Aortic Calcification Score Research Articles

Abstract 4140136: Aortic Valve Calcification Density Performs Better Compared to Absolute Aortic Valve Calcification in Aortic Stenosis Risk Stratification

Aortic valve calcification (AVC) scores can be used to stratify aortic stenosis (AS) severity. Current practice guidelines recommend use of absolute AVC scores without considering body surface area or aortic annulus size. We investigated whether size variation in aortic annular area should be considered in identifying optimal AVC cutoffs for patients with severe AS. This was a retrospective analysis of AS patients that underwent AVC assessment during 2018-2023. Outcomes were composite of valve intervention or all-cause mortality. AVC density was defined by dividing AVC by echo-derived left ventricular tract area. Receiver operator curve analysis determined optimal AVC density scores. Absolute AVC cutoffs of >1200AU for females and >2000AU for males were used to identify severe AS. The study included 749 patients (mean age 78 years, 46% female). Median CT-annulus area was larger for males compared with females (532mm 2 [Q1, Q3: 479, 582] vs. 413mm 2 [370, 458], p<0.001). There was a strong association of absolute AVC with CT-annulus area for both males and females (Spearman coefficient: 0.87 and 0.83, p<0.01 each) respectively (Figure 1). The optimal AVC density cutoffs for males and females were 427 and 326, respectively (accuracy 76%, sensitivity 83%, specificity 51%). Composite outcomes were better differentiated with AVC density (males: HR 2.48, 95% CI: 1.82-3.37, p<0.001; females: HR 2.37 (1.71-3.28), p<0.001) compared with absolute AVC scores (males: HR 1.81 (1.43-2.30), p<0.001; females: HR 2.11 (1.62-2.74), p<0.001) (Figure 2). AVC is strongly associated with CT-annulus area and risk stratification is improved with the use of AVC density compared with absolute AVC. This may be especially helpful in patients with extremes of annulus area sizes.

Autonomous cortisol secretion promotes vascular calcification in vivo and in vitro under hyperaldosteronism.

Autonomous cortisol secretion (ACS) is not uncommon in patients with primary aldosteronism (PA). However, the cardiovascular burden of ACS due to its dysregulated cortisol secretion remains poorly understood. Thus, we examined the effects of ACS on vascular calcification in a hyperaldosteronism environment in vitro and in vivo. A total of 339 patients with PA with adrenal incidentaloma and low-dose dexamethasone suppression test data (cutoff level: cortisol > 1.8 μg/dL) from a prospectively maintained database were enrolled; abdominal aortic calcification (AAC) scores were quantitatively estimated. Human aortic smooth muscle cells (HAOSMCs) were used as in vitro model of vascular calcification. In this study, 65 of the 339 patients with PA had ACS; 274 did not. Patients with PA/ACS had a higher AAC score (1171.0 ± 2434.0 vs. 489.5 ± 1085.3, P = 0.012) than patients without ACS. ACS was independently associated with AAC score (β = 0.139, P = 0.004) in multivariate analysis, and post-suppression cortisol level was significantly correlated with the AAC score (P = 0.004). In the HAOSMC model, co-treatment with cortisol synergistically stimulated alkaline phosphatase activity and calcium deposition in a hyperaldosteronism environment. The stimulatory effect of cortisol was abolished by the mineralocorticoid receptor (MR) antagonist eplerenone, but not glucocorticoid receptor antagonist mifepristone, indicating a MR-dependent mechanism. In conclusion, the presence of ACS is associated with heavier vascular calcification in patients with PA. Aldosterone and cortisol synergistically activate HAOSMC calcification via MR signaling, via a process that can be attenuated by eplerenone.

Correlation between circulating dephosphorylated uncarboxylated matrix Gla protein and vascular calcification in peritoneal dialysis patients.

To explore the association between serum Dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP) and abdominal aortic calcification (AAC) in peritoneal dialysis (PD) patients. A total 128 PD patients and 120 healthy controls were enrolled into the study. Serum dp-ucMGP was measured by enzyme-linked immunosorbent assay. Abdominal lateral plain radiography was used to evaluate the abdominal aortic calcification score (AACS). PD patients were divided into two groups according to the presence or absence of AAC. The relationships between dp-ucMGP levels and AACS were assessed by Spearman analysis and the value of dp-ucMGP in predicting AAC was evaluated by receiver operating characteristic (ROC). Serum dp-ucMGP in PD patients were significantly higher than controls (p < 0.05). And PD patients with AAC had higher serum dp-ucMGP than that of PD patients without AAC (p < 0.05). The serum dp-ucMGP levels was positively associated with AACS (r = 0.794, p < 0.0001) in PD patients. The multivariate logistic regression analyses showed that serum dp-ucMGP was independent factors of AAC in PD patients (OR = 2.555, 95% CI = 1.415-4.609). The area under ROC curve of dp-ucMGP was 0.9227, the corresponding sensitivity was 0.86, and the specificity was 0.92. Serum dp-ucMGP levels were positively associated with the AACS in PD patients. Higher serum dp-ucMGP level is independently associated with AAC in PD patients.

A novel marker of cardiovascular risk stratification: the role of total cardiovascular calcium score using cardiac CT

Abstract Introduction It is widely accepted that coronary and valve calcification measured by cardiac CT, individually, are associated with cardiovascular events and mortality. However, the role of an encompassing marker of cardiovascular atherosclerosis could be more representative of the real cardiovascular risk. Objectives To determine the prognostic value of a combined coronary, valvular and aortic calcium score to predict long-term major adverse cardiac and cerebrovascular events (MACCE). Methods We conducted a single center study on 316 consecutive patients who underwent cardiac CT scan between January 2018 and December 2019. We excluded patients with poor imaging quality, constrictive pericarditis, prosthetic valves and/or devices. The calcium score of coronary arteries (CA), mitral valve (MV), aortic valve (AoV), ascending aorta (AAo) and aortic arch (AAc) were calculated from non-contrast ECG-gated CT using the Agatston method and were combined to derive a valvular (VA=MV+AoV), total cardiac (TC=CA+VA) and total cardiovascular (TCV=TC+AAo+AAc) calcium scores (Fig.1A). The primary endpoint was a composite of MACCE, defined as all-cause death, stroke, myocardial infarction and hospital admission for heart failure. Results A total of 275 CT scans were suitable for analysis. Mean age was 59.6±12.3 years, 48.4% were female. A total of 183 (66.7%) patients presented calcification in at least one location. Patients with calcification on any of the prespecified locations had higher prevalence of hypertension, dyslipidemia and type 2 diabetes mellitus (DM) than those without any calcium (p&amp;lt;0.05). After a median follow-up of 3.18 [IQR 2.84-3.69] years, 40 (14.5%) patients had met the primary endpoint. Regression analyses demonstrated that all CA, VA, TC and TCV scores were independent predictors of MACCE (p&amp;lt;0.05 for all). The best prediction models included calcium score (all combinations), age, sex, type 2 DM and smoking status (Fig.1B). The model with TCV score was the most powerful predictor of MACCE (χ2 47.8), followed by TC score (χ2 43.1). Of interest, the model with CA score had the poorest performance (χ2 35.4). Conclusion Coronary calcium score is a quick way to stratify risk in clinical practice, but its performance is too focused on coronary events. Total cardiovascular calcium score, however, is more encompassing, also quick to measure, and a more truthful depiction of the patient’s cardiac and cerebrovascular risk, potentially allowing a more tailored and timely approach to risk factors in clinical practice.

Effect of Denosumab or Alendronate on Vascular Calcification: Secondary Analysis of SALTIRE2 Randomized Controlled Trial.

Patients with osteoporosis demonstrate increased vascular calcification but the effect of osteoporosis treatments on vascular calcification remains unclear. The present study aimed to examine whether coronary or aortic calcification are influenced by denosumab and alendronic acid treatment. In a double-blind randomized controlled SALTIRE2 (Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis) trial, patients with aortic stenosis were randomized 2:1:2:1 to denosumab, placebo injection, alendronic acid, or placebo capsule. Participants underwent serial imaging with computed tomography and 18F-sodium fluoride positron emission tomography for the assessment of vascular calcium burden and calcification activity, respectively. We report the prespecified secondary analyses of 24-month change in coronary calcium score, and 12-month changes in thoracic aorta calcium score, coronary and aortic 18F-sodium fluoride activity. One hundred fifty patients with aortic stenosis (72±8 years; 21% female) were randomized to denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25). There were no differences in change in coronary calcium scores between placebo (16 [-64 to 148] Agatston units) and either denosumab (94 [0-212] Agatston units, P=0.24) or alendronic acid (34 [-62 to 134], P=0.99). There were no differences in change in thoracic aorta calcium scores between placebo (132 [22-512] Agatston units) and either denosumab (118 [11-340], P=0.75) or alendronic acid (116 [26-498] Agatston units, P=0.62). There were no differences in changes in coronary or aortic 18F-sodium fluoride activity between treatment groups. Neither alendronic acid nor denosumab are associated with changes in the activity or progression of coronary or aortic calcification. Osteoporosis treatments do not appear to have major impact on vascular calcification of atherosclerosis. https://www.clinicaltrials.gov; Unique identifier: NCT02132026.

