Jason J. Sico

HIV Infection and the Risk of Acute Myocardial Infarction

IMPORTANCE Whether people infected with human immunodeficiency virus (HIV) are at an increased risk of acute myocardial infarction (AMI) compared with uninfected people is not clear. Without demographically and behaviorally similar uninfected comparators and without uniformly measured clinical data on risk factors and fatal and nonfatal AMI events, any potential association between HIV status and AMI may be confounded. OBJECTIVE To investigate whether HIV is associated with an increased risk of AMI after adjustment for all standard Framingham risk factors among a large cohort of HIV-positive and demographically and behaviorally similar (ie, similar prevalence of smoking, alcohol, and cocaine use) uninfected veterans in care. DESIGN AND SETTING Participants in the Veterans Aging Cohort Study Virtual Cohort from April 1, 2003, through December 31, 2009. PARTICIPANTS After eliminating those with baseline cardiovascular disease, we analyzed data on HIV status, age, sex, race/ethnicity, hypertension, diabetes mellitus, dyslipidemia, smoking, hepatitis C infection, body mass index, renal disease, anemia, substance use, CD4 cell count, HIV-1 RNA, antiretroviral therapy, and incidence of AMI. MAIN OUTCOME MEASURE Acute myocardial infarction. RESULTS We analyzed data on 82 459 participants. During a median follow-up of 5.9 years, there were 871 AMI events. Across 3 decades of age, the mean (95% CI) AMI events per 1000 person-years was consistently and significantly higher for HIV-positive compared with uninfected veterans: for those aged 40 to 49 years, 2.0 (1.6-2.4) vs 1.5 (1.3-1.7); for those aged 50 to 59 years, 3.9 (3.3-4.5) vs 2.2 (1.9-2.5); and for those aged 60 to 69 years, 5.0 (3.8-6.7) vs 3.3 (2.6-4.2) (P < .05 for all). After adjusting for Framingham risk factors, comorbidities, and substance use, HIV-positive veterans had an increased risk of incident AMI compared with uninfected veterans (hazard ratio, 1.48; 95% CI, 1.27-1.72). An excess risk remained among those achieving an HIV-1 RNA level less than 500 copies/mL compared with uninfected veterans in time-updated analyses (hazard ratio, 1.39; 95% CI, 1.17-1.66). CONCLUSIONS AND RELEVANCE Infection with HIV is associated with a 50% increased risk of AMI beyond that explained by recognized risk factors.

Validating Smoking Data From the Veteran’s Affairs Health Factors Dataset, an Electronic Data Source

INTRODUCTION We assessed smoking data from the Veterans Health Administration (VHA) electronic medical record (EMR) Health Factors dataset. METHODS To assess the validity of the EMR Health Factors smoking data, we first created an algorithm to convert text entries into a 3-category smoking variable (never, former, and current). We compared this EMR smoking variable to 2 different sources of patient self-reported smoking survey data: (a) 6,816 HIV-infected and -uninfected participants in the 8-site Veterans Aging Cohort Study (VACS-8) and (b) a subset of 13,689 participants from the national VACS Virtual Cohort (VACS-VC), who also completed the 1999 Large Health Study (LHS) survey. Sensitivity, specificity, and kappa statistics were used to evaluate agreement of EMR Health Factors smoking data with self-report smoking data. RESULTS For the EMR Health Factors and VACS-8 comparison of current, former, and never smoking categories, the kappa statistic was .66. For EMR Health Factors and VACS-VC/LHS comparison of smoking, the kappa statistic was .61. CONCLUSIONS Based on kappa statistics, agreement between the EMR Health Factors and survey sources is substantial. Identification of current smokers nationally within the VHA can be used in future studies to track smoking status over time, to evaluate smoking interventions, and to adjust for smoking status in research. Our methodology may provide insights for other organizations seeking to use EMR data for accurate determination of smoking status.

