Associations between semi-quantitative evaluation of intracranial arterial calcification and total cerebral small vessel disease burden score: a retrospective case-control study.

Background and purpose: Arteriosclerotic cerebral small vessel disease (aCSVD) is a cause of cognitive impairment, dementia, and stroke. Developing a better understanding of the risk factor of aCSVD is key to reducing the incidence of these conditions. This study investigated the association between intracranial arterial calcification (IAC) and total cerebral small vessel disease (CSVD) burden score. Materials and methods: This is a retrospective study, the subjects were transient ischemic attack (TIA) or acute ischemic stroke (AIS) patients. The data of 303 inpatients admitted to our study hospital between December 2018 and July 2020 were analyzed. Four imaging markers of CSVD (lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces) were evaluated by magnetic resonance imaging, and a total CSVD burden score was calculated. The experimental group was divided into four subgroups according to total CSVD burden score (1-4 points). Patients without CSVD (0 points) served as the control group. Head computerized tomography (CT) scans were used to assess ICA, using Babiarz's method. The correlations between IAC and single imaging markers of CSVD were determined using Spearman's rank correlation. Binary logic regression analysis and multivariate ordered logic regression analysis were used to determine the associations between IAC and aCSVD. Results: IAC was positively correlated with total CSVD burden score (r = 0.681), deep white matter hyperintensities (r = 0.539), periventricular white matter hyperintensities (r = 0.570), cerebral microbleeds (r = 0.479), lacunes (r = 0.541), and enlarged perivascular spaces (r = 0.554) (all p < 0.001). After adjusting for the confounding factors of age, diabetes, and hypertension, aCSVD was independently associated with IAC grade 1-2 [odds ratio (OR) = 23.747, 95% confidence interval (CI) = 8.376-67.327] and IAC grade 3-4 (OR = 30.166, 95% CI = 8.295-109.701). aCSVD severity was independently associated with IAC grade 3-4 (OR = 4.697, 95% CI = 1.349-16.346). Conclusion: IAC is associated with the total CSVD burden score and single imaging signs.

Lower Extremity Arterial Calcification Predicts Referral to a Closed Unit After Primary Total Hip Arthroplasty.

BACKGROUND: We aimed to determine the association between lower extremity arterial calcification (LEAC) and referral to a closed unit (CU), length of stay, 90-day readmissions, and 1-year mortality in primary total hip arthroplasty (THA) patients. METHODS: We retrospectively analyzed 705 patients who underwent primary THA, identifying 64 patients (9.13%) who had LEAC and 641 who did not have LEAC. Patients who had LEAC were older (77 ± 10.0 versus 67 ± 11.5 years; P < 0.001) and had more comorbidities, except for a history of thromboembolic and oncologic diseases (P > 0.05). A preoperative antero-posterior pelvic radiograph was used to assess the presence of LEAC. Admission to CU, length of stay, 90-day readmissions, and 1-year mortality were recorded. A logistic regression model was used to identify risk factors for referral to CU. RESULTS: Patients who had LEAC had a higher incidence of admission to the ICU (8 of 64 [12.5%] versus 8 of 641 [1.09%]; P < 0.001), a longer hospital stay (4.7 ± 1.8 versus 4.2 ± 1.3 days; P = 0.006), more readmissions (16 of 64 [25%] vs. 33 of 641 [5.15%]; P < 0.001), and a higher 1-year mortality rate (6 of 64 [9.3%] versus 0 of 641 [0%]; P < 0.001) than patients who did not have LEAC. Of the patients who had LEAC admitted to CU, only 3 of 8 had a previous indication to do so in the preoperative assessment performed by the Department of Anesthesiology, while all non-LEAC ones referred to CU did so. Logistic regression analysis showed that LEAC was a risk factor for admission to CU (odds ratio [OR] = 4.77; 95% confidence interval [CI]: 1.12 to 20.25, P = 0.034). CONCLUSIONS: The presence of LEAC was a risk factor for transfer to CU, longer in-hospital stays, more readmissions, and a higher 1-year mortality rate. Identifying patients who have LEAC can aid in the preoperative assessment and risk stratification of patients planned for primary THA.