Effects of intravenous sodium thiosulfate on vascular calcification in dialysis patients with end-stage renal disease: a systematic review and meta-analysis.

In dialysis patients, vascular calcification is a common complication and is closely related to the morbidity and mortality of cardiovascular disease. We performed a systematic review to determine the efficacy and safety of sodium thiosulfate (STS) in the progression of vascular calcification in dialysis patients with end-stage renal disease. The PubMed, Web of Science, Embase, Cochrane Library, Wanfang, CNKI, China Biology Medicine disc and Weipu databases were searched up to 9 March 2022 for clinical trials to synthesise findings on the efficacy and safety of STS in the progression of vascular calcification in dialysis patients. The primary outcome was coronary artery calcification scores (CACS) or abdominal aortic calcification scores (AACS) or Kauppila index. The secondary outcome was pulse-wave velocity (PWV). Laboratory data were shown in safety data. A random-effect model was used to provide the summary measures of effect [standardised mean difference (SMD) and 95% confidence interval (CI)]. Seven randomised, controlled trials and one nonrandomised, controlled trial involving 370 patients were included. Six studies reported that the progression of CACS or AACS was slower in the intravenous STS group compared with the control group (SMD -3.24, 95% CI: -5.29, -1.18, p = 0.002). Two studies showed the increase in PWV was less in the STS group compared with the control group (SMD -0.52, 95% CI: -0.92, -0.13, p = 0.009). During the trial period, a lower high-sensitivity C-reactive protein level (SMD 1.61, 95% CI: 0.19, 3.04, p = 0.03), a decrease in serum bicarbonate level (SMD 0.67, 95% CI: 0.22, 1.11, p = 0.003) and an increase in serum phosphate level (SMD -0.32, 95% CI: -0.62, -0.03, p = 0.03) were noted in the intravenous STS group compared with the control group. However, serum calcium and parathyroid hormone levels showed no difference between the two groups after the trials. The most common adverse events were temporary nausea and vomiting, which occurred in 12.5 to 75% of patients. Intravenous STS may slow down the progression of vascular calcification and ameliorate arterial stiffness in dialysis patients. Reliably defining the efficacy and safety of intravenous STS in attenuating the progression of vascular calcification requires a high-quality trial with a large sample size.

Cardiac Biomarkers are Associated with Incident Fracture Risk in Advanced Chronic Kidney Disease

Cardiovascular disease is associated with increased fracture risk in the general population. Few data exist on the association between cardiovascular health and incident fracture risk in patients with advanced CKD, a high-risk population for fractures. We aimed to assess the link between fracture risk and cardiovascular health in a prospective cohort of 210 patients with CKD stage G4–5. Incident fractures were recorded during a prospective follow-up of 5 years. Laboratory parameters, abdominal aortic calcification score, echocardiography, ultrasound assessment of brachial artery flow-mediated dilatation and carotid intima-media thickness, and maximal stress ergometry were obtained at baseline. A total of 51 fractures were observed in 40 (19%) patients during follow-up. In separate multivariable Cox proportional hazards models adjusted for age, gender, and baseline eGFR, TnT (HR 1.007, CI 95% 1.003–1.010, p < 0.001) and ProBNP (HR 1.000, CI 95% 1.000–1.000, p = 0.017) were associated with incident fractures and the association persisted after adjusting for coronary artery disease (CAD). The patients unable to perform the ergometry test had a higher risk of incident fractures compared to others (36.1% vs 15.5%, p = 0.009). A cardiovascular composite risk score summarizing TnT, ProBNP, and ergometry data was independently associated with incident fractures in a multivariable Cox model (HR 1.373, CI 95% 1.180–1.599, p < 0.001). Patients with the lowest score were observed with no fractures, while patients with the highest score were observed with a fracture risk of 40.5% during follow-up. Risk of incident fractures is associated with biomarkers of cardiovascular health and a composite cardiovascular risk score in patients with advanced CKD.

