Aortic calcification: A postmortem CT validation study in a middle-aged population.

BACKGROUND: Computed tomography (CT)-detected aortic calcification is strongly associated with aortic stiffness and is an accurate predictor of cardiovascular and all-cause mortality and cognitive decline. Some previous pathologic studies have shown calcium accumulation in the medial layer of the vessel wall, while others have suggested localisation in the atherosclerotic intimal layer. OBJECTIVES: The aim of this study was to histologically validate CT findings of aortic calcification for detectability and location in the aortic wall. METHODS: We acquired postmortem CT images and collected 170 aortic tissue samples from five different locations in the thoracic and abdominal aorta of 40 individuals who underwent autopsy. Microscopic slides were stained with haematoxylin and eosin and elastic van Gieson stain. Calcified lesions were characterised and calcifications were manually annotated in the intima and media. The presence and morphology of calcifications were scored on CT images. RESULTS: The mean age of the autopsied individuals was 63 years, and 28 % died of cardiovascular disease. Calcifications were present in 74/170 (44 %) samples. Calcification was more common in the abdominal aorta than in the thoracic aorta. In all samples with calcifications, 99 % were located in the intimal layer. Only 16/170 samples had a small amount of medial arterial calcification. The histological results showed an 85 % concordance for the presence or absence of CT calcifications. There was complete inter-method agreement for annularity of calcifications in 68 % of the samples (linear weighted kappa 0.68 (95 %CI 0.60-0.77). CONCLUSIONS: Aortic calcifications visible on CT are located in the intimal layer of the abdominal aorta wall, at least in aortas that are not aneurysmatic or dissected. The presence and annularity of these calcifications can be reliably determined by CT.

Inflammation of the periodontium associates with risk of future cardiovascular events.

BACKGROUND: While growing evidence suggests a link between periodontal disease (PD) and cardiovascular disease (CVD), the independence of this association and the pathway remain unclear. Herein, we tested the hypotheses that: (1) inflammation of the periodontium (PDinflammation ) predicts future CVD independently of disease risk factors shared between CVD and PD, and (2) the mechanism linking the two diseases involves heightened arterial inflammation. METHODS: 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT) imaging was performed in 304 individuals (median age 54 years; 42.4% male) largely for cancer screening; individuals without active cancer were included. PDinflammation and arterial inflammation were quantified using validated 18 F-FDG-PET/CT methods. Additionally, we evaluated the relationship between PDinflammation and subsequent major adverse cardiovascular events (MACE) using Cox models and log-rank tests. RESULTS: Thirteen individuals developed MACE during follow-up (median 4.1 years). PDinflammation associated with arterial inflammation, remaining significant after adjusting for PD and CVD risk factors (standardized ß [95% CI]: 0.30 [0.20-0.40], P < 0.001). PDinflammation predicted subsequent MACE (standardized HR [95% CI]: 2.25 [1.47 to 3.44], P <0.001, remaining significant in multivariable models), while periodontal bone loss did not. Furthermore, mediation analysis suggested that arterial inflammation accounts for 80% of the relationship between PDinflammation and MACE (standardized log odds ratio [95% CI]: 0.438 [0.019-0.880], P = 0.022). CONCLUSION: PDinflammation is independently associated with MACE via a mechanism that may involve increased arterial inflammation. These findings provide important support for an independent relationship between PDinflammation and CVD.

Coiling of the Internal Carotid Artery is Associated with Hypertension in Patients Suspected of Stroke.

PURPOSE: The etiology of coiling (i.e. severe elongation) of the extracranial part of the internal carotid artery (ICA) is poorly understood with the proposed etiology being congenital, atherosclerotic or hypertension. The objective was to investigate the association of coiling with hypertension, carotid artery atherosclerosis and other cardiovascular risk factors. METHODS: A case control study was performed in patients suspected of stroke, with (cases) or without (controls) coiling of the ICA determined on compute tomography angiography (CTA). Baseline characteristics included age, gender, hypertension, diabetes, smoking and hypercholesterolemia. Coiling of the ICA and atherosclerotic plaque at the carotid bifurcation were assessed on CTA. Logistic regression analyses were conducted. RESULTS: Coiling was identified in 108 patients with a median age of 71 years. Cases were compared with 256 controls with a median age of 69 years. Hypertension was present in 63% of the patients with coiling compared to 51% in the control group. Univariable analysis showed that hypertension was significantly associated with coiling, with an odds ratio of 1.65 (95% confidence interval (CI) 1.04-2.61, p = 0.034). Multivariable analysis corrected for age and sex resulted in an odds ratio of 1.71 (95% CI 1.05-2.80, p = 0.032), while correcting for atherosclerotic plaque at the bifurcation yielded an odds ratio of 1.63 (95% CI 1.00-2.66, p = 0.049). Age and atherosclerotic plaque were not significantly associated with coiling. CONCLUSION: The main finding of this study was the significant association of hypertension with coiling of the ICA and the absence of an association with age, plaques and atherosclerotic risk factors other than hypertension.