HIV status and the risk of ischemic stroke among men

Objective: Given conflicting data regarding the association of HIV infection and ischemic stroke risk, we sought to determine whether HIV infection conferred an increased ischemic stroke risk among male veterans. Methods: The Veterans Aging Cohort Study–Virtual Cohort consists of HIV-infected and uninfected veterans in care matched (1:2) for age, sex, race/ethnicity, and clinical site. We analyzed data on 76,835 male participants in the Veterans Aging Cohort Study–Virtual Cohort who were free of baseline cardiovascular disease. We assessed demographics, ischemic stroke risk factors, comorbid diseases, substance use, HIV biomarkers, and incidence of ischemic stroke from October 1, 2003, to December 31, 2009. Results: During a median follow-up period of 5.9 (interquartile range 3.5–6.6) years, there were 910 stroke events (37.4% HIV-infected). Ischemic stroke rates per 1,000 person-years were higher for HIV-infected (2.79, 95% confidence interval 2.51–3.10) than for uninfected veterans (2.24 [2.06–2.43]) (incidence rate ratio 1.25 [1.09–1.43]; p < 0.01). After adjusting for demographics, ischemic stroke risk factors, comorbid diseases, and substance use, the risk of ischemic stroke was higher among male veterans with HIV infection compared with uninfected veterans (hazard ratio 1.17 [1.01–1.36]; p = 0.04). Conclusions: HIV infection is associated with an increased ischemic stroke risk among HIV-infected compared with demographically and behaviorally similar uninfected male veterans.

Prehypertension, Hypertension, and the Risk of Acute Myocardial Infarction in HIV-Infected and -Uninfected Veterans

BACKGROUND Compared to uninfected people, human immunodeficiency virus (HIV)-infected individuals may have an increased risk of acute myocardial infarction (AMI). Currently, HIV-infected people are treated to the same blood pressure (BP) goals (<140/90 or <130/80 mm Hg) as their uninfected counterparts. Whether HIV-infected people with elevated BP have excess AMI risk compared to uninfected people is not known. This study examines whether the association between elevated BP and AMI risk differs by HIV status. METHODS The Veterans Aging Cohort Study Virtual Cohort (VACS VC) consists of HIV-infected and -uninfected veterans matched 1:2 on age, sex, race/ethnicity, and clinical site. For this analysis, we analyzed 81 026 people with available BP data from VACS VC, who were free of cardiovascular disease at baseline. BP was the average of the 3 routine outpatient clinical measurements performed closest to baseline (first clinical visit after April 2003). BP categories used in the analyses were based on criteria of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Analyses were performed using Cox proportional hazards regression. RESULTS Over 5.9 years (median), 860 incident AMIs occurred. Low/high prehypertensive and untreated/treated hypertensive HIV-infected individuals had increased AMI risk compared to uninfected, untreated normotensive individuals (hazard ratio [HR], 1.60 [95% confidence interval {CI}, 1.07-2.39]; HR, 1.81 [95% CI, 1.22-2.68]; HR, 2.57 [95% CI, 1.76-3.76]; and HR, 2.76 [95% CI, 1.90-4.02], respectively). CONCLUSIONS HIV, prehypertensive BP, and hypertensive BP were associated with an increased risk of AMI in a cohort of HIV-infected and -uninfected veterans. Future studies should prospectively investigate whether HIV interacts with BP to further increase AMI risk.

Anemia is associated with poor outcomes in patients with less severe ischemic stroke

Anemia is a known predictor of in-hospital mortality among patients with such vascular conditions as acute myocardial infarction, congestive heart failure, and chronic kidney disease. The role of anemia in patients with acute ischemic stroke is less well understood. We sought to examine the association between anemia at hospital admission and the combined outcome of in-hospital mortality and discharge to hospice in patients with acute ischemic stroke. We evaluated data from a retrospective cohort of consecutive ischemic stroke patients presenting within 48 hours of symptom onset at 5 hospitals between 1998 and 2003. Anemia was defined as an admission hematocrit value of <30%. Less severe stroke was defined as an admission National Institutes of Health Stroke Scale score of <10. The outcome was the combined endpoint of in-hospital mortality or discharge to hospice. Among 1306 patients with stroke, anemia was present on admission in 6.4%, and the combined outcome of death or discharge to hospice was present in 10.1%. Anemia was not associated with outcome in patients with severe stroke (anemia, 17.2% [5 of 29] vs no anemia, 28,4% [98 of 345]; P = .20), but was associated with outcome in patients with less severe stroke (anemia, 13.0% [7 of 54] vs no anemia, 2.5% [22 of 878]; P < .0001). After adjustment for stroke severity, admission anemia was independently associated with outcome in patients with less severe stroke (adjusted odds ratio, 4.17; 95% confidence interval, 1.47-11.90), but not in patients with more severe strokes (adjusted odds ratio, 0.82; 95% confidence interval, 0.30-2.22). Our data indicate that anemia is associated with in-hospital mortality or discharge to hospice in patients with less severe ischemic stroke.