Oral pyrophosphate protects Abcc6-/- mice against vascular calcification induced by chronic kidney disease.

One of the hallmarks of chronic kidney disease (CKD) is the development of vascular calcification. Inorganic pyrophosphate is a potent inhibitor of calcification, and previous studies have reported low plasma pyrophosphate levels in hemodialysis patients. A long-term mouse model of CKD-accelerated vascular calcification was developed to study pyrophosphate metabolism and to test whether oral pyrophosphate supplementation attenuates the propensity for arterial calcification. CKD was induced by repeated injections of aristolochic acid in wild-type and Abcc6-/- mice, which tend to develop vascular calcifications. CKD accelerated the development of vascular calcifications in Abcc6-/- mice, in the aorta and small renal arteries, and decreased circulating pyrophosphate levels. Oral pyrophosphate supplementation for 6 months attenuated CKD-induced vascular calcification in this model. These results show that oral pyrophosphate may be of interest in preventing vascular calcification in patients with CKD. KEY MESSAGES: Chronic kidney disease accelerates the development of vascular calcification in pyrophosphate-deficient mice. Oral pyrophosphate supplementation for 6 months attenuates chronic kidney disease-induced vascular calcification in a mouse model. Oral pyrophosphate may be of interest in preventing vascular calcification in patients with chronic kidney disease.

Deep transfer learning for detection of breast arterial calcifications on mammograms: a comparative study.

INTRODUCTION: Breast arterial calcifications (BAC) are common incidental findings on routine mammograms, which have been suggested as a sex-specific biomarker of cardiovascular disease (CVD) risk. Previous work showed the efficacy of a pretrained convolutional network (CNN), VCG16, for automatic BAC detection. In this study, we further tested the method by a comparative analysis with other ten CNNs. MATERIAL AND METHODS: Four-view standard mammography exams from 1,493 women were included in this retrospective study and labeled as BAC or non-BAC by experts. The comparative study was conducted using eleven pretrained convolutional networks (CNNs) with varying depths from five architectures including Xception, VGG, ResNetV2, MobileNet, and DenseNet, fine-tuned for the binary BAC classification task. Performance evaluation involved area under the receiver operating characteristics curve (AUC-ROC) analysis, F1-score (harmonic mean of precision and recall), and generalized gradient-weighted class activation mapping (Grad-CAM++) for visual explanations. RESULTS: The dataset exhibited a BAC prevalence of 194/1,493 women (13.0%) and 581/5,972 images (9.7%). Among the retrained models, VGG, MobileNet, and DenseNet demonstrated the most promising results, achieving AUC-ROCs > 0.70 in both training and independent testing subsets. In terms of testing F1-score, VGG16 ranked first, higher than MobileNet (0.51) and VGG19 (0.46). Qualitative analysis showed that the Grad-CAM++ heatmaps generated by VGG16 consistently outperformed those produced by others, offering a finer-grained and discriminative localization of calcified regions within images. CONCLUSION: Deep transfer learning showed promise in automated BAC detection on mammograms, where relatively shallow networks demonstrated superior performances requiring shorter training times and reduced resources. RELEVANCE STATEMENT: Deep transfer learning is a promising approach to enhance reporting BAC on mammograms and facilitate developing efficient tools for cardiovascular risk stratification in women, leveraging large-scale mammographic screening programs. KEY POINTS: • We tested different pretrained convolutional networks (CNNs) for BAC detection on mammograms. • VGG and MobileNet demonstrated promising performances, outperforming their deeper, more complex counterparts. • Visual explanations using Grad-CAM++ highlighted VGG16's superior performance in localizing BAC.

Associations of phosphorus concentrations with medial arterial calcification in lower-extremity arteries and diabetic foot in people with diabetes: a retrospective cross-sectional study.