Deep learning from dual-energy information for whole-heart segmentation in dual-energy and single-energy non-contrast-enhanced cardiac CT.

PURPOSE: Deep learning-based whole-heart segmentation in coronary computed tomography angiography (CCTA) allows the extraction of quantitative imaging measures for cardiovascular risk prediction. Automatic extraction of these measures in patients undergoing only non-contrast-enhanced CT (NCCT) scanning would be valuable, but defining a manual reference standard that would allow training a deep learning-based method for whole-heart segmentation in NCCT is challenging, if not impossible. In this work, we leverage dual-energy information provided by a dual-layer detector CT scanner to obtain a reference standard in virtual non-contrast (VNC) CT images mimicking NCCT images, and train a three-dimensional (3D) convolutional neural network (CNN) for the segmentation of VNC as well as NCCT images. METHODS: Eighteen patients were scanned with and without contrast enhancement on a dual-layer detector CT scanner. Contrast-enhanced acquisitions were reconstructed into a CCTA and a perfectly aligned VNC image. In each CCTA image, manual reference segmentations of the left ventricular (LV) myocardium, LV cavity, right ventricle, left atrium, right atrium, ascending aorta, and pulmonary artery trunk were obtained and propagated to the corresponding VNC image. These VNC images and reference segmentations were used to train 3D CNNs in a sixfold cross-validation for automatic segmentation in either VNC images or NCCT images reconstructed from the non-contrast-enhanced acquisition. Automatic segmentation in VNC images was evaluated using the Dice similarity coefficient (DSC) and average symmetric surface distance (ASSD). Automatically determined volumes of the cardiac chambers and LV myocardium in NCCT were compared to reference volumes of the same patient in CCTA by Bland-Altman analysis. An additional independent multivendor multicenter set of single-energy NCCT images from 290 patients was used for qualitative analysis, in which two observers graded segmentations on a five-point scale. RESULTS: Automatic segmentations in VNC images showed good agreement with reference segmentations, with an average DSC of 0.897 ± 0.034 and an average ASSD of 1.42 ± 0.45 mm. Volume differences [95% confidence interval] between automatic NCCT and reference CCTA segmentations were -19 [-67; 30] mL for LV myocardium, -25 [-78; 29] mL for LV cavity, -29 [-73; 14] mL for right ventricle, -20 [-62; 21] mL for left atrium, and -19 [-73; 34] mL for right atrium, respectively. In 214 (74%) NCCT images from the independent multivendor multicenter set, both observers agreed that the automatic segmentation was mostly accurate (grade 3) or better. CONCLUSION: Our automatic method produced accurate whole-heart segmentations in NCCT images using a CNN trained with VNC images from a dual-layer detector CT scanner. This method might enable quantification of additional cardiac measures from NCCT images for improved cardiovascular risk prediction.

CT calcification patterns of peripheral arteries in patients without known peripheral arterial disease.

