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

INTRODUCTION: Abdominal 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). METHODS: We 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. RESULTS: The 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]. DISCUSSION: MAC 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.

Reference distributions of aortic calcification and association with Framingham risk score.

Evidence supporting aortic calcification as a leverageable cardiovascular risk factor is rapidly growing. Given aortic calcification's potential as a clinical correlate, we assessed granular vertebral-indexed calcification measurements of the abdominal aorta in a well curated reference population. We evaluated the relationship of aortic calcification measurements with Framingham risk scores. After exclusion, 4073 participants from the Reference Analytic Morphomic Population with varying vertebral levels were included. The percent of the aortic wall calcified was used to assess calcification burden at the L1-L4 levels. Descriptive statistics of participants, sex-specific vertebral indexed calcification measurements, relational plots, and relevant associations are reported. Mean aortic attenuation was higher in female than male participants. Overall, mean aortic calcium was higher with reference to inferior abdominal aortic measurements and demonstrated significant differences across all abdominal levels [L3 Area (mm[Formula: see text]): Females 6.34 (sd 16.60), Males 6.23 (sd 17.21); L3 Volume (mm[Formula: see text]): Females 178.90 (sd 474.19), Males 195.80 (sd 547.36); Wall Calcification (%): Females (L4) 6.97 (sd 16.03), Males (L3) 5.46 (13.80)]. Participants with elevated calcification had significantly higher Framingham risk scores compared to participants with normal calcification scores. Opportunistically measuring aortic calcification may inform further cardiovascular risk assessment and enhance cardiovascular event surveillance efforts.

Variation in aorta attenuation in contrast-enhanced CT and its implications for calcification thresholds.

BACKGROUND: CT contrast media improves vessel visualization but can also confound calcification measurements. We evaluated variance in aorta attenuation from varied contrast-enhancement scans, and quantified expected plaque detection errors when thresholding for calcification. METHODS: We measured aorta attenuation (AoHU) in central vessel regions from 10K abdominal CT scans and report AoHU relationships to contrast phase (non-contrast, arterial, venous, delayed), demographic variables (age, sex, weight), body location, and scan slice thickness. We also report expected plaque segmentation false-negative errors (plaque pixels misidentified as non-plaque pixels) and false-positive errors (vessel pixels falsely identified as plaque), comparing a uniform thresholding approach and a dynamic approach based on local mean/SD aorta attenuation. RESULTS: Females had higher AoHU than males in contrast-enhanced scans by 65/22/20 HU for arterial/venous/delayed phases (p < 0.001) but not in non-contrast scans (p > 0.05). Weight was negatively correlated with AoHU by 2.3HU/10kg but other predictors explained only small portions of intra-cohort variance (R2 < 0.1 in contrast-enhanced scans). Average AoHU differed by contrast phase, but considerable overlap was seen between distributions. Increasing uniform plaque thresholds from 130HU to 200HU/300HU/400HU produces respective false-negative plaque content losses of 35%/60%/75% from all scans with corresponding false-positive errors in arterial-phase scans of 95%/60%/15%. Dynamic segmentation at 3SD above mean AoHU reduces false-positive errors to 0.13% and false-negative errors to 8%, 25%, and 70% in delayed, venous, and arterial scans, respectively. CONCLUSION: CT contrast produces heterogeneous aortic enhancements not readily determined by demographic or scan protocol factors. Uniform CT thresholds for calcified plaques incur high rates of pixel classification errors in contrast-enhanced scans which can be minimized using dynamic thresholds based on local aorta attenuation. Care should be taken to address these errors and sex-based biases in baseline attenuation when designing automatic calcification detection algorithms intended for broad use in contrast-enhanced CTs.

A correction score to compare aortic calcification in contrast enhanced and non-contrast measurements from computed tomography scans.