BACKGROUND: The aim of this study was to investigate the associations of blood phosphorus levels with the risk of developing medial arterial calcification (MAC) in lower-limb arteries and diabetic foot (DF) in diabetes patients. We sought to enhance the understanding of the pathophysiology of diabetic complications and develop strategies to mitigate diabetes-related risks. METHODS: We conducted a retrospective analysis of 701 diabetic patients from the Department of Endocrinology at Sun Yat-Sen Memorial Hospital (2019-2023). We utilized multimodel-adjusted logistic regression to investigate the associations of serum phosphorus levels and the risk of developing MAC and DF. Restricted cubic spline plots were employed to model the relationships, and threshold analysis was used to identify inflection points. Subgroup analyses were performed to explore variations across different demographics. The diagnostic utility of phosphorus concentrations was assessed via the C index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: Of the 701 patients (mean age 63.9 years; 401 (57.20%) were male), 333 (47.50%) had MAC, and 329 (46.93%) had DF. After controlling for numerous confounding variables, each one-unit increase in phosphorus concentrations was associated with an increased risk of developing MAC (OR 2.65, 95% CI 1.97-3.57, p < 0.001) and DF (OR 1.54, 95% CI 1.09-2.18, p = 0.014). Phosphorus levels demonstrated a linear risk association, with risk not being uniform on either side of the inflection point, which was approximately 3.28 mg/dL for MAC and varied for DF (3.26 to 3.81 mg/dL). Adding the phosphorus as an independent component to the diagnostic model for MAC and DF increased the C index, NRI, and IDI to varying degrees. CONCLUSIONS: Elevated serum phosphorus levels are significantly associated with an increased risk of developing MAC and DF among diabetic people. These findings suggest that phosphorus management could be integrated into routine diagnostic processes to improve the identification and management of lower-extremity diabetic complications.

Breast Arterial Calcifications on Mammography: Awareness and Reporting Preferences Amongst Referring Physicians in Canada.

Purpose: Breast arterial calcifications (BAC) on mammography have been correlated with increased cardiovascular risk. The Canadian Society of Breast Imaging released a position statement on BAC reporting in January 2023. This study evaluates the awareness of the clinical significance of BAC and reporting preferences of referring physicians in Canada. Methods: A 15-question survey was distributed to Canadian physicians who may review mammography results via regional and subspecialty associations and on social media following local institutional ethical approval. Responses were collected over 10 weeks from February to April 2023. Results: Seventy-two complete responses were obtained. We are unable to determine the response rate, given the means of distribution. Only 17% (12/72) of responding physicians were previously aware of the association between BAC and increased cardiovascular risk, and 51% (37/72) preferred the inclusion of BAC in the mammography report. Fifty-six percent (40/72) indicated that BAC reporting would prompt further investigation, and 63% (45/72) would inform patients that their mammogram showed evidence of BAC. Sixty-nine percent (50/72) would find grading of BAC beneficial and 71% (51/72) agreed that there is a need for national guidelines. Conclusion: Less than a quarter of responding Canadian referring physicians were previously aware of the association between BAC and cardiovascular risk, although half of respondents indicated a preference for BAC reporting on mammography. Most participating physicians would inform their patients of the presence of BAC and consider further cardiovascular risk management. There was consensus that a national BAC grading system and clinical management guidelines would be beneficial.

The Complex Mechanisms and the Potential Effects of Statins on Vascular Calcification: A Narrative Review.

Vascular calcification (VC) is a complex process of calcium deposition on the arterial wall and atherosclerotic plaques and involves interaction between vascular smooth muscle cells, inflammatory and VC mediators. The latter are independent predictors of cardiovascular morbidity and mortality and potential targets of pharmaceutical therapy. This paper is a narrative review of the complex mechanisms of VC development and in this context the potential anti-atherosclerotic effects of statins. At the initial stages of atherosclerosis VC correlates with atherosclerosis burden and in the long-term with cardiovascular morbidity and mortality. A plethora of animal and clinical studies have proposed statins as the cornerstone of primary and secondary prevention of atherosclerotic cardiovascular disease. Based on coronary computed tomography data, high doses of statins may have negligible or even positive effects on the progression of coronary artery calcification. Growing data support an increase in atherosclerotic plaque calcification in peripheral arteries (e.g., carotids), after long-term, statin-therapy. Despite the paradox of increasing VC, those effects of statins have been associated with higher plaque stability, reducing the risk of consequent adverse events. Statins seem to promote a "favorable" atherosclerotic calcification, suppressing atherosclerotic lesion expansion and their vulnerability. More studies are required to clarify the underlying mechanisms.

