Body mass index is associated with pulmonary gas and blood distribution mismatch in COVID-19 acute respiratory failure. A physiological study.

Background: The effects of obesity on pulmonary gas and blood distribution in patients with acute respiratory failure remain unknown. Dual-energy computed tomography (DECT) is a X-ray-based method used to study regional distribution of gas and blood within the lung. We hypothesized that 1) regional gas/blood mismatch can be quantified by DECT; 2) obesity influences the global and regional distribution of pulmonary gas and blood; 3) regardless of ventilation modality (invasive vs. non-invasive ventilation), patients' body mass index (BMI) has an impact on pulmonary gas/blood mismatch. Methods: This single-centre prospective observational study enrolled 118 hypoxic COVID-19 patients (92 male) in need of respiratory support and intensive care who underwent DECT. The cohort was divided into three groups according to BMI: 1. BMI<25 kg/m2 (non-obese), 2. BMI = 25-40 kg/m2 (overweight to obese), and 3. BMI>40 kg/m2 (morbidly obese). Gravitational analysis of Hounsfield unit distribution of gas and blood was derived from DECT and used to calculate regional gas/blood mismatch. A sensitivity analysis was performed to investigate the influence of the chosen ventilatory modality and BMI on gas/blood mismatch and adjust for other possible confounders (i.e., age and sex). Results: 1) Regional pulmonary distribution of gas and blood and their mismatch were quantified using DECT imaging. 2) The BMI>40 kg/m2 group had less hyperinflation in the non-dependent regions and more lung collapse in the dependent regions compared to the other BMI groups. In morbidly obese patients, gas and blood were more evenly distributed; therefore, the mismatch was lower than in other patients (30% vs. 36%, p < 0.05). 3) An increase in BMI of 5 kg/m2 was associated with a decrease in mismatch of 3.3% (CI: 3.67% to -2.93%, p < 0.05). Neither the ventilatory modality nor age and sex affected the gas/blood mismatch (p > 0.05). Conclusion: 1) In a hypoxic COVID-19 population needing intensive care, pulmonary gas/blood mismatch can be quantified at a global and regional level using DECT. 2) Obesity influences the global and regional distribution of gas and blood within the lung, and BMI>40 kg/m2 improves pulmonary gas/blood mismatch. 3) This is true regardless of the ventilatory mode and other possible confounders, i.e., age and sex. Trial Registration: Clinicaltrials.gov, identifier NCT04316884, NCT04474249.

Longitudinal Assessment of Inflammatory Activity in Acute Type B Aortic Dissection with Integrated Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging.

OBJECTIVE: The significance of the inflammatory response in the natural course of acute type B aortic dissection (ATBAD) is unknown. The aim was to characterise inflammation and its transformation over time in ATBAD using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) with contrast enhanced magnetic resonance imaging (MRI). METHODS: Ten patients underwent FDG-PET/MRI within two weeks of ATBAD (acute phase), three to four months (subacute phase), nine to 12 months (early chronic phase), and 21 to 24 months (late chronic phase) after ATBAD. Target background ratios (TBRs) were measured in the ascending aorta, aortic arch, and descending aorta. MRI inflammatory markers were assessed in the descending aorta. RESULTS: Ten patients were included: median age 69 years, median clinical follow up 32 months. In the acute phase there was increased FDG uptake in the descending aorta (maximum TBR 5.8, SD [standard deviation] 1.3) compared with the ascending aorta (TBR 3.3, SD 0.8, p < .010) and arch (TBR 4.2, SD 0.6, p = .010). The maximum TBR of the descending aorta decreased from the acute to subacute phase (TBR 3.5, SD 0.6, p = .010) and further to the early chronic phase (TBR 2.9, SD 0.4, p = .030) but was stable thereafter. The acute phase maximum TBR in the ascending aorta (TBR 3.3) and arch (TBR 4.2) decreased to the subacute phase (ascending: TBR 2.8, SD 0.6, p = .020; arch: TBR 2.7, SD 0.4, p = .010) and was stable thereafter. Four patients underwent surgical aortic repair (three for aortic dilatation at one, five, and 28 months and one for visceral ischaemia at three weeks). MRI signs of inflammation were present in all surgically treated patients vs. two of six of medically treated patients (p= .048). CONCLUSION: ATBAD is associated with increased FDG uptake in the acute phase primarily in the descending aorta, but also involving the aortic arch and ascending aorta, indicating an inflammatory response in the whole aorta. Inflammation subsides early in the ascending aorta and arch (three months), whereas it stabilised later in the descending aorta (nine to 12 months). MRI signs of inflammation were more frequent in patients who later needed surgical treatment and merit further investigation.

