Detection of Aortic Calcification during Vertebral Fracture Assessment (VFA) Compared to Digital Radiography

Background: Cardiovascular disease is the most common cause of mortality among post-menopausal women. Our objective was to determine whether or not lateral spine images obtained on a bone densitometer to detect prevalent vertebral fracture can also accurately detect radiographic abdominal aortic calcification (AAC), an important risk factor for cardiovascular disease independent of clinical risk factors. Methodology/Principal Findings: One hundred seventy four postmenopausal women had bone densitometry, lateral spine densitometry imaging (called vertebral fracture assessment, or VFA), and lateral spine digital radiographs. Radiographs and VFA images were scored for AAC using a previously validated 24 point scale and a simplified, new 8 point scale (AAC-8). One hundred fifty six (90%) of the VFA images were evaluable for AAC. The non-parametric intraclass correlation coefficient between VFA and radiographic 24 point and AAC-8 readings, respectively, were 0.80 (95% C.I. 0.68–0.87) and 0.76 (95% C.I. 0.65–0.84). Areas under receiver operating characteristics (ROC) curves for VFA to detect those with a radiographic 24-point AAC score ≥5 were 0.86 (95% C.I. 0.77–0.94) using the 24 point scale and 0.84 (95% C.I. 0.76–0.92) using the AAC-8 scale. Conclusion/Significance: VFA imaging intended to detect prevalent vertebral fracture can also detect radiographic AAC, an important cardiovascular disease risk factor. Since bone densitometry is recommended for all women age 65 and older, VFA imaging at the time of bone densitometry offers an opportunity to assess this risk factor in the post-menopausal female population at very little incremental time and expense

SCOL: Supervised Contrastive Ordinal Loss for Abdominal Aortic Calcification Scoring on Vertebral Fracture Assessment Scans

Abdominal Aortic Calcification (AAC) is a known marker of asymptomatic Atherosclerotic Cardiovascular Diseases (ASCVDs). AAC can be observed on Vertebral Fracture Assessment (VFA) scans acquired using Dual-Energy X-ray Absorptiometry (DXA) machines. Thus, the automatic quantification of AAC on VFA DXA scans may be used to screen for CVD risks, allowing early interventions. In this research, we formulate the quantification of AAC as an ordinal regression problem. We propose a novel Supervised Contrastive Ordinal Loss (SCOL) by incorporating a label-dependent distance metric with existing supervised contrastive loss to leverage the ordinal information inherent in discrete AAC regression labels. We develop a Dual-encoder Contrastive Ordinal Learning (DCOL) framework that learns the contrastive ordinal representation at global and local levels to improve the feature separability and class diversity in latent space among the AAC-24 genera. We evaluate the performance of the proposed framework using two clinical VFA DXA scan datasets and compare our work with state-of-the-art methods. Furthermore, for predicted AAC scores, we provide a clinical analysis to predict the future risk of a Major Acute Cardiovascular Event (MACE). Our results demonstrate that this learning enhances inter-class separability and strengthens intra-class consistency, which results in predicting the high-risk AAC classes with high sensitivity and high accuracy.Comment: Accepted in conference MICCAI 202

Association of abdominal aortic calcification with peripheral quantitative computed tomography bone measures in older women: The Perth longitudinal study of ageing women

We have previously shown that abdominal aortic calcification (AAC), a marker of advanced atherosclerotic disease, is weakly associated with reduced hip areal bone mineral density (aBMD). To better understand the vascular–bone health relationship, we explored this association with other key determinants of whole-bone strength and fracture risk at peripheral skeletal sites. This study examined associations of AAC with peripheral quantitative computed tomography (pQCT)-assessed total, cortical and trabecular volumetric BMD (vBMD), bone structure and strength of the radius and tibia among 648 community-dwelling older women (mean ± SD age 79.7 ± 2.5 years). We assessed associations between cross-sectional (2003) and longitudinal (progression from 1998/1999–2003) AAC assessed on lateral dual-energy X-ray absorptiometry (DXA) images with cross-sectional (2003) and longitudinal (change from 2003 to 2005) pQCT bone measures at the 4% radius and tibia, and 15% radius. Partial Spearman correlations (adjusted for age, BMI, calcium treatment) revealed no cross-sectional associations between AAC and any pQCT bone measures. AAC progression was not associated with any bone measure after adjusting for multiple comparisons, despite trends for inverse correlations with total bone area at the 4% radius (rs = − 0.088, p = 0.044), 4% tibia (rs = − 0.085, p = 0.052) and 15% radius (rs = − 0.101, p = 0.059). Neither AAC in 2003 nor AAC progression were associated with subsequent 2-year pQCT bone changes. ANCOVA showed no differences in bone measures between women with and without AAC or AAC progression, nor across categories of AAC extent. Collectively, these finding suggest that peripheral bone density and structure, or its changes with age, are not associated with central vascular calcification in older women