The Impact Of Small Artery Disease (SAD) and Medial Arterial Calcification (MAC) Scores on Chronic Wound and Amputation Healing: Can It Tell Us More?

Plenary Session Presentation at the Vascular and Endovascular Surgical Society 28th Annual Winter Meeting; Sun Valley Resort, Sun Valley, ID January 18 - 21, 2024 OBJECTIVES: In 2021, Ferraresi et al. created a novel scoring system based on the impact of small artery disease (SAD) and medial arterial calcification (MAC) on wound healing. SAD and MAC scores functioned similar to WIfI but with minimal resource expenditure. Despite its potential, few studies have expanded on the original dataset. We aim to validate SAD and MAC's impact on wound healing outcomes and determine their utility in relation to current predictive models. METHODS: Single-institution retrospective review was used to identify amputations for chronic (>1mo) podiatric wounds between 2015-2020. Foot x-ray (MAC) or angiography (SAD) <6 months of index procedure was required. Primary outcomes included major amputation, wound healing, major adverse limb events (MALE), and amputation-free survival (AFS). Statistical analysis included chi-square, one-way ANOVA, non-parametric correlation, Kaplan-Meier, Cox regression, and Akaike (AIC)/ Bayesian Inclusion Criteria (BIC) model comparison. RESULTS: Of 136 limbs, 67 received SAD scores (0-2) and 128 received MAC scores (0-2). SAD cohorts exhibited similar comorbidity profiles with exception of coronary disease, heart failure, and chronic kidney disease. MAC cohorts were notably disparate in prevalence of multiple conditions. High mean SAD/MAC scores were seen in severe (3-vessel) below-ankle disease (p=.001* [SAD], p=.041* [MAC]). Both SAD and MAC correlated with lower mean toe pressure (p=.043* [SAD], p=<.001* [MAC]), while only MAC correlated with higher overall WIfI score (p=.029*). No significant procedural differences were noted. However, higher re-admission rates (73.9% [2] vs. 46.9% [0], p=.014*) and all-cause mortality (65.2% [2] vs. 26.0% [0], p=.002*) were noted with higher MAC. Survival analysis revealed higher one-year major amputation rates (p=.036*), impaired wound healing (p<.001*), and lower amputation-free survival (p=.001*) with increasing MAC severity. Additionally, MAC-2 patients underwent amputation at faster rates than MAC-0 patients (HR 5.25, 95% CI [1.82, 9.77]) with longer times to wound healing (HR 0.21, 95% CI [0.08, 0.53]). Model comparison suggested a combination of WIfI and MAC could improve accuracy of predicted time to major amputation, wound healing, and amputation-free survival. CONCLUSIONS: MAC scoring showed significant promise both as individual predictor and adjunct to current predictive models of long-term wound healing outcomes. Routine use of MAC scoring in CLTI evaluation, especially when non-invasive testing is unavailable, could promote timely referral for intervention and efficient resource utilization in limited-resource or critical care settings. Further investigation is necessary to determine MAC's impact on revascularization and how scoring can be used to guide surgical decision making.

The role of the kynurenine pathway in cardiovascular disease.

The kynurenine pathway (KP) serves as the primary route for tryptophan metabolism in most mammalian organisms, with its downstream metabolites actively involved in various physiological and pathological processes. Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) serve as the initial and pivotal enzymes of the KP, with IDO playing important and intricate roles in cardiovascular diseases. Multiple metabolites of KP have been observed to exhibit elevated concentrations in plasma across various cardiovascular diseases, such as atherosclerosis, hypertension, and acute myocardial infarction. Multiple studies have indicated that kynurenine (KYN) may serve as a potential biomarker for several adverse cardiovascular events. Furthermore, Kynurenine and its downstream metabolites have complex roles in inflammation, exhibiting both inhibitory and stimulatory effects on inflammatory responses under different conditions. In atherosclerosis, upregulation of IDO stimulates KYN production, mediating aromatic hydrocarbon receptor (AhR)-induced exacerbation of vascular inflammation and promotion of foam cell formation. Conversely, in arterial calcification, this mediation alleviates osteogenic differentiation of vascular smooth muscle cells. Additionally, in cardiac remodeling, KYN-mediated AhR activation exacerbates pathological left ventricular hypertrophy and fibrosis. Interventions targeting components of the KP, such as IDO inhibitors, 3-hydroxyanthranilic acid, and anthranilic acid, demonstrate cardiovascular protective effects. This review outlines the mechanistic roles of KP in coronary atherosclerosis, arterial calcification, and myocardial diseases, highlighting the potential diagnostic, prognostic, and therapeutic value of KP in cardiovascular diseases, thus providing novel insights for the development and application of related drugs in future research.

