Anatomical Markers Associated With the Presence of Intracranial Aneurysms in Individuals Screened for Aneurysms

BACKGROUND Hemodynamic stress is linked to the development of intracranial aneurysms (IAs) and may be influenced by anatomic variation of intracranial arteries. We assessed diameters and bifurcation angles of intracranial arteries forming the circle of Willis in a cohort of individuals screened for the presence of IAs. METHODS Individuals with and without IAs identified at screening with magnetic resonance angiography were compared. Diameters and bifurcation angles of the following arteries were measured using semiautomatic methods: A1 and A2 segments of the anterior cerebral artery, M1 and M2 segments of the middle cerebral artery, P1 segments of the posterior cerebral artery, posterior communicating artery (Pcom), internal carotid artery, vertebral artery, and basilar artery. We employed univariate general linear models to assess group differences. This included subgroup comparisons between individuals with IAs at specific locations and matched controls, and comparisons on group level between individuals with and without IAs, corrected for age and sex. RESULTS In 94 of the 1049 individuals (9.0%) included, IAs were detected. Individuals with middle cerebral artery IAs had wider ipsilateral M2–M2 bifurcation angles compared with controls (121±25° versus 97±19°; P<0.01). Individuals with anterior communicating artery IAs showed smaller angles for the A1–A2 bifurcation (106±16° versus 120±17°; P = 0.02), while those with Pcom IAs had wider Pcom–C7 bifurcation angles (147±14° versus 127±17°; P = 0.02) and smaller diameters below the ipsilateral internal carotid artery top (2.86±0.36 mm versus 3.10±0.33 mm; P = 0.03) compared with controls. CONCLUSION We found associations between wider M2–M2 bifurcation angles or narrower A1–A2 bifurcation angles and IA presence, consistent with prior literature. Moreover, we uncovered previously unexplored associations, including wider Pcom–C7 bifurcation angles and smaller internal carotid artery diameters in individuals with Pcom IAs. Future research should explore the potential of these markers in predicting IAs in at‐risk populations during follow‐up screenings

Epoetin Beta and C-Terminal Fibroblast Growth Factor 23 in Patients With Chronic Heart Failure and Chronic Kidney Disease

Background In patients with chronic heart failure and chronic kidney disease, correction of anemia with erythropoietin-stimulating agents targeting normal hemoglobin levels is associated with an increased risk of cardiovascular morbidity and mortality. Emerging data suggest a direct effect of erythropoietin on fibroblast growth factor 23 (FGF23), elevated levels of which have been associated with adverse outcomes. We investigate effects of erythropoietin-stimulating agents in patients with both chronic heart failure and chronic kidney disease focusing on FGF23. Methods and Results In the EPOCARES (Erythropoietin in CardioRenal Syndrome) study, we randomized 56 anemic patients (median age 74 [interquartile range 69-80] years, 66% male) with both chronic heart failure and chronic kidney disease into 3 groups, of which 2 received epoetin beta 50 IU/kg per week for 50 weeks, and the third group served as control. Measurements were performed at baseline and after 2, 26, and 50 weeks. Data were analyzed using linear mixed-model analysis. After 50 weeks of erythropoietin-stimulating agent treatment, hematocrit and hemoglobin levels increased. Similarly, C-terminal FGF23 levels, in contrast to intact FGF23 levels, rose significantly due to erythropoietin-stimulating agents as compared with the controls. During median follow-up for 5.7 (2.0-5.7) years, baseline C-terminal FGF23 levels were independently associated with increased risk of mortality (hazard ratio 2.20; 95% CI, 1.35-3.59; P=0.002). Conclusions Exogenous erythropoietin increases C-terminal FGF23 levels markedly over a period of 50 weeks, elevated levels of which, even at baseline, are significantly associated with an increased risk of mortality. The current results, in a randomized trial setting, underline the strong relationship between erythropoietin and FGF23 physiology in patients with chronic heart failure and chronic kidney disease. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00356733

Atherosclerotic renal artery stenosis is prevalent in cardiorenal patients but not associated with left ventricular function and myocardial fibrosis as assessed by cardiac magnetic resonance imaging

