Nonvascular Disease Research Articles

Conventional and genetic associations of BMI with major vascular and non-vascular disease incidence and mortality in a relatively lean Chinese population: U-shaped relationship revisited.

Higher body mass index (BMI) is associated with higher incidence of cardiovascular and some non-cardiovascular diseases (CVDs/non-CVDs). However, uncertainty remains about its associations with mortality, particularly at lower BMI levels. The prospective China Kadoorie Biobank recruited >512 000 adults aged 30-79years in 2004-08 and genotyped a random subset of 76 000 participants. In conventional and Mendelian randomization (MR) analyses, Cox regression yielded adjusted hazard ratios (HRs) associating measured and genetically predicted BMI levels with incident risks of major vascular events (MVEs; conventional/MR 68 431/23 621), ischaemic heart disease (IHD; 50 698/12 177), ischaemic stroke (IS; 42 427/11 897) and intracerebral haemorrhage (ICH; 7644/4712), and with mortality risks of CVD (15 427/6781), non-CVD (26 915/4355) and all causes (42 342/6784), recorded during ∼12years of follow-up. Overall, the mean BMI was 23.8 (standard deviation: 3.2) kg/m2 and 13% had BMIs of <20 kg/m2. Measured and genetically predicted BMI showed positive log-linear associations with MVE, IHD and IS, but a shallower positive association with ICH in conventional analyses. Adjusted HRs per 5 kg/m2 higher genetically predicted BMI were 1.50 (95% CI 1.41-1.58), 1.49 (1.38-1.61), 1.42 (1.31-1.54) and 1.64 (1.58-1.69) for MVE, IHD, IS and ICH, respectively. These were stronger than associations in conventional analyses [1.21 (1.20-1.23), 1.28 (1.26-1.29), 1.31 (1.29-1.33) and 1.14 (1.10-1.18), respectively]. At BMIs of ≥20 kg/m2, there were stronger positive log-linear associations of BMI with CVD, non-CVD and all-cause mortality in MR than in conventional analyses. Among relatively lean Chinese adults, higher genetically predicted BMI was associated with higher risks of incident CVDs. Excess mortality risks at lower BMI in conventional analyses are likely not causal and may reflect residual reverse causality.

Tumor ablation including carotid artery resection and simultaneous reconstruction: A retrospective study

The study purpose is to review the surgical approach and evaluate the results in cases of head and neck malignancies with internal carotid artery invasion.The anatomical site of the primary tumor varied including a fixed massive metastatic neck disease of an occult intraoral carcinoma of the right tonsil, a recurrent metastatic neck tumor after laryngectomy for glottic primary carcinoma and a metastatic malignant melanoma of an unknown primary origin. In all cases carotid artery was invaded and therefore resected. An extended Javid shunt was performed between common carotid artery (CCA) and internal carotid artery (ICA) followed by CCA grafting with an interposition saphenous vein graft. In one case the vagus nerve was also grafted with an interposition sural graft.The total patient number was three. By clinical examination, follow-up and duplex scanning, the patency of the carotid grafts, vascular and non-vascular complications, disease recurrence and survival were analysed. Additionally, there was a double metachronous reconstruction for recurrence, giving the opportunity to study the graft adoption and response to disease.Internal carotid artery invasion portends a poor prognosis. The results show that carotid artery resection followed by the appropriate reconstruction yields a chance for cure or can provide reasonable palliation.

Insights into single-timepoint ASL hemodynamics: what visual assessment and spatial coefficient of variation can tell

