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.

A case report of ventricular fibrillation following Shockwave intravascular lithotripsy during percutaneous coronary intervention.

BACKGROUND: Shockwave intravascular lithotripsy (S-IVL) is widely used during percutaneous coronary intervention (PCI) of calcified coronary arteries. Ventricular capture beats during S-IVL are common but arrhythmias are rare. CASE PRESENTATION: A 75-year-old woman was scheduled for PCI to a short, heavily calcified chronic total occlusion of the right coronary artery. After wiring of the occlusion, S-IVL was used to predilated the calcified stenosis. During S-IVL, the patient developed ventricular fibrillation twice. CONCLUSION: To our knowledge, this is only the second reported case of VF during S-IVL. Although very rare, it is important to be aware of this potential and serious complication.

Association between dietary folate intake and severe abdominal aorta calcification in adults: A cross-sectional analysis of the national health and nutrition examination survey.

BACKGROUND: Prior studies have established a connection between folate intake and cardiovascular disease (CVD). Abdominal aortic calcification (AAC) has been introduced as a good predictor of CVD events, but no previous study has investigated the relationship between dietary folate intake and severe AAC. Therefore, the study aims to explore the association between dietary folate intake and severe AAC in the United States (US) middle-aged and elderly population. METHODS: This study employed cross-sectional data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to examine the relationship between dietary folate intake and severe AAC. Two 24-h dietary recall interviews were conducted to assess dietary folate intake and its sources, while a DXA scan was used to determine the AAC score. To analyze the association between dietary folate intake and severe AAC, a multivariable logistic regression model was applied, and a subgroup analysis was performed. RESULTS: Our analysis utilized data from 2640 participants aged 40 years and above, including 288 individuals diagnosed with severe AAC. After adjusting for confounding factors, we observed an inverted L-shaped association between folate intake and severe AAC. Upon further adjustment for specific confounding factors and covariates, the multivariable-adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the second, third, and fourth quartiles of folate intake, using the first quartile as the reference, were as follows: 1.24 (0.86-1.79), 0.86 (0.58-1.27), and 0.63 (0.41-0.97), respectively. Subgroup analysis results were consistent with the logistic regression models, indicating concordant findings. Moreover, no significant interaction was observed in the subgroup analyses. CONCLUSIONS: The study findings suggest an inverted L-shaped association between dietary folate intake and severe AAC. However, additional prospective investigations are necessary to explore the impact of dietary folate intake on severe AAC in patients.

Efficacy of intravascular lithotripsy (IVL) in coronary stenosis with severe calcification: A multicenter systematic review and meta-analysis.

BACKGROUND: With heavily calcified coronary and peripheral artery lesions, lesion preparation is crucial before stent placement to avoid underexpansion, associated with stent thrombosis or restenosis and patency failure in the long-term. Intravascular lithotripsy (IVL) technology disrupts superficial and deep calcium by using localized pulsative sonic pressure waves, making it to a promising tool for patients with severe calcification in coronary bed. AIMS: The aim of the study is to systematically review and summarize available data regarding the safety and efficacy of IVL for lesion preparation in severely calcified coronary arteries before stenting. METHODS: This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies assessing the characteristics and outcomes of patients undergoing IVL before stent implantation. The diameter of the vessel lumen before and after IVL, as well as stent implantation, were analyzed. The occurrence of major adverse cardiovascular events (MACE) was assessed using a random-effects model. RESULTS: This meta-analysis comprised 38 studies including 2977 patients with heavily calcified coronary lesions. The mean age was 72.2 ± 9.1 years, with an overall IVL clinical success of 93% (95% confidence interval [CI]: 91%-95%, I2 = 0%) and procedural success rate of 97% (95% CI: 95%-98%, I2 = 73.7%), while the in-hospital and 30-days incidence of MACE, myocardial infarction (MI), and death were 8% (95% CI: 6%-11%, I2 = 84.5%), 5% (95% CI: 2%-8%, I2 = 85.6%), and 2% (95% CI: 1%-3%, I2 = 69.3%), respectively. There was a significant increase in the vessel diameter (standardized mean difference [SMD]: 2.47, 95% CI: 1.77-3.17, I2 = 96%) and a decrease in diameter stenosis (SMD: -3.44, 95% CI: -4.36 to -2.52, I2 = 97.5%) immediately after IVL application, while it was observed further reduction in diameter stenosis (SMD: -6.57, 95% CI: -7.43 to -5.72, I2 = 95.8%) and increase in the vessel diameter (SMD: 4.37, 95% CI: 3.63-5.12, I2 = 96.7%) and the calculated lumen area (SMD: 3.23, 95% CI: 2.10-4.37, I2 = 98%), after stent implantation. The mean acute luminal gain following IVL and stent implantation was estimated to be 1.27 ± 0.6 and 1.94 ± 1.1 mm, respectively. Periprocedural complications were rare, with just a few cases of perforations, dissection, or no-reflow phenomena recorded. CONCLUSIONS: IVL seems to be a safe and effective strategy for lesion preparation in severely calcified lesions before stent implantation in coronary arteries. Future prospective studies are now warranted to compare IVL to other lesion preparation strategies.