Epigallocatechin-3-gallate inhibits osteogenic differentiation of vascular smooth muscle cells through the transcription factor JunB.

Medial arterial calcification (MAC) accompanying chronic kidney disease (CKD) leads to increased vessel wall stiffness, myocardial ischemia, heart failure, and increased cardiovascular morbidity and mortality. Unfortunately, there are currently no drugs available to treat MAC. The natural polyphenol epigallocatechin-3-gallate (EGCG) has been demonstrated to protect against cardiovascular disease; however, whether EGCG supplementation inhibits MAC in CKD remains unclear. In this study, we utilize a CKD-associated MAC model to investigate the effects of EGCG on vascular calcification and elucidate the underlying mechanisms involved. Our findings demonstrate that EGCG treatment significantly reduces calcium phosphate deposition and osteogenic differentiation of VSMCs in vivo and in vitro in a dose-dependent manner. In addition, through RNA sequencing (RNA-seq) analysis, we show a significant activation of the transcription factor JunB both in CKD mouse arteries and in osteoblast-like VSMCs. Notably, EGCG effectively suppresses CKD-associated MAC by inhibiting the activity of JunB. In addition, overexpression of JunB can abolish while knockdown of JunB can enhance the inhibitory effect of EGCG on the osteogenic differentiation of VSMCs. Furthermore, EGCG supplementation inhibits MAC in CKD via modulation of the JunB-dependent Ras/Raf/MEK/ERK signaling pathway. In conclusion, our study highlights the potential therapeutic value of EGCG for managing CKD-associated MAC, as it mitigates this pathological process through targeted inactivation of JunB.

ß,γ-Methylene-ATP and its metabolite medronic acid affect both arterial media calcification and bone mineralization in non-CKD and CKD rats.

Arterial media calcification or pathological deposition of calcium-phosphate crystals in the vessel wall contributes significantly to the high mortality rate observed in patients with CKD. Extracellular nucleotides (ie, ATP or UTP) regulate the arterial calcification process by interacting with (1) purinergic receptors and (2) breakdown via ecto-nucleotidases, such as ectonucleotide pyrophosphatase/phosphodiesterase NPP1 or NPP3, affecting the local levels of calcification inhibitor, pyrophosphate, and stimulator inorganic phosphate (PPi/Pi ratio). Also, it has been shown that ATP analogs (ie, ß,γ-methylene-ATP [ß,γ-meATP]) inhibit vascular smooth muscle cell calcification in vitro. In the first experiment, daily dosing of ß,γ-meATP (2 mg/kg) was investigated in rats fed a warfarin diet to trigger the development of non-CKD-related arterial medial calcifications. This study showed that ß,γ-meATP significantly lowered the calcium scores in the aorta and peripheral vessels in warfarin-exposed rats. In a second experiment, daily dosing of 4 mg/kg ß,γ-meATP and its metabolite medronic acid (MDP) was analyzed in rats fed an adenine diet to promote the development of CKD-related arterial medial calcification. Administration of ß,γ-meATP and MDP did not significantly decrease aortic calcification scores in this model. Moreover, both compounds induced deleterious effects on physiological bone mineralization, causing an imminent risk for worsening the already compromised bone status in CKD. Due to this, it was not possible to raise the dosage of both compounds to tackle CKD-related arterial calcification. Again, this points out the difficult task of targeting solely ectopic calcifications without negatively affecting physiological bone mineralization. On the other hand, aortic mRNA expression of Enpp1 and Enpp3 was significantly and positively associated with aortic calcification scores, suggesting that normalizing the aortic NPP1/3 activity to control values might be a possible target to treat (CKD-induced) arterial media calcifications.

