Jeffrey J. Wing

Population-Based Incidence and Prevalence of Systemic Lupus Erythematosus: The Michigan Lupus Epidemiology and Surveillance Program

OBJECTIVE To estimate the incidence and prevalence of systemic lupus erythematosus (SLE) in a sociodemographically diverse southeastern Michigan source population of 2.4 million people. METHODS SLE cases fulfilling the American College of Rheumatology classification criteria (primary case definition) or meeting rheumatologist-judged SLE criteria (secondary definition) and residing in Wayne or Washtenaw Counties during 2002-2004 were included. Case finding was performed from 6 source types, including hospitals and private specialists. Age-standardized rates were computed, and capture-recapture was performed to estimate underascertainment of cases. RESULTS The overall age-adjusted incidence and prevalence (ACR definition) per 100,000 persons were 5.5 (95% confidence interval [95% CI] 5.0-6.1) and 72.8 (95% CI 70.8-74.8). Among females, the incidence was 9.3 per 100,000 persons and the prevalence was 128.7 per 100,000 persons. Only 7 cases were estimated to have been missed by capture-recapture, adjustment for which did not materially affect the rates. SLE prevalence was 2.3-fold higher in black persons than in white persons, and 10-fold higher in females than in males. Among incident cases, the mean ± SD age at diagnosis was 39.3 ± 16.6 years. Black SLE patients had a higher proportion of renal disease and end-stage renal disease (ESRD) (40.5% and 15.3%, respectively) as compared to white SLE patients (18.8% and 4.5%, respectively). Black patients with renal disease were diagnosed as having SLE at younger age than white patients with renal disease (mean ± SD 34.4 ± 14.9 years versus 41.9 ± 21.3 years; P = 0.05). CONCLUSION SLE prevalence was higher than has been described in most other population-based studies and reached 1 in 537 among black female persons. There were substantial racial disparities in the burden of SLE, with black patients experiencing earlier age at diagnosis, >2-fold increases in SLE incidence and prevalence, and increased proportions of renal disease and progression to ESRD as compared to white patients.

Population-Based Incidence and Prevalence of Systemic Lupus Erythematosus

OBJECTIVE To estimate the incidence and prevalence of systemic lupus erythematosus (SLE) in a sociodemographically diverse southeastern Michigan source population of 2.4 million people. METHODS SLE cases fulfilling the American College of Rheumatology classification criteria (primary case definition) or meeting rheumatologist-judged SLE criteria (secondary definition) and residing in Wayne or Washtenaw Counties during 2002-2004 were included. Case finding was performed from 6 source types, including hospitals and private specialists. Age-standardized rates were computed, and capture-recapture was performed to estimate underascertainment of cases. RESULTS The overall age-adjusted incidence and prevalence (ACR definition) per 100,000 persons were 5.5 (95% confidence interval [95% CI] 5.0-6.1) and 72.8 (95% CI 70.8-74.8). Among females, the incidence was 9.3 per 100,000 persons and the prevalence was 128.7 per 100,000 persons. Only 7 cases were estimated to have been missed by capture-recapture, adjustment for which did not materially affect the rates. SLE prevalence was 2.3-fold higher in black persons than in white persons, and 10-fold higher in females than in males. Among incident cases, the mean ± SD age at diagnosis was 39.3 ± 16.6 years. Black SLE patients had a higher proportion of renal disease and end-stage renal disease (ESRD) (40.5% and 15.3%, respectively) as compared to white SLE patients (18.8% and 4.5%, respectively). Black patients with renal disease were diagnosed as having SLE at younger age than white patients with renal disease (mean ± SD 34.4 ± 14.9 years versus 41.9 ± 21.3 years; P = 0.05). CONCLUSION SLE prevalence was higher than has been described in most other population-based studies and reached 1 in 537 among black female persons. There were substantial racial disparities in the burden of SLE, with black patients experiencing earlier age at diagnosis, >2-fold increases in SLE incidence and prevalence, and increased proportions of renal disease and progression to ESRD as compared to white patients.

Predictors of highly prevalent brain ischemia in intracerebral hemorrhage

This study was undertaken to determine the prevalence, characteristics, risk factors, and temporal profile of concurrent ischemic lesions in patients with acute primary intracerebral hemorrhage (ICH).

Type I Interferons Are Associated with Subclinical Markers of Cardiovascular Disease in a Cohort of Systemic Lupus Erythematosus Patients

