Small apolipoprotein(a) isoforms may predict primary patency following peripheral arterial revascularization.

Background: High lipoprotein (a) [Lp(a)] is associated with adverse limb events in patients undergoing lower extremity revascularization. Lp(a) levels are genetically pre-determined, with LPA gene encoding for two apolipoprotein (a) [apo(a)] isoforms. Isoform size variations are driven by the number of kringle IV type 2 (KIV-2) repeats. Lp(a) levels are inversely correlated with isoform size. In this study, we examined the role of Lp(a) levels, apo(a) size and inflammatory markers with lower extremity revascularization outcomes. Methods: 25 subjects with chronic peripheral arterial disease (PAD), underwent open or endovascular lower extremity revascularization (mean age of 66.7±9.7 years; F=12, M=13; Black=8, Hispanic=5, and White=12). Pre- and post-operative medical history, self-reported symptoms, ankle brachial indices (ABIs), and lower extremity duplex ultrasounds were obtained. Plasma Lp(a), apoB100, lipid panel, and pro-inflammatory markers (IL-6, IL-18, hs-CRP, TNFα) were assayed preoperatively. Isoform size was estimated using gel electrophoresis and weighted isoform size ( wIS ) calculated based on % isoform expression. Firth logistic regression was used to examine the relationship between Lp(a) levels, and wIS with procedural outcomes: symptoms (better/worse), primary patency at 2-4 weeks, ABIs, and re-intervention within 3-6 months. We controlled for age, sex, history of diabetes, smoking, statin, antiplatelet and anticoagulation use. Results: Median plasma Lp(a) level was 108 (44, 301) nmol/L. The mean apoB100 level was 168.0 ± 65.8 mg/dL. These values were not statistically different among races. We found no association between Lp(a) levels and w IS with measured plasma pro-inflammatory markers. However, smaller apo(a) wIS was associated with occlusion of the treated lesion(s) in the postoperative period [OR=1.97 (95% CI 1.01 - 3.86, p<0.05)]. The relationship of smaller apo(a) wIS with re-intervention was not as strong [OR=1.57 (95% CI 0.96 - 2.56), p=0.07]. We observed no association between wIS with patient reported symptoms or change in ABIs. Conclusions: In this small study, subjects with smaller apo(a) isoform size undergoing peripheral arterial revascularization were more likely to experience occlusion in the perioperative period and/or require re-intervention. Larger cohort studies identifying the mechanism and validating these preliminary data are needed to improve understanding of long-term peripheral vascular outcomes. Key Findings: 25 subjects with symptomatic PAD underwent open or endovascular lower extremity revascularization in a small cohort. Smaller apo(a) isoforms were associated with occlusion of the treated lesion(s) within 2-4 weeks [OR=1.97 (95% CI 1.01 - 3.86, p<0.05)], suggesting apo(a) isoform size as a predictor of primary patency in the early period after lower extremity intervention. Take Home Message: Subjects with high Lp(a) levels, generally have smaller apo(a) isoform sizes. We find that, in this small cohort, patients undergoing peripheral arterial revascularization subjects with small isoforms are at an increased risk of treated vessel occlusion in the perioperative period. Table of Contents Summary: Subjects with symptomatic PAD requiring lower extremity revascularization have high median Lp(a) levels. Individuals with smaller apo(a) weighted isoform size (wIS) have lower primary patency rates and/or require re-intervention.

Rural-Urban Differences in Diagnosed Cervical Artery Dissection in New York State.

BACKGROUND: Cervical artery dissection (CeAD) is a leading cause of stroke in young adults. Incidence estimates may be limited by under- or overdiagnosis. OBJECTIVE: We aimed to investigate if CeAD diagnosis would be higher in urban centers compared to rural regions of New York State (NYS). METHODS: For this ecological study, administrative codes were used to identify CeAD discharges in the NYS Statewide Planning and Research Cooperative System (SPARCS) from 2009 to 2014. Rural Urban Commuting Area (RUCA) codes were taken from the US Department of Agriculture and included the classifications metropolitan, micropolitan, small town, and rural. Negative binomial models were used to calculate effect estimates and 95% confidence limits (eß; 95% CL) for the association between RUCA classification and the number of dissections per ZIP code. Models were further adjusted by population. RESULTS: Population information was obtained from the US Census Bureau on 1,797 NYS ZIP codes (70.7% of NYS ZIP codes), 826 of which had at least 1 CeAD-related discharge from 2009 to 2014. Nonrural ZIP codes were more likely to report more CeAD cases relative to rural areas even after adjusting for population (metropolitan effect = eß 5.00; 95% CI: 3.75-6.66; micropolitan effect 3.02; 95% CI: 2.16-4.23; small town effect 2.34; 95% CI: 1.58-3.47). CONCLUSIONS: CeAD diagnosis correlates with population density as defined by rural-urban status. Our results could be due to underdiagnosis in rural areas or overdiagnosis with increasing urbanicity.