BACKGROUND: Aortic wall calcification shows strong promise as a cardiovascular risk factor. While useful for visual enhancement of vascular tissue, enhancement creates heterogeneity between scans with and without contrast. We evaluated the relationship between aortic calcification in routine abdominal computed tomography scans (CT) with and without contrast. METHODS: Inclusion was limited to those with abdominal CT-scans with and without contrast enhancement within 120 days. Analytic Morphomics, a semi-automated computational image processing system, was used to provide standardized, granular, anatomically indexed measurements of aortic wall calcification from abdominal CT-scans. Aortic calcification area (ACA) and aortic wall calcification percent (ACP) and were the outcomes of interest. Multiple linear regression was used to evaluate the relationship of aortic measurements. Models were further controlled for age and sex. Stratification of measurements by vertebral level was also performed. RESULTS: A positive association was observed for non-contrast calcification in ACP ß 0.74 (95% CI 0.72, 0.76) and ACA ß 0.44 (95% 0.43, 0.45). Stratified results demonstrated the highest coefficient of determination at L2 for percent and L3 for area models [R2 0.91 (ACP) 0.74 (ACA)]. Adjusted lumber-level associations between non-contrast and contrast measurements ranged from (ß 0.69-0.82) in ACP and (ß 0.37-0.54) in ACA. CONCLUSION: A straightforward correction score for comparison of abdominal aortic calcification measurements in contrast-enhanced and non-contrast scans is discussed. Correction of aortic calcification from CT scans can reduce scan heterogeneity and will be instrumental in creating larger cardiovascular cohorts as well as cardiovascular risk surveillance programs.

Associations of adiponectin and leptin with brain natriuretic peptide in African Americans: the Jackson Heart Study.

Brain natriuretic peptide (BNP) is elevated in decompensated systolic and diastolic heart failure. The plasma levels of adipokines, such as adiponectin and leptin, may provide evidence for mechanistic differences in BNP concentrations. African-American-specific associations are limited in the literature. The objective of this study was to evaluate the associations of adiponectin and leptin with BNP among African Americans. METHODS: Linear and logistic regressions were used to test the associations between adiponectin, leptin, and plasma BNP in 3738 participants of the Jackson Heart Study (JHS), a single-site prospective cohort study of African Americans in Jackson, Mississippi. RESULTS: A direct relationship of adiponectin was observed in multiple multivariate-adjusted linear models: in men (ß = 0.41-0.47), and in women (ß = 0.32-0.38). Those in the highest quartile of adiponectin expression were twice as likely to have elevated BNP levels after adjustment [odds ratio 2.66 (95% confidence interval, 1.66-4.34)]. An inverse relationship of leptin with BNP was observed (ß = -0.15) but attenuated after adjustment for aldosterone, renin, and adiponectin. CONCLUSIONS: Different linear associations of adiponectin and leptin with BNP were observed. Odds of elevated adiponectin were observed with elevated BNP in multivariate-adjusted models. This paradoxical relationship of adiponectin and plasma BNP is possibly explained through adiponectin resistance.

Morphomic calcification score from clinical CT scans: A proxy for coronary artery calcium.

BACKGROUND: Screening of cardiovascular risk is essential in preventing cardiac events and quantifying asymptomatic risk. Coronary artery calcium (CAC) scores are a well-established in predicting cardiovascular risk, but require specialized computed tomography (CT) scans. Given the relationship of aortic calcification with cardiovascular risk, we sought to determine whether aortic calcification measures from incidental CT scans may approximate CAC. STUDY DESIGN: Retrospective CT scans and corresponding volumetric CAC scores were obtained from patients at the University of Michigan. Aortic calcifications were measured in 166 scans. Correlations between a novel morphomic calcium (MC) percent score and CAC score were evaluated using Kendall's correlation coefficients. Comparison of receiver operating characteristic (ROC) curves based on MC at different vertebral levels showed the highest predictive values for measures taken at L4. RESULTS: MC at L4 shows promise in predicting CAC (AUC 0.90 in non-contrast scans, 0.70 in post-contrast scans). Proposed MC threshold are (4.21% for best sensitivity, B 12.93% for balance, C = 19.26% for specificity) in scans without contrast enhancement and (D = 7.31 for sensitivity, E 8.06 for specificity) in scans with contrast enhancement. CONCLUSION: The MC score demonstrates promising potential in approximating CAC, particularly at the L4 level. The utilization of MC from incidental CT scans may be useful for assessment of cardiovascular risk. The ability to extract MC from contrast scans makes it especially valuable to patients receiving additional medical or surgical care. Recognition of high-risk patients would allow the use of indicated preventative strategies to avoid hard cardiovascular events in at risk patients.