Background Systemic lupus erythematosus (SLE) patients have a striking increase in cardiovascular (CV) comorbidity not fully explained by the Framingham risk score. Recent evidence from in vitro studies suggests that type I interferons (IFN) could promote premature CV disease (CVD) in SLE. We assessed the association of type I IFN signatures with functional and anatomical evidence of vascular damage, and with biomarkers of CV risk in a cohort of lupus patients without overt CVD. Methodology/Principal Findings Serum type I IFN activity (induction of five IFN-inducible genes; IFIGs) from 95 SLE patient and 38 controls was quantified by real-time PCR. Flow mediated dilatation (FMD) of the brachial artery and carotid intima media thickness (CIMT) were quantified by ultrasound, and coronary calcification by computed tomography. Serum vascular biomarkers were measured by ELISA. We evaluated the effect of type I IFNs on FMD, CIMT and coronary calcification by first applying principal components analysis to combine data from five IFIGs into summary components that could be simultaneously modeled. Three components were derived explaining 97.1% of the total IFIG variation. Multivariable linear regression was utilized to investigate the association between the three components and other covariates, with the outcomes of FMD and CIMT; zero-inflated Poisson regression was used for modeling of coronary calcification. After controlling for traditional CV risk factors, enhanced serum IFN activity was significantly associated with decreased endothelial function in SLE patients and controls (p<0.05 for component 3), increased CIMT among SLE patients (p<0.01 for components 1 and 2), and severity of coronary calcification among SLE patients (p<0.001 for component 3). Conclusions Type I IFNs are independently associated with atherosclerosis development in lupus patients without history of overt CVD and after controlling for Framingham risk factors. This study further supports the hypothesis that type I IFNs promote premature vascular damage in SLE.

Association of Chronic Kidney Disease With Cerebral Microbleeds in Patients With Primary Intracerebral Hemorrhage

Background and Purpose— To investigate the relationship between chronic kidney disease (CKD) and MRI-defined cerebral microbleeds (CMB), a harbinger of future intracerebral hemorrhage (ICH), among patients with a recent history of primary ICH. Methods— Using data from a predominantly black cohort of patients with a recent ICH-enrolled in an observational study between September 2007 and June 2011, we evaluated the association between CKD (defined as estimated low glomerular filtration rate<60 mL/min per 1.73 m2) and CMB on gradient-echo MRI. Multivariable models were generated to determine the contribution of CKD to the presence, number, and location of CMB. Results— Of 197 subjects with imaging data, mean age was 59 years, 48% were women, 73% were black, 114 (58%) had ≥1 CMBs, and 52 (26%) had CKD. Overall, CKD was associated with presence of CMB (adjusted odds ratio, 2.70; 95% confidence interval [CI], 1.10–6.59) and number of CMB (adjusted relative risk, 2.04; 95% CI, 1.27–3.27). CKD was associated with CMB presence (adjusted odds ratio, 3.44; 95% CI, 1.64–7.24) and number (adjusted relative risk, 2.46; 95% CI, 1.11–5.42) in black patients, but not CMB presence (adjusted odds ratio, 3.00; 95% CI, 0.61–14.86) or number (adjusted relative risk, 1.03; 95% CI: 0.22–4.89) in non-Hispanic white patients (interactions by race were statistically not significant). Conclusions— CKD is associated with a greater presence and number of CMB in ICH patients, particularly in patients of black race. Future studies should assess whether low estimated glomerular filtration rate may be a CMB risk marker or potential therapeutic target for mitigating the development of CMB.

Positional therapy in ischemic stroke patients with obstructive sleep apnea

BACKGROUND Obstructive sleep apnea (OSA) is common in stroke patients and is associated with poor functional outcome. The effects of positional therapy in ischemic stroke patients with OSA have not been investigated. We tested the hypothesis that ischemic stroke patients have less severe OSA during positional therapy that promotes nonsupine positioning. METHODS We conducted a randomized, controlled, cross-over study. Sleep apnea screening studies were performed on two consecutive nights, using a portable respiratory monitoring system, on 18 subjects within the first 14days of ischemic stroke. An apnea-hypopnea index (AHI) ⩾5 established the diagnosis of OSA. Subjects were randomized to positional therapy that included the use of a therapeutic pillow on either the first or second night. On the control night, subjects used the hospital pillow and were positioned ad lib. Treatment effect on AHI was estimated using a repeated measures model. RESULTS All ischemic stroke subjects studied had OSA. The predominantly male group had a median age of 58years, BMI of 29kg/m(2), NIH Stroke Scale score of 3, and a median AHI on the nontherapeutic night of 39 (interquartile range: 21-54). Positional therapy reduced the amount of supine positioning by 36% (95% CI: 18-55% (P<0.001)). The AHI was reduced by 19.5% (95% CI: 4.9-31.9% (P=0.011)), when using positional therapy compared to sleeping ad lib. CONCLUSIONS Positional therapy to avoid supine positioning modestly reduces sleep apnea severity after ischemic stroke, and may therefore improve outcomes.

