiovascular health across midlife and late-life with late-life cerebral vascular disease are lacking. Our aim was to examine whether midlife or late-life cardiovascular health as well as changes of cardiovascular health within midlife and between midlife and late-life were associated with prevalence of magnetic resonance imaging markers of cerebral vascular disease at late-life. Prospective cohort study including 1638 participants from the Atherosclerosis Risk in Communities Study who took part in 2 visits at midlife (mean ages, 53 and 59 years), and a late-life visit (mean age, 76 years). A cardiovascular health Life's Simple 7 score (range, 0-12/0-14, depending on diet availability) including 6 out of 7 items was calculated at each visit, with weight assigned to each item as poor (0), intermediate (1), or ideal (2). Participants underwent 3T brain magnetic resonance imaging scans in late-life visit. Outcomes were white matter hyperintensity volume, microbleeds, and lacunar, subcortical, and cortical infarcts at late-life. Linear and logistic regression models were used to assess the associations of cardiovascular health in midlife and late-life, and improvement of cardiovascular health within midlife, and from midlife to late-life with magnetic resonance imaging markers of cerebral vascular disease, adjusting for potential confounders. A higher cardiovascular health in midlife, improvement of cardiovascular health within midlife, higher cardiovascular health at late-life, and improvement of cardiovascular health from midlife to late-life were associated with a lower prevalence of cerebral vascular disease markers. For example, improvement in cardiovascular health (per point) from midlife to late-life was associated with smaller white matter hyperintensity volume (β, -0.07 [95% CI, -0.10 to -0.04]) and lower odds of microbleeds (odds ratio, 0.93 [0.90-0.97]), lacunar (odds ratio, 0.93 [0.89-0.97]), subcortical (odds ratio, 0.93 [0.89-0.97]), and cortical infarcts (odds ratio, 0.92 [0.87-0.97]). Improving cardiovascular health within midlife and from midlife to late-life may prevent development of cerebral vascular disease.

Abstract 56: Changes In Cardiovascular Health Within Midlife And From Midlife To Late-life Associated With MRI Markers Of Cerebral Vascular Disease In Late-life

Introduction: Cardiovascular health may be used for prevention of cerebral vascular disease. We evaluated whether improvement of cardiovascular health within midlife and from midlife to late-life were each associated with lower prevalence of MRI markers of cerebral vascular disease at late-life. Methods: 1,638 participants from the Atherosclerosis Risk in Communities (ARIC) Study took part in two visits at midlife (mean ages 53 at ARIC visit 1 and 59 at visit 3), and a late-life visit (mean age 76). A cardiovascular health Life’s Simple 7 score (range 0-12/0-14, depending on diet availability) including six/seven items was calculated at each visit, with weight assigned to each item as poor (0), intermediate (1), or ideal (2). Participants underwent 3T brain MRI scans in 2011-2013 (late-life visit). Outcomes were white matter hyperintensity volume, microbleeds, and lacunar, subcortical, and cortical infarcts at late-life. Linear and logistic regression models were used to assess the associations of cardiovascular health with MRI markers of cerebral vascular disease. Results: Thirty nine percent of participants had high cardiovascular health at midlife visit 1, 32% at midlife visit 3, and 33% at late-life. Improvement of cardiovascular health within midlife and from midlife to late-life were each associated with a lower prevalence of cerebral vascular disease markers. For example, improvement in cardiovascular health (per point) from midlife to late-life was associated with smaller white matter hyperintensity volume (Beta:-0.07 [95%CI:-0.10,-0.04]), and lower odds of microbleeds (OR:0.93 [0.90,0.97]), lacunar (OR:0.93 [0.89,0.97)], subcortical (OR:0.93 [0.89,0.97])], and cortical infarcts (OR:0.92 [0.87,0.97)] (Figure). Conclusions: Improving cardiovascular health within midlife and from midlife to late-life may prevent development of cerebral vascular disease.

Abstract 14573: High Performance of Artificial Intelligence-Based Model for Scoring Breast Arterial Calcification on Mammograms

Purpose: Mammographically detected breast arterial calcification (BAC) has been reported as a surrogate marker for coronary vascular disease (CVD). BAC is often not reported, reducing the power of this risk marker. Here we assess a deep-learning algorithm for BAC quantification, and in cases where the software identified BAC but the readers did not, assess correlation with clinical CVD. Methods: Screening digital mammograms (n=285, 1232 images) were selected from a tertiary Australian hospital from a sample of patients who underwent CVD screening (137 confirmed CVD). Two readers identified binary presence/absence of BAC. A deep learning software (cmAngio™ , CureMetrix, USA) quantified BAC score (scale 0-100). Reader-software discordance was adjudicated by a third observer. Area under the curve (AUC) was used to assess performance with 95% confidence intervals (CI) presented. Interobserver agreement was assessed by Cohen’s kappa (k). Results: Interobserver agreement for visual BAC was good (k=0.78, CI:0.71-0.85, p&lt;0.01). BAC scores ranged from 0-100, with 12% scoring 0. The algorithm had high performance, AUC 0.92 (CI:0.88-0.96, p&lt;0.001) vs initial reader assessment, increasing to AUC 0.98 (CI:0.97-0.99, p&lt;0.001) after adjudicated assessment. At an empirical threshold of BAC score ≥5 to denote BAC presence, BAC prevalence was 38% (109/285) by software, and 31% (87/285) visually. In cases where only the software identified BAC (n=35), BAC scores were all &lt;25, with 37% (n=13) having confirmed CVD and 9% (n=3) myocardial infarction. Conclusion: cmAngio demonstrates excellent performance for detecting BAC on screening mammograms. Faint BAC may be missed by human readers, is better identified by the software, and in these cases there is a high rate of CVD suggesting use in a screening population may improve risk prediction for CVD.

Effect of anti-inflammatory therapy on vascular biomarkers for subclinical cardiovascular disease in rheumatoid arthritis patients

ObjectiveTo assess the effect of 4 years of anti-inflammatory therapy on markers of subclinical vascular disease in rheumatoid arthritis patients.MethodsCarotid intima media thickness (IMT), augmentation index (AIx@75) and pulse wave velocity (PWV) measurements were performed repeatedly in 61 RA patients (30 early RA starting with csDMARDs and 31 established RA starting with adalimumab) for 4 years. These markers were also measured in 29 controls with osteoarthritis at baseline (BL).ResultsIMT and AIx@75 at BL were higher in RA compared to OA, while PWV was higher in OA. In RA patients, AIx@75 and PWV decreased in the first 6 months after starting anti-inflammatory therapy. At 48 M, the level of AIx@75 remained lower than before therapy, while PWV at 48 M was comparable to BL (AIx@75: BL 28% (95% confidence interval 25–30%), 6 M 23% (20–26%), 48 M 25% (22–28%); PWV: BL 8.5 (7.8–9.2), 6 M 8.0 (7.1–8.9), 48 M 8.6 (7.6–9.6) m/s). IMT remained stable. There was an effect of disease activity (longitudinally, adjusted for changes over time) on IMT, AIx@75 and PWV.ConclusionThis study suggests modest beneficial changes in some surrogate markers of subclinical vascular disease after anti-inflammatory therapy. These changes were associated with improvement in disease activity markers. Whether or not these beneficial changes ultimately predict a reduction in clinicalcardiovascular endpoints remains to be established in prospective studies.