<p>Abstract</p> <p>Background</p> <p>Atherosclerotic renal artery stenosis (ARAS) is common in cardiovascular diseases and associated with hypertension, renal dysfunction and/or heart failure. There is a paucity of data about the prevalence and the role of ARAS in the pathophysiology of combined chronic heart failure (CHF) and chronic kidney disease (CKD). We investigated the prevalence in patients with combined CHF/CKD and its association with renal function, cardiac dysfunction and the presence and extent of myocardial fibrosis.</p> <p>Methods</p> <p>The EPOCARES study (ClinTrialsNCT00356733) investigates the role of erythropoietin in anaemic patients with combined CHF/CKD. Eligible subjects underwent combined cardiac magnetic resonance imaging (cMRI), including late gadolinium enhancement, with magnetic resonance angiography of the renal arteries (MRA).</p> <p>Results</p> <p>MR study was performed in 37 patients (median age 74 years, eGFR 37.4 ± 15.6 ml/min, left ventricular ejection fraction (LVEF) 43.3 ± 11.2%), of which 21 (56.8%) had ARAS (defined as stenosis >50%). Of these 21 subjects, 8 (21.6%) had more severe ARAS >70% and 8 (21.6%) had a bilateral ARAS >50% (or previous bilateral PTA). There were no differences in age, NT-proBNP levels and medication profile between patients with ARAS versus those without. Renal function declined with the severity of ARAS (p = 0.03), although this was not significantly different between patients with ARAS versus those without. Diabetes mellitus was more prevalent in patients without ARAS (56.3%) against those with ARAS (23.8%) (p = 0.04). The presence and extent of late gadolinium enhancement, depicting myocardial fibrosis, did not differ (p = 0.80), nor did end diastolic volume (p = 0.60), left ventricular mass index (p = 0.11) or LVEF (p = 0.15). Neither was there a difference in the presence of an ischemic pattern of late enhancement in patients with ARAS versus those without.</p> <p>Conclusions</p> <p>ARAS is prevalent in combined CHF/CKD and its severity is associated with a decline in renal function. However, its presence does not correlate with a worse LVEF, a higher left ventricular mass or with the presence and extent of myocardial fibrosis. Further research is required for the role of ARAS in the pathophysiology of combined chronic heart and renal failure.</p

Anatomical Markers Associated With the Presence of Intracranial Aneurysms in Individuals Screened for Aneurysms

Background Hemodynamic stress is linked to the development of intracranial aneurysms (IAs) and may be influenced by anatomic variation of intracranial arteries. We assessed diameters and bifurcation angles of intracranial arteries forming the circle of Willis in a cohort of individuals screened for the presence of IAs. Methods Individuals with and without IAs identified at screening with magnetic resonance angiography were compared. Diameters and bifurcation angles of the following arteries were measured using semiautomatic methods: A1 and A2 segments of the anterior cerebral artery, M1 and M2 segments of the middle cerebral artery, P1 segments of the posterior cerebral artery, posterior communicating artery (Pcom), internal carotid artery, vertebral artery, and basilar artery. We employed univariate general linear models to assess group differences. This included subgroup comparisons between individuals with IAs at specific locations and matched controls, and comparisons on group level between individuals with and without IAs, corrected for age and sex. Results In 94 of the 1049 individuals (9.0%) included, IAs were detected. Individuals with middle cerebral artery IAs had wider ipsilateral M2–M2 bifurcation angles compared with controls (121±25° versus 97±19°; P<0.01). Individuals with anterior communicating artery IAs showed smaller angles for the A1–A2 bifurcation (106±16° versus 120±17°; P = 0.02), while those with Pcom IAs had wider Pcom–C7 bifurcation angles (147±14° versus 127±17°; P = 0.02) and smaller diameters below the ipsilateral internal carotid artery top (2.86±0.36 mm versus 3.10±0.33 mm; P = 0.03) compared with controls. Conclusion We found associations between wider M2–M2 bifurcation angles or narrower A1–A2 bifurcation angles and IA presence, consistent with prior literature. Moreover, we uncovered previously unexplored associations, including wider Pcom–C7 bifurcation angles and smaller internal carotid artery diameters in individuals with Pcom IAs. Future research should explore the potential of these markers in predicting IAs in at‐risk populations during follow‐up screenings

Epoetin Beta and C-Terminal Fibroblast Growth Factor 23 in Patients With Chronic Heart Failure and Chronic Kidney Disease

Background In patients with chronic heart failure and chronic kidney disease, correction of anemia with erythropoietin-stimulating agents targeting normal hemoglobin levels is associated with an increased risk of cardiovascular morbidity and mortality. Emerging data suggest a direct effect of erythropoietin on fibroblast growth factor 23 (FGF23), elevated levels of which have been associated with adverse outcomes. We investigate effects of erythropoietin-stimulating agents in patients with both chronic heart failure and chronic kidney disease focusing on FGF23. Methods and Results In the EPOCARES (Erythropoietin in CardioRenal Syndrome) study, we randomized 56 anemic patients (median age 74 [interquartile range 69-80] years, 66% male) with both chronic heart failure and chronic kidney disease into 3 groups, of which 2 received epoetin beta 50 IU/kg per week for 50 weeks, and the third group served as control. Measurements were performed at baseline and after 2, 26, and 50 weeks. Data were analyzed using linear mixed-model analysis. After 50 weeks of erythropoietin-stimulating agent treatment, hematocrit and hemoglobin levels increased. Similarly, C-terminal FGF23 levels, in contrast to intact FGF23 levels, rose significantly due to erythropoietin-stimulating agents as compared with the controls. During median follow-up for 5.7 (2.0-5.7) years, baseline C-terminal FGF23 levels were independently associated with increased risk of mortality (hazard ratio 2.20; 95% CI, 1.35-3.59; P=0.002). Conclusions Exogenous erythropoietin increases C-terminal FGF23 levels markedly over a period of 50 weeks, elevated levels of which, even at baseline, are significantly associated with an increased risk of mortality. The current results, in a randomized trial setting, underline the strong relationship between erythropoietin and FGF23 physiology in patients with chronic heart failure and chronic kidney disease. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00356733