PurposeArterial spin labeling (ASL) represents a noninvasive perfusion biomarker, and, in the study of nonvascular disease, the use of the single-timepoint ASL technique is recommended. However, the obtained cerebral blood flow (CBF) maps may be highly influenced by delayed arterial transit time (ATT). Our aim was to assess the complexity of hemodynamic information of single-timepoint CBF maps using a new visual scale and comparing it with an ATT proxy, the “coefficient of spatial variation” (sCoV).Material and methodsIndividual CBF maps were estimated in a memory clinic population (mild cognitive impairment, dementia and cognitively unimpaired controls) and classified into four levels of delayed perfusion based on a visual rating scale. Calculated measures included global/regional sCoVs and common CBF statistics, as mean, median and standard deviation. One-way ANOVA was performed to compare these measures across the four groups of delayed perfusion. Spearman correlation was used to study the association of global sCoV with clinical data and CBF statistics.ResultsOne hundred and forty-four participants (72 ± 7 years, 53% women) were included in the study. The proportion of maps with none, mild, moderate, and severe delayed perfusion was 15, 20, 37, and 28%, respectively. SCoV demonstrated a significant increase (p < 0.05) across the four groups, except when comparing none vs mild delayed perfusion groups (pBonf > 0.05). Global sCoV values, as an ATT proxy, ranged from 67 ± 4% (none) to 121 ± 24% (severe delayed) and were significantly associated with age and CBF statistics (p < 0.05).ConclusionThe impact of ATT delay in single-time CBF maps requires the use of a visual scale or sCoV in clinical or research settings.

Assessment of the aortic tunica media histological changes in relation with the cause of death.

The authors set out to evaluate the correlations between three of the main morphological aortic parameters (elastic fibers - FE, collagen fibers - FCOL, and smooth muscle fibers - FM) and the cause of death. Study groups included 25 cases died of a vascular disease (V_P), 37 cases died of a non-vascular disease (NV_P) and 28 cases died of a violent/suspect non-pathological cause of death (V_Dth), the latter group representing also the control group. Four aortic cross-sections (base, arch, thoracic, and abdominal regions) were collected during autopsy from the selected cases, fixed in 10% buffered formalin and first of all photographed together with a calibrating ruler. Then, they were embedded in paraffin, sectioned off at 4 μm and stained with Hematoxylin-Eosin (HE) and Orcein. The obtained histological slides were transformed into virtual slides. Fibrillary components amounts were using a custom-made software, developed in MATLAB (MathWorks, USA). Statistical tools used were Pearson's correlation test, t-test (two-sample assuming equal variances) and one-way analysis of variance (ANOVA) test. The amounts of the three fibrillary components of the aortic tunica media had a synchronous variation in all aortic regions in each of the three groups, excepting FCOL in the group of patients died from vascular pathology, which presented only a trend of synchronous variation along the aorta. FE had their lowest values and FCOL had their highest values in patients died from vascular pathology. FCOL had always higher levels than FE in people died from any pathological condition, vascular or non-vascular. FM had always at least two times lower level than that of the other types of fibers, regardless of whether the person died due to a pathological condition or not. The different pathological conditions causing death are influencing the fibrillary composition of aortic tunica media. Further studies are required to reveal other changes in the morphology of aortic wall in particular and vascular wall in general that could be related with different pathological conditions affecting the entire organism.

THU334 Trends In GLP-1 Agonist Utilization In Diabetics With And Without Vascular Disease

Abstract Disclosure: P. Sargin: None. M. Barahona: None. H. Rubayet: None. G. Leef: None. GLP-1 agonists (GLP1) have emerged as a breakthrough class of drugs for the management of Type 2 Diabetes (T2DM). Data from cardiovascular outcomes trials has shown benefits in patients with known atherosclerotic vascular disease, including reduced cardiovascular mortality and stroke. These agents are now considered preferred therapy, however, prior studies have shown low rates of utilization. We hypothesized that recent guidelines and provider education may lead to increased prescribing of GLP1. We analyzed a large, multicenter database to investigate recent trends in GLP1 utilization in patients with T2DM and vascular disease. We extracted all patients from the database with T2DM and excluded patients with diagnoses of Type 1 Diabetes, thyroid cancer, pancreatitis, or MEN syndrome type 2, or age &amp;gt;90. We then stratified the cohort to compare patients with a diagnosis of ischemic heart disease, peripheral vascular disease, or cerebrovascular disease since January 1st, 2021 against diabetic patients without these diagnoses. Patients were compared for rates of prescription of diabetes medications and baseline characteristics including age, sex, race, BMI, HgA1c, and creatinine. Our search generated a total of 408553 patients with T2DM and vascular disease (defined as at least one of the following: ischemic heart disease, peripheral vascular disease, cerebrovascular disease), and 520383 with T2DM and no known vascular disease. The vascular disease cohort was 56% male, 68% white, mean age 70±13. Ischemic heart disease was present in 78%, cerebrovascular disease in 43%, and peripheral vascular disease in 22%. The non-vascular disease cohort was 54% female, 57% white, mean age 63±16. In the vascular disease cohort, 56% were prescribed insulin, 47% metformin, 17% SGLT2, and 14% GLP1. In the non-vascular disease cohort, 43% were prescribed metformin, 32% insulin, 11% GLP1, and 8% SGLT2. The P-value was less than 0.001 for all comparisons. Rates of the utilization of GLP1 agents in our database are still relatively low, but higher than has been reported before. This might suggest a favorable trend compared with prior studies on this topic, although they are not directly comparable due to different patient populations. With only 14% of the T2DM-vascular disease population receiving one of these agents (after excluding those with a documented contraindication), more work needs to be done to enable all patients who would benefit from these medications to access them. Presentation: Thursday, June 15, 2023