Abdominal aortic calcification on lateral spine images captured during bone density testing and late-life dementia risk in older women: A prospective cohort study

Background: Dementia after the age of 80 years (late-life) is increasingly common due to vascular and non-vascular risk factors. Identifying individuals at higher risk of late-life dementia remains a global priority. Methods: In prospective study of 958 ambulant community-dwelling older women ( ≥ 70 years), lateral spine images (LSI) captured in 1998 (baseline) from a bone density machine were used to assess abdominal aortic calcification (AAC). AAC was classified into established categories (low, moderate and extensive). Cardiovascular risk factors and apolipoprotein E (APOE) genotyping were evaluated. Incident 14.5-year late-life dementia was identified from linked hospital and mortality records. Findings: At baseline women were 75.0 ± 2.6 years, 44.7% had low AAC, 36.4% had moderate AAC and 18.9% had extensive AAC. Over 14.5- years, 150 (15.7 %) women had a late-life dementia hospitalisation (n = 132) and/or death (n = 58). Compared to those with low AAC, women with moderate and extensive AAC were more likely to suffer late-life dementia hospitalisations (9.3 %, 15.5 %, 18.3 %, respectively) and deaths (2.8 %, 8.3 %, 9.4 %, respectively). After adjustment for cardiovascular risk factors and APOE, women with moderate and extensive AAC had twice the relative hazards of late-life dementia (moderate, aHR 2.03 95 % CI 1.38 – 2.97; extensive, aHR 2.10 95 % CI 1.33 – 3.32), compared to women with low AAC. Interpretation: In community-dwelling older women, those with more advanced AAC had higher risk of late-life dementia, independent of cardiovascular risk factors and APOE genotype. Given the widespread use of bone density testing, simultaneously capturing AAC information may be a novel, non-invasive, scalable approach to identify older women at risk of late-life dementia

Abdominal aortic calcification, bone mineral density and fractures: a systematic review and meta-analysis protocol

INTRODUCTION: Abdominal aortic calcification (AAC) is associated with low bone mass and increased fracture risk. Two previous meta-analyses have investigated the association between AAC and fracture. However, these meta-analyses only identified articles until December 2016, undertook limited searches and did not explore potential sources of between-study heterogeneity. We aim to undertake a sensitive and comprehensive assessment of the relationship between AAC, bone mineral density (BMD) as well as prevalent and incident fractures. METHODS: We will search MEDLINE, EMBASE, Web of Science core collection and Google Scholar (top 200 articles sorted by relevance) from their inception to 1 June 2018. Reference lists of included studies and previous systematic reviews will be hand searched for additional eligible studies. Retrospective and prospective cohort studies (cross-sectional, case-control and longitudinal) reporting the association between AAC, BMD and fracture at any site will be included. At least two investigators will independently: (A) evaluate study eligibility and extract data, with a third investigator to adjudicate when discrepancies occur, (B) assess study quality by the Newcastle-Ottawa Scale for each cohort/study. The meta-analysis will be reported in adherence to the Meta-analysis of Observational Studies in Epidemiology criteria. AAC will be grouped as either: (1) AAC present or absent, (2) AAC categorised as \u27low\u27 (referent-lowest reported group) versus \u27high\u27 (all other groups) or (3) dose-response when AAC was assessed in ≥3 groups. Where primary event data were reported in individual studies, pooled risk differences and risk ratios with 95% CI will be calculated, from which, a summary estimate will be determined using DerSimonian-Laird random effects models. For the AAC and BMD pooled analyses, estimates will be expressed as standardised mean difference with 95% CI. We will examine the likelihood of publication bias and where possible, investigate potential reasons for between-study heterogeneity using subgroup analyses and meta-regression. ETHICS AND DISSEMINATION: The study will be submitted to a peer- reviewed journal and disseminated via research presentations. PROSPERO REGISTRATION NUMBER: CRD42018088019

