The association between serum soluble klotho levels and abdominal aorta calcification in older adults.

BACKGROUND: The mutation of the mouse klotho gene leads to a syndrome resembling aging including calcification of the aorta. OBJECTIVE: To examine the relationship between serum soluble klotho levels and abdominal aorta calcification (AAC) in subjects aged 60-79 years. METHODS: The National Health and Nutrition Examination Survey data were analyzed using logistic regression models to examine the independent association between soluble klotho tertile levels and the Kauppila AAC-24 score. RESULTS: A total of 1042 participants with a median klotho level of 796 pg/ml comprised the study sample. Overall, the prevalence of AAC was 39.2% and severe AAC was seen in 15.6% subjects. Participants with klotho levels ≤ 700 pg/ml were twice as likely (OR 2.21 (95% CI 1.15-4.26) to have severe AAC than their counterparts with klotho levels ≥ 906 pg/ml. CONCLUSIONS: Soluble klotho levels were inversely associated with severe AAC in older adults.

Study on the Prevalence of Vascular Calcification in Different Types of Arteries and Influencing Factors in Maintenance Peritoneal Dialysis Patients.

OBJECTIVE: To investigate the occurrence of vascular calcification (VC) in different types of arteries in patients with maintenance peritoneal dialysis (PD) patients and its influencing factors. METHODS: This study enrolled PD patients with stable status who has received PD treatment for more than 6 months in Peking University People's Hospital. We used plain X-ray films of abdomen, pelvis, and hands to quantitatively evaluate VC of large artery (abdominal aorta, iliac artery), medium artery (femoral artery, radial artery), and small artery (finger arteries). Two radiologists read and scored radiographs blindly. Demographic data, clinical characteristics, Charlson comorbidity index (CCI), baseline and time-average laboratory indices including parameters of calcium phosphorus metabolism, serum albumin, PD adequacy were collected. A logistic regression model was used to estimate the influencing factors of different sites of VC. RESULTS: (1) 154 PD patients were enrolled in this study: seventy-eight males, mean age was 60.4 ± 13.9 years, and median PD duration was 24 (16.39) months. The major primary disease was diabetic nephropathy (39%). (2) Among the 154 PD patients, the proportion of calcification of large artery was the highest (found in 100 patients, accounting for 64.9%); then the medium artery (66, 42.9%); and 15 of small artery, accounting for 9.7%. (3) Logistic regression showed that older age, longer dialysis duration, lower baseline serum intact parathyroid hormone (iPTH), and higher CCI scores were independent risk factors of large artery calcification (p < 0.05), and higher CCI scores, higher baseline serum triglycerides (TG), lower baseline serum iPTH, and time-average iPTH were independent risk factors of medium and small arteries. CONCLUSIONS: In PD patients, the occurrence of large artery calcification was higher than others. Among different sites of VC, the abdominal aortic calcification was most likely to occur, and the proportion of small artery calcification was low. Calcification of medium and small arteries can exist alone without calcification of large artery. Large artery calcification was more likely to occur in patients with older age, longer dialysis duration, lower baseline serum iPTH levels and higher CCI scores. Patients with higher CCI scores, higher baseline TG and lower baseline iPTH, and time-average iPTH were more likely to develop small and medium artery calcification.

Abdominal Aorta Calcification Identified on DXA Scans and the Risk of Mortality in Adults.

BACKGROUND: Abdominal aortic calcification (AAC) on lateral lumbar radiographs increases the risk of cardiovascular events and mortality. However, data on the association between AAC detected in dual energy X-ray absorptiometry (DXA) and the risk of mortality in the general population are scarce. METHODS: The present study was based on data from participants aged ≥40 years in the National Health and Nutrition Examination Survey (NHANES) cycle of 2013 to 2014. Vertebral assessment of lateral spine DXA scans was used to provide AAC measurements at vertebrae L1-L4. The extent of AAC was defined according to the Kauppila AAC-24 scores (0-1, 2-5, ≥6), and the NHANES 2019 public-use linked mortality files were used to assess mortality status. RESULTS: Of the 2,962 participants who were included in this study, with a mean age of 57.4 years and a median follow-up of 69.9 months, 252 (8.5%) died. Of the deaths, 84 (33.3%) occurred due to cardiovascular disease. The Cox proportional hazards models revealed that participants with AAC-24 scores ≥6 were 1.7 times more likely to die than those with AAC-24 scores 0-1 (Hazard ratio, 1.75; 95% confidence interval, 1.13-2.71). Moreover, older adults and women with AAC-24 scores ≥6 were 2.8 and 2.4 times more likely to die than their counterparts with AAC-24 scores 0-1, respectively. Conversely, a non-significant risk of cardiovascular mortality was found among participants with AAC-24 scores ≥6. CONCLUSIONS: The extent of AAC detected on vertebral fracture assessment DXA was associated with an increased risk of all-cause mortality in adults, particularly older adults and women.