Outcomes of Oral Anticoagulation in Atrial Fibrillation Patients With or Without Comorbid Vascular Disease: Insights From the GARFIELD-AF Registry

BackgroundMany patients with atrial fibrillation suffer from comorbid vascular disease. The comparative efficacy and safety of different types of oral anticoagulation (OAC) in this patient group have not been widely studied. MethodsAdults with newly diagnosed atrial fibrillation were recruited into the prospective observational registry, GARFIELD-AF, and followed for 24 months. Associations of vascular disease with clinical outcomes were analyzed using adjusted hazard ratios (HR) obtained via Cox proportional-hazard modeling. Outcomes of OAC vs no OAC, and of non-vitamin K antagonist OAC (NOAC) vs vitamin K antagonist (VKA) treatment, were compared by overlap propensity-weighted Cox proportional-hazard models. ResultsOf 51,574 atrial fibrillation patients, 25.9% had vascular disease. Among eligible atrial fibrillation patients, those with vascular disease received OAC less frequently than those without (63% vs 73%). Over 2-year follow-up, patients with vascular disease showed a higher risk of all-cause mortality (HR 1.30; 95% confidence interval [CI], 1.16-1.47) and cardiovascular mortality (HR 1.59; 95% CI, 1.28-1.97). OAC was associated with a significant decrease in all-cause mortality and non-hemorrhagic stroke, and increased risk of major bleeding in non-vascular disease. In vascular disease, similar but non-significant trends existed for stroke and major bleeding. A significantly lower risk of all-cause mortality (HR 0.74; 95% CI, 0.61-0.90) and major bleeding (HR 0.45; 95% CI, 0.29-0.70) was observed in vascular disease patients treated with NOACs, compared with VKAs. ConclusionsAtrial fibrillation patients with a history of vascular disease have worse long-term outcomes than those without. The association of NOACs vs VKA with clinical outcomes was more evident in atrial fibrillation patients with vascular disease.

Physical activity and risk of chronic kidney disease: systematic review and meta-analysis of 12 cohort studies involving 1,281,727 participants

The role of regular physical activity in preventing vascular and non-vascular disease is well established. Chronic kidney disease (CKD) is a major cause of global morbidity and mortality and largely preventable, but it is uncertain if regular physical activity can reduce the risk of CKD. Using a systematic review and meta-analysis of published observational cohort studies in the general population, we sought to assess the association between physical activity and CKD risk. Relevant studies with at least one-year of follow-up were sought from inception until 02 May 2022 in MEDLINE, Embase, Web of Science, and manual search of relevant articles. Relative risks (RRs) with 95% confidence intervals (CIs) for the maximum versus the minimal amount of physical activity groups were pooled using random effects meta-analysis. The quality of the evidence was evaluated using the GRADE tool. A total of 12 observational cohort studies comprising 1,281,727 participants and 66,217 CKD events were eligible for the analysis. The pooled multivariable-adjusted RR (95% CI) of CKD comparing the most versus the least physically active groups was 0.91 (0.85–0.97). The association was consistent across several study level subgroups. Exclusion of any single study at a time from the meta-analysis did not change the direction or significance of the association. There was no evidence of small study effects among contributing studies. The GRADE quality of the evidence was low. In the general population, individuals who are most physically active have a lowered risk of CKD compared to those who are not or least physically active. CRD42022327640.