Association Of Manually Derived Aortic Calcium Scores With Cardiovascular Outcomes In Core320 Patients

Association Of Manually Derived Aortic Calcium Scores With Cardiovascular Outcomes In Core320 Patients

The significance of serum SLC7A11 levels in the occurrence of vascular calcification in maintenance peritoneal dialysis patients.

This research aimed to explore the serum levels of solute carrier family 7 member 11 (SLC7A11) in patients with maintenance peritoneal dialysis (MPD) and its correlation with vascular calcification (VC) and clinical results. This present prospective observational cohort study enrolled 189 patients with MPD who were undergoing regular peritoneal dialysis for over 3 months in our hospital from February 2020 to July 2022. The abdominal aortic calcification score was used to assess the VC condition of MPD patients. The serum SLC7A11, interleukin (IL)-6, IL-1β and C-reactive protein levels were measured by enzyme-linked immunosorbent assay (ELISA). Demographic and clinical statistics were collected. All patients were followed up for 1 year and the overall survival time (OS) of all patients were recorded. All data used SPSS 18.0 for statistical analyses. Patients with moderate/severe calcification in MPD had a longer duration of dialysis, higher serum levels of phosphate (P) and calcium (Ca) and lower serum levels of SLC7A11. Spearman's analysis revealed a negative correlation between serum SLC7A11 levels and the levels of P, Ca and IL-1β. Additionally, we observed an association between serum SLC7A11 levels and clinical prognosis as well as the extent of VC in MPD patients. Multivariate logistic regression analysis indicated that dialysis duration, SLC7A11, and P were risk factors for VC in MPD patients. The serum SLC7A11 levels decreased remarkably in MPD patients with moderate/severe calcification. This study may provide new targets and comprehensive approach to cardiovascular protection in patients with chronic kidney disease.

#2610 Low skeletal muscle mass and low skeletal muscle quality are associated with thoracic aorta calcification in dialysis patients

Abstract Background and Aims Cardiovascular disease (CVD) is the leading cause of mortality in dialysis patients. Thoracic aorta calcification (TAC) is a common cardiovascular complication in dialysis patients and is independently associated with CVD. Sarcopenia, particularly low skeletal muscle mass, has been found to be associated with increased cardiovascular risk in dialysis patients. This study aims to explore the relationship between skeletal muscle quality and skeletal muscle mass at the first lumbar vertebra (L1) level determined by opportunistic CT scans (chest CT) and TAC, with the goal of providing valuable opportunities for identifying and intervening in high-risk CVD patients. Method We included 2514 patients for cross-sectional analysis, who underwent dialysis in four centers in China from 2020 to 2023 and all had chest CT scans including the L1 level. Additionally, we conducted a follow-up study on TAC in patients who initiated dialysis between 2014 and 2019 as part of the earlier research, including 215 patients who had undergone at least two chest CT scans for cohort analysis. At the L1 level, we assessed skeletal muscle quality [by skeletal muscle density (SMD), HU] and skeletal muscle mass [by skeletal muscle index (SMI), cm2/m2] in dialysis patients. Measurements of thoracic aorta calcification scores (TACS) and calcification scores for three segments of the thoracic aorta, including ascending aorta calcification score (ATACS), aortic arch calcification score (AoACS), and descending thoracic aorta calcification score (DTACS), were obtained in dialysis patients. Patients were divided based on their annual calcification score growth rate: those with a rate greater than or equal to the average annual increase were classified into the rapid progression group, while those with a rate less than the average were classified into the slow progression group (including those with no progression). Multivariable linear regression models were employed to assess the relationships between SMI and SMD with TACS. Multivariable logistic regression models were used to evaluate the associations of SMl and SMD with the risk of rapid progression of TACS. Results The mean (SD) age of participants was 56 (15) years, with 58.2% being male. The prevalence of TAC was 82.2%, while the prevalence of ascending thoracic aorta calcification (ATAC), aortic arch calcification (AoAC), and descending thoracic aorta calcification (DTAC) was 21.4%, 75.3%, and 68.8%, respectively. Over an average follow-up period of 3.22 years, the progression rate of TAC was 85.6%. Comparing the highest quartile of SMD to the lowest quartile, a significant inverse association was observed with TAC (beta −1.19, 95% CI −1.55— −0.83; P &amp;lt; 0.001). Similarly, comparing the highest quartile of SMI to the lowest quartile, a significant inverse association was found with TAC (beta −0.59, 95% CI −0.92— −0.26; P = 0.001). SMI and SMD, as continuous variables, were both significantly negatively correlated with TAC. Higher SMD was associated with a reduced risk of rapid progression of TAC; after full adjustment, for every 1 SD increase in SMD, the risk of TAC rapid progression decreased by 46% (aOR 0.54, 95% CI 0.32—0.91; P = 0.021). SMI showed no significant association with the rapid progression of TAC. The associations of SMI and SMD with AoAC and DTAC were consistent with their associations with TAC, except for ATAC. The ROC curve analysis indicated that incorporating SMD into the model enhanced the discriminative ability for stratifying the risk of rapid progression of thoracic aorta calcification. Conclusion After adjusting for cardiovascular risk factors and inflammatory markers, higher skeletal muscle quality and higher skeletal muscle mass were significantly associated with lower TAC. Improving skeletal muscle quality in initial dialysis patients may reduce the risk of rapid TAC progression.