Influenza-Like Illness is Associated with Increased Short-Term Risk of Cervical Artery Dissection.

INTRODUCTION: Non-traumatic Cervical Artery Dissection (CeAD) is a leading cause of ischemic stroke in the young. Influenza-like illnesses (ILI) trigger ischemic strokes. We hypothesized that influenza and ILI are associated with CeAD. METHODS: In a case-crossover study within the New York State (NYS) Department of Health Statewide Planning and Research Cooperative System (2006-2014), we used ICD-9 codes to exclude major trauma and to define CeAD, influenza, and the Centers for Disease Control defined ILI. We estimated the association of ILI and influenza with CeAD by comparing their prevalence in intervals immediately prior (0-30,0-90,0-180, and 0-365 days) to CeAD (case period) to their prevalence exactly one and two years earlier (control periods). Conditional logistic regression models generated odds ratios and 95% confidence intervals (OR, 95% CI). Models were adjusted for NYS estimates of influenza prevalence rates. RESULTS: Our sample included 3,610 cases of CeAD (mean age 52±16 years, 54.7% male, 6.2% Hispanic, 9.9% Black, 68.7% White). During case periods, 7.3% had one or more ILI. ILI was more likely within 90 days of CeAD compared to the same time interval one and two years before (0-15 days: adjusted OR 1.88, 95%CI 1.20-2.94; 0-30 days: adjusted OR 1.74, 95%CI 1.22-2.46; 0-90 days: adjusted OR 1.35, 95%CI 1.00-1.81). Influenza trended with CeAD (adjusted OR 1.86, 95%CI 0.37-9.24), but these results were not statistically significant, due to limited instances of confirmed influenza. CONCLUSIONS: ILI may increase risk of CeAD for 15 days, and possibly up to three months.

Medical Student Assessment in the Time of COVID-19.

BACKGROUND: Medical student education in the era of the COVID-19 outbreak is vastly different than the standard education we have become accustomed to. Medical student assessment is an important aspect of adjusting curriculums in the era of increased virtual learning. METHODS: Students took our previously validated free response clinical skills exam (CSE) at the end of the scheduled clerkship as an open-book exam to eliminate any concern for breaches in the honor code and then grades were adjusted based on historic norms. The National Board of Medical Examiners (NBME) shelf exam was taken with a virtual proctor. Students whose clerkship was affected by the COVID-19 pandemic were compared to the students from a similarly timed surgery block the previous 3 years. Primary outcomes included CSE and NBME exam scores. Secondary outcomes included clinical evaluations and the percentage of students who received grades of Honors, High Pass, and Pass. After the surgery clerkship was completed, we surveyed all students who participated in the surgery clerkship during the COVID-19 crisis. RESULTS: There were 19 students during the COVID-interrupted clerkship and 61 students in similarly timed clerkships between 2017 and 2019. Prior to adjustment and compared to historic scores, the COVID-interrupted clerkship group scored higher on the CSE, NBME exam, and performance evaluations (median, CSE:75.2 vs 68.7, shelf:68.0 vs 64.0, performance evaluation mean: 2.96 vs 2.78). The percentage of students with an honors was marginally higher in the group affected by COVID (42% vs 32%). Out of 19 students surveyed, 9 students responded. Seven students stated they would have preferred a closed-book CSE, citing a few drawbacks of the open-book format such as modifying their exam preparation, being discouraged from thinking prior to searching online during the test, and second guessing their answers. CONCLUSIONS: During the initial outbreak of COVID-19, we found that an open book exam and a virtually proctored shelf exam was a reasonable option. However, to avoid adjustments and student dissatisfaction, we would recommend virtual proctoring if available.

Geographic Analysis of Mobile Stroke Unit Treatment in a Dense Urban Area: The New York City METRONOME Registry.