Machine-learning assessed abdominal aortic calcification is associated with long-term fall and fracture risk in community-dwelling older Australian women

Abdominal aortic calcification (AAC), a recognized measure of advanced vascular disease, is associated with higher cardiovascular risk and poorer long-term prognosis. AAC can be assessed on dual-energy X-ray absorptiometry (DXA)-derived lateral spine images used for vertebral fracture assessment at the time of bone density screening using a validated 24-point scoring method (AAC-24). Previous studies have identified robust associations between AAC-24 score, incident falls, and fractures. However, a major limitation of manual AAC assessment is that it requires a trained expert. Hence, we have developed an automated machine-learning algorithm for assessing AAC-24 scores (ML-AAC24). In this prospective study, we evaluated the association between ML-AAC24 and long-term incident falls and fractures in 1023 community-dwelling older women (mean age, 75 ± 3 years) from the Perth Longitudinal Study of Ageing Women. Over 10 years of follow-up, 253 (24.7%) women experienced a clinical fracture identified via self-report every 4–6 months and verified by X-ray, and 169 (16.5%) women had a fracture hospitalization identified from linked hospital discharge data. Over 14.5 years, 393 (38.4%) women experienced an injurious fall requiring hospitalization identified from linked hospital discharge data. After adjusting for baseline fracture risk, women with moderate to extensive AAC (ML-AAC24 ≥ 2) had a greater risk of clinical fractures (hazard ratio [HR] 1.42; 95% confidence interval [CI], 1.10–1.85) and fall-related hospitalization (HR 1.35; 95% CI, 1.09–1.66), compared to those with low AAC (ML-AAC24 ≤ 1). Similar to manually assessed AAC-24, ML-AAC24 was not associated with fracture hospitalizations. The relative hazard estimates obtained using machine learning were similar to those using manually assessed AAC-24 scores. In conclusion, this novel automated method for assessing AAC, that can be easily and seamlessly captured at the time of bone density testing, has robust associations with long-term incident clinical fractures and injurious falls. However, the performance of the ML-AAC24 algorithm needs to be verified in independent cohorts. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Cruciferous vegetable intake is inversely associated with extensive abdominal aortic calcification in elderly women: a cross-sectional study

We have previously shown higher intake of cruciferous vegetables is inversely associated with carotid artery intima-media thickness. To further test the hypothesis that an increased consumption of cruciferous vegetables is associated with reduced indicators of structural vascular disease in other areas of the vascular tree, we aimed to investigate the cross-sectional association between cruciferous vegetable intake and extensive calcification in the abdominal aorta. Dietary intake was assessed, using a food frequency questionnaire, in 684 older women from the Calcium Intake Fracture Outcome Study. Cruciferous vegetables included cabbage, Brussels sprouts, cauliflower and broccoli. Abdominal aortic calcification (AAC) was scored using the Kauppila AAC24 scale on dual energy x-ray absorptiometry (DXA) lateral spine images, and was categorised as “not extensive” (0-5) or “extensive” (≥6). Mean age was 74.9 (SD 2.6) y, median cruciferous vegetable intake was 28.2 (IQR 15.0-44.7) g/d, and 128/684 (18.7%) women had extensive AAC scores. Those with higher intakes of cruciferous vegetables ( \u3e 44.6 g/d) were associated with a 46% lower odds of having extensive AAC in comparison to those with lower intakes ( \u3c 15.0 g/d) after adjustment for lifestyle, dietary and cardiovascular disease risk factors (ORQ4 vs Q1=0.54, 95%CI 0.30, 0.97, P=0.036). Total vegetable intake and each of the other vegetable types were not related to extensive AAC (P \u3e 0.05 for all). This study strengthens the hypothesis that higher intake of cruciferous vegetables may protect against vascular calcification

Association between abdominal aortic calcification, bone mineral density and fracture in older women

Although a relationship between vascular disease and osteoporosis has been recognized, its clinical importance for fracture risk evaluation remains uncertain. Abdominal aortic calcification (AAC), a recognized measure of vascular disease detected on single‐energy images performed for vertebral fracture assessment, may also identify increased osteoporosis risk. In a prospective 10‐year study of 1,024 older predominantly Caucasian women (mean age 75.0±2.6 years) from the Perth Longitudinal Study of Aging cohort we evaluated the association between AAC, skeletal structure and fractures. AAC and spine fracture were assessed at the time of hip densitometry and heel quantitative ultrasound. AAC was scored 0 to 24 (AAC24) and categorized into; low AAC (score 0 and 1, n=459), moderate AAC (score 2‐5, n=373) and severe AAC (score \u3e 6, n=192). Prevalent vertebral fractures were calculated using the Genant semi‐quantitative method. AAC24 scores were inversely related to hip bone mineral density (BMD) (rs=‐0.077, p=0.013) and heel broadband ultrasound attenuation (rs=‐0.074, p=0.020) and stiffness index (rs=‐0.073, p=0.022). In cross‐sectional analyses women with moderate to severe AAC were more likely to have prevalent fracture and LSI detected lumbar spine but not thoracic spine fractures (Mantel‐Haentzel test of trend p \u3c 0.05). For 10‐year incident clinical fractures and fracture‐related hospitalizations women with moderate to severe AAC (AAC24 score \u3e1) had increased fracture risk (HR 1.48 [1.15‐1.91], p=0.002; HR 1.46 [1.07‐1.99], p=0.019, respectively) compared to women with low AAC. This relationship remained significant after adjusting for age and hip BMD for clinical fractures (HR 1.40 [1.08‐1.81], p=0.010) but was attenuated for fracture‐related hospitalizations (HR 1.33 [0.98‐1.83], p=0.073). In conclusion, older women with more marked AAC are at higher risk of fracture, not completely captured by bone structural predictors. These findings further support the concept that vascular calcification and bone pathology may share similar mechanisms of causation that remain to be fully elucidated

Prognostic value of abdominal aortic calcification: A systematic review and meta‐analysis of observational studies

Background The prognostic importance of abdominal aortic calcification (AAC) viewed on noninvasive imaging modalities remains uncertain. Methods and Results We searched electronic databases (MEDLINE and Embase) until March 2018. Multiple reviewers identified prospective studies reporting AAC and incident cardiovascular events or all‐cause mortality. Two independent reviewers assessed eligibility and risk of bias and extracted data. Summary risk ratios (RRs) were estimated using random‐effects models comparing the higher AAC groups combined (any or more advanced AAC) to the lowest reported AAC group. We identified 52 studies (46 cohorts, 36 092 participants); only studies of patients with chronic kidney disease (57%) and the general older‐elderly (median, 68 years; range, 60–80 years) populations (26%) had sufficient data to meta‐analyze. People with any or more advanced AAC had higher risk of cardiovascular events (RR, 1.83; 95% CI, 1.40–2.39), fatal cardiovascular events (RR, 1.85; 95% CI, 1.44–2.39), and all‐cause mortality (RR, 1.98; 95% CI, 1.55–2.53). Patients with chronic kidney disease with any or more advanced AAC had a higher risk of cardiovascular events (RR, 3.47; 95% CI, 2.21–5.45), fatal cardiovascular events (RR, 3.68; 95% CI, 2.32–5.84), and all‐cause mortality (RR, 2.40; 95% CI, 1.95–2.97). Conclusions Higher‐risk populations, such as the elderly and those with chronic kidney disease with AAC have substantially greater risk of future cardiovascular events and poorer prognosis. Providing information on AAC may help clinicians understand and manage patients\u27 cardiovascular risk better

Baseline age and time to major fracture in younger postmenopausal women

To estimate the incidence of first hip or clinical vertebral fracture or major osteoporotic (hip, clinical vertebral, proximal humerus or wrist) fracture in postmenopausal women receiving their first bone mineral density (BMD) test before age 65