#2382 Renal tubule-derived EVs carrying complement 3 aggravate CKD vascular calcification by downregulating autophagy in vascular smooth muscle cells

Abstract Background and Aims Vascular calcification (VC) is a serious complication of chronic kidney disease (CKD) patients, recognized in KDIGO guidelines as a leading risk factor for cardiovascular diseases. Despite acknowledgment, the mechanisms of VC in CKD remain unclear. The kidneys intricately regulate blood vessel pathophysiology. Clinical studies suggest a correlation between elevated blood complement levels in CKD and arterial calcification, hinting at complement involvement in CKD-associated VC. Renal-origin complement, a significant source of circulating complement, activates in CKD. Extracellular vesicles (EVs), mediating intercellular communication, transport complement-related proteins in various physiological and pathological processes. Studies suggest that plasma EV rather than EV-depleted plasma causes pathogenic calcium salt deposition in smooth muscle cells. This study explores how renal-origin EVs carrying complement mediate CKD-associated VC. Method From October 2021 to August 2023, data from 110 clinical patients were gathered, encompassing both blood C3 levels and CT images of the thoracic aorta. Subsequently, we conducted a scoring analysis of the CT images and carried out correlation analyses. A CKD-associated VC model was induced by feeding C57BL/6j mice an adenine and high-phosphate diet for 16 weeks. Techniques, including WB, PCR, and immunofluorescence, detected complement activation and localization in renal tissues. EVs were isolated from kidney tissue and plasma and identified by NTA, electron microscopy, WB, etc. WB examined C3 and tubular markers of EVs. At the same time, the Elisa method was used to detect C3 in plasma, plasma EV, and EV-depleted plasma. Immunofluorescence investigated tubular-derived EVs uptake in calcified arteries. Tubular-derived EVs, C3a, C3aR receptor inhibitors (SB290157), and autophagy inhibitors (3-MA) intervened in high-phosphate-induced vascular smooth muscle cells (VSMCs). PCR and WB assessed calcification indicators, complement receptors, and autophagy-related indicators. Alizarin Red staining observed calcification nodules. Transcriptome sequencing was performed on control, high-phosphate, and renal tubular-derived EV intervention groups of VSMCs. An in vivo model infused renal tubular-derived EVs and injected C3aR inhibitors and autophagy inhibitors, measuring complement activation and VC indicators. Results There is a correlation between C3 and thoracic aorta calcium score in CKD patients, with a correlation coefficient of 0.3750 (P &amp;lt; 0.01). The CKD-associated VC mice model revealed complement C3 activation in renal tubules, secreted into the blood through EVs. The C3 proportion of plasma EV in CKD patients was significantly higher than that in the control group, but there was no statistical difference between the EV-depleted plasma control group and the CKD group. Immunofluorescence indicated tubular-derived EV uptake by the calcified vascular wall. In vitro, tubular-derived EVs enhanced VSMC osteogenic differentiation and upregulated C3aR, mimicking C3a intervention effects. C3aR receptor inhibitors produced opposing effects. Transcriptome sequencing suggested renal tubular-derived EVs downregulated VSMC autophagy-related pathways; in vitro autophagy inhibition reversed osteogenic differentiation. In vivo, reinfusing renal tubular-derived EVs exacerbated complement activation and VC, while injecting C3aR inhibitors and autophagy inhibitors alleviated CKD-associated VC. Conclusion This study confirms that tubular-derived EVs carrying C3 downregulate autophagy in VSMCs, mediating CKD-associated VC. These findings provide insights into understanding CKD-associated VC initiation and progression, revealing potential therapeutic targets.

Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway

ABSTRACT Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.

Independent Associations of Aortic Calcification with Cirrhosis and Liver Related Mortality in Veterans with Chronic Liver Disease

IntroductionAbdominal aortic calcifications (AAC) are incidentally found on medical imaging and useful cardiovascular burden approximations. The Morphomic Aortic Calcification Score (MAC) leverages automated deep learning methods to quantify and score AACs. While associations of AAC and non-alcoholic fatty liver disease (NAFLD) have been described, relationships of AAC with other liver diseases and clinical outcome are sparse. This study’s purpose was to evaluate AAC and liver-related death in a cohort of Veterans with chronic liver disease (CLD).MethodsWe utilized the VISN 10 CLD cohort, a regional cohort of Veterans with the three forms of CLD: NAFLD, hepatitis C (HCV), alcohol-associated (ETOH), seen between 2008 and 2014, with abdominal CT scans (n = 3604). Associations between MAC and cirrhosis development, liver decompensation, liver-related death, and overall death were evaluated with Cox proportional hazard models.ResultsThe full cohort demonstrated strong associations of MAC and cirrhosis after adjustment: HR 2.13 (95% CI 1.63, 2.78), decompensation HR 2.19 (95% CI 1.60, 3.02), liver-related death HR 2.13 (95% CI 1.46, 3.11), and overall death HR 1.47 (95% CI 1.27, 1.71). These associations seemed to be driven by the non-NAFLD groups for decompensation and liver-related death [HR 2.80 (95% CI 1.52, 5.17; HR 2.34 (95% CI 1.14, 4.83), respectively].DiscussionMAC was strongly and independently associated with cirrhosis, liver decompensation, liver-related death, and overall death. Surprisingly, stratification results demonstrated comparable or stronger associations among those with non-NAFLD etiology. These findings suggest abdominal aortic calcification may predict liver disease severity and clinical outcomes in patients with CLD.

β,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, β,γ-methylene-ATP [β,γ-meATP]) inhibit vascular smooth muscle cell calcification in vitro. In the first experiment, daily dosing of β,γ-meATP (2mg/kg) was investigated in rats fed a warfarin diet to trigger the development of non-CKD-related arterial medial calcifications. This study showed that β,γ-meATP significantly lowered the calcium scores in the aorta and peripheral vessels in warfarin-exposed rats. In a second experiment, daily dosing of 4mg/kg β,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 β,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.

Impact of Arterial Calcification on Cardiovascular and Renal Outcomes in Kidney Transplant Patients

Plain Language SummaryArterial calcification, accumulation of calcium in the arterial walls, vascular stiffness, and loss of elasticity of blood vessels can contribute to the development of cardiovascular diseases. Patients with chronic kidney disease and those undergoing dialysis have a considerably increased risk of vascular calcification. Even after kidney transplantation when kidney function has been restored, the prevalence of vascular calcification and subsequent cardiovascular disease remains high. Coronary artery calcification score and abdominal aortic calcification score are both well-established markers of vascular calcification. However, the impact of pretransplant vascular calcification scores on cardiovascular and renal outcomes in kidney transplant patients has not been established. When we analyzed 944 Korean kidney transplant patients, both vascular calcification scores were significantly associated with cardiovascular outcomes after kidney transplantation, but were not associated with renal outcomes. We also demonstrated that the addition of coronary artery calcification scores led to a modest improvement in the prediction performance for kidney transplant outcomes. Our findings suggest a potential role of pretransplant screening of coronary calcification scores and aortic calcification scores in risk stratification for post-kidney transplant outcomes.

Myosteatosis and aortic calcium score on abdominal CT as prognostic markers in non-dialysis chronic kidney disease patients

We aimed to examine the relationship between abdominal computed tomography (CT)-based body composition data and both renal function decline and all-cause mortality in patients with non-dialysis chronic kidney disease (CKD). This retrospective study comprised non-dialysis CKD patients who underwent consecutive unenhanced abdominal CT between January 2010 and December 2011. CT-based body composition was measured using semiautomated method that included visceral fat, subcutaneous fat, skeletal muscle area and density, and abdominal aortic calcium score (AAS). Sarcopenia and myosteatosis were defined by decreased skeletal muscle index (SMI) and decreased skeletal muscle density, respectively, each with specific cutoffs. Risk factors for CKD progression and survival were identified using logistic regression and Cox proportional hazard regression models. Survival between groups based on myosteatosis and AAS was compared using the Kaplan–Meier curve. 149 patients (median age: 70 years) were included; 79 (53.0%) patients had sarcopenia and 112 (75.2%) had myosteatosis. The median AAS was 560.9 (interquartile range: 55.7–1478.3)/m2. The prognostic factors for CKD progression were myosteatosis [odds ratio (OR) = 4.31, p = 0.013] and high AAS (OR = 1.03, p = 0.001). Skeletal muscle density [hazard ratio (HR) = 0.93, p = 0.004] or myosteatosis (HR = 4.87, p = 0.032) and high AAS (HR = 1.02, p = 0.001) were independent factors for poor survival outcomes. The presence of myosteatosis and the high burden of aortic calcium were significant factors for CKD progression and survival in patients with non-dialysis CKD.

Circulatory endostatin level and risk of cardiovascular events in patients with end-stage renal disease on hemodialysis.

Endostatin is released during extracellular matrix remodeling and is involved in the development of vascular pathology and cardiovascular (CV) disease. However, the role of circulating endostatin as a biomarker of vascular calcification and CV events in patients undergoing hemodialysis (HD) remains unclear. A total of 372 patients undergoing HD were prospectively recruited. Plasma endostatin levels were measured at baseline, and their associations with circulating mineral bone disease (MBD) biomarkers and abdominal aortic vascular calcification scores were analyzed. The primary endpoint was defined as a composite of CV and cardiac events. Plasma levels of patients in endostatin tertile 3 were significantly associated with low-density lipoprotein cholesterol levels and predialysis systolic blood pressure in multivariate analysis. However, endostatin levels did not correlate with circulating MBD biomarkers or vascular calcification scores. Patients in endostatin tertile 3 had a significantly higher cumulative event rate for the composite of CV events (p = 0.006). Endostatin tertile 3 was also associated with an increased cumulative rate of cardiac events (p = 0.04). In multivariate Cox regression analyses, endostatin tertile 3 was associated with a 4.37-fold risk for composite CV events and a 3.88-fold risk for cardiac events after adjusting for multiple variables. Higher circulating endostatin levels were independently associated with atherosclerotic risk factors but did not correlate with MBD markers or vascular calcification. Higher circulating endostatin levels were associated with a greater risk of composite CV events in patients undergoing HD, and endostatin is a biomarker that helps to determine the high risk of CV events.

Predictive factors of thoracic aortic calcification in patients candidate for cardiac surgery

BackgroundThe presence of the severe thoracic aortic calcification (TAC) in cardiac surgery patients is associated with adverse post-operative outcome. However, the relationship between cardiovascular risk factors and aortic plaque burden remains unknown. The objective of this study was to determine the predictive factors of TAC in patients candidate for cardiac surgery.MethodsPatients who underwent thoracic CT scan prior to cardiac surgery between August 2020 to April 2021 were included. Of 556 patients, 209 (36.7%) had a thoracic aortic calcium score (TACS) ≥ 400 mm [3] and were compare with the remaining patients. Predictors of severe TAC were assessed through stepwise multivariable logistic regression analysis.ResultsThe patients with TACS ≥ 400 had a higher mean age (67.3 ± 7.1 vs. 55.7 ± 10.6; p < 0.001) with a higher frequency of diabetes mellitus (40.7% vs. 30.8%; p = 0.018), dyslipidemia (49.8% vs. 38.6%; p = 0.010), hypertension (60.8% vs. 44.7%; p < 0.001), opium addiction (18.2% vs. 11.2%; p = 0.023), peripheral vascular disease (PVD) (7.7% vs. 2.3%; p = 0.005) as compared with TACS < 400. The multiple determinants of TAC were PVD (OR = 2.86) followed by opium addiction, diabetes and age.ConclusionsThoracic CT scan prior to cardiac surgery for patients with older age, diabetes, opium addiction and PVD is recommended. Our study could serve as a foundation for future research endeavors aimed at establishing a risk score for TAC.