Associations Between Visceral Fat, Abdominal Muscle, and Coronary Artery Calcification: A Cross-Sectional Analysis of the Multi-Ethnic Study of Atherosclerosis.

The associations of body composition components, including muscle and adipose tissue, and markers of subclinical coronary artery disease are unclear. We examined the relation between abdominal computed tomography (CT)-derived measures of the area and density of fat and muscle with coronary artery calcification (CAC), using data from the Multi-Ethnic Study of Atherosclerosis (MESA). A total of 1,974 randomly selected MESA participants free of coronary heart disease underwent abdominal CT scans at examinations 2 or 3, with the resulting images interrogated for abdominal body composition. Using 6 cross-sectional slices spanning L2 to L5, the Medical Imaging Processing Analysis and Visualization software was used to determine abdominal muscle and fat composition using appropriate Hounsfield units ranges. CT chest scans were used to obtain CAC scores, calculated using the Agatston method and spatially weighted calcium score. Multivariable linear and logistic regression analyses were performed to assess the relation between abdominal visceral fat and muscle area and density to prevalent CAC. A total of 1,089 participants had a CAC >0, with an average CAC score of 310. In the fully adjusted model, for every 10-cm2 increase in visceral fat area, the likelihood of having a CAC greater than 0 increased by 0.60% (p <0.001). In the minimally adjusted model, abdominal muscle area was significantly associated with CAC >0, which became nonsignificant in the fully adjusted model. For the density of visceral fat, every 1-Hounsfield unit increase (less lipid-dense fat tissue), the likelihood of having a CAC score >0 decreased by 0.29% (p <0.05). No significant relation was observed between density of abdominal muscle and CAC >0. A greater area and higher lipid density of abdominal visceral fat were associated with an increased likelihood of having CAC, whereas there was no significant relation between abdominal muscle area or density and CAC. The quantity and the quality of fat have associations, with an important marker of subclinical atherosclerosis, CAC, and their significance with respect to cardiovascular outcomes, require further evaluation.

A Prospective, Multicenter, Real-World Registry of Coronary Lithotripsy in Calcified Coronary Arteries: The REPLICA-EPIC18 Study.

BACKGROUND: Intravascular lithotripsy (IVL) has demonstrated effectiveness in the treatment of calcified lesions in selected patients with stable coronary disease. OBJECTIVES: The authors sought to assess the performance of coronary IVL in calcified coronary lesions in a real-life, all comers, setting. METHODS: The REPLICA-EPIC18 study prospectively enrolled consecutive patients treated with IVL in 26 centers in Spain. An independent core laboratory performed the angiographic analysis and event adjudication. The primary effectiveness endpoint assessed procedural success (successful IVL delivery, final diameter stenosis <20%, and absence of in-hospital major adverse cardiovascular events [MACE]). The primary safety endpoint measured freedom from MACE at 30 days. A predefined substudy compared outcomes between acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) patients. RESULTS: A total of 426 patients (456 lesions) were included, 63% of the patients presenting with ACS. IVL delivery was successful in 99% of cases. Before IVL, 49% of lesions were considered undilatable. The primary effectiveness endpoint was achieved in 66% of patients, with similar rates among CCS patients (68%) and ACS patients (65%). Likewise, there were no significant differences in angiographic success after IVL between CCS and ACS patients. The rate of MACE at 30 days (primary safety endpoint) was 3% (1% in CCS and 5% in ACS patients [P = 0.073]). CONCLUSIONS: Coronary IVL proved to be a feasible and safe procedure in a "real-life" setting, effectively facilitating stent implantation in severely calcified lesions. Patients with ACS on admission showed similar angiographic success rates but showed a trend toward higher 30-day MACE compared with patients with CCS. (REPLICA-EPIC18 study [Registry of Coronary Lithotripsy in Spain]; NCT04298307).

Modic Changes in the Lumbar Spine: Exploring Their Association with Abdominal Aortic Calcification as a Potential Indicator of Systemic Atherosclerosis.