Adjunctive GnRH-a treatment attenuates depletion of ovarian reserve associated with cyclophosphamide therapy in premenopausal SLE patients

Background: We measured antimullerian hormone (AMH), a marker of ovarian reserve, in women with lupus treated with cyclophosphamide (CYC) (group I), CYC plus gonadotropin-releasing hormone agonist (GnRH-a) (group II) or neither (group III). We hypothesized that AMH would be diminished in women exposed to CYC versus women receiving adjunctive GnRH-a treatment or no CYC exposure. Methods: Forty-eight premenopausal lupus patients were retrospectively divided into three treatment groups: CYC alone (group I, n = 11), CYC + GnRH-a (group II, n = 10) and neither (group III, n = 27). Serum AMH levels between groups were compared using a nonparametric test (Wilcoxon rank-sum). Multiple linear regression adjusting for age was performed. Results: AMH (ng/mL) levels at the last collection were significantly lower in group I versus group III (mean ± SD: 0.18 ± 0.20 group I vs 1.33 ± 1.59 group III; p = 0.015), and versus group II (mean ± SD: 0.86 ± 1.06; p = 0.018). When centered on age 30 years, average AMH levels for group I, group II and group III were 0.20, 0.44 and 1.00, respectively. When adjusted for age, AMH between all groups was significantly different (p<0.0001). Conclusion: Posttreatment AMH levels were significantly higher among patients receiving CYC + GnRH-a compared to CYC alone, suggesting that GnRH-a coadministration mitigates CYC-induced ovarian injury.

Racial Disparities in Tissue Plasminogen Activator Treatment Rate for Stroke A Population-Based Study

Background and Purpose— Some prior studies have shown that racial disparities exist in intravenous tissue plasminogen activator (tPA) use for acute ischemic stroke. We sought to determine whether race was associated with tPA treatment for stroke in a predominantly black urban population. Methods— Systematic chart abstraction was performed on consecutive hospitalized patients with ischemic stroke from all 7 acute care hospitals in the District of Columbia from February 1, 2008, to January 31, 2009. Results— Of 1044 patients with ischemic stroke, 74% were black, 19% non-Hispanic white, and 5% received intravenous tPA. Blacks were one third less likely than whites to receive intravenous tPA (3% versus 10%, P<0.001). However, blacks were also less likely than whites to present within 3 hours of symptom onset (13% versus 21%, P=0.004) and also less likely to be tPA-eligible (5% versus 13%, P<0.001). Of those who presented within 3 hours, blacks were almost half as likely to be treated with intravenous tPA than whites (27% versus 46%, P=0.023). The treatment rate for tPA-eligible patients was similar for blacks and whites (70% versus 76%, P=0.62). Conclusions— In this predominantly black urban population hospitalized for acute ischemic stroke, blacks were significantly less likely to be treated with intravenous tPA due to contraindications to treatment, delayed presentation, and stroke severity. Effective interventions designed to increase treatment in this population need to focus on culturally relevant education programs designed to address barriers specific to this population.

Age- and ethnic-specific sex differences in stroke risk.

BACKGROUND In white populations, age seems to modify the effect of sex on stroke risk, and compared with men, women are protected from stroke until approximately age 75 to 85 years, after which the protection is lost or reversed. Compared with non-Hispanic whites (NHWs), Mexican Americans (MAs) are at higher risk of stroke; however, age- and sex-specific stroke incidence data are currently not available for this population. OBJECTIVE This study was performed to compare the age-specific sex differences in stroke risk in MAs and NHWs. METHODS Data were derived from the BASIC (Brain Attack Surveillance in Corpus Christi) Project, a population-based stroke surveillance study conducted in Nueces County Texas. Incident strokes (n = 2421, including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) that occurred between January 1, 2000 and May 25, 2007 in individuals aged 45 years or older were included in the analysis. Poisson regression using the generalized additive models framework was used to analyze the relationship between sex, age (5-year intervals), and race/ethnicity (NHW or MA) and incident stroke risk. RESULTS Among both NHWs and MAs aged 45 to 79 years, men were at higher risk of stroke than women were. The magnitude of increased stroke risk in men compared with women diminished with age, and after age 79 years, no sex difference in stroke risk was observed. CONCLUSIONS Reasons for the loss of protection from stroke in aging women of all races/ethnicities are not fully understood, and further study is warranted.

Door-to-Door Capture of Incident and Prevalent Stroke Cases in Durango, Mexico: The Brain Attack Surveillance in Durango Study

Background and Purpose— Stroke incidence and prevalence estimates in developing countries should include stroke cases not presenting to hospital. We performed door-to-door stroke case ascertainment in Durango Municipality, Mexico, to estimate stroke incidence and prevalence and to determine the error made by only ascertaining hospital cases. Methods— Between September 2008 and March 2009, 1996 housing units were randomly sampled to screen for stroke in Durango Municipality residents 35 years of age and older. Field workers utilized a validated screening tool. Those screening positive were referred to a neurologist for history and examination and a head CT scan. Prevalence and cumulative incidence from the door-to-door surveillance were calculated and compared with previously reported hospitalization rates during the same defined time. Results— Respondents included 2437 subjects from 1419 homes. The refusal rate was 3.8%. Twenty subjects had verified or probable stroke. The prevalence of probable or verified stroke was 7.7 per 1000 (95% CI, 4.3 per 1000–11.2 per 1000). Five patients had a stroke during the time of the hospital surveillance, yielding a cumulative incidence of 232.3 per 100 000 (95% CI, 27.8–436.9). Two of the 5 cases were captured by door-to-door surveillance but not by hospital surveillance. Conclusions— This study provides the first community-based stroke prevalence and incidence estimates in Mexico. The wide confidence intervals, despite the large number of surveyed housing units, suggest the need for more advanced sampling strategies for stroke surveillance in the developing world.