Breast arterial calcification is associated with sarcopenia in peri- and post-menopausal women.

PURPOSE: Breast arterial calcification (BAC) refers to medial calcium deposition in breast arteries and is detectable via mammography. Sarcopenia, which is characterised by low skeletal muscle mass and quality, is associated with several serious clinical conditions, increased morbidity, and mortality. Both BAC and sarcopenia share common pathologic pathways, including ageing, diabetes, and chronic kidney disease. Therefore, this study evaluated the relationship between BAC and sarcopenia as a potential indicator of sarcopenia. METHODS: This study involved women aged >40. BAC was evaluated using digital mammography and was defined as vascular calcification. Sarcopenia was assessed using abdominal computed tomography. The cross-sectional skeletal mass area was measured at the third lumbar vertebra level. The skeletal mass index was obtained by dividing the skeletal mass area by height in square meters(m2). Sarcopenia was defined as a skeletal mass index of ≤38.5 cm2/m2. A multivariable model was used to evaluate the relationship between BAC and sarcopenia. RESULTS: The study involved 240 participants. Of these, 36 (15 %) were patients with BAC and 204 (85 %) were without BAC. Sarcopenia was significantly higher among the patients with BAC than in those without BAC (72.2 % vs 17.2 %, P < 0.001). The multivariable model revealed that BAC and age were independently associated with sarcopenia (odds ratio[OR]: 7.719, 95 % confidence interval[CI]: 3.201-18.614, and P < 0.001 for BAC and OR: 1.039, 95 % CI: 1.007-1.073, P = 0.01 for age). CONCLUSION: BAC is independently associated with sarcopenia. BAC might be used as an indicator of sarcopenia on screening mammography.

Quantitative Abdominal Arterial Calcification Correlates with Kidney Transplant Waitlist Mortality.

INTRODUCTION: The scarcity of available organs for kidney transplantation has resulted in a substantial waiting time for patients with end-stage kidney disease. This prolonged wait contributes to an increased risk of cardiovascular mortality. Calcification of large arteries is a high-risk factor in the development of cardiovascular diseases, and it is common among candidates for kidney transplant. The aim of this study was to correlate abdominal arterial calcification (AAC) score value with mortality on the waitlist. METHODS: We modified the coronary calcium score and used it to quantitate the AAC. We conducted a retrospective clinical study of all adult patients who were listed for kidney transplant, between 2005 and 2015, and had abdominal computed tomography scan. Patients were divided into two groups: those who died on the waiting list group and those who survived on the waiting list group. RESULTS: Each 1,000 increase in the AAC score value of the sum score of the abdominal aorta, bilateral common iliac, bilateral external iliac, and bilateral internal iliac was associated with increased risk of death (HR 1.034, 95% CI: 1.013, 1.055) (p = 0.001). This association remained significant even after adjusting for various patient characteristics, including age, tobacco use, diabetes, coronary artery disease, and dialysis status. CONCLUSION: The study highlights the potential value of the AAC score as a noninvasive imaging biomarker for kidney transplant waitlist patients. Incorporating the AAC scoring system into routine imaging reports could facilitate improved risk assessment and personalized care for kidney transplant candidates.

Pedal medial arterial calcification in diabetic foot ulcers: A significant risk factor of amputation and mortality.