BACKGROUND: This was a cross-sectional study on the correlation between abdominal aortic calcification (AAC) and Modic changes (MC). Little is known regarding the etiology of MC in the lumbar spine. Currently, insufficient vascularization of the endplate has been proposed to contribute to the appearance of MC. Our objective was to investigate whether AAC, a marker for a poor vascular status, is associated with MC in patients suffering from degenerative disc disease. METHODS: Radiologic images of patients (n = 130) suffering from degenerative lumbar disc disease were reviewed. Type and severity of MC were assessed using magnetic resonance images, and severity of AAC was evaluated using computed tomography images or fluoroscopy. Both items were dichotomized into minimal and relevant grades. The correlation between them was studied using Spearman's correlation test, with age as a covariate. RESULTS: Of the patients, 113 (87%) demonstrated MC (31% type I, 63% type II, and 6% type III) (55% relevant grade), and 68% had AAC (44% relevant grade). Spearman statistical analysis revealed that AAC was correlated with age (P < 0.001), whereas MC were not (P = 0.142). AAC severity was significantly correlated with MC, remaining so after age adjustment (P < 0.05). While MC type I lacked correlation with AAC, MC type II were significantly correlated with AAC (0.288, P = 0.015); however, this association lost significance after adjusting for age (P = 0.057). CONCLUSIONS: AAC and MC (mainly MC type II) are associated, indicating that reduced blood supply or even a poor systemic vascularization status due to atherosclerotic disease may play a role in the formation of MC. Future studies focusing on the etiology of MC should pay more attention to patients' vascular status and determinants of abdominal aorta calcification.

Cerebral white matter hyperintensities indicate severity and progression of coronary artery calcification.

Cerebral white matter hyperintensities (WMH) have been associated with subclinical atherosclerosis including coronary artery calcification (CAC). However, previous studies on this association are limited by only cross-sectional analysis. We aimed to explore the relationship between WMH and CAC in elderly individuals both cross-sectionally and longitudinally. The study population consisted of elderly stroke- and dementia-free participants from the community-based Austrian Stroke Prevention Family Study (ASPFS). WMH volume and CAC levels (via Agatston score) were analyzed at baseline and after a 6-year follow-up period. Of 324 study participants (median age: 68 years), 115 underwent follow-up. Baseline WMH volume (median: 4.1 cm3) positively correlated with baseline CAC levels in multivariable analysis correcting for common vascular risk factors (p = 0.010). While baseline CAC levels were not predictive for WMH progression (p = 0.447), baseline WMH volume was associated CAC progression (median Agatston score progression: 27) in multivariable analysis (ß = 66.3 ± 22.3 [per cm3], p = 0.004). Ten of 11 participants (91%) with severe WMH (Fazekas Scale: 3) at baseline showed significant CAC progression > 100 during follow-up. In this community-based cohort of elderly individuals, WMH were associated with CAC and predictive of its progression over a 6-year follow-up. Screening for coronary artery disease might be considered in people with more severe WMH.

Novel plasma biomarkers of coronary artery calcium incidence or progression: Insights from the prospective multi-ethnic Dallas Heart Study cohort.

BACKGROUND AND AIMS: Identifying the association of novel plasma biomarkers with coronary artery calcium (CAC) incidence or progression may provide insights into the pathophysiology of atherogenesis and plaque formation. METHODS: Participants of the Dallas Heart Study (DHS), a multi-ethnic cohort of ambulatory individuals at low-intermediate risk for future atherosclerotic cardiovascular disease (ASCVD), who had their blood tested for 31 biomarkers reflecting multiple pathophysiological pathways, underwent 2 serial non-contrast computed tomography assessments for CAC a median ∼7 years apart. The collected biomarkers were explored for association with CAC incidence or progression using univariate and multivariate analysis. RESULTS: A total of 1424 participants were included; mean age 43 years, 39 % male, and nearly half African-American. Over a 7-year interval between the two CAC measurements, 340 participants (23.9 %) had CAC incidence or progression, 105 (7.4 %) with incident CAC, and 309 (21.7 %) with CAC progression. Although several plasma biomarkers were associated with CAC incidence or progression in a univariate model, only soluble intercellular adhesion molecule-1 (sICAM-1), related to atherosclerosis by the inflammatory pathway, remained independently associated in a multivariate model adjusted for traditional risk factors. CONCLUSIONS: Further studies are needed to characterize the role of sICAM-1 in CAC evolvement to establish whether it has a pivotal mechanistic contribution or is rather an innocent bystander. Alternate measures of coronary atherosclerosis may be needed to elucidate contributors to atherosclerosis incidence or progression.

Liver and spleen predominantly mediate calciprotein particle clearance in a rat model of chronic kidney disease.