The prevalence of pancreatic incidentalomas in patients undergoing surveillance for abdominal aortic aneurysms

BackgroundSerial imaging in patients with aortic aneurysms may identify non-vascular disease. However, the prevalence and clinical history of pancreatic incidentalomas in this population is unknown. MethodsRetrospective cross-sectional study of adults who underwent computed tomography angiography (CTA) surveillance imaging for abdominal or thoracoabdominal aortic aneurysm at a single academic institution between 2015 and 2020. Descriptive statistics were used for patients with pancreatic lesions. ResultsOf 249 patients, 18 (7.2 %) had a pancreatic incidentaloma. Compared to patients without a lesion, those with a lesion were more likely female (50.0 % vs 24.2 %, p = 0.02) and less likely a smoker (72.2 % vs 90.0 %, p = 0.02). 3 patients with pancreatic lesions underwent intervention, and 1 patient received additional imaging. 2 patients had a surgical oncology referral. ConclusionsPancreatic incidentalomas are common in patients with aortic aneurysm, but lesion characteristics and management vary. Results suggest that a multi-disciplinary approach, thorough documentation, and referral to pancreatic specialists may be warranted.

Cassava diseases caused by Xanthomonas phaseoli pv. manihotis and Xanthomonas cassavae.

Xanthomonas phaseoli pv. manihotis (Xpm) and X. cassavae (Xc) are two bacterial pathogens attacking cassava. Cassava bacterial blight (CBB) is a systemic disease caused by Xpm, which might have dramatic effects on plant growth and crop production. Cassava bacterial necrosis is a nonvascular disease caused by Xc with foliar symptoms similar to CBB, but its impacts on the plant vigour and the crop are limited. In this review, we describe the epidemiology and ecology of the two pathogens, the impacts and management of the diseases, and the main research achievements for each pathosystem. Because Xc data are sparse, our main focus is on Xpm and CBB.

Editors' note: WMH and long-term outcomes in ischemic stroke: A systematic review and meta-analysis

Cerebral microvascular ischemic disease is a leading cause of dementia in the adult population. In their meta-analysis of data from more than 70,000 patients with ischemic stroke, Dr. Georgakis and colleagues examined the association between severity of white matter disease on baseline CT or MRI with 4 outcome measures—all-cause dementia, long-term functional impairment, recurrent stroke, or death due to any cause. Using an elegant mixed-effects regression model, adjusting for multiple hypothesis testing, the investigators observed a significant increased risk of each of these outcome measures among patients with moderate to severe white matter disease when compared with patients with mild to no white matter disease. In response, Dr. Gupta reminds the reader that white matter disease is etiologically heterogeneous and does not always indicate microvascular ischemia—it may be migraine or medication-related—and therefore may not universally portend an increased risk of vascular dementia or other morbidity. The investigators acknowledge this limitation of their meta-analysis; however, the relationship between (nonspecific) white matter disease and clinical outcomes remains robust. Whether the effect may be more strongly driven by patients with microvascular white matter disease and is attenuated by patients with toxic or nonvascular white matter disease remains to be clarified. Cerebral microvascular ischemic disease is a leading cause of dementia in the adult population. In their meta-analysis of data from more than 70,000 patients with ischemic stroke, Dr. Georgakis and colleagues examined the association between severity of white matter disease on baseline CT or MRI with 4 outcome measures—all-cause dementia, long-term functional impairment, recurrent stroke, or death due to any cause.

Characteristics and prognosis of IgG4-related periaortitis/periarteritis: A systematic literature review.