Unusual presentations of nervous system infection by Cryptococcus neoformans

Nervous system infections by Cryptococcus neoformans may occur not only in congenital or acquired immunodeficiency syndromes, but also in immunocompetent hosts. Neurological manifestations of C. neoformans infection include meningitis and, less commonly, parenchymal CNS granulomatous disease. This paper provides detailed clinical descriptions of highly unusual neurological manifestations of cryptococcal nervous system infections. Medical records and diagnostic data including magnetic resonance imaging, histopathology, serology, and CSF analysis were reviewed. A conus medullaris abscess was found in a patient infected with the human immunodeficiency virus (HIV). A patient with Hodgkins disease was diagnosed with cryptococcal meningitis and dermatitis mimicking ophthalmic zoster. An immunocompetent patient presented with recurrent cerebral infarctions in the setting of cryptococcal meningitis. Cryptococcal infections of the nervous system can cause severe neurological disability when diagnosis is delayed. Sensitive and specific tests are readily available and should be considered when an unusual clinical presentation is encountered.

Infarct location and sleep apnea: evaluating the potential association in acute ischemic stroke

BACKGROUND The literature about the relationship between obstructive sleep apnea (OSA) and stroke location is conflicting with some studies finding an association and others demonstrating no relationship. Among acute ischemic stroke patients, we sought to examine the relationship between stroke location and the prevalence of OSA; OSA severity based on apnea-hypopnea index (AHI), arousal frequency, and measure of hypoxia; and number of central and obstructive respiratory events. METHODS Data were obtained from patients who participated in a randomized controlled trial (NCT01446913) that evaluated the effectiveness of a strategy of diagnosing and treating OSA among patients with acute ischemic stroke and transient ischemic attack. Stroke location was classified by brain imaging reports into subdivisions of lobes, subcortical areas, brainstem, cerebellum, and vascular territory. The association between acute stroke location and polysomnographic findings was evaluated using logistic regression for OSA presence and negative binomial regression for AHI. RESULTS Among 73 patients with complete polysomnography and stroke location data, 58 (79%) had OSA. In unadjusted models, no stroke location variable was associated with the prevalence or severity of OSA. Similarly, in multivariable modeling, groupings of stroke location were also not associated with OSA presence. CONCLUSIONS These results indicate that OSA is present in the majority of stroke patients and imply that stroke location cannot be used to identify a group with higher risk of OSA. The results also suggest that OSA likely predated the stroke. Given this high overall prevalence, strong consideration should be given to obtaining polysomnography for all ischemic stroke patients.

Necrotising cryptococcal vasculitis in an HIV-negative woman.

An 84‐year‐old woman with a past medical history significant for haemolytic anaemia necessitating chronic steroid therapy presented with skin induration and erythema initially thought to be cellulitis. After a rapid progression of symptoms and failure to respond to antibiotics, a clinical diagnosis of necrotising vasculitis was made. Necrotising cryptococcal vasculitis was confirmed by histopathology and culture.