Calciprotein particles (CPPs) provide an efficient mineral buffering system to prevent the complexation of phosphate and calcium in the circulation. However, in chronic kidney disease (CKD), the phosphate load exceeds the mineral buffering capacity, resulting in the formation of crystalline CPP2 particles. CPP2 have been associated with cardiovascular events and mortality. Moreover, CPP2 have been demonstrated to induce calcification in vitro. In this study, we examined the fate of CPP2 in a rat model of CKD. Calcification was induced in Sprague-Dawley rats by 5/6 nephrectomy (5/6-Nx) combined with a high-phosphate diet. Control rats received sham surgery and high-phosphate diet. Twelve weeks after surgery, kidney failure was significantly induced in 5/6-Nx rats as determined by enhanced creatinine and urea plasma levels and abnormal kidney histological architecture. Subsequently, radioactive and fluorescent (FITC)-labeled CPP2 ([89Zr]Zr-CPP2-FITC) were injected intravenously to determine clearance in vivo. Using positron emission tomography scans and radioactive biodistribution measurements, it was demonstrated that [89Zr]Zr-CPP2-FITC are mainly present in the liver and spleen in both 5/6-Nx and sham rats. Immunohistochemistry showed that [89Zr]Zr-CPP2-FITC are predominantly taken up by Kupffer cells and macrophages. However, [89Zr]Zr-CPP2-FITC could also be detected in hepatocytes. In the different parts of the aorta and in the blood, low values of [89Zr]Zr-CPP2-FITC were detectable, independent of the presence of calcification. CPP2 are cleared rapidly from the circulation by the liver and spleen in a rat model of CKD. In the liver, Kupffer cells, macrophages, and hepatocytes contribute to CPP2 clearance.NEW & NOTEWORTHY Calciprotein particles (CPPs) buffer calcium and phosphate in the blood to prevent formation of crystals. In CKD, increased phosphate levels may exceed the buffering capacity of CPPs, resulting in crystalline CPPs that induce calcification. This study demonstrates that labeled CPPs are predominantly cleared from the circulation in the liver by Kupffer cells, macrophages, and hepatocytes. Our results suggest that targeting liver CPP clearance may reduce the burden of crystalline CPP in the development of vascular calcification.

Association between lower extremity arterial calcification and coronary arterial calcification in a population at increased risk of cardiovascular disease.

INTRODUCTION: There is conflicting evidence whether lower extremity arterial calcification coincides with coronary arterial calcification (CAC). The aims of this study were to investigate the associations between (1) femoral and crural calcification with CAC, and (2) femoral and crural calcification pattern with CAC. RESEARCH DESIGN AND METHODS: This cross-sectional study included 405 individuals (74% men, 62.6±10.9 years) from the ARTEMIS cohort study at high risk of cardiovascular disease (CVD) who underwent a CT scan of the femoral, crural and coronary arteries. High CVD risk was defined as history/presence of cerebrovascular disease, coronary artery disease, abdominal aortic aneurysm, renal artery stenosis, peripheral artery disease or CVD risk factors: diabetes mellitus type 2, hypertension, hyperlipidemia. Calcification score within each arterial bed was expressed in Agatston units. Dominant calcification patterns (intimal, medial, absent/indistinguishable) were determined via a CT-guided histologically validated scoring algorithm. Multivariable-adjusted multinomial logistic regression analyses were used. Replication was performed in an independent population of individuals with diabetes mellitus type 2 (Early-HFpEF cohort study). RESULTS: Every 100-point increase in femoral and crural calcification score was associated with 1.23 (95% CI=1.09 to 1.37, p<0.001) and 1.28 (95% CI=1.11 to 1.47, p=0.001) times higher odds of having CAC within tertile 3 (high) versus tertile 1 (low), respectively. The association appeared stronger for crural versus femoral arteries. Moreover, the presence of femoral intimal (OR=10.81, 95% CI=4.23 to 27.62, p<0.001), femoral medial (OR=10.37, 95% CI=3.92 to 27.38, p<0.001) and crural intimal (OR=6.70, 95% CI=2.73 to 16.43, p<0.001) calcification patterns were associated with higher odds of having CAC within tertile 3 versus tertile 1, independently from concomitant calcification score. This association appeared stronger for intimal versus medial calcification patterns. The replication analysis yielded similar results. CONCLUSIONS: Higher femoral and crural calcification scores were associated with higher CAC. Moreover, the presence of femoral intimal, femoral medial and crural intimal calcification patterns was associated with increased CAC. It appears that arterial calcification is a systemic process which occurs simultaneously in various arterial beds.

Cardiac troponins and coronary artery calcium score: a systematic review.