PURPOSE: In the last few years histologic studies of peripheral arteries have shown that both intimal and medial calcifications are found in patients in an early, asymptomatic stage and that differentiation between medial and intimal calcifications is possible. The aim of this study was to assess the computed tomography (CT) calcification characteristics in peripheral arteries and to explore potential patterns in subjects without peripheral arterial disease (PAD). METHOD: Retrospectively, 204 patients without known PAD were studied. The thin slice CT-imaging characteristics severity, annularity, thickness and continuity were scored in the following arteries: plantar and dorsal, crural, femoro-popliteal, iliac and the abdominal aorta. Interrelation was assessed using linear regression and significance was tested by Chi-Square tests. RESULTS: In the crural arteries two calcification patterns with strong associations were found. Pattern 1: continuous-annular 93.5 % (29/31), continuous-thin and thin-annular both 73 % (27/37, p < 0.001) and pattern 2: thick-discontinuous 91.7 % (44/48), thick-dotted 68.8 % (33/48), patchy-dotted 59.3 % (16/27, p < 0.001). Similar associations were found in the femoro-popliteal artery, but not in the plantar, dorsal, iliac arteries and aorta. CONCLUSIONS: In the crural and femoropopliteal arteries at least two morphological patterns can be distinguished on CT that, compared to a CT-histologically validated score, may represent an intimal and medial calcification pattern.

The Association Between Marital Status, Coronary Computed Tomography Imaging Biomarkers, and Mortality in a Lung Cancer Screening Population.

PURPOSE: The purpose of this study was to elucidate the impact of being unmarried on coronary computed tomography (CT) imaging biomarkers and mortality in a lung cancer screening population. MATERIALS AND METHODS: In this retrospective case-control study, 5707 subjects (3777 married; mean age: 61.9±5.1 y and 1930 unmarried; mean age: 61.9±5.3 y) underwent low-dose CT as part of the National Lung Screening Trial (NLST). The median follow-up time was 6.5 (Q1-Q3: 5.6 to 6.9) years. Being unmarried was defined as never married, widowed, separated, or divorced. Being married was defined as married or living as married. Our primary endpoint was cardiovascular disease (CVD)-related death; our secondary endpoint was all-cause mortality. Coronary CT imaging biomarkers (calcium score, density, and volume) on low-dose chest CT scan were calculated using dedicated automatic software. Weighted Cox proportional-hazards regression was performed to examine the association between marital status and death. Kaplan-Meier curves were generated to visualize subject survival. RESULTS: Being unmarried was significantly associated with an increased risk for CVD-related death (hazard ratio [HR]: 1.58; 95% confidence interval [CI]: 1.31-1.91) and all-cause mortality (HR: 1.39; 95% CI: 1.26-1.53), which remained significant even after adjusting for traditional cardiovascular risk factors (HR CVD death: 1.75; 1.44-2.12 and HR all-cause mortality: 1.58; 95% CI: 1.43-1.74) and coronary calcium score (HR CVD death: 1.58; 95% CI: 1.31-1.91 and HR all-cause mortality: 1.40; 95% CI: 1.27-1.54). CONCLUSIONS: Being unmarried is associated with an increased CVD-related death and all-cause mortality mainly due to cardiovascular etiology. On the basis of this, marital status might be taken into consideration when assessing individuals' health status.

Sex Differences in Coronary Artery and Thoracic Aorta Calcification and Their Association With Cardiovascular Mortality in Heavy Smokers.

OBJECTIVES: The aim of this study was to investigate sex differences in the prevalence, extent, and association of coronary artery calcium (CAC) and thoracic aorta calcium (TAC) scores with cardiovascular mortality in a population eligible for lung screening. BACKGROUND: CAC and TAC scores derived from chest computed tomography (CT) might be useful biomarkers for individualized cardiovascular disease prevention and could be especially relevant in high-risk populations such as heavy smokers. Therefore, it is important to know the prevalence of arterial calcifications in male and female heavy smokers, and if there are differences in the predictive value calcifications carry. METHODS: We performed a nested case-control study with 5,718 participants of the CT arm of the NLST (National Lung Screening Trial). Prevalence and extent of CAC and TAC were resampled to the full cohort to provide unbiased estimates of the typical calcium burden of male and female heavy smokers. Weighted Cox proportional hazards regression was used to assess differences in the association of CAC and TAC scores with all-cause and cardiovascular mortality. RESULTS: CAC was substantially more common and more severe in men (prevalence: 81% vs. 60%; median volume: 104 mm³ vs. 12 mm³). Women had CAC comparable to that of men who were 10 years younger. TAC was equally common in men and women, with a tendency to be more pronounced in women (prevalence: 92% vs. 93%; median volume: 388 mm³ vs. 404 mm³). Both types of calcification were associated with increased cardiovascular and all-cause mortality. TAC scores improved the prediction of coronary heart disease mortality over CAC in men, but not in women. In both sexes, TAC, but not CAC, was associated with cardiovascular mortality other than coronary heart disease. CONCLUSIONS: CAC develops later in women, whereas TAC develops equally in both sexes. CAC is strongly associated with coronary heart disease, whereas TAC is especially associated with extracardiac vascular mortality in either sex.