Immunoglobulin G4 (IgG4)-related disease is a systemic chronic fibroinflammatory disease that can affect almost every organ of the body. IgG4-related periaortitis/periarteritis is a newly recognized subset of IgG4-related disease, and its characteristics and prognosis remain unclear. We investigated the clinical characteristics and prognosis of IgG4-related periaortitis/periarteritis. We performed a systematic literature review of IgG4-related periaortitis/periarteritis. Additionally, we have summarized the characteristics and prognosis of IgG4-related coronary arteritis. We investigated 248 patients with IgG4-related periaortitis/periarteritis. All studies reported the condition in elderly patients, and male predominance was observed. The infra-renal abdominal aorta and iliac arteries were the most commonly affected sites. Most reports showed the serum C-reactive protein elevation in this disease entity, in contrast to non-vascular IgG4-related disease. Based on radiological findings observed in 27 patients with IgG4-related coronary arteritis, vasculitic lesions were classified into 3 types: stenotic (67% of patients), aneurysmal (42%), and diffuse wall thickening type (92%). Serum IgG4 level, but not C-reactive protein level, was associated with the number of affected organs in IgG4-related coronary arteritis. Corticosteroid treatment with or without cardiac surgery or percutaneous coronary intervention was effective in most patients with IgG4-related coronary arteritis; however, 33% of patients showed an unfavorable clinical course including disease progression, relapse, or death. Pre-treatment stenosis and/or aneurysms were associated with progression of stenosis or aneurysm after corticosteroid treatment. Most clinical characteristics were similar between the IgG4-related periaortitis/periarteritis and the non-vascular IgG4-related disease groups; however, serum C-reactive protein level elevation was observed only in the former. Although corticosteroid treatment was effective, this disease can be life-threatening secondary to myocardial infarction, aortic dissection, and aneurysmal rupture. Pre-treatment evaluation of stenosis or aneurysms is important for predicting progression of stenosis or aneurysm after corticosteroid treatment.

2204 Characterizing specialized pro-resolving lipid mediators and synthesis pathways in veterans with peripheral artery disease

OBJECTIVES/SPECIFIC AIMS: Specialized pro-resolving lipid mediators (SPM) actively counter proinflammatory cascades. A deficit of SPMs is one possible mechanism through which inflammation leads to the development of atherosclerotic disease. The purpose of this study is to characterize the profiles of intermediates of SPM synthesis pathways and end-product SPMs in the plasma of patients with peripheral artery disease (PAD). METHODS/STUDY POPULATION: A cross-sectional sample of 52 patients with PAD was recruited at the San Francisco Veterans Affairs Medical Center. PAD was defined as the presence of claudication symptoms and an ankle-brachial index &lt;0.9, or a history of revascularization for claudication. Patients were excluded if they were taking immunosuppressive medications, had a severe acute illness (infection, surgery, illness, critical limb ischemia) within the last 30 days, or had severe hepatic, renal, or nonvascular inflammatory disease. Intermediates of SPM synthesis pathways and end-product SPMs were measured in plasma samples of patients by liquid chromatography-tandem mass spectrometry. RESULTS/ANTICIPATED RESULTS: The average age of the cohort was 69±6.3 and patient comorbidities reflected common comorbidities associated with PAD (hypertension 96%, hyperlipidemia 87%, diabetes mellitus 42%, coronary artery disease 34%). Rutherford categories, measurements of PAD symptom severity, ranged from 0 to III (0 10%, I 40%, II 27%, III 23%). Three EPA products were measured: 18-hydroxyeicosapentaenoic acid (18-HEPE), resolvin E1 (RvE1), and resolvin E2 (RvE2). 18-HEPE, an intermediate of SPM synthesis, was detectable in the plasma of every patient (median: 105 pg/mL, IQR: 54.9–195), whereas the SPM end-products, RvE1 and RvE2, were only detectable in 6 and 10 patients, respectively. In total, 7 DHA products were measured: 14-hydroxydocosahexaenoic acid (14-HDHA), 17-HDHA, resolvin D1 (RvD1), resolvin D2 (RvD2), protectin D1, protectin DX, and maresin 1. The intermediates 14-HDHA (median: 6546 pg/mL, IQR: 3329–12061) and 17-HDHA (median: 644 pg/mL, IQR: 340–1056) were detectable in the plasma of every patient. However, the end-products RvD1, RvD2, protectin D1, protecin DX, and maresin 1 were identified in less than half of the cohort. DISCUSSION/SIGNIFICANCE OF IMPACT: We report the presence of several intermediates of SPM synthesis pathways (18-HEPE, 14-HDHA, and 17-HDHA) in every patient but the presence of SPM end-products in only a limited portion of the cohort. These results suggest that some patients with PAD may have a deficit of SPMs. Further investigation is required to better understand the role of SPMs and mediators of resolution of inflammation in PAD.