Abstract 41: Independent Prediction of Mortality From Opportunistic Screening of Aortic Calcification

Introduction: Abdominal aortic calcifications (AAC), often discovered during diagnostic medical imaging, have recently gained traction as valuable indicators of cardiovascular health. The morphomic aortic calcification score (MAC) uses dynamic thresholding and machine learning algorithms to automatically segment, process, and grade AAC from medical imaging. This study’s purpose was to evaluate AAC and mortality in patients over the age of 65 with previous diagnostic imaging. Methods: A novel community sample of 6655 participants had received an abdominal CT scan between 1999-2022 at Michigan Medicine. Participants were 65 years or older and without diagnosed cardiovascular disease at scan time. MAC threshold of 4.21% abdominal aortic wall coverage at the L3 level was used to prioritize sensitivity. Cox models were used to evaluate the associations between MAC and mortality. Model 1 was unadjusted; model 2 controlled for diabetes, subcutaneous-visceral fat ratio, and biological sex; model 3 added age. Effect modification was evaluated between MAC and age, as well as MAC and sex. Results: Mean follow up time was 3,916 (sd 1661) days. From the initial scan, 1306 deaths were observed at 10 years (19.62%), and 2277 deaths overall (34.21%). The proportional hazard assumption held. Models indicated significant hazard ratios for MAC and mortality: model 1 (unadjusted) HR 1.36 (95% CI 1.23, 1.50); model 2 (adjusted) HR 1.28 (1.14, 1.44); model 3 (model 2 + age) HR 1.15 (95% CI 1.03, 1.31). No effect modification was observed between MAC and age or sex. Discussion: MAC, a novel measure of abdominal aortic calcification, was independently associated with mortality in a hospital-based community sample of patients over the age of 65. Interestingly, the addition of age attenuated the MAC-mortality relationship, but significance remained. This work highlights the independent effects of abdominal aortic calcification and potential utility as a factor of future mortality in opportunistic screening of asymptomatic populations.

YKL-40 (chitinase-3-like protein 1) serum levels are associated with abdominal aortic calcification in hemodialysis patients.

Vascular calcification (VC) is highly prevalent and predicts cardiovascular mortality in dialysis patients. The mechanisms are still unclear. Inflammation is a well-known inducer of VC. YKL-40 has been suggested as a novel biomarker of inflammation and has been demonstrated to be associated with cardiovascular mortality in hemodialysis patients. This study aims to evaluate the relationship between serum YKL-40 and VC in hemodialysis (HD) patients. A total of 109 HD patients and 31 healthy controls were enrolled in the study from September 2014 to December 2014. We evaluated the abdominal aortic calcification (AAC) score by plain X-ray films of the abdomen and measured serum YKL-40 concentrations using enzyme-linked immunosorbent assay. We also examined the relationship between YKL-40 levels and AAC scores in HD patients. Serum YKL-40 levels in HD patients were significantly higher than those in healthy controls [199.8 (144.8, 288.7) vs. 71.9 (52.8, 89.3)ng/ml; P < 0.001]. There was a tendency that YKL-40 levels in diabetic hemodialysis patients were higher than those in nondiabetic patients [217.8 (155.3, 335.8) vs. 192.9 (135.9, 274.4)ng/ml; P = 0.093]. A significant positive correlation was found between serum YKL-40 level and AAC score in these patients (r = 0.410, P = 0.003). Multiple regression analysis showed that Ln(YKL-40) was independently associated with AAC score in HD patients (P = 0.044). This study showed high serum YKL-40 concentrations in chronic HD patients and that YKL-40 was independently associated with increased AAC in hemodialysis patients.