The effect of emphysema on readmission and survival among smokers with heart failure.

Heart Failure (HF) and chronic obstructive pulmonary disease (COPD) are morbid diseases that often coexist. In patients with coexisting disease, COPD is an independent risk factor for readmission and mortality. However, spirometry is often inaccurate in those with active heart failure. Therefore, we investigated the association between the presence of emphysema on computed tomography (CT) and readmission rates in smokers admitted with heart failure (HF). The cohort included a consecutive group of smokers discharged with HF from a tertiary center between January 1, 2014 and April 1, 2014 who also had a CT of the chest for dyspnea. The primary endpoint was any readmission for HF before April 1, 2016; secondary endpoints were 30-day readmission for HF, length of stay and all-cause mortality. Over the study period, there were 225 inpatient smokers with HF who had a concurrent chest CT (155 [69%] males, age 69±11 years, ejection fraction [EF] 46±18%, 107 [48%] LVEF of < 50%). Emphysema on CT was present in 103 (46%) and these were older, had a lower BMI, more pack-years, less diabetes and an increased afterload. During a follow-up of 2.1 years, there were 110 (49%) HF readmissions and 55 (24%) deaths. When separated by emphysema on CT, any readmission, 30-day readmission, length of stay and mortality were higher among HF patients with emphysema. In multivariable regression, emphysema by CT was associated with a two-fold higher (adjusted HR 2.11, 95% CI 1.41-3.15, p < 0.001) risk of readmission and a trend toward increased mortality (adjusted HR 1.70 95% CI 0.86-3.34, p = 0.12). In conclusion, emphysema by CT is a frequent finding in smokers hospitalized with HF and is associated with adverse outcomes in HF. This under recognized group of patients with both emphysema and heart failure may benefit from improved recognition and characterization of their co-morbid disease processes and optimization of therapies for their lung disease.

Presence, Characteristics, and Prognostic Associations of Carotid Plaque Among People Living With HIV.

BACKGROUND: Data from broad populations have established associations between incidental carotid plaque and vascular events. Among people living with HIV (PLWHIV), the risk of vascular events is increased; however, whether incidental carotid plaque is increased and there is an association between incidental carotid plaque, plaque characteristics, and vascular events among PLWHIV is unclear. METHODS AND RESULTS: Data from the multi-institutional Research Patient Data Registry were used. Presence and characteristics (high-risk plaque, including spotty calcification and low attenuation) of carotid plaque by computerized tomography among PLWHIV without known vascular disease were described. Data were compared with uninfected controls similar in age, sex, and cardiovascular risk factors, including diabetes mellitus, hyperlipidemia, and cigarette smoking to cases. Primary outcome was an atherosclerotic cardiovascular disease event, and secondary outcome was ischemic stroke. Cohort consisted of 209 PLWHIV (45±10 years, 72% male) and 168 controls. Using computerized tomography, PLWHIV without vascular disease had higher rates of any carotid plaque (34% versus 25%; P=0.04), noncalcified (18% versus 5%; P<0.001) and high-risk plaque (25% versus 16%; P=0.03). Over a follow-up of 3 years, 19 atherosclerotic cardiovascular disease events (9 strokes) occurred. Carotid plaque was independently associated with a 3-fold increase in atherosclerotic cardiovascular disease events among PLWHIV (hazard ratio, 2.91; confidence interval, 1.10-7.7, P=0.03) and a 4-fold increased risk of stroke (hazard ratio, 4.43; confidence interval, 1.17-16.70; P=0.02); high-risk plaque was associated with a 3-fold increased risk of atherosclerotic cardiovascular disease events and a 4-fold increased risk of stroke. CONCLUSIONS: There is an increase in incidental carotid plaque, noncalcified plaque, and high-risk plaque among PLWHIV, and the presence and characteristics of carotid plaque are associated with subsequent vascular events.

Coronary CT angiography in the emergency department utilizing second and third generation dual source CT.