An early diagnosis of atherosclerosis, particularly in subclinical status, can play a remarkable role in reducing mortality and morbidity. Because of coronary artery calcification (CAC) nature in radiation exposure, finding biomarkers associated with CAC could be useful in identifying individuals at high risk of CAC score. In this review, we focused on the association of cardiac troponins (hs-cTns) and CAC to achieve insight into the pathophysiology of CAC. In October 2022, we systematically searched Web of Science, Scopus, PubMed, and Embase databases to find human observational studies which have investigated the association of CAC with cardiac troponins. To appraise the included articles, we used the Newcastle Ottawa scale (NOS). Out of 520 records, 10 eligible studies were included. Based on findings from longitudinal studies and cross-sectional analyses, troponin T and I were correlated with occurrence of CAC and its severity. Two of the most important risk factors that affect the correlation between hs-cTns serum levels and CAC were age and gender. The elevation of cardiac troponins may affect the progression of CAC and future cardiovascular diseases. Verifying the association between cardiac troponins and CAC may lead to identify individuals exposed to enhanced risk of cardiovascular disease (CVD) complications and could establish innovative targets for pharmacological therapy.

Denosumab Decreases Epicardial Adipose Tissue Attenuation in Dialysis Patients with Secondary Hyperparathyroidism and Low Bone Mass.

INTRODUCTION: Denosumab preceding elective surgery is an alternative option when parathyroidectomy is not immediately possible. Denosumab (an osteoprotegerin mimic) may play a role in the cardiovascular system, which is reflected in the features of epicardial adipose tissue (EAT) and coronary artery calcification (CAC). METHODS: We investigated the effects of denosumab on EAT attenuation (EATat) and CAC in dialysis patients with secondary hyperparathyroidism (SHPT). This cohort study included patients on dialysis with SHPT. The baseline characteristics of dialysis patients and propensity score-matched non-dialysis patients were compared. Computed tomography scans of the dialysis patients (dialysis group with denosumab, n = 24; dialysis group without denosumab, n = 21) were obtained at baseline and at 6 months of follow-up. RESULTS: At baseline, the dialysis group patients had a higher EATat-median (-71.00 H ± 10.38 vs. -81.60 H ± 6.03; p < 0.001) and CAC (1,223 A [248.50-3,315] vs. 7 A [0-182.5]; p < 0.001) than the non-dialysis group. At follow-up, the dialysis group without denosumab showed an increase in Agatston score (1,319.50 A [238.00-2,587.50] to 1,552.00 A [335.50-2,952.50]; p = 0.001) without changes in EATat-median (-71.33 H ± 11.72 to -70.86 H ± 12.67; p = 0.15). The dialysis group with denosumab showed no change in Agatston score (1,132.2 A [252.25-3,260.5] to 1,199.50 A [324.25-2,995]; p = 0.19) but a significant decrease of EATat-median (-70.71 H ± 9.30 to -74.33 H ± 10.28; p = 0.01). CONCLUSIONS: Denosumab may reverse EATat and retard CAC progression in dialysis patients with SHPT.

Plasma proteomics for prediction of subclinical coronary artery calcifications in primary prevention.

BACKGROUND AND AIMS: Recent developments in high-throughput proteomic technologies enable the discovery of novel biomarkers of coronary atherosclerosis. The aims of this study were to test if plasma protein subsets could detect coronary artery calcifications (CAC) in asymptomatic individuals and if they add predictive value beyond traditional risk factors. METHODS: Using proximity extension assays, 1,342 plasma proteins were measured in 1,827 individuals from the Impaired Glucose Tolerance and Microbiota (IGTM) study and 883 individuals from the Swedish Cardiopulmonary BioImage Study (SCAPIS) aged 50-64 years without history of ischaemic heart disease and with CAC assessed by computed tomography. After data-driven feature selection, extreme gradient boosting machine learning models were trained on the IGTM cohort to predict the presence of CAC using combinations of proteins and traditional risk factors. The trained models were validated in SCAPIS. RESULTS: The best plasma protein subset (44 proteins) predicted CAC with an area under the curve (AUC) of 0.691 in the validation cohort. However, this was not better than prediction by traditional risk factors alone (AUC = 0.710, P = .17). Adding proteins to traditional risk factors did not improve the predictions (AUC = 0.705, P = .6). Most of these 44 proteins were highly correlated with traditional risk factors. CONCLUSIONS: A plasma protein subset that could predict the presence of subclinical CAC was identified but it did not outperform nor improve a model based on traditional risk factors. Thus, support for this targeted proteomics platform to predict subclinical CAC beyond traditional risk factors was not found.