Age-specific association between blood pressure and vascular and non-vascular chronic diseases in 0·5 million adults in China: a prospective cohort study.

SummaryBackgroundThe age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main stroke types (ischaemic stroke and intracerebral haemorrhage). We aimed to investigate this relationship among adults in China.Methods512 891 adults (59% women) aged 30–79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs) relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average (usual) systolic blood pressure.FindingsDuring a median follow-up of 9 years (IQR 8–10), there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging). At ages 40–79 years (mean age at event 64 years [SD 9]), usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120–180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 [95% CI 1·28–1·34]) and ischaemic stroke (1·30 [1·29–1·31]), but the association with intracerebral haemorrhage was about twice as steep (1·68 [1·65–1·71]). HRs for vascular disease were twice as steep at ages 40–49 years than at ages 70–79 years. Usual systolic blood pressure was also positively associated with incident chronic kidney disease (1·40 [1·35–1·44]) and diabetes (1·14 [1·12–1·15]). About half of all vascular deaths in China were attributable to elevated blood pressure (ie, systolic blood pressure >120 mm Hg), accounting for approximately 1 million deaths (<80 years of age) annually.InterpretationAmong adults in China, systolic blood pressure was continuously related to major vascular disease with no evidence of a threshold down to 120 mm Hg. Unlike previous studies in high-income countries, blood pressure was more strongly associated with intracerebral haemorrhage than with ischaemic stroke. Even small reductions in mean blood pressure at a population level could be expected to have a major impact on vascular morbidity and mortality.FundingUK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, and the National Science Foundation of China.

Abstract WP212: Rapid Point-of-care Nr2 Peptide Test for Acute Stroke Detection

Background and Objectives: Time delay is a challenge in using biomarkers in guiding acute ischemic stroke (IS) therapy. Therapeutic decisions must be made quickly and standard blood draws with transport to a laboratory results in delay of results and possible degradation of biomarkers. We report the initial experience with rapid nanoparticle lateral flow (nLF) tests on fingerstick blood samples for the NR2 peptide (NP), a fragment of the NMDA receptor. This extends our prior research (PLoS ONE, 2012, 7, e42362). Methods: Capillary blood (20 microliter) withdrawn less than 15 hours after IS onset was developed within 5 min yielding test (T) and control ( C ) bands in a nLF assay (DRD/CIS Biotech, Inc, Atlanta, GA). An Epson V700 scanner and ImageJ software (Rasband, W.S., ImageJ, U. S. NIH, Bethesda, Maryland) were used to quantify the LF bands. Plasma measurements of NP using MP-ELISA were carried out as well. Patient Selection: Patients (n=13) with thrombotic and embolic stroke and controls (n=16) with non-vascular disease of the CNS and healthy volunteers were enrolled. Diagnosis of ischemic stroke was confirmed by clinical evaluation and neuroimaging (CT, MRI and transcranial doppler). Increased NR2 peptide was detected in plasma of 9/13 patients with IS, i.e., the rapid test showed 2 lines (control and test). In some patients both lines are visualized equally others the T-line is stained less intensively. In the control group there is only one band (16/16) Elevated NP correlated with new lesion areas on DWI/MRI with a slope of ~ 1ng per 5 ml stroke volume. Conclusions: NR2 peptide is elevated with IS and may be detected by rapid fingerstick tests. Plasma NR2 peptide levels correlate with stroke volume.