BACKGROUND: Coronary computed tomography angiography (coronary CTA) allows efficient triage of low to intermediate risk patients with suspected acute coronary syndrome (ACS) in the emergency department (ED). Techniques for coronary CTA acquisition in the ED continue to evolve with the establishment of standardized scan protocols and the introduction of newer generations of CT hardware. OBJECTIVES: To evaluate qualitative and quantitative image quality and radiation dose exposure of coronary CTA acquired on 2nd versus 3rd generation dual source CT (DSCT) scanners using a standardized institutional scan protocol designed for the ED. METHODS: A retrospective observational case-control study was performed of 246 ED patients referred to coronary CTA with suspicion of ACS (56.5% male; mean age 53.3 ± 11.6 years) between October 2013 and August 2015.123 consecutive patients were scanned on 3rd generation DSCT, and a cohort of 123 patients matched by age, BMI and heart rate were identified who had undergone 2nd generation DSCT imaging utilizing the same standard clinical protocol. Qualitative and quantitative image quality parameters and radiation exposures were evaluated. RESULTS: Qualitative image quality was significantly higher using 3rd generation DSCT as compared to 2nd generation (p < 0.001). Mean attenuation in the proximal coronary arteries was also significantly higher on 3rd generation DSCT than for 2nd generation (586 HU vs. 426 HU in the left main coronary artery (LM), p < 0.001). Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) values, however, were lower in 3rd generation DSCT than 2nd generation (SNR 11.2 [9.9-13.4] vs 13.5 [11.0-15.5] and CNR 12.4 [10.9-14.8] vs 15.2 [12.8-17.9] in the LM, p < 0.001). Median effective dose was also lower for 3rd generation DSCT than for 2nd generation (2.9 [2.3-5.0] mSv and 3.7 mSv [2.5-5.7], respectively) although this trend did not reach statistical significance (p = 0.065). CONCLUSION: Qualitative image quality and mean CT attenuation values of the assessed coronary segments were significantly higher using 3rd generation DSCT. SNR and CNR were lower on 3rd generation DSCT, however this was accompanied by a trend toward lower radiation dose exposure when using the same standard institutional protocol.

Coronary artery calcium in breast cancer survivors after radiation therapy.

The purpose of the current study is to investigate whether breast cancer survivors after radiation therapy have a higher burden of coronary artery calcium as a potential surrogate of radiation-induced accelerated coronary artery disease. 333 patients were included. 54 patients underwent chest CT ≥ 6 months after the start of radiation therapy (radiation therapy group), while 279 patients had a CT scan either prior to or without undergoing radiation therapy (RT). Coronary artery calcium was quantified from CT by applying a threshold-based automated algorithm. Mean age at diagnosis was similar (p = 0.771) between RT (57.4 ± 13.1 years) and NoRT (58.0 ± 11.9 years). Median time between radiation therapy and CT was 2 years. The groups showed no significant differences in race, smoking history, cancer laterality, or cancer stage. 39 (72.2%) of RT patients had a coronary artery calcium score of 0, compared to 201 (72.0%) in patients without radiation therapy. Median coronary artery calcium burden for both groups was not significantly different (p = 0.982), nor when comparing patients who underwent left- versus right-sided radiation therapy (p = 0.453). When adjusting for the time between diagnosis and CT, radiation therapy patients had a significantly lower risk of a positive coronary artery calcium score. In conclusion, breast cancer survivors after radiation therapy are not more likely to show coronary artery calcium on follow-up CT imaging. Our results thus do not support radiation-induced accelerated coronary artery disease as an explanation for higher rates of heart disease in this group.

Impact on Image Quality and Radiation Dose of Third-Generation Dual-Source Computed Tomography of the Coronary Arteries.