Quality of care for veterans with transient ischemic attack and minor stroke

Importance The timely delivery of guideline-concordant care may reduce the risk of recurrent vascular events for patients with transient ischemic attack (TIA) and minor stroke. Although many health care organizations measure stroke care quality, few evaluate performance for patients with TIA or minor stroke, and most include only a limited subset of guideline-recommended processes. Objective To assess the quality of guideline-recommended TIA and minor stroke care across the Veterans Health Administration (VHA) system nationwide. Design, Setting, and Participants This cohort study included 8201 patients with TIA or minor stroke cared for in any VHA emergency department (ED) or inpatient setting during federal fiscal year 2014 (October 1, 2013, through September 31, 2014). Patients with length of stay longer than 6 days, ventilator use, feeding tube use, coma, intensive care unit stay, inpatient rehabilitation stay before discharge, or receipt of thrombolysis were excluded. Outlier facilities for each process of care were identified by constructing 95% CIs around the facility pass rate and national pass rate sites when the 95% CIs did not overlap. Data analysis occurred from January 16, 2016, through June 30, 2017. Main Outcomes and Measures Ten elements of care were assessed using validated electronic quality measures. Results In the 8201 patients included in the study (mean [SD] age, 68.8 [11.4] years; 7877 [96.0%] male; 4856 [59.2%] white), performance varied across elements of care: brain imaging by day 2 (6720/7563 [88.9%]; 95% CI, 88.2%-89.6%), antithrombotic use by day 2 (6265/7477 [83.8%]; 95% CI, 83.0%-84.6%), hemoglobin A1c measurement by discharge or within the preceding 120 days (2859/3464 [82.5%]; 95% CI, 81.2%-83.8%), anticoagulation for atrial fibrillation by day 7 after discharge (1003/1222 [82.1%]; 95% CI, 80.0%-84.2%), deep vein thrombosis prophylaxis by day 2 (3253/4346 [74.9%]; 95% CI, 73.6%-76.2%), hypertension control by day 90 after discharge (4292/5979 [71.8%]; 95% CI, 70.7%-72.9%), neurology consultation by day 1 (5521/7823 [70.6%]; 95% CI, 69.6%-71.6%), electrocardiography by day 2 or within 1 day prior (5073/7570 [67.0%]; 95% CI, 65.9%-68.1%), carotid artery imaging by day 2 or within 6 months prior (4923/7685 [64.1%]; 95% CI, 63.0%-65.2%), and moderate- to high-potency statin prescription by day 7 after discharge (3329/7054 [47.2%]; 95% CI, 46.0%-48.4%). Performance varied substantially across facilities (eg, neurology consultation had a facility outlier rate of 53.0%). Performance was higher for admitted patients than for patients cared for only in EDs with the greatest disparity for carotid artery imaging (4478/5927 [75.6%] vs 445/1758 [25.3%]; P < .001). Conclusions and Relevance This national study of VHA system quality of care for patients with TIA or minor stroke identified opportunities to improve care quality, particularly for patients who were discharged from the ED. Health care systems should engage in ongoing TIA care performance assessment to complement existing stroke performance measurement.

Thrombocytopenia and In-hospital Mortality Risk among Ischemic Stroke Patients

BACKGROUND Thrombocytopenia has been associated with increased mortality in nonstroke conditions. Because its role in acute ischemic stroke is less well understood, we sought to determine whether thrombocytopenia at admission for acute ischemic stroke was associated with in-hospital mortality. METHODS We used data from a retrospective cohort of stroke patients (1998-2003) at 5 U.S. hospitals. Risk factors considered included conditions that can lead to thrombocytopenia (e.g., liver disease), increase bleeding risk (e.g., hemophilia), medications with antiplatelet effects (e.g., aspirin), and known predictors of mortality (e.g., National Institutes of Health Stroke Scale and Charlson Comorbidity Index scores). Logistic regression modeling evaluated the adjusted association between thrombocytopenia, defined as platelets <100,000/μL, and in-hospital mortality. RESULTS Among 1233 acute ischemic stroke patients, thrombocytopenia was present in 2.3% (n = 28). A total of 6.1% (n = 75) of patients died in the hospital. In unadjusted analyses, thrombocytopenia was associated with higher mortality (8/28 [28.6%] v 67/1205 [5.6%]; P < .0001). Thrombocytopenia was also independently associated with in-hospital mortality after adjustment for National Institutes of Health Stroke Scale score and comorbidities, with an odds ratio of 6.6 (95% confidence interval 2.3-18.6). CONCLUSIONS Admission thrombocytopenia among patients presenting with acute ischemic stroke predicts in-hospital mortality.