Background Mobile stroke units (MSUs) reduce time to intravenous thrombolysis in acute ischemic stroke. Whether this advantage exists in densely populated urban areas with many proximate hospitals is unclear. Methods and Results We evaluated patients from the METRONOME (Metropolitan New York Mobile Stroke) registry with suspected acute ischemic stroke who were transported by a bi-institutional MSU operating in Manhattan, New York, from October 2016 to September 2017. The comparison group included patients transported to our hospitals via conventional ambulance for acute ischemic stroke during the same hours of MSU operation (Monday to Friday, 9 am to 5 pm). Our exposure was MSU care, and our primary outcome was dispatch-to-thrombolysis time. We estimated mean differences in the primary outcome between both groups, adjusting for clinical, demographic, and geographic factors, including numbers of nearby designated stroke centers and population density. We identified 66 patients treated or transported by MSU and 19 patients transported by conventional ambulance. Patients receiving MSU care had significantly shorter dispatch-to-thrombolysis time than patients receiving conventional care (mean: 61.2 versus 91.6 minutes; P=0.001). Compared with patients receiving conventional care, patients receiving MSU care were significantly more likely to be picked up closer to a higher mean number of designated stroke centers in a 2.0-mile radius (4.8 versus 2.7, P=0.002). In multivariable analysis, MSU care was associated with a mean decrease in dispatch-to-thrombolysis time of 29.7 minutes (95% CI, 6.9-52.5) compared with conventional care. Conclusions In a densely populated urban area with a high number of intermediary stroke centers, MSU care was associated with substantially quicker time to thrombolysis compared with conventional ambulance care.

Electrocardiographic left atrial abnormality and silent vascular brain injury: The Northern Manhattan Study.

HYPOTHESIS: We hypothesized that P wave terminal Force in the V1 lead (PTFV1) would be associated with leukoaraiosis and subclinical infarcts, especially cortical infarcts, in a population-based, multi-ethnic cohort. METHODS: PTFV1 was collected manually from baseline electrocardiograms of clinically stroke-free Northern Manhattan Study participants. Investigators read brain MRIs for superficial infarcts, deep infarcts, and white matter hyperintensity volume (WMHV). WMHV was adjusted for head size and log transformed, achieving a normal distribution. Logistic regression models investigated the association of PTFV1 with cortical and with all subclinical infarcts. Linear regression models examined logWMHV. Models were adjusted for demographics and risk factors. RESULTS: Among 1174 participants with PTFV1 measurements, the mean age at MRI was 70 ± 9 years. Participants were 14.4% white, 17.6% black, and 65.8% Hispanic. Mean PTFV1 was 3587.35 ± 2315.62 µV-ms. Of the 170 subclinical infarcts, 40 were cortical. PTFV1 ≥ 5000 µV-ms was associated with WMHV in a fully adjusted model (mean difference in logWMHV 0.15, 95% confidence interval 0.01-0.28). PTFV1 exhibited a trend toward an association with cortical infarcts (unadjusted OR per SD change logPTFV1 1.30, 95% CI 0.94-1.81), but not with all subclinical infarcts. CONCLUSION: Electrocardiographic evidence of left atrial abnormality was associated with leukoaraiosis.

Brain vascular intima vulnerability among HIV-positive and negative individuals.

OBJECTIVE: To test whether HIV is associated with brain large artery vulnerable intima. DESIGN: Cross-sectional study of autopsied HIV-positive (HIV+) cases sex and age-matched to HIV-negative (HIV-) controls. METHODS: Brain large arteries from 302 autopsied cases (50% HIV+) were evaluated morphometrically for the presence of atherosclerosis, size of necrotic core, and fibrous cap thickness. Intima vulnerability was measured as intima elastolytic score [0-5, based on intimal metalloproteinases (MMP)-2, MMP-3, and MMP-9, and tissue inhibitor for MMP-1 and MMP-2 staining], intima inflammatory score (0-3, based on intimal presence of CD3 and CD68 cells and TNF-α staining), neoangiogenesis (factor VIII staining), and apoptosis (caspase 3 staining). Hierarchical generalized linear models were used to obtain the beta estimates and their 95% confidence intervals, adjusting for demographics and vascular risk factors. RESULTS: The prevalence of atherosclerosis did not differ by HIV status. Necrotic cores filled larger proportions of the intima in HIV+ individuals with CD4 cell count above 200 cells/µl at death compared to HIV- controls (adjusted B = 11.6%, P = 0.04). HIV+ individuals had greater elastolytic scores (adjusted B = 0.34, P = 0.02), especially those with less than 200 CD4 cells/µl at death (adjusted B = 0.41, P = 0.01). Intima inflammation, neoangiogenesis, and apoptosis were not different among HIV+ cases versus HIV- controls. CONCLUSION: Individuals with HIV and CD4 cell count at least 200 cells/µl at death had relatively larger necrotic cores, whereas those with HIV and CD4 cell count below 200 cells/µl at death had evidence of increased connective tissue remodeling in the intima. These findings suggest an increased potential for endothelial erosion, thrombosis, and plaque rupture that may relate to higher risk for vascular events.

Clinical risk factors for acute ischaemic and haemorrhagic stroke in patients with infective endocarditis.

BACKGROUND: Stroke as a complication of infective endocarditis portends a poor prognosis, yet risk factors for stroke subtypes have not been well defined. AIM: To identify risk factors associated with ischaemic and haemorrhagic strokes. METHODS: A retrospective patient chart review was performed at a single US academic centre to identify risk factors and imaging for patients who were 18 years or older with infectious endocarditis (IE) and stroke diagnoses. Differences in patient characteristics by stroke status were assessed using univariate analysis, χ2 or student's t-test as well as logistic regression models for multivariable analyses and correlation matrices to identify possible collinearity between variables and to obtain odds ratios (OR) and their 95% confidence intervals. RESULTS: A final sample of 1157 participants was used for this analysis. The total number of non-surgical strokes was 178, with a prevalence of 15.4% (78% ischaemic, 10% parenchymal haemorrhages, 8% subarachnoid haemorrhages and 4% mixed ischaemic/haemorrhagic). Multivariate risk factors for ischaemic stroke included prior stroke (OR 2.0, 1.3-3.1), Staphylococcus infection (OR 2.0, 1.3-3.0), mitral vegetations (OR 2.2, 1.4-3.3) and valvular abscess (OR 2.7, 1.7-4.3). Risk factors for haemorrhagic stroke included fungal infection (OR 6.4, 1.2-34.0), male gender (OR 3.5, 1.4-8.3) and rheumatic heart disease (OR 3.3, 1.1-10.4). CONCLUSION: Among patients with IE, there exist characteristics that relate differentially to ischaemic and haemorrhagic stroke risk.

Electrocardiographic Left Atrial Abnormality and Risk of Stroke: Northern Manhattan Study.

BACKGROUND AND PURPOSE: Electrocardiographic left atrial abnormality has been associated with stroke independently of atrial fibrillation (AF), suggesting that atrial thromboembolism may occur in the absence of AF. If true, we would expect an association with cryptogenic or cardioembolic stroke rather than noncardioembolic stroke. METHODS: We conducted a case-cohort analysis in the Northern Manhattan Study, a prospective cohort study of stroke risk factors. P-wave terminal force in lead V1 was manually measured from baseline ECGs of participants in sinus rhythm who subsequently had ischemic stroke (n=241) and a randomly selected subcohort without stroke (n=798). Weighted Cox proportional hazard models were used to examine the association between P-wave terminal force in lead V1 and stroke etiologic subtypes while adjusting for baseline demographic characteristics, history of AF, heart failure, diabetes mellitus, hypertension, tobacco use, and lipid levels. RESULTS: Mean P-wave terminal force in lead V1 was 4452 (±3368) µV*ms among stroke cases and 3934 (±2541) µV*ms in the subcohort. P-wave terminal force in lead V1 was associated with ischemic stroke (adjusted hazard ratio per SD, 1.20; 95% confidence interval, 1.03-1.39) and the composite of cryptogenic or cardioembolic stroke (adjusted hazard ratio per SD, 1.31; 95% confidence interval, 1.08-1.58). There was no definite association with noncardioembolic stroke subtypes (adjusted hazard ratio per SD, 1.14; 95% confidence interval, 0.92-1.40). Results were similar after excluding participants with a history of AF at baseline or new AF during follow-up. CONCLUSIONS: ECG-defined left atrial abnormality was associated with incident cryptogenic or cardioembolic stroke independently of the presence of AF, suggesting atrial thromboembolism may occur without recognized AF.