The aim of this study was to assess the image quality (IQ) and radiation dose of third-generation dual-source computed tomography (CT) coronary angiography (cCTA) in comparison with 64-slice single-source CT. This retrospective study included 140 patients (73 men, mean age 62 ± 11 years) with low-to-intermediate probability of coronary artery disease who underwent either third-generation dual-source cCTA using prospectively electrocardiography-triggered high-pitch spiral acquisition (n = 70) (group 1) or retrospective electrocardiography-gated cCTA on a 64-slice CT system (n = 70) (group 2). Contrast-to-noise and signal-to-noise ratios were measured within the aorta and coronary arteries. Subjective IQ was assessed using a 5-point Likert scale. Effective dose was estimated using specific conversion factors. The contrast-to-noise ratio of group 1 was significantly higher than group 2 at all levels (all p <0.001). Signal-to-noise ratio of group 1 was also significantly higher than group 2 (p <0.05), except for the distal left circumflex artery. Subjective IQ for group 1 was rated significantly better than for group 2 (median score [25th to 75th percentile]: 1 [1 to 2] vs 2 [2 to 3]; p <0.001). The median effective dose was 1.55 mSv (1.09 to 1.88) in group 1 versus 12.29 mSv (11.63 to 14.36) in group 2 (p <0.001) which corresponds to a mean radiation dose reduction of 87.4%. In conclusion, implementation of third-generation dual-source CT system for cCTA leads to improved IQ with significant radiation dose savings.

Association of Arterial and Lymph Node Inflammation With Distinct Inflammatory Pathways in Human Immunodeficiency Virus Infection.

Importance: Human immunodeficiency virus (HIV) infection is associated with a high risk of cardiovascular disease and increased arterial inflammation. In HIV, inflammation is also increased within lymph nodes (LNs), tissues known to harbor the virus even among treated and suppressed individuals. Objective: To test the hypothesis that arterial inflammation is linked to HIV disease activity and to inflammation within HIV-infected tissues (LNs). Design, Setting, and Participants: For this case-control study, participants were recruited from the SCOPE (Observational Study of the Consequences of the Protease Inhibitor Era) cohort, a clinic-based cohort of individuals receiving care at San Francisco General Hospital and the San Francisco Veteran's Affairs Medical Center. Arterial and LN inflammation were measured using 18F-fluorodeoxyglucose positron emission tomography. Detailed immunophenotyping was performed, along with measurement of viral activity/persistence and of circulating inflammatory biomarkers. Main Outcomes and Measures: Arterial and LN inflammation. Results: A total of 74 men were studied (45 HIV-infected men with a median age of 53 years [interquartile range, 49-59 years] and 29 uninfected male controls with a median age of 52 years [interquartile range, 46-56 years]). Lymph node inflammation was higher in HIV-infected individuals and correlated with markers of viral disease activity (viral load, CD8+ T cells, and CD4/CD8 ratio) and CD4+ T-cell activation. Uninfected controls had the lowest LN activity (mean [SD] maximum axillary LN standardized uptake value, 1.53 [0.56]), the elite controller and ART-suppressed groups had intermediate levels of LN (mean [SD] maximum axillary LN standardized uptake value, 2.12 [0.87] and 2.32 [1.79], respectively), and the noncontrollers had the highest activity (mean [SD] maximum axillary LN standardized uptake value, 8.82 [3.08]). Arterial inflammation was modestly increased in HIV-infected individuals and was positively correlated with circulating inflammatory biomarkers (high-sensitivity C-reactive protein and IL-6) and activated monocytes (CD14dimCD16+; nonclassical) but not with markers of HIV. While LN and arterial inflammation were increased in HIV, inflammatory activity in these tissues was not related (r = 0.09, P = .56). Conclusions and Relevance: While LNs and, to a lesser degree, the arterial wall are inflamed in HIV, inflammation in these tissues is not closely linked. Namely, measures of HIV disease activity are strongly associated with LN inflammation but not with arterial inflammation. These data suggest that LN and arterial inflammation do not share underlying pathways of immune activation and also that therapeutic interventions that reduce viral disease activity may not predictably reduce arterial inflammation in HIV or its downstream consequence (ie, cardiovascular disease).

Automatic Coronary Artery Calcium Scoring on Radiotherapy Planning CT Scans of Breast Cancer Patients: Reproducibility and Association with Traditional Cardiovascular Risk Factors.