Different chest HRCT scan protocols change the extent of ground glass opacities.

BACKGROUND: Ground glass opacity (GGO) is the main HRCT feature representing alveolitis in systemic sclerosis-associated interstitial lung disease (SSc-ILD), but may also represent other conditions such as atelectasis or edema. It is unclear how much this is affected by the HRCT scan protocol used. We aimed to compare the performance of three different HRCT protocols to evaluate the degree of SSc-ILD related changes. METHODS: Eleven patients with SSc underwent chest HRCT scan by three different protocols: First, a supine scan after lying down for 15 minutes, then two scans in alternating order: A prone position scan, and a supine position scan after performing 10 deep breaths using a positive expiratory pressure (PEP) device. The HRCT scans were evaluated by the Warrick score system for ILD-related findings. RESULTS: The three HRCT protocols were compared and resulted in different mean (95% CI) Warrick scores: 9.4 (5.3-13.4) in supine after rest; 7.5 (95% CI 3.8-11.1) in prone and 7.6 (95% CI 4.2-11.1) in supine after PEP. When comparing supine after rest to prone and supine after PEP, the latter two scans had a significantly lower score (p = 0.001 for both comparisons). In all cases, only sub-scores for ground glass opacities differed, while sub-scores for fibrosis-related changes did not change. CONCLUSIONS: Different HRCT scan protocols significantly altered the Warrick severity score for SSc-ILD findings, primarily because of changes in ground glass opacities. These differences may be clinically meaningful.

Chest dual-energy CT to assess the effects of steroids on lung function in severe COVID-19 patients.

BACKGROUND: Steroids have been shown to reduce inflammation, hypoxic pulmonary vasoconstriction (HPV) and lung edema. Based on evidence from clinical trials, steroids are widely used in severe COVID-19. However, the effects of steroids on pulmonary gas volume and blood volume in this group of patients are unexplored. OBJECTIVE: Profiting by dual-energy computed tomography (DECT), we investigated the relationship between the use of steroids in COVID-19 and distribution of blood volume as an index of impaired HPV. We also investigated whether the use of steroids influences lung weight, as index of lung edema, and how it affects gas distribution. METHODS: Severe COVID-19 patients included in a single-center prospective observational study at the intensive care unit at Uppsala University Hospital who had undergone DECT were enrolled in the current study. Patients' cohort was divided into two groups depending on the administration of steroids. From each patient's DECT, 20 gas volume maps and the corresponding 20 blood volume maps, evenly distributed along the cranial-caudal axis, were analyzed. As a proxy for HPV, pulmonary blood volume distribution was analyzed in both the whole lung and the hypoinflated areas. Total lung weight, index of lung edema, was estimated. RESULTS: Sixty patients were analyzed, whereof 43 received steroids. Patients not exposed to steroids showed a more extensive non-perfused area (19% vs 13%, p < 0.01) and less homogeneous pulmonary blood volume of hypoinflated areas (kurtosis: 1.91 vs 2.69, p < 0.01), suggesting a preserved HPV compared to patients treated with steroids. Moreover, patients exposed to steroids showed a significantly lower lung weight (953 gr vs 1140 gr, p = 0.01). A reduction in alveolar-arterial difference of oxygen followed the treatment with steroids (322 ± 106 mmHg at admission vs 267 ± 99 mmHg at DECT, p = 0.04). CONCLUSIONS: The use of steroids might cause impaired HPV and might reduce lung edema in severe COVID-19. This is consistent with previous findings in other diseases. Moreover, a reduced lung weight, as index of decreased lung edema, and a more homogeneous distribution of gas within the lung were shown in patients treated with steroids. TRIAL REGISTRATION: Clinical Trials ID: NCT04316884, Registered March 13, 2020.

A quantitative analysis of extension and distribution of lung injury in COVID-19: a prospective study based on chest computed tomography.

BACKGROUND: Typical features differentiate COVID-19-associated lung injury from acute respiratory distress syndrome. The clinical role of chest computed tomography (CT) in describing the progression of COVID-19-associated lung injury remains to be clarified. We investigated in COVID-19 patients the regional distribution of lung injury and the influence of clinical and laboratory features on its progression. METHODS: This was a prospective study. For each CT, twenty images, evenly spaced along the cranio-caudal axis, were selected. For regional analysis, each CT image was divided into three concentric subpleural regions of interest and four quadrants. Hyper-, normally, hypo- and non-inflated lung compartments were defined. Nonparametric tests were used for hypothesis testing (α = 0.05). Spearman correlation test was used to detect correlations between lung compartments and clinical features. RESULTS: Twenty-three out of 111 recruited patients were eligible for further analysis. Five hundred-sixty CT images were analyzed. Lung injury, composed by hypo- and non-inflated areas, was significantly more represented in subpleural than in core lung regions. A secondary, centripetal spread of lung injury was associated with exposure to mechanical ventilation (p < 0.04), longer spontaneous breathing (more than 14 days, p < 0.05) and non-protective tidal volume (p < 0.04). Positive fluid balance (p < 0.01), high plasma D-dimers (p < 0.01) and ferritin (p < 0.04) were associated with increased lung injury. CONCLUSIONS: In a cohort of COVID-19 patients with severe respiratory failure, a predominant subpleural distribution of lung injury is observed. Prolonged spontaneous breathing and high tidal volumes, both causes of patient self-induced lung injury, are associated to an extensive involvement of more central regions. Positive fluid balance, inflammation and thrombosis are associated with lung injury. Trial registration Study registered a priori the 20th of March, 2020. Clinical Trials ID NCT04316884.

[Covid-19 - radiologic and histologic features]. / Radiologisk och histologisk bild för en ökad förståelse vid covid-19.

We here describe the current knowledge about the radiologic and histologic pulmonary features of covid-19, caused by SARS-CoV-2, and present lung histology from a case with fatal disease. Initial findings on computed tomography (CT) typically include peripheral multifocal bilateral ground-glass opacities, and correspondingly microscopic alveolar edema. This is followed by peripheral consolidations with air bronchogram and perilobular pattern on CT, signs of organizing pneumonia, corresponding to loose (potentially reversible) fibrosis. The posterior parts of the lungs and the lower lobes are typically more markedly affected. In severe disease with acute respiratory distress syndrome, thickened interlobular septa and crazy paving pattern appear on CT, which corresponds to histologic diffuse alveolar damage with, depending on the stage of the disease, features such as edema, hyaline membranes, reactive epithelium, inflammation, and fibrosis.

Feasibility of Assessing Inflammation in Asymptomatic Abdominal Aortic Aneurysms With Integrated 18F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging.

OBJECTIVE: This study aimed to evaluate the feasibility of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) combined with contrast enhanced magnetic resonance imaging (MRI) to identify inflammation in asymptomatic abdominal aortic aneurysms (AAA). METHODS: FDG PET/MRI was performed on 15 patients with asymptomatic infrarenal AAAs >45 mm diameter. Prevalence of FDG uptake and MRI findings of inflammatory changes (oedema, wall thickening, and late gadolinium enhancement [LGE]) in the aortic wall were investigated at three levels: suprarenal aorta; non-aneurysmal aortic neck; and AAA. RESULTS: The median diameter of the AAAs was 54 mm (range 47-65 mm) and the median expansion rate in the last 12 months was 3 mm (range 1-13 mm). The standard uptake value (SUV) of FDG in the aneurysmal wall (SUVmax 2.5) was higher than the blood pool (SUVmax 1.0; p < .001). The maximum target to background ratio was higher in the suprarenal aorta (mean ± SD; 3.1 ± 0.6) and aortic neck (2.7 ± 0.5) than in the aneurysmal aorta (2.5 ± 0.5; p < .001). Thirty-six FDG hotspots were observed in the aneurysmal wall of 13 patients. Wall thickening and LGE were identified in eight patients. The number of FDG hotspots correlated with recent AAA growth (r = 0.62, p = .01). The recent aneurysm expansion rate was higher in aneurysms with LGE than in those without (7 mm vs. 2 mm; p = .03). MRI inflammatory changes were observed in nine of 36 hot spots (25%) and in three of 13 patients with focal FDG uptake. CONCLUSION: Fully integrated FDG PET/MRI can be used to study inflammation in asymptomatic AAAs. Heterogenous uptake of FDG in the aneurysmal wall indicates increased glucose metabolism, suggesting an ongoing inflammation. However, these FDG hotspots rarely correspond to MRI findings of inflammation, raising the question of which type of cellular activity is present in these areas. The presence of LGE and FDG hotspots both correlated to recent aneurysm growth, and their usefulness as clinical markers of aneurysm growth warrant additional investigation.

The association of body mass index, weight gain and central obesity with activity-related breathlessness: the Swedish Cardiopulmonary Bioimage Study.

INTRODUCTION: Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m2) is rapidly increasing globally and its impact on breathlessness is unclear. METHODS: This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score ≥1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex. RESULTS: We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m2; and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness. CONCLUSION: Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.

Total atherosclerotic burden measured by magnetic resonance imaging is related to five-year decline in cognitive function.

OBJECTIVE: The aim of this study was to explore whether total atherosclerotic burden is related to future decline in performance on cognitive tests. METHODS: The total atherosclerotic burden (TAS) was assessed by whole-body magnetic resonance angiography (WBMRA) in 305 subjects at age 70 in the study Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS). The mini-mental state examination (MMSE) and trail making tests (TMT) A and B were evaluated at ages 75 and 80 in 190 of those subjects. No subject with a diagnosis of dementia was included in the sample. RESULTS: MMSE did not change during the 5 years of follow-up, while TMT A and B increased by 4 and 7 s, respectively. TAS at age 70 was significantly related to the individual change in TMT B (P<0·0001) between age 75 and 80, when adjusted for sex, education level, TMT B at age 75 and Framingham score at age 70. No such relationship was seen for the change in TMT A (P = 0·10). The relationship between TAS and the change in MMSE was of borderline significance (P = 0·025). CONCLUSION: A relationship was found between the total atherosclerotic burden and future decline in performance on TMT B, highlighting a role of global atherosclerosis in the cognitive decline seen during ageing.

Total atherosclerotic burden by whole body magnetic resonance angiography predicts major adverse cardiovascular events.

OBJECTIVE: The purpose of the present study was to investigate the relationship between the Total Atherosclerotic Score (TAS), a measurement of the overall atherosclerotic burden of the arterial tree by whole body magnetic resonance angiography (WBMRA), and the risk of major adverse cardiovascular events (MACE), defined as cardiac death, myocardial infarction, stroke and/or coronary revascularization, assuming that TAS predicts MACE. METHODS AND RESULTS: 305 randomly selected 70 year-old subjects (47% women) underwent WBMRA. Their atherosclerotic burden was evaluated and TAS > 0, that is atherosclerotic changes, were found in 68% of subjects. During follow-up (mean 4.8 years), MACE occurred in 25 subjects (8.2%). Adjusting for multiple risk factors, TAS was associated with MACE (OR 8.86 for any degree of vessel lumen abnormality, 95%CI 1.14-69.11, p = 0.037). In addition, TAS improved discrimination and reclassification when added to the Framingham risk score (FRS), and ROC (Receiver Operator Curve) increased from 0.681 to 0.750 (p = 0.0421). CONCLUSION: In a population-based sample of 70 year old men and women WBMRA, with TAS, predicted MACE independently of major cardiovascular risk factors.

An evaluation of the ability of Dichelobacter nodosus to survive in soil.

BACKGROUND: Dichelobacter nodosus is the causative agent of footrot in sheep. The survival of the bacterium in soil is of importance for the epidemiology of the disease. The investigation evaluates the survival of D. nodosus in soil with and without added hoof powder stored under different temperatures. RESULTS: An experimental setup was used with bacteriological culture and real-time polymerase chain reaction (PCR), and the results indicate that the bacteria can survive in soil for longer time than previously expected. The survival time was found to be dependent on temperature and the addition of hoof powder to the soil, with the longest survival time estimated to be 24 days in soil samples with hoof powder stored at 5°C. CONCLUSION: Our findings indicate that the survival time of D. nodosus and its ability to infect susceptible sheep on pasture under different climatic conditions should be studied further.

Comparison of computed tomography and autopsy in detection of injuries after unsuccessful cardiopulmonary resuscitation.

AIM: Computed tomography (CT) has been suggested as an aid or even a replacement for autopsy. The aim of this trial was to study the conformity of the two methods in finding injuries in non-surviving patients after unsuccessful cardiopulmonary resuscitation. METHODS: In this prospective study, 31 patients were submitted to a CT prior to autopsy after unsuccessful resuscitation attempts. Pathological findings were noted by both the radiologist and the pathologists in a specified protocol. The pathologists and radiologist were blinded from each other's results. RESULTS: CT and autopsy revealed rib fractures in 22 and 24 patients respectively (kappa=0.83). In 8 patients, CT revealed more rib fractures than autopsy; and in 12 patients, autopsy revealed more rib fractures than CT. In 7 patients, neither method showed any rib fractures. The mean difference between the two methods in detecting rib fractures was 0.16 (S.D.: ± 3.174, limits of agreement: -6.19 to 6.51). The kappa value for sternal fractures was 0.49. A total of 260 pathological findings were noted by CT and 244 by autopsy. The average patient showed a median of 9 injuries (every fracture counted as one injury), independent of the method used in detecting the injuries. CONCLUSIONS: There was a strong concordance between the two methods in finding rib fractures but not sternal fractures and these results support the concept of CT as a valuable complement to autopsy in detecting rib fractures after unsuccessful cardiopulmonary resuscitation but not as a replacement. Other injuries did not show the same concordance.

Circulating levels of secretory- and lipoprotein-associated phospholipase A2 activities: relation to atherosclerotic plaques and future all-cause mortality.

AIMS: Secretory- and lipoprotein-associated phospholipases A2 (sPLA2 and Lp-PLA2) are enzymes both suggested to be of importance for atherosclerosis. We investigated relationships between the activities of these enzymes in the circulation and atherosclerosis as well as future clinical events. METHODS AND RESULTS: The population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study included 1016 randomly selected subjects, all aged 70. The prevalence of carotid artery plaques was recorded by ultrasound (n= 954), and arterial stenosis was assessed by whole-body magnetic resonance angiography (WBMRA, n= 302). Secretory-associated phospholipase A2 [odds ratio 1.23 for 1 SD increase, 95% confidence interval (CI): 1.05-1.44, P= 0.007], but not Lp-PLA2 (P= 0.26), activity was significantly related to carotid atherosclerosis and to the amount of stenosis at WBMRA (P= 0.006) following adjustment for multiple risk factors (waist circumference, serum triglycerides, body mass index, C-reactive protein, high density lipoprotein-C, low density lipoprotein-C, triglycerides, GFR, fasting glucose, blood pressure, statin use, and exercise habits). Secretory-associated phospholipase A2 [hazard ratio (HR) 1.45 for 1 SD increase, 95% CI: 1.15-1.84, P= 0.001], but not Lp-PLA2 (HR 0.95, P= 0.55), activity was a significant risk factor for all-cause mortality (114 had died) during 7.0 years follow-up after adjustment for the risk factors described above. In a sample of 1029 post-myocardial infarction (MI) patients (French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction), sPLA2 (adjusted HR 1.32 for 1 unit increase, 95% CI: 1.02-1.71, P= 0.036), but not Lp-PLA2 (HR 1.03, P= 0.90), activity predicted death or recurrent MI during 1-year follow-up (n= 136 cases). CONCLUSION: sPLA2 activity was related to atherosclerosis and predicted all-cause mortality in a sample of elderly subjects, as well as death or MI in post-MI patients.

Brachial artery hyperaemic blood flow velocity in relation to established indices of vascular function and global atherosclerosis: the Prospective Investigation of the Vasculature in Uppsala Seniors study.

BACKGROUND: Systolic to diastolic blood flow velocity (SDFV) ratio in the brachial artery recently proved to be related to cardiovascular risk and carotid atherosclerosis. We hypothesized that the SDFV ratio was related to established markers of vascular function and global atherosclerosis. METHODS: Established markers of endothelial function in forearm resistance vessels, flow-mediated vasodilation and arterial stiffness were assessed in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study including 1016 individuals aged 70. Whole-body magnetic resonance angiography was performed in a random 306 of the participants. Atherosclerotic lesions were summarized in a total atherosclerotic score (TAS). Before and during hyperaemia of the brachial artery, systolic and diastolic blood flow velocities were measured by Doppler. RESULTS: The SDFV ratio was positively related to endothelium-independent vasodilatation, while inverse relations were found to flow-mediated dilation, common carotid artery distensibility and the stroke volume to pulse pressure ratio. Endothelium-dependent vasodilatation and total peripheral resistance index were not significantly related to the SDFV ratio. The SDFV ratio (P = 0·015) and the blood flow increase (BFI) during hyperaemia (P = 0·020) were both significantly related to TAS after gender adjustment. When adjusted for the Framingham risk score, both the SDFV ratio (P = 0·057) and BFI (P = 0·078) lost somewhat in significance. CONCLUSION: The SDFV ratio was related to established markers of both vasodilation and arterial compliance, and to global atherosclerosis. Future larger studies have to evaluate whether the SDFV ratio is related to global atherosclerosis independently of traditional risk factors.

Atherosclerosis measured by whole body magnetic resonance angiography and carotid artery ultrasound is related to arterial compliance, but not to endothelium-dependent vasodilation - the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.

BACKGROUND: Arterial compliance and endothelium-dependent vasodilation are two characteristics of the vessel wall. In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, we studied the relationships between arterial compliance and endothelium-dependent vasodilation versus atherosclerosis as measured with two imaging modalities. METHODS: In the population-based PIVUS study (1016 subjects aged 70), arterial compliance was determined by ultrasound in the carotid artery and the stroke volume to pulse pressure ratio by echocardiography, while endothelium-dependent vasodilation was assessed by the invasive forearm technique with acetylcholine and brachial artery ultrasound. Intima-media thickness was evaluated by ultrasound in the carotid artery (n = 954). Stenosis in the carotid, aorta, renal, upper and lower leg arteries were determined by magnetic resonance angiography in a random subsample of 306 subjects. RESULTS: After adjustments for gender, Framingham risk score, obesity, myocardial infarction and stroke, distensibility in the carotid artery and the stroke volume to pulse pressure ratio were both significantly related to a weighted index of stenosis in the five arterial territories evaluated by magnetic resonance angiography (p<0.02 for both). Distensibility in the carotid artery (P = 0.021), but not the stroke volume to pulse pressure ratio (P = 0.08), was also significantly related to intima-media thickness. CONCLUSION: In the elderly population, atherosclerosis is mainly related to arterial compliance, but not to endothelium-dependent vasodilation in peripheral conduit or resistance vessels.

Relationship between circulating FGF23 and total body atherosclerosis in the community.

BACKGROUND: Fibroblast growth factor-23 (FGF23) is a regulator of mineral metabolism and has been suggested to play a role in vascular calcification in chronic kidney disease (CKD). Data on the association between FGF23 and atherosclerosis, both in CKD and in the community, is limited. METHODS: The total body atherosclerosis score (AS) was determined by a magnetic resonance imaging-based angiography in 306 elderly men and women, representing a subsample of the community-based PIVUS cohort. Subjects were divided into three categories based on AS: AS = 0, low AS and high AS. Serum FGF23 was measured using a two-site monoclonal antibody ELISA. RESULTS: In continuous and multi-category regression models, higher FGF23 was associated with a significant increase in the odds of having a high AS (OR 1.43, CI 1.06-1.92 to OR 3.01, CI 1.52-5.99). This association was stronger in individuals with eGFR <60 mL/min/1.73 m(2) (n = 27), reaching a nearly 6-fold increase in the odds for a high AS in the upper FGF23 tertile (OR 5.64, CI 2.78-11.5). We found weaker support for a relationship between FGF23 and the presence of atherosclerosis as subjects in the highest FGF23 tertile had an increased risk for an AS > 0 in crude models (OR 1.93, CI 1.05-3.55), but this was not statistically significant in adjusted (OR 1.42, CI 0.74-1.72) models. CONCLUSIONS: We provide novel evidence supporting an association between serum FGF23 and total body atherosclerosis in the community. Additional studies are warranted to determine the prospective relationship between FGF23 and atherosclerosis, and whether FGF23 is a modifiable cardiovascular risk factor.