AIMS: Pedal medial arterial calcification (MAC) is frequently observed in individuals with diabetic foot ulcers (DFUs). However, the impact of pedal MAC on individuals with DFUs remains uncertain. The main aim of this study was to evaluate the association between pedal MAC with amputation and mortality outcomes. METHODS: A prospective, observational cohort study was conducted at West China Hospital from January 2012 to December 2021. Logistic regression analyses, Kaplan-Meier survival method, and Cox proportional hazards models were employed to evaluate the relationship between pedal MAC and amputation as well as mortality. RESULTS: A total of 979 patients were enrolled in the study. Peripheral artery disease (PAD) was observed in 53% of patients with DFUs, and pedal MAC was found in 8%. Over a median follow-up of 46 (23-72) months, foot amputation was performed on 190 patients, and mortality occurred in 246 patients. Pedal MAC showed a significant association with amputation both in unadjusted analysis (odds ratio [OR] = 2.98, 95% confidence interval [CI] = 1.86-4.76, p < .001) and after adjusting sex, age, albumin levels, hemoglobin levels, and diabetic retinopathy status (OR 2.29, 95% CI 1.33-3.93, p = .003). The risk of amputation was found to be twofold higher in individuals with PAD and pedal MAC compared to those with PAD alone (OR 2.05, 95% CI 1.10-3.82, p = .024). Furthermore, the presence of pedal MAC was significantly associated with an increased risk of mortality (p = .005), particularly among individuals with DFUs but without PAD (HR 4.26, 95% CI 1.90-9.52, p < .001), rather than in individuals presenting with both DFUs and PAD. CONCLUSION: The presence of pedal MAC is significantly associated with both amputation and mortality in individuals with DFUs. Moreover, pedal MAC could provide additional value to predict amputation other than PAD.

Arterial Calcification Disappearance in Breast Imaging: A Key Indicator for Transition to Invasive Ductal Carcinoma.

A woman in her 70s, initially suspected of having fibroadenoma due to a well-defined mass in her breast, underwent regular mammography and ultrasound screenings. Over several years, no appreciable alterations in the mass were observed, maintaining the fibroadenoma diagnosis. However, in the fourth year, an ultrasound indicated slight enlargement and peripheral irregularities in the mass, even though the mammography images at that time showed no alterations. Interestingly, mammography images over time showed the gradual disappearance of previously observed arterial calcification around the mass. Pathological examination eventually identified the mass as invasive ductal carcinoma. Although the patient had breast tissue arterial calcification typical of atherosclerosis, none was present around the tumor-associated arteries. This case highlights the importance of monitoring arterial calcification changes in mammography, suggesting that they are crucial indicators in breast cancer diagnosis, beyond observing size and shape alterations.

Endovascular retrieval of an entrapped balloon in a tibial artery.

Balloon entrapment is a rare complication of angioplasty in calcified or recalcitrant lesions. A 65-year-old man with chronic limb-threatening ischemia underwent balloon angioplasty of his heavily calcified tibial arteries with a low-profile, tapered, compliant balloon. The balloon became entrapped within the posterior tibial artery and required multiple endovascular maneuvers to deflate and separate the balloon from the calcified arterial wall. This case report describes several adjunctive techniques for retrieval of an entrapped balloon in small, calcified arteries before consideration of surgical removal. These techniques allow for minimally invasive retrieval and continuation of endovascular treatment thereafter.

Assessing breast arterial calcification in mammograms and its implications for atherosclerotic cardiovascular disease risk.

PURPOSE: Breast arterial calcifications (BAC) are incidentally observed on mammograms, yet their implications remain unclear. We investigated lifestyle, reproductive, and cardiovascular determinants of BAC in women undergoing mammography screening. Further, we investigated the relationship between BAC, coronary arterial calcifications (CAC) and estimated 10-year atherosclerotic cardiovascular (ASCVD) risk. METHODS: In this cross-sectional study, we obtained reproductive history and CVD risk factors from 215 women aged 18 or older who underwent mammography and cardiac computed tomographic angiography (CCTA) within a 2-year period between 2007 and 2017 at hospital. BAC was categorized as binary (present/absent) and semi-quantitatively (mild, moderate, severe). CAC was determined using the Agatston method and recorded as binary (present/absent). Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated, accounting for age as a confounding factor. ASCVD risk over a 10-year period was calculated using the Pooled Cohort Risk Equations. RESULTS: Older age, systolic and diastolic blood pressures, higher parity, and younger age at first birth (≤28 years) were significantly associated with greater odds of BAC. Women with both BAC and CAC had the highest estimated 10-year risk of ASCVD (13.30 %). Those with only BAC (8.80 %), only CAC (5.80 %), and no BAC or CAC (4.40 %) had lower estimated 10-year risks of ASCVD. No association was detected between presence of BAC and CAC. CONCLUSIONS: These findings support the hypothesis that BAC on a screening mammogram may help to identify women at potentially increased risk of future cardiovascular disease without additional cost and radiation exposure.