Comparisons of Manual Tape Measurement and Morphomics Measurement of Patients with Upper Extremity Lymphedema.

BACKGROUND: Lymphedema is a debilitating condition characterized by swelling from lymph fluid exceeding transport capacity. A gold standard for arm measurement is not established, and measurement methods vary. This study evaluates the comparability of the tape measure and Analytic Morphomics in deriving limb circumference measurements in patients with upper extremity lymphedema. METHODS: Fifteen participants with diagnosed upper limb lymphedema were included between July 2013 and June 2017 at Chang Gung Memorial Hospital in Taipei, Taiwan. Affected and unaffected arm circumferences were measured using a flexible tape or morphomic measurement at 10 cm above and below the elbow. Computed tomography scans were standardized, processed, smoothed with a piecewise polynomial algorithm for Analytic Morphomics of arm circumference. Comparative plots, mean percent difference, and adjusted coefficient of determination (R 2) were utilized to compare the consistency of both measurement procedures. RESULTS: The tape measure and Analytic Morphomics demonstrated consistent measures of arm circumference. On the affected arm, the mean (95% CI) difference in arm circumference between methods was 1.60 cm (0.99-2.20) above, and 0.57 cm (0.23-0.91) below the elbow. Mean percent differences in circumference was 6.65% (SD 3.52%) above and 1.38% (SD 2.11%) below the elbow. The adjusted R 2 for both methods was 94% above and 96% below the elbow. CONCLUSIONS: Analytic Morphomics showed strong consistency with the manual tape measure of arm circumference measurement in those with upper extremity lymphedema. Analytic Morphomics present an opportunity for a precise, granular measurement of limb composition for assessment of disease state and patient planning.

Computed tomography correlation of skeletal landmarks and vascular anatomy in civilian adult trauma patients: Implications for resuscitative endovascular balloon occlusion of the aorta.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a valuable resuscitative adjunct in a variety of clinical settings. In resource-limited or emergency environments, REBOA may be required with delayed or absent image-guidance or verification. Catheter insertion lengths may be informed by making computed tomography (CT) correlations of skeletal landmarks with vascular lengths. METHODS: Between 2000 and 2015 at a single civilian tertiary care center, 2,247 trauma patients with CT imaging were identified, yielding 1,789 patients with adequate contrast opacification of the arterial system in the chest, abdomen, and pelvis. Individual scans were analyzed using MATLAB software, with custom high-throughput image processing algorithms applied to correlate centerline vascular anatomy with musculoskeletal landmarks. Data were analyzed using R version 3.3. RESULTS: The median centerline distance from the skin access to the aortic bifurcation was longer by 0.3 cm on the right than on the left side. Median aortic zone I length was 21.6 (interquartile range, 20.3-22.9) cm, while zone III was 8.7 (7.8-9.5) cm. Torso extent (TE) correlation to zone I was much higher than that for zone III (R2, 0.58 vs. 0.26 (right) and 0.58 vs. 0.27 (left); p < 0.001). Assuming a 4-cm balloon length, optimal fixed insertion length would be 48 cm and 28 cm for zones I and III (error, 0.4% vs. 33.3%), respectively, although out of zone placements can be reduced if adjusted for TE (error, 0% vs. 26.4%). CONCLUSION: Computed tomography morphometry suggests that a fixed REBOA catheter insertion length of 48 cm for zone I and 28 cm for zone III is optimal (on average, for average-height individuals), with improved accuracy by formulaic adjustments for TE. High residual error for zone III placement may require redesign of existing catheter balloon lengths or consideration of the relative risk associated with placing the balloon catheter too low or too high. LEVEL OF EVIDENCE: Prognostic/epidemiological, level III.

Associations of Apelin, Visfatin, and Urinary 8-Isoprostane With Severe Hypertension in African Americans: The MH-GRID Study.

BACKGROUND: Apelin is an adipokine directly associated with adiposity, insulin resistance, and decreased blood pressure. Urinary 8-isoprostane is a marker of chronic oxidative endothelial stress. Visfatin, an adipokine that acts by binding and activating the insulin receptor, has been associated with hypertension. As severe hypertension (SH) is highly prevalent among African Americans (AA), we aimed to assess the association of these biomarkers with SH status. METHODS: A sample of 250 AA participants (134 normotensive controls and 116 with SH (including 98 treatment controlled, SCH: severe controlled hypertension, and 18 treatment resistant, SRH: severe resistant hypertension)) from the Minority Health Genomics and Translational Research Bio-Repository Database (MH-GRID) in metro Atlanta had blood analyzed for apelin and visfatin and urine for 8-isoprostane. T-tests, sex-specific age-adjusted correlation coefficients, and multivariable logistic regression models were used to assess the association of biomarkers with hypertensive status. RESULTS: Levels of apelin and 8-isoprostane were not statistically different between controls and SCH or SRH. Statistically significant differences were present in levels of visfatin between controls (1.03±0.84 pg/ml), SCH (1.34±1.14 pg/ml), and SRH (1.59±0.85 pg/ml). After multivariable adjustment, categorization in the middle 2 quartiles of urinary 8-isoprostane were associated with SH. In similar models, categorization into the highest quartile of visfatin was associated with SH (odds ratio = 2.80; 95% confidence interval: 1.02-7.02). A continuous association of visfatin with SH was present. CONCLUSION: In our community sample of AA, there were increased odds of SH with increased levels of urinary 8-isoprostane and visfatin, but not with apelin.

The effects of alcohol, cannabis, and cigarette use on the initiation, reinitiation and persistence of non-medical use of opioids, sedatives, and tranquilizers in adults.

BACKGROUND: Non-medical prescription drug use (NMPDU) has been a growing concern due to increased prevalence and severity of consequences. Epidemiological research has identified alcohol, cannabis, and cigarette use to be associated with NMPDU and initiation. However, studies have not examined stages of NMPDU in relation to other substances, which can highlight salient factors associated with high risk stages of NMPDU, such as reinitiation and persistence. METHODS: This study used an adult sample from the National Epidemiologic Survey of Alcohol and Related Conditions Wave 1 (2001-2002) and Wave 2 (2004-2005) data. We examined non-users, prior users, and current users of opioids and sedatives/tranquilizers at risk of initiation, reinitiation, and persistence between Wave 1 and Wave 2 in relation to early-onset and frequency of cannabis, cigarette, and alcohol use, controlling for sociodemographics. RESULTS: Early-onset of cigarette and alcohol use increased the odds of opioid use initiation; early-onset of cannabis, cigarette, and alcohol use increased the odds of sedative/tranquilizer use initiation and opioid reinitiation, persistence, while early-onset cannabis increased the odds of sedative/tranquilizer reinitiation and persistence. Frequency of cannabis and cigarette use predicted all three stages of opioid use, initiation/reinitiation of sedatives/tranquilizers, and frequency of cannabis use alone predicted sedative/tranquilizer persistence. CONCLUSIONS: This study provided evidence that differentiating among those who have experienced initiation, reinitiation, or persistence of NMPDU via early-onset and frequency of alcohol, cigarettes, and cannabis is vital, as there are specific aspects that influence risk. Therefore, tailoring interventions at different stages to reduce NMPDU is crucial.