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.

Shockwave Lithotripsy of Calcific Stenosis of the Distal Abdominal Aorta to Facilitate Transcatheter Aortic Valve Replacement.

The transfemoral approach for transcatheter aortic valve replacement (TAVR) is superior to alternative access strategies. Only transfemoral access has been shown to have better clinical outcomes than surgical aortic valve replacement. In our patient, severe calcification of the distal abdominal aorta posed difficulty in using transfemoral access for TAVR. We applied intravascular lithotripsy (IVL) to the distal abdominal aorta to achieve necessary luminal gain facilitating bioprosthetic aortic valve deployment.

Cardiovascular parameters on computed tomography are independently associated with in-hospital complications and outcomes in level-1 trauma patients.

BACKGROUND: In-hospital complications after trauma may result in prolonged stays, higher costs, and adverse functional outcomes. Among reported risk factors for complications are pre-existing cardiopulmonary comorbidities. Objective and quick evaluation of cardiovascular risk would be beneficial for risk assessment in trauma patients. Studies in non-trauma patients suggested an independent association between cardiovascular abnormalities visible on routine computed tomography (CT) imaging and outcomes. However, whether this applies to trauma patients is unknown. PURPOSE: To assess the association between cardiopulmonary abnormalities visible on routine CT images and the development of in-hospital complications in patients in a level-1 trauma center. METHODS: All trauma patients aged 16 years or older with CT imaging of the abdomen, thorax, or spine and admitted to the UMC Utrecht in 2017 were included. Patients with an active infection upon admission or severe neurological trauma were excluded. Routine trauma CT images were analyzed for visible abnormalities: pulmonary emphysema, coronary artery calcifications, and abdominal aorta calcification severity. Drug-treated complications were scored. The discharge condition was measured on the Glasgow Outcome Scale. RESULTS: In total, 433 patients (median age 50 years, 67% male, 89% ASA 1-2) were analyzed. Median Injury Severity Score and Glasgow Coma Scale score were 9 and 15, respectively. Seventy-six patients suffered from at least one complication, mostly pneumonia (n = 39, 9%) or delirium (n = 19, 4%). Left main coronary artery calcification was independently associated with the development of any complication (OR 3.9, 95% CI 1.7-8.9). An increasing number of calcified coronary arteries showed a trend toward an association with complications (p = 0.07) and was significantly associated with an adverse discharge condition (p = 0.02). Pulmonary emphysema and aortic calcifications were not associated with complications. CONCLUSION: Coronary artery calcification, visible on routine CT imaging, is independently associated with in-hospital complications and an adverse discharge condition in level-1 trauma patients. The findings of this study may help to identify trauma patients quickly and objectively at risk for complications in an early stage without performing additional diagnostics or interventions.

Calcification of the abdominal aorta is an under-appreciated cardiovascular disease risk factor in the general population.

Calcification of large arteries is a high-risk factor in the development of cardiovascular diseases, however, due to the lack of routine monitoring, the pathology remains severely under-diagnosed and prevalence in the general population is not known. We have developed a set of machine learning methods to quantitate levels of abdominal aortic calcification (AAC) in the UK Biobank imaging cohort and carried out the largest to-date analysis of genetic, biochemical, and epidemiological risk factors associated with the pathology. In a genetic association study, we identified three novel loci associated with AAC (FGF9, NAV9, and APOE), and replicated a previously reported association at the TWIST1/HDAC9 locus. We find that AAC is a highly prevalent pathology, with ~ 1 in 10 adults above the age of 40 showing significant levels of hydroxyapatite build-up (Kauppila score > 3). Presentation of AAC was strongly predictive of future cardiovascular events including stenosis of precerebral arteries (HR~1.5), myocardial infarction (HR~1.3), ischemic heart disease (HR~1.3), as well as other diseases such as chronic obstructive pulmonary disease (HR~1.3). Significantly, we find that the risk for myocardial infarction from elevated AAC (HR ~1.4) was comparable to the risk of hypercholesterolemia (HR~1.4), yet most people who develop AAC are not hypercholesterolemic. Furthermore, the overwhelming majority (98%) of individuals who develop pathology do so in the absence of known pre-existing risk conditions such as chronic kidney disease and diabetes (0.6% and 2.7% respectively). Our findings indicate that despite the high cardiovascular risk, calcification of large arteries remains a largely under-diagnosed lethal condition, and there is a clear need for increased awareness and monitoring of the pathology in the general population.

Radiological Features for Frailty Assessment in Patients Requiring Emergency Laparotomy.

INTRODUCTION: As the number of elderly patients requiring surgical intervention rises, it is believed that frailty syndrome has a greater impact on perioperative course than on chronological age. The aim of this study was to evaluate the efficacy of various imaging features for frailty assessment in patients undergoing emergency laparotomy. METHODS: The study included all patients that qualified for emergency surgery with preoperative CT scans between 2016 and 2020 in the Second Department of General Surgery. Multiple trauma patients were excluded from the analysis. The modified frailty index and brief geriatric assessment were used in the analysis. CT images were reviewed for the assessment of osteopenia, sarcopenia, sarcopenic obesity, renal volume and abdominal aorta calcification rate. RESULTS: A total of 261 patients were included in the analysis. Multivariate logistic regression identified every next ASA class (OR: 4.161, 95%CI: 1.672-10.355, p = 0.002), intraoperative adverse events (OR: 12.397, 95%CI: 2.166-70.969, p = 0.005) and osteopenia (OR: 4.213, 95%CI: 1.235-14.367, p = 0.022) as a risk factor for 30-day mortality. Our study showed that every next ASA class (OR: 1.952, 95%Cl: 1.171-3.256, p = 0.010) and every point of the BGA score (OR: 1.496, 95%Cl: 1.110-2.016, p = 0.008) are risk factors for major complications. CONCLUSIONS: Osteopenia was the best parameter for perioperative mortality risk stratification in patients undergoing emergency surgical intervention. Sarcopenia (measured as psoas muscle area), sarcopenic obesity, aortic calcifications and mean kidney volume do not predict poor outcomes in those patients. None of the radiological markers appeared to be useful for the prediction of perioperative morbidity.

Abdominal aortic calcification: from ancient friend to modern foe.

BACKGROUND: Abdominal aortic calcifications were already ubiquitous in ancient populations from all continents. Although nowadays generally considered as an innocent end stage of stabilised atherosclerotic plaques, increasing evidence suggests that arterial calcifications contribute to cardiovascular risk. In this review we address abdominal aortic calcification from an evolutionary perspective and review the literature on histology, prevalence, risk factors, clinical outcomes and pharmacological interventions of abdominal aortic calcification. DESIGN: The design of this study was based on a literature review. METHODS: Pubmed and Embase were systematically searched for articles on abdominal aortic calcification and its synonyms without language restrictions. Articles with data on histology, prevalence, risk factors clinical outcomes and/or pharmacological interventions were selected. RESULTS: Abdominal aortic calcification is highly prevalent in the general population and prevalence and extent increase with age. Prevalence and risk factors differ between males and females and different ethnicities. Risk factors include traditional cardiovascular risk factors and decreased bone mineral density. Abdominal aortic calcification is shown to contribute to arterial stiffness and is a strong predictor of cardiovascular events and mortality. Several therapies to inhibit arterial calcification have been developed and investigated in small clinical trials. CONCLUSIONS: Abdominal aortic calcification is from all eras and increasingly acknowledged as an independent contributor to cardiovascular disease. Large studies with long follow-up must be carried out to show whether inhibition of abdominal aortic calcification will further reduce cardiovascular risk.

A Decreased Level of Soluble Klotho Can Predict Cardiovascular Death in No or Mild Abdominal Aortic Calcification Hemodialysis Patients.

Background: Soluble Klotho plays an important role in cardiovascular disease and death in chronic kidney disease (CKD). We assessed the relationship between serum soluble Klotho (sKL) level and outcome in MHD patients. Methods: Soluble Klotho was detected by ELISA. Cox regression analysis and Kaplan-Meier analysis showed the relationship between sKL and cardiovascular disease (CVD) mortality in maintenance hemodialysis (MHD) patients. Results: There were 45 cases (35.2%) of all-cause death and 36 cases (28.1%) of CVD mortality. Multivariate linear regression analysis showed that Log[iPTH] (γ = -0.224, P = 0.015) was an independent predictor of sKL level. Cox regression showed that lower sKL was associated with higher CVD mortality rate [OR = 0.401, 95% CI (0.183-0.867), P = 0.022]. Kaplan-Meier analysis showed that the CVD mortality rate increased significantly in patients with low sKL (P = 0.006). Compared with high sKL patients, low sKL patients with no or mild vascular calcification [aortic calcification score (AACs) ≤ 4] had no significant difference in all-cause mortality rate. The CVD mortality rate was significantly lower in high sKL patients (P = 0.004) than in those with low sKL. In the severe calcification group (AACs ≥ 5), all-cause and CVD mortality rates were similar between different sKL groups (P = 0.706 and 0.488, respectively). The area under the receiver-operating characteristic curve (AUC) of soluble Klotho for predicting the CVD in MHD patients with AACs ≤ 4 was 0.796 (0.647-0.946, P = 0.017), sensitivity was 0.921, and specificity was 0.50 for a cutoff value of 307.69 pg/ml. Conclusions: Lower sKL was associated with higher CVD mortality rate. Lower sKL concentration in MHD patients with no or mild calcification can predict CVD mortality.

Relationship between Smoking and Abdominal Aorta Calcification on Computed Tomography.

BACKGROUND: Cigarette smoking increases the risk of atherosclerosis, which often develops as vascular calcification on radiologic examinations. This study evaluated the relationship between smoking-related factors and incidental abdominal aorta calcification (AAC) detected by computed tomography (CT) among middle-aged and elderly men. METHODS: We assessed the abdominal CT findings of 218 men aged 40 to 81 years who underwent health checkups. The associations between smoking factors and AAC were analyzed using logistic regression analysis to adjust for confounding variables such as age, lifestyle factors, and chronic diseases. RESULTS: Adjusting for confounding variables, the risk of AAC was significantly increased in association with smoking for at least 20 years (adjusted odds ratio [AOR], 5.22; 95% confidence interval [CI], 1.82-14.93), smoking 10+ pack-years (10-20 pack-years: AOR, 4.54; 95% CI, 1.07-5.68; >20 pack-years: AOR, 5.28; 95% CI, 2.10-13.31), and a history of smoking (former smoker: AOR, 2.10; 95% CI, 1.07-5.68; current smoker: AOR, 5.05; 95% CI, 2.08-12.26). In terms of the daily smoking amount, even a low smoking level increased the risk of AAC. CONCLUSION: These findings suggest that smoking for 20+ years, smoking 10+ pack-years, and even a low level of smoking daily increases the likelihood of developing AAC. Clinicians should recommend that patients quit smoking and stress the importance of smoking duration when promoting health in middle-aged and elderly patients.

Fetuin-A and vascular calcification in Indian end-stage renal disease population.

Fetuin-A levels, its correlation with vascular calcification and other biochemical markers of chronic kidney disease-mineral and bone disorder (CKD-MBD) has not been studied in Indian end-stage renal disease population. Forty patients on dialysis for more than 3 months were studied. Biochemical parameters of CKD-MBD, highly sensitive-C reactive protein (hs-CRP), lipid profile and fetuin-A levels were estimated. Multi-slice computed tomography (MSCT) at the level of L1-L4 was done, and calcification score calculated using AJ 130 smart score. Levels of fetuin-A were correlated with calcification score and biochemical markers of CKD-MBD. Mean fetuin-A levels were 0.33 ± 0.098 g/l. Positive correlation of abdominal aortic calcification scores was found with age (P < 0.01) and duration of dialysis (P = 0.018). No correlation was detected between MSCT score, calcium phosphate product, intact parathyroid hormone, vitamin D, triglycerides and fetuin-A, and there was no correlation between fetuin-A levels, age, dialysis duration and calcium phosphate product but a significant correlations with vitamin D3 (P = 0.034), serum albumin (P = 0.002) was detected. Inverse correlation with hs-CRP was obtained. Patients with ischemic heart disease had numerically lower levels of fetuin-A (P = 0.427) and numerically higher MSCT score (P = 0.135). Patients with low hs-CRP (<10) had numerically higher fetuin-A levels (P = 0.090) and significantly low MSCT scores (P = 0.020). Calcium deposition seen on MSCT increases with age and duration of dialysis but is not related to fetuin-A levels. Inconclusive relationship exists with other parameters of CKD-MBD. Large controlled studies are needed to establish the role of fetuin-A in vascular calcification in Indian population.

Lifestyle-Related Diseases Affect Surgical Outcomes after Posterior Lumbar Interbody Fusion.

Study Design Retrospective study. Objective Hyperlipidemia (HL) and hypertension (HT) lead to systemic atherosclerosis. Not only atherosclerosis but also bone fragility and/or low bone mineral density result from diabetes mellitus (DM) and chronic kidney disease (CKD). The purpose of this study was to examine whether these lifestyle-related diseases affected surgical outcomes after posterior lumbar interbody fusion (PLIF). Methods The subjects comprised 122 consecutive patients who underwent single-level PLIF for degenerative lumbar spinal disorders. The clinical results were assessed using the Japanese Orthopaedic Association (JOA) score before surgery and at 2 years postoperatively. The fusion status was graded as union in situ, collapsed union, or nonunion at 2 years after surgery. The abdominal aorta calcification (AAC) score was assessed using preoperative lateral radiographs of the lumbar spine. Results HL did not significantly affect the JOA score recovery rate. On the other hand, HT and CKD (stage 3 to 4) had a significant adverse effect on the recovery rate. The recovery rate was also lower in the DM group than in the non-DM group, but the difference was not significant. The AAC score was negatively correlated with the JOA score recovery rate. The fusion status was not significantly affected by HL, HT, DM, or CKD; however, the AAC score was significantly higher in the collapsed union and nonunion group than in the union in situ group. Conclusions At 2 years after PLIF, the presence of HT, CKD, and AAC was associated with significantly worse clinical outcomes, and advanced AAC significantly affected fusion status.

Serum fetuin-A levels and abdominal aortic calcification in healthy men - The STRAMBO study.

Vascular calcification results from an imbalance between increased extracellular levels of calcium and phosphate, reduced solubility, and low levels of calcification inhibitors in blood or the vascular wall. Fetuin-A is a major circulating calcification inhibitor. Rodent models of fetuin-A deficit indicate its calcification inhibiting potential. Clinical studies suggest its role as a biomarker in vascular disease. This cross-sectional study was performed in a cohort of 974 men aged ≥ 40 years (average 68 years) consisting of men holding health insurance cover with Mutuelle des Travailleurs de la Région Lyonnaise. Abdominal aortic calcification (AAC) was assessed semi-quantitatively on lateral dual energy X-ray absorptiometry (DXA) spine scans. Serum fetuin-A was measured by an immunoassay. After adjustment for confounders (age, lifestyle, body composition, health status, treatment, glomerular filtration rate [GFR], hormones, and cytokines), prevalence of severe AAC (AAC score>4) decreased with increasing fetuin-A levels (OR=0.68 per SD increase, 95% CI: 0.54-0.84, p<0.001). After adjustment for confounders, low fetuin-A and hypertension were each associated with higher odds of AAC>4. Coexistence of low serum fetuin-A levels and heavy smoking, elevated fibroblast growth factor 23 levels or low serum dickkopf-1 levels were associated with higher odds of AAC>4. Similar results were obtained for 789 men with GFR>60 mL/min/1.73 m(2). Similar results were obtained when severe AAC was defined as AAC score >3 or AAC>5. Thus, lower serum fetuin-A levels are associated with severe AAC, suggesting that poor calcification inhibitory potential contributes to vascular calcification, independently of renal impairment.

Coronary and abdominal aorta calcification in rheumatoid arthritis: relationships with traditional cardiovascular risk factors, disease characteristics, and concomitant treatments.

OBJECTIVE: To assess the influence of traditional cardiovascular (CV) risk factors, disease characteristics, and concomitant treatments in patients with rheumatoid arthritis (RA) on coronary artery calcification (CAC) and abdominal aorta calcification (AAC). METHODS: In our cross-sectional study, 75 patients with RA were compared with 75 age-matched and sex-matched control participants. The CAC and AAC scores were measured by computed tomography in patients with no clinical evidence of coronary artery disease. The relationships between the presence or absence of CAC and AAC and traditional CV risk factors, disease characteristics, and concomitant treatments in patients with RA were assessed in a multiple logistic regression analysis. RESULTS: The RA and control groups did not differ significantly in terms of age, sex composition, or the prevalence of traditional CV risk factors. AAC and CAC were more prevalent and severe in patients with RA than in controls. Older age (OR=1.15, p<0.01) and hypertension (OR=3.77, p=0.04) were found to be independently associated with CAC, whereas current use of methotrexate (MTX; OR=0.12, p=0.01) was found to be associated with the absence of CAC. Older age (OR per yr=1.17, p<0.001) and erosive arthritis (OR=3.78, p=0.03) were found to be independently associated with AAC. CONCLUSION: Our study demonstrates that in patients with RA, (1) CAC and AAC are more prevalent and more severe compared with age-matched and sex-matched control participants, (2) current use of MTX is a major determinant of the absence of CAC, and (3) erosive arthritis is a major determinant of AAC.