OBJECTIVES: Coronary artery calcium (CAC) is a strong and independent predictor of cardiovascular disease (CVD) risk. This study assesses reproducibility of automatic CAC scoring on radiotherapy planning computed tomography (CT) scans of breast cancer patients, and examines its association with traditional cardiovascular risk factors. METHODS: This study included 561 breast cancer patients undergoing radiotherapy between 2013 and 2015. CAC was automatically scored with an algorithm using supervised pattern recognition, expressed as Agatston scores and categorized into five categories (0, 1-10, 11-100, 101-400, >400). Reproducibility between automatic and manual expert scoring was assessed in 79 patients with automatically determined CAC above zero and 84 randomly selected patients without automatically determined CAC. Interscan reproducibility of automatic scoring was assessed in 294 patients having received two scans (82% on the same day). Association between CAC and CVD risk factors was assessed in 36 patients with CAC scores >100, 72 randomly selected patients with scores 1-100, and 72 randomly selected patients without CAC. Reliability was assessed with linearly weighted kappa and agreement with proportional agreement. RESULTS: 134 out of 561 (24%) patients had a CAC score above zero. Reliability of CVD risk categorization between automatic and manual scoring was 0.80 (95% Confidence Interval (CI): 0.74-0.87), and slightly higher for scans with breath-hold. Agreement was 0.79 (95% CI: 0.72-0.85). Interscan reliability was 0.61 (95% CI: 0.50-0.72) with an agreement of 0.84 (95% CI: 0.80-0.89). Ten out of 36 (27.8%) patients with CAC scores above 100 did not have other cardiovascular risk factors. CONCLUSIONS: Automatic CAC scoring on radiotherapy planning CT scans is a reliable method to assess CVD risk based on Agatston scores. One in four breast cancer patients planned for radiotherapy have elevated CAC score. One in three patients with high CAC scores don't have other CVD risk factors and wouldn't have been identified as high risk.

Relationship Between Measures of Adiposity, Arterial Inflammation, and Subsequent Cardiovascular Events.

BACKGROUND: The objective of this study was to evaluate how different measures of adiposity are related to both arterial inflammation and the risk of subsequent cardiovascular events. METHODS AND RESULTS: We included individuals who underwent (18)F-fluorodeoxyglucose positron emission tomography/computed tomography imaging for oncological evaluation. Subcutaneous adipose tissue (SAT) volume, visceral adipose tissue (VAT) volume, and VAT/SAT ratio were determined. Additionally, body mass index, metabolic syndrome, and aortic (18)F-fluorodeoxyglucose uptake (a measure of arterial inflammation) were determined. Subsequent development of cardiovascular disease (CVD) events was adjudicated. The analysis included 415 patients with a median age of 55 (P25-P75: 45-65) and a median body mass index of 26.4 (P25-P75: 23.4-30.9) kg/m(2). VAT and SAT volume were significantly higher in obese individuals. VAT volume (r=0.290; P<0.001) and VAT/SAT ratio (r=0.208; P<0.001) were positively correlated with arterial inflammation. Thirty-two subjects experienced a CVD event during a median follow-up of 4 years. Cox proportional hazard models showed that VAT volume and VAT/SAT ratio were associated with CVD events (hazard ratio [95% confidence interval]: 1.15 [1.06-1.25]; P<0.001; 3.60 [1.88-6.92]; P<0.001, respectively). Body mass index, metabolic syndrome, and SAT were not predictive of CVD events. CONCLUSIONS: Measures of visceral fat are positively related to arterial inflammation and are independent predictors of subsequent CVD events. Individuals with higher measures of visceral fat as well as elevated arterial inflammation are at highest risk for subsequent CVD events. The findings suggest that arterial inflammation may explain some of the CVD risk associated with adiposity.

Inter-observer and inter-examination variability of manual vertebral bone attenuation measurements on computed tomography.

OBJECTIVE: To determine inter-observer and inter-examination variability of manual attenuation measurements of the vertebrae in low-dose unenhanced chest computed tomography (CT). METHODS: Three hundred and sixty-seven lung cancer screening trial participants who underwent baseline and repeat unenhanced low-dose CT after 3 months because of an indeterminate lung nodule were included. The CT attenuation value of the first lumbar vertebrae (L1) was measured in all CTs by one observer to obtain inter-examination reliability. Six observers performed measurements in 100 randomly selected CTs to determine agreement with limits of agreement and Bland-Altman plots and reliability with intraclass correlation coefficients (ICCs). Reclassification analyses were performed using a threshold of 110 HU to define osteoporosis. RESULTS: Inter-examination reliability was excellent with an ICC of 0.92 (p < 0.001). Inter-examination limits of agreement ranged from -26 to 28 HU with a mean difference of 1 ± 14 HU. Inter-observer reliability ICCs ranged from 0.70 to 0.91. Inter-examination variability led to 11.2 % reclassification of participants and inter-observer variability led to 22.1 % reclassification. CONCLUSIONS: Vertebral attenuation values can be manually quantified with good to excellent inter-examination and inter-observer reliability on unenhanced low-dose chest CT. This information is valuable for early detection of osteoporosis on low-dose chest CT. KEY POINTS: • Vertebral attenuation values can be manually quantified on low-dose unenhanced CT reliably. • Vertebral attenuation measurements may be helpful in detecting subclinical low bone density. • This could become of importance in the detection of osteoporosis.