Prevalence and progression of arterial calcifications on computed tomography in humans with knee osteoarthritis.

OBJECTIVES: Ectopic bone deposition plays an important role in osteoarthritis (OA) and in arterial wall disease. We aimed to investigate the prevalence and progression of arterial calcifications on whole-body computed tomography (CT) in persons with knee OA. METHODS: We included 118 (36 male) participants who satisfied the clinical American College of Rheumatology classification criteria for knee OA. Baseline investigations included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Kellgren-Lawrence grading. At baseline and after two years, a whole-body CT was performed using the same scanner and protocol. Calcifications were quantified in the carotid, brachiocephalic, coronary, thoracic aortic, abdominal aortic, iliac, femoropopliteal and crural arteries. Multivariable linear and logistic regression modeling was used for analyses. RESULTS: At baseline males were 66.9 ± 7.7 and females were 68.0 ± 5.6 years old. Calcifications were common, all participants except two females had some calcification, and prevalence ranged between 41.8% and 94.4% for various arterial beds. Baseline femoropopliteal calcifications were associated with a higher Kellgren-Lawrence grade (more severe knee OA). Median annual progression rate was 13.1% in males and 15.7% in females. Structural OA severity was not associated with progression, but a five points lower (worse) WOMAC was associated with 1% faster progression of arterial calcifications (p= 0.008). CONCLUSION: Around age 70 nearly all persons with knee OA have arterial calcifications, which progress substantially. For further investigation into shared causality intervention studies are needed.

Pedal medial arterial calcification influences the outcomes of isolated infra-malleolar interventions for chronic limb-threatening ischemia.

OBJECTIVE: Inframalleolar disease is present in most diabetic patients presenting with tissue loss. Inframalleolar (pedal) artery disease and pedal medial arterial calcification (pMAC) are associated with major amputation in patients with chronic limb-threatening ischemia (CLTI). This study aimed to examine the impact of pMAC on the outcomes after isolated inframalleolar (pedal artery) interventions. METHODS: A database of lower extremity endovascular intervention for patients with tissue loss between 2007 and 2022 was retrospectively queried. Patients with CLTI were selected, and those undergoing isolated inframalleolar intervention on the dorsalis pedis and medial and lateral tarsal arteries and who had foot x-rays were identified. X-rays were assessed blindly for pMAC and scored on a scale of 0 to 5. Patients with concomitant superficial femoral artery and tibial interventions were excluded. Intention to treat analysis by the patient was performed. Amputation-free survival (survival without major amputation) was evaluated. RESULTS: A total of 223 patients (51% female; 87% Hispanic; average age, 66 years; 323 vessels) underwent isolated infra-malleolar intervention for tissue loss. All patients had diabetes, 96% had hypertension, 79% had hyperlipidemia, and 63% had chronic renal insufficiency (55% of these were on hemodialysis). Most of the patients had Wound, Ischemia, and foot Infection (WIfI) stage 3 disease and had various stages of pMAC: severe (score = 5) in 48%, moderate (score = 2-4) in 31%, and mild (score = 0-1) in 21% of the patients. Technical success was 94%, with a median of one vessel treated per patient. All failures were in severe pMAC. Overall, major adverse cardiovascular events was 0.9% at 90 days after the procedure. Following the intervention, most patients underwent a planned forefoot amputation (single digit, multiple digits, ray amputation, or trans-metatarsal amputation). WIfI ischemic grade was improved by 51%. Wound healing at 3 months was 69%. Those not healing underwent below-knee amputations. The overall 5-year amputation-free survival rate was 35% ± 9%. The severity of pMAC was associated with decreased AFS. CONCLUSIONS: Increasing severity of pMAC influences the technical and long-term outcomes of infra-malleolar intervention in diabetes. Severe pMAC is associated with amputation and should be considered as a variable in the shared decision-making of diabetic patients with CLTI.