Effect on non-vascular outcomes of lowering LDL cholesterol in patients with chronic kidney disease: results from the Study of Heart and Renal Protection

BackgroundReducing LDL cholesterol (LDL-C) with statin-based therapy reduces the risk of major atherosclerotic events among patients with chronic kidney disease (CKD), with no evidence of an excess risk of cancer or death from any non-vascular cause. However, non-randomized data have suggested that statin therapy may have effects (both adverse and beneficial) on particular non-vascular conditions that do not cause death.MethodsThe Study of Heart and Renal Protection (SHARP) randomized patients with CKD to simvastatin 20 mg plus ezetimibe 10 mg (simvastatin/ezetimibe) daily versus matching placebo. Participants were followed up at least 6 monthly and all post-randomization serious adverse events (SAEs) were recorded. This supplementary analysis reports the effects of treatment on non-vascular SAEs, overall, by system of disease, by baseline characteristics, and by duration of follow-up.ResultsDuring a median of 4.9 years follow-up, similar numbers of participants in the two groups experienced at least one non-vascular SAE (3551 [76.4%] simvastatin/ezetimibe vs 3537 [76.6%] placebo; risk ratio [RR] 0.99, 95% confidence interval [CI] 0.95–1.04). There was no good evidence of any significant effect of simvastatin/ezetimibe on SAEs attributed to any particular nonvascular disease system (of 43 comparisons, only 3 yielded an uncorrected p value < 0.05, of which the smallest was p = 0.02). The relative risk of any nonvascular SAE did not vary significantly among particular prognostic subgroups or by duration of follow-up.ConclusionsIn the SHARP trial, allocation to simvastatin/ezetimibe combination therapy was not associated with any significant non-vascular hazard.Trials registrationSHARP was retrospectively registered after the first participant was enrolled in 2003 at ISRCTN (ISRCTN54137607 on 31 January 2005: http://www.isrctn.com/ISRCTN54137607) and ClinicalTrials.gov (NCT00125593 on 29 July 2005: https://clinicaltrials.gov/ct2/show/NCT00125593).

POOR LONG-TERM OUTCOME OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY IN NONPROLIFERATIVE MACULAR TELANGIECTASIA TYPE 2.

To investigate long-term effects after intravitreal inhibition of vascular endothelial growth factor in nonproliferative macular telangiectasia type 2. Nine patients with macular telangiectasia type 2 treated with 12 monthly intravitreal ranibizumab injections in 1 eye were investigated again after a mean follow-up of 6.0 ± 0.4 years. Functional assessment included best-corrected visual acuity and microperimetry testing. Morphologic investigations included optical coherence tomography imaging and fluorescein angiography. Mean visual acuity at baseline was similar in treated and control eyes (both 20/50; range: 20/32-20/125 in the treated eyes and 20/25-20/100 in the untreated eyes). None of the eyes had a neovascular membrane or a paracentral scotoma. At the last follow-up, more eyes of the treatment group had lost 2 or more lines on best-corrected visual acuity testing (4 vs. 1) and more eyes had developed an absolute paracentral scotoma (7 vs. 2). A secondary neovascular membrane had formed in four of the treated and in none of the untreated eyes. Vascular endothelial growth factor inhibition with monthly dosing over 1 year had no beneficial effect 5 years after cessation of therapy. The worse outcome in the treated eyes may be due to selection bias, small sample size, or a potential adverse effect of vascular endothelial growth factor inhibition in a degenerative, primarily nonvascular disease as macular telangiectasia type 2.

Abstract T MP55: Utility of 4D-MRA to Measure Blood Flow Velocity in Cerebral Major Arteries

Transcranial Doppler is widely used clinically to measure blood flow velocity (BFV) in cerebral major arteries. This method, however, has a limitation in that its successful measurement depends on the accessibility of patients’ cranial window and the technical ability of operators. We therefore developed a novel method to measure BFV in cerebral major arteries with 4D-MRA, which was less susceptible to patients and the conditions of the operators. Methods: 4D-MRA was performed with a 3T MR unit (Achieva TX; Philips Medical Systems) using arterial spin labeling methods. The blood flow through the internal carotid arteries (ICA) and the basilar artery (BA) within imaging range was visualized by using look-locker readout methods. BFV was calculated by dividing the flow distance traveled in the arteries by the time elapsed. BFV of 34 patients (non-vascular disease:11, ICA stenotic disease:6, moyamoya disease:9, and cerebral aneurysm:8) were measured using the 4D-MRA method and the 2D phase contrast method. Results: In the case of patients with non-vascular diseases, mean BFV of the right ICA, the left ICA, and the BA was 24.5±7.0, 23.3±6.9, and 17.2±5.1 cm/sec, respectively. Correlation between BFV values from the 4D-MRA method and those from the 2D phase contrast method was statistically significant (r=0.78, p&lt;0.01). In the case of patients with ICA severe stenosis (more than 90%), BFV of the stenotic ICA was decreased to 9~11cm/sec (40~50% of BFV of the contralateral ICA). In the case of patients with advanced-stage moyamoya disease, BFV of the ICA was decreased to 9~16cm/sec (30~50% of BFV of the BA). The BFV decreases were related to CBF reduction in some cases if the development of the collateral circulation was insufficient. In the patients with aneurysm, BFV of the artery proximal to aneurysm tended to be increased except for the decrease in cavernous ICA giant aneurysm. Conclusions: We could steadily obtain BFV in all patients by using the 4D-MRA method without any operational difficulties. In this preliminary study, we observed BFV decrease in ICA stenotic disease and moyamoya disease, and BFV increase in cerebral aneurysm. This novel 4D-MRA method to measure BFV may become a promising tool for pathophysiological evaluation of cerebrovascular diseases.

Abstract No. 459 - Treating nonvascular disease with the Amplatzer vascular plug: an illustrative review of novel applications in interventional radiology practice

Abstract No. 459 - Treating nonvascular disease with the Amplatzer vascular plug: an illustrative review of novel applications in interventional radiology practice

Cause-specific Mortality after Stroke: Relation to Age, Sex, Stroke Severity, and Risk Factors in a 10-Year Follow-up Study

We investigated cause-specific mortality in relation to age, sex, stroke severity, and cardiovascular risk factor profile in the Copenhagen Stroke Study cohort with 10 years of follow-up. In a Copenhagen community, all patients admitted to the hospital with stroke during 1992-1993 (n = 988) were registered on admission. Evaluation included stroke severity, computed tomography scan, and a cardiovascular risk profile. Cause of death within 10 years according to death certificate information was classified as stroke, heart/arterial disease, or nonvascular disease. Competing-risks analyses were performed by cause-specific Cox regression after multiple imputation of missing data, assuming that values were missing at random. Death was due to stroke in 310 patients (31%), to heart/arterial disease in 209 patients (21%), and to nonvascular diseases in 289 patients (29%); 180 patients were still alive after 10 years (18%). Stroke was the dominant cause of death during first year, with an absolute risk of 20.2% versus 5.2% for heart/arterial disease and 6.5% for nonvascular disease. The subsequent absolute risk of death per year was 2.8% for stroke, 4.5% for heart/arterial disease, and 5.2% for nonvascular disease. Death after stroke was associated with older age, male sex, greater stroke severity, and diabetes regardless of the cause of death. Previous stroke and hemorrhagic stroke were associated with death by stroke, ischemic heart disease was associated with death by heart/arterial disease and atrial fibrillation was associated with death by cardiovascular disease (stroke or heart/arterial disease). Hypertension, smoking, and alcohol consumption were not associated with cause-specific death.

Methyl iodide poisoning presenting as a mimic of acute stroke: a case report.

IntroductionStroke mimics are usually non-vascular disease processes. These raise the possibility of a stroke and are common in clinical practice. It is necessary to distinguish these mimics in order to provide early and appropriate management, as well as reduce possible harm on our patient.Case presentationWe report the case of a 50-year-old Caucasian man who developed symptoms suggestive of posterior circulation stroke after he was exposed to methyl iodide at his workplace. Results of stroke investigations of our patient were negative, and a detailed occupational history clinched the diagnosis. Acute presentation with a stroke-like picture is rare in cases of methyl iodide poisoning. We have attempted to discuss the differential diagnosis of stroke mimics through a review of literature.ConclusionStroke mimics are difficult to diagnose in an emergency room situation and may be initially treated as stroke. This case report underlines the importance of history taking, especially occupational history, in the differential diagnosis of stroke. We also stress the need to recognize mimics at presentation in order to arrive at an early and appropriate management of patients.