Supraclavicular Brown Adipose Tissue 18F-FDG Uptake and Cardiovascular Disease.

UNLABELLED: Preclinical data suggest a negative correlation between brown adipose tissue (BAT) and the degree of coronary atherosclerosis. We sought to evaluate the relationship between (18)F-FDG uptake in supraclavicular BAT in relation to arterial inflammation and subsequent cardiovascular disease (CVD) events in humans. METHODS: Individuals who underwent (18)F-FDG PET/CT for clinical indications but who did not have either cancer or known atherosclerotic disease at the time of imaging were included. A radiologist masked to clinical data measured (18)F-FDG uptake within BAT (in the supraclavicular region) as well as in subcutaneous adipose tissues. Tissue density was evaluated using CT (Hounsfield units). Arterial inflammation was assessed by measuring arterial (18)F-FDG uptake and calculating target-to-background ratio. CVD events were independently adjudicated by masked cardiologists. Thereafter, the relationship between BAT activity and CVD events was evaluated. RESULTS: A total of 443 patients (age, 55 y [44-66 y]; 44% men; body mass index [BMI], 26 [range, 23-31]) were included, and 30 patients experienced a cardiovascular event during a median follow-up of 4 y. BAT activity negatively correlated with arterial inflammation (r = -0.178, P < 0.01), a relationship that persisted after correcting for age and BMI (r = -0.147, P < 0.01). When either high sensitivity or high accuracy thresholds (from receiver-operating curve analyses) were used to define elevated BAT, high BAT was associated with a reduced risk of CVD events (P = 0.048), even after correcting for age (P = 0.037). CONCLUSION: Our results suggest that increased supraclavicular BAT activity is inversely associated with arterial inflammation, independently of age and BMI. Additionally, increased BAT may be associated with fewer cardiovascular events.

Increased arterial inflammation in individuals with stage 3 chronic kidney disease.

PURPOSE: While it is well known that patients with chronic kidney disease (CKD) are at increased risk for the development and progression of atherosclerosis, it is not known whether arterial inflammation is increased in mild CKD. The aim of this study was to compare arterial inflammation using 18F-FDG PET/CT in patients with CKD and in matched controls. METHODS: This restrospective study included 128 patients undergoing FDG PET/CT imaging for clinical indications, comprising 64 patients with stage 3 CKD and 64 control patients matched by age, gender, and cancer history. CKD was defined according to guidelines using a calculated glomerular filtration rate (eGFR). Arterial inflammation was measured in the ascending aorta as FDG uptake on PET. Background FDG uptake (venous, subcutaneous fat and muscle) were recorded. Coronary artery calcification (CAC) was assessed using the CT images. The impact of CKD on arterial inflammation and CAC was then assessed. RESULTS: Arterial inflammation was higher in patients with CKD than in matched controls (standardized uptake value, SUV: 2.41 ± 0.49 vs. 2.16 ± 0.43; p = 0.002). Arterial SUV correlated inversely with eGFR (r = -0.299, p = 0.001). Venous SUV was also significantly elevated in patients with CKD, while subcutaneous fat and muscle tissue SUVs did not differ between groups. Moreover, arterial SUV remained significantly elevated in patients with CKD compared to controls after correcting for muscle and fat background, and also remained significant after adjusting for clinical risk factors. Further, CKD was associated with arterial inflammation (SUV) independent of the presence of subclinical atherosclerosis (CAC). CONCLUSION: Moderate CKD is associated with increased arterial inflammation beyond that of controls. Further, the increased arterial inflammation is independent of presence of subclinical atherosclerosis. Current risk stratification tools may underestimate the presence of atherosclerosis in patients with CKD and thereby the risk of cardiovascular events.