PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (49)
 

Clipboard (0)
None

Select a Filter Below

Journals
more »
Year of Publication
Document Types
author:("vili, Luis M")
1.  Predictors of the Rate of Change in Disease Activity over Time in LUMINA, a Multiethnic US Cohort of Patients with Systemic Lupus Erythematosus: LUMINA LXX 
Lupus  2010;19(6):727-733.
The objectives of the present study were (1) to clarify and quantify the relationship between age and disease duration with the rate of change in disease activity over time in patients with systemic lupus erythematosus (SLE) and (2) to explore other possible factors associated with this rate of change. To this end, SLE patients from LUMINA were studied if they had ≥3 visits in which disease activity (Systemic Lupus Activity Measure-Revised or SLAM-R) had been ascertained. Variables associated with the rate (slope) of change in disease activity (obtained by regressing the SLAM-R scores against the length of time from diagnosis to last visit) were examined by univariable and multivariable analyses. Five-hundred forty-two of the 632 patients had ≥3 SLAM-R scores. In multivariable analyses Caucasians exhibited the fastest decline in disease activity; Texan Hispanics exhibited the slowest, trailed by the African Americans. Longer disease duration and HLA-DRB1*1503 positivity were associated with a slower decline whereas a greater number of ACR criteria and abnormal laboratory parameters (white blood cell and platelet counts, hematocrit and serum creatinine) were associated with a faster decline. These findings complement existing knowledge on SLE disease activity and are potentially useful to clinicians managing these patients.
doi:10.1177/0961203309359289
PMCID: PMC3964002  PMID: 20118158
Lupus; disease activity; rate of change; ethnicity; cohort
3.  Peripheral Vascular Damage in Systemic Lupus Erythematosus: Data from LUMINA, a Large Multiethnic Cohort 
Lupus  2009;18(14):1303-1308.
Summary
To determine the factors associated with peripheral vascular damage in systemic lupus erythematosus (SLE) patients and its impact on survival from LUMINA, a longitudinal multiethnic cohort. Peripheral vascular damage was defined by the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI). Factors associated with peripheral vascular damage were examined by univariable and multivariable logistic regression models and its impact on survival by a Cox multivariable regression. Thirty-four (5.3%) of 637 patients (90% women, mean [SD] age 36.5 [12.6] (16-87) years developed peripheral vascular damage. Age and the SDI (without peripheral vascular damage) were statistically significant (odds ratio [OR] =1.05, 95% confidence interval [CI] 1.01-1.08; p=0.0107 and OR=1.30, 95% CI 0.09-1.56; p=0.0043, respectively) in multivariable analyses. Azathioprine, warfarin and statins were also statistically significant, glucocorticoid use was borderline statistically significant (OR=1.03, 95% CI 0.10-1.06; p=0.0975). In the survival analysis, peripheral vascular damage was independenly associated with a diminished survival (Hazard Ratio =2.36; 95% CI 1.07-5.19; p=0.0334). In short, age was independently associated with peripheral vascular damage, but so was the presence of damage in others organs (ocular, neuropsychiatric, renal, cardiovascular, pulmonary, musculoskeletal and integument) and some medications (probably reflecting more severe disease). Peripheral vascular damage also negatively affected survival.
doi:10.1177/0961203309105877
PMCID: PMC3758688  PMID: 19850658
4.  Association of hand or knee osteoarthritis with diabetes mellitus in a population of Hispanics from Puerto Rico 
Background
Although a higher prevalence of osteoarthritis (OA) has been reported among diabetes mellitus (DM) patients, inconsistencies and limitations of observational studies have precluded a conclusive association.
Objective
To evaluate the association of hand or knee OA with DM in a population of Hispanics from Puerto Rico.
Methods
A cross-sectional study was performed in 202 subjects (100 adult DM patients as per the National Diabetes Data Group Classification, and 102 non-diabetic subjects). OA of hand and knee was ascertained using the American College of Rheumatology classification criteria. Sociodemographic characteristics, health-related behaviors, comorbidities, pharmacotherapy and DM clinical manifestations were determined. Multivariable logistic regression was used to evaluate the association of DM with hand or knee OA, and to evaluate factors associated with hand or knee OA among DM patients.
Results
The mean (standard deviation, SD) age for DM patients was 51.6 (13.1) years; 64.0% were females. The mean (SD) DM duration was 11.0 (10.4) years. The prevalence of OA in patients with DM and non-diabetics subjects was 49.0% and 26.5%, respectively (p<0.01). In the multivariable analysis, patients with DM had 2.18 the odds of having OA when compared to non-diabetic subjects (95% CI: 1.12–4.24). In a sub-analysis among DM patients, female patients were more likely to have hand or knee OA (OR [95% CI]: 5.06 [1.66–15.66]), whereas patients who did not use insulin alone for DM therapy were more likely to have OA (OR [95% CI]: 4.44 [1.22–16.12]).
Conclusion
In this population of Hispanics from Puerto Rico, DM patients were more likely to have OA of hands or knees than non-diabetic subjects. This association was retained in multivariable models accounting for established risk factors for OA. Among DM patients, females were at greater risk for OA, whereas the use of insulin was negatively associated.
doi:10.1097/RHU.0b013e31827cd578
PMCID: PMC3815459  PMID: 23319016
diabetes mellitus; osteoarthritis; metabolic disorders; musculoskeletal disorders
5.  Time to Neuropsychiatric Damage Occurrence in LUMINA: A Multiethnic Lupus Cohort 
Lupus  2009;18(9):822-830.
The aims of this study were to examine the predictors of time-to-neuropsychiatric (NP) damage and its impact on mortality in 632 systemic lupus erythematosus (SLE) African American, Hispanic and Caucasian LUMINA patients, age ≥ 16 years and disease duration ≤ 5 years at baseline (T0). Time-to-NP damage and its impact on mortality were examined by Cox proportional hazards regressions. One-hundred eighty-five (29.3%) patients developed NP-damage over a mean (SD) disease duration of 5.6 (3.7) years. After adjusting for neuropsychiatric manifestations present, older age [Hazard ratio (HR)=1.02; 95% [Confidence interval (CI) 1.00–1.04)], Caucasian ethnicity (HR=1.87; 95% CI 1.22-2.87), disease activity over the disease course (HR=1.16; 95% CI 1.12–1.21), diabetes (HR=3.47; 95% CI 1.44–8.38) and abnormal illness-related behaviors (HR=1.05; 95% CI 1.02–1.08) were associated with a shorter time to NP-damage. Photosensitivity (HR=0.65; 95% CI 0.44–0.95), anemia (HR=0.56; 95% CI 0.31–0.98), Raynaud’s phenomenon (HR=0.49; 95% CI 0.34–0.72), a medium dose of prednisone (HR=0.56; 95% CI 0.35–0.92) and hydroxychloroquine use (HR=0.58; 95% CI 0.36–0.93) were associated with a longer time. NP-damage did not contribute to mortality. Older age, Caucasian ethnicity, disease activity and abnormal illness-related behaviors are associated with a shorter time-to-NP damage; hydroxychloroquine and a medium dose of prednisone with a longer time.
doi:10.1177/0961203309104392
PMCID: PMC3759150  PMID: 19578107
6.  Variable association of reactive intermediate genes with systemic lupus erythematosus (SLE) in populations with different African ancestry 
The Journal of rheumatology  2013;40(6):842-849.
Objective
Little is known about the genetic etiology of systemic lupus erythematosus (SLE) in individuals of African ancestry, despite its higher prevalence and greater disease severity. Overproduction of nitric oxide (NO) and reactive oxygen species are implicated in the pathogenesis and severity of SLE, making NO synthases and other reactive intermediate related genes biological candidates for disease susceptibility. This study analyzed variation in reactive intermediate genes for association with SLE in two populations with African ancestry.
Methods
A total of 244 SNPs from 53 regions were analyzed in non-Gullah African Americans (AA; 1432 cases and 1687 controls) and the genetically more homogeneous Gullah of the Sea Islands of South Carolina (133 cases and 112 controls) and. Single-marker, haplotype, and two-locus interaction tests were computed for these populations.
Results
The glutathione reductase gene GSR (rs2253409, P=0.0014, OR [95% CI]=1.26 [1.09–1.44]) was the most significant single-SNP association in AA. In the Gullah, the NADH dehydrogenase NDUFS4 (rs381575, P=0.0065, OR [95%CI]=2.10 [1.23–3.59]) and nitric oxide synthase gene NOS1 (rs561712, P=0.0072, OR [95%CI]=0.62 [0.44–0.88]) were most strongly associated with SLE. When both populations were analyzed together, GSR remained the most significant effect (rs2253409, P=0.00072, OR [95%CI]=1.26 [1.10–1.44]). Haplotype and two-locus interaction analyses also uncovered different loci in each population.
Conclusion
These results suggest distinct patterns of association with SLE in African-derived populations; specific loci may be more strongly associated within select population groups.
doi:10.3899/jrheum.120989
PMCID: PMC3735344  PMID: 23637325
systemic lupus erythematosus; African Americans; genetic association studies; oxygen compounds; single nucleotide polymorphism
7.  African–American and Hispanic ethnicities, renal involvement and obesity predispose to hypertension in systemic lupus erythematosus: results from LUMINA, a multiethnic cohort (LUMINAXLV) 
Annals of the Rheumatic Diseases  2006;66(5):618-622.
Objective
To examine the predictors of the occurrence of hypertension in a large multiethnic US cohort.
Patients and methods
There were 614 patients with systemic lupus erythematoses (SLE; ⩾4 American College of Rheumatology revised criteria) with ⩽5 years of disease duration at entry into the cohort (T0) and of Hispanic (Texan or Puerto Rican), African–American or Caucasian ethnicity. T0 variables were compared between patients who did and did not develop hypertension (blood pressure ⩾140/90 mm Hg on at least two occasions and/or the use of antihypertensive drugs) after T0. Significant and clinically relevant variables were then examined by a stepwise logistic regression model.
Results
A total of 379 patients without hypertension at T0 were included (patients who developed hypertension prior to SLE diagnosis (n = 126) or before T0 (n = 109) were excluded). Predictors of hypertension were African–American and Texan–Hispanic ethnicities, renal involvement and a higher body mass index.
Conclusions
Traditional cardiovascular risk factors, disease‐related factors and ethnicity play a role in the occurrence of hypertension in patients with SLE. Controlling renal involvement and optimising body weight may prevent the occurrence of hypertension.
doi:10.1136/ard.2006.059311
PMCID: PMC1954629  PMID: 17107981
8.  Association of Discoid Lupus with Clinical Manifestations and Damage Accrual in PROFILE: A Multiethnic Lupus Cohort 
Arthritis care & research  2012;64(5):704-712.
Objective
To determine the clinical manifestations and disease damage associated with discoid rash in a large multiethnic systemic lupus erythematosus (SLE) cohort.
Methods
SLE patients (per ACR criteria), age ≥ 16 years, disease duration ≤ 10 years at enrollment, and defined ethnicity (African American, Hispanic or Caucasian), from a longitudinal cohort were studied. Socioeconomic-demographic features, clinical manifestations and disease damage [as per the Systemic Lupus International Collaborating Clinics Damage Index (SDI)] were determined. The association of DLE with clinical manifestations and disease damage was examined using multivariable logistic regression.
Results
A total of 2,228 SLE patients were studied. The mean (standard deviation, SD) age at diagnosis was 34.3 (12.8) years and the mean (SD) disease duration was 7.9 (6.0) years; 91.8% were women. Discoid lupus was observed in 393 (17.6%) of patients with SLE. In the multivariable analysis, patients with discoid lupus were more likely to be smokers and of African-American ethnicity, and to have malar rash, photosensitivity, oral ulcers, leukopenia and vasculitis. DLE patients were less likely to be of Hispanic (from Texas) ethnicity, and to have arthritis, end-stage renal disease (ESRD), and antinuclear, anti-dsDNA and anti-phospholipid antibodies. Patients with DLE had more damage accrual, particularly chronic seizures, scarring alopecia, scarring of the skin, and skin ulcers.
Conclusion
In this cohort of SLE patients, discoid lupus was associated with several clinical features including serious manifestations such as vasculitis and chronic seizures.
doi:10.1002/acr.21581
PMCID: PMC3559016  PMID: 22190480
discoid rash; systemic lupus erythematosus; disease damage
9.  Utilization of Health Services and Prescription Patterns among Lupus Patients Followed by Primary Care Physicians and Rheumatologists in Puerto Rico 
Ethnicity & disease  2008;18(2 Suppl 2):S2-205-10.
Objective
To examine the utilization of health services and prescription patterns among patients with systemic lupus erythematosus (SLE) followed by primary care physicians and rheumatologists in Puerto Rico.
Methods
The insurance claims submitted by physicians to a health insurance company of Puerto Rico in 2003 were examined. The diagnosis of lupus was determined by using the International Classification of Diseases, Ninth Revision, code for SLE (710.0). Of 552,733 insured people, 665 SLE patients were seen by rheumatologists, and 92 were followed by primary care physicians. Demographic features, selected co-morbidities, healthcare utilization parameters, and prescription patterns were examined. Fisher exact test, χ2 test, and analysis of variances were used to evaluate differences between the study groups.
Results
SLE patients followed by rheumatologists had osteopenia/osteoporosis diagnosed more frequently than did patients followed by primary care physicians. The frequency of high blood pressure, diabetes mellitus, hypercholesterolemia, coronary artery disease, and renal disease was similar for both groups. Rheumatologists were more likely to order erythrocyte sedimentation rate, anti-dsDNA antibodies, and serum complements. No differences were observed for office or emergency room visits, hospitalizations, and utