Tomas Hansen

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.

Relation between insulin and aortic stiffness: A population-based study

Recent studies have suggested that a high pulse wave velocity (PWV), a measure of aortic stiffness, may be a stronger risk factor for cardiovascular disease (CVD) than a high blood pressure (BP). The relation between insulin, believed to play an important role in the development and clinical course of high BP, and PWV is not yet clear. Therefore, we decided to examine the relationship between insulin and PWV in a large population-based study. The study population consisted of a random sample of 1213 women and 1207 men (age range, 41–72 years) without a history of myocardial infarction or stroke. Fasting insulin was determined together with conventional risk factors for CVD. PWV was recorded transcutaneously by a mechanical electrical principle with one transducer positioned over the left common carotid artery, and another over the left femoral artery. In univariate analysis, insulin was highly significantly related to PWV (standardized regression coefficient: 0.0669±0.0051; P<0.001). In multivariate analysis, controlling for all well-established predictors of PWV, such as age, systolic BP or mean BP and pulse pressure, sex, and heart rate, as well as controlling for conventional risk factors for CVD and use of BP-lowering drugs, the level of insulin remained a significant predictor of PWV (standardized regression coefficient: 0.0122±0.0048; P=0.012). In conclusion, the present study found that a higher insulin level was related to a higher PWV. This indicates that hyperinsulinaemia may affect BP and risk of CVD by increasing aortic stiffness.

Ankle brachial index <0.9 underestimates the prevalence of peripheral artery occlusive disease assessed with whole-body magnetic resonance angiography in the elderly.

Background: Whole-body magnetic resonance angiography (WBMRA) permits noninvasive vascular assessment, which can be utilized in epidemiological studies. Purpose: To assess the relation between a low ankle brachial index (ABI) and high-grade stenoses in the pelvic and leg arteries in the elderly. Material and Methods: WBMRA was performed in a population sample of 306 subjects aged 70 years. The arteries below the aortic bifurcation were graded after the most severe stenosis according to one of three grades: 0–49% stenosis, 50–99% stenosis, or occlusion. ABI was calculated for each side. Results: There were assessable WBMRA and ABI examinations in 268 (right side), 265 (left side), and 258 cases (both sides). At least one ⩾50% stenosis was found in 19% (right side), 23% (left side), and 28% (on at least one side) of the cases. The corresponding prevalences for ABI <0.9 were 4.5%, 4.2%, and 6.6%. An ABI cut-off value of 0.9 resulted in a sensitivity, specificity, and positive and negative predictive value of 20%, 99%, 83%, and 84% on the right side, and 15%, 99%, 82%, and 80% on the left side, respectively, for the presence of a ⩾50% stenosis in the pelvic or leg arteries. Conclusion: An ABI <0.9 underestimates the prevalence of peripheral arterial occlusive disease in the general elderly population.

The Prevalence and Quantification of Atherosclerosis in an Elderly Population Assessed by Whole-Body Magnetic Resonance Angiography

Objective—The principal aim of the present study was to explore the feasibility of using whole-body magnetic resonance angiography to assess atherosclerosis in different vascular territories in a cohort of elderly. Methods and Results—Three hundred six 70-year-old subjects (145 women, 161 men) recruited from a population-based cohort study (Prospective Investigation of the Vasculature in Uppsala Seniors, ie, the PIVUS study) underwent 1.5-T whole-body magnetic resonance angiography with gadodiamide. The arteries were divided into 26 segments. In total, 7956 vessel segments were evaluated with 7900 segments (99.3%) possible to evaluate. Of these, 7186 segments (91%) were normal. Luminal narrowing of ≥50% was observed in 9 (1.5%) of the renal arteries, 12 (1.8%) of the carotid arteries, in 31 segments (1.1%) of the pelvic/upper leg territories, and in 136 segments (6.2%) of territories in the lower leg. Approximately one-third of the sample had no vascular abnormalities, one-third had stenoses of <50%, and the remainder had stenoses ≥50% or occlusions. Six subjects (2%) had aortic aneurysms. In subjects without evident vascular disease, 26% had significant vascular abnormalities. Conclusions—Whole-body magnetic resonance angiography performed with a clinical scanner can be used for quantifying atherosclerosis in different vascular territories in a single examination in an elderly population.

Visceral adipose tissue, adiponectin levels and insulin resistance are related to atherosclerosis as assessed by whole-body magnetic resonance angiography in an elderly population

OBJECTIVE The principal aim of this study was to determine whether the amount of visceral adipose tissue (VAT) is more related than subcutaneous adipose tissue (SAT) to atherosclerosis assessed by whole-body MRA (WBMRA). A further objective was to investigate whether traditional risk factors, inflammation, or adipokines could explain the hypothesized relationship between VAT and atherosclerosis. METHODS Men and women aged 70 were recruited from the general population into the Prospective Investigation of The Vasculature in Uppsala Seniors (PIVUS) and 306 of them underwent WBMRA in a clinical 1.5-T scanner. The arterial tree was assessed for degree of stenosis or occlusion and a total atherosclerotic score (TAS) was established. Information on risk factors and BMI and on SAT and VAT, segmented on an axial MR scan was collected. Adiponectin, leptin, and high sensitive C-reactive protein (hsCRP) were measured in serum. HOMA index was used as a marker of insulin resistance. RESULTS VAT was related to TAS independently of gender, total obesity (BMI), amount of SAT, hsCRP and also to the traditional risk factors included in the Framingham risk score (FRS) in an elderly population. Adiponectin or the HOMA insulin resistance, but not leptin or VAT, together with FRS was significantly related to TAS in a multiple censored regression model. CONCLUSION Adiponectin attenuated the relationship between VAT and TAS, suggesting that adiponectin and insulin resistance is an important link between visceral adiposity and atherosclerosis.

Patient specific biomodel of the whole aorta : the importance of calcified plaque removal

BACKGROUND The use of anatomical models produced by 3D printing technique (rapid prototyping, RP) is gaining increased acceptance as a complementary tool for planning complex surgical interventions. This paper describes a method for creating a patient specific replica of the whole aorta. METHODS Computed tomography angiography (CTA) DICOM-data was converted to a three-dimensional computer aided design-model (CAD) of the inner wall of the aorta representing the lumen where the calcified plaque contribution was removed in a multi-step editing-manoeuvre. The edited CAD-model was used for creating a physical plaster model of the true lumen in a 3D-printer. Elastic and transparent silicon was applied onto the plaster model, which was then removed leaving a silicon replica of the aorta. RESULTS The median (interquartile range) difference between diameters obtained from CTA- and RP plaster-model at 19 predefined locations was 0.5 mm (1 mm) which corresponds to a relative median difference of 4.6% (7.0%). The average wall thickness of the silicone model was 3.5 mm. The elasticity property and performance during intervention was good with an acceptable transparency. CONCLUSIONS The integration of RP-techniques with CAD based reconstruction of 3D-medical imaging data provides the needed tools for making a truly patient specific replica of the whole aorta with high accuracy. Plaque removal postprocessing is necessary to obtain a true inner wall configuration.

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.

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.

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.

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 others 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.