Lower extremity artery stenosis distribution in an unselected elderly population and its relation to a reduced ankle-brachial index.

OBJECTIVE: This study evaluated the distribution and degree of symmetry of lower extremity artery stenoses in an unselected elderly population and its relation to a reduced ankle-brachial index (ABI) measurement. METHODS: This was a population-based study set in a university hospital comprising 306 randomly selected 70-year-old individuals participating in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Whole-body magnetic resonance angiography (MRA) and bilateral ABI measurements were performed in each participant. The prevalence of stenosis >or=50% was evaluated in nine different arterial segments in both legs: common iliac artery (CIA), external iliac artery (EIA), common femoral artery (CFA), superficial femoral artery (SFA), popliteal artery (PA), tibioperoneal trunk (TPTr), anterior tibial artery (ATA), posterior tibial artery (PTA), and peroneal artery. The relations between the prevalences of stenosis in different arterial segments in the right and left leg were assessed. An evaluation was made of the relation between a >or=50% stenosis and an ABI <0.9 in the different segments. RESULTS: The prevalence of stenosis was 0% to 21%. In all segments, a stenosis was more commonly found in one of the legs only than in both legs. The prevalence of >or=50% stenosis in the right leg only, left leg only, and both legs was 0.3%, 0.7%, and 0% in the CIA; 0.3%, 1.0%, and 0.7% in the EIA; 0%, 0%, and 0% in the CFA; 2.0%, 1.3%, and 0.7% in the SFA; 0.7%, 0.7%, and 0.3% in the PA; 1.0%, 0.7%, and 0% in the TPTr; 5.6%, 6.3%, and 8.6% in the ATA; 0.7%, 1.7%, and 0% in the peroneal artery; and in 2.0%, 2.7%, and 3.4% in the PTA. When the legs were compared, a significant correlation was found for the presence of a >or=50% stenosis in the EIA, SFA, PA, ATA, and PTA. Seventeen participants showed ABI <0.9. In logistic regression analysis with ABI <0.9 as dependent variable, stenosis in SFA, ATA, and PTA were the major independent variables to explain a low ABI in both of the legs. CONCLUSIONS: The distribution of stenosis differs substantially when legs are compared. Despite this difference, stenosis in SFA, ATA, and PTA was the major determinant of a low ABI in both of the legs.

Whole-body screening of atherosclerosis with magnetic resonance angiography.

With whole-body magnetic resonance angiography (WBMRA), it is possible to examine the whole arterial tree except intracranial and coronary vessels in a single examination without the risks involved in ionizing radiation or arterial cannulation. Whole-body magnetic resonance angiography is well suited for repeated clinical examinations in patients with systemic diseases such as vasculitis or atherosclerosis and can also be used for scientific purposes. On the basis of the WBMRA overview, a possible further development of the WBMRA concept can be to perform further acquisitions at sites with atherosclerotic plaques with higher-resolution scans to determine the degree of stenosis more accurately or to achieve plaque characterization. A total validation of WBMRA compared with digital subtraction angiography (DSA) is not possible owing to the hazards of ionizing radiation. Studies have shown a high sensitivity and specificity for the pelvic and lower limb arteries in comparison with DSA. No systematic validation against DSA has been performed for the renal, aortic, and carotid arteries. Various methods have been used, however, for confirmation of vascular abnormalities found on WBMRA such as ultrasonography, dedicated MRA, or DSA, with reasonably high agreement. The WBMRA method has not been studied with regard to prediction of future cardiovascular (CV) events, as have intima media thickness, coronary artery calcium scoring, and the ankle-brachial index. The full usefulness of WBMRA in an epidemiological setting and as a complementary screening tool for assessing CV risk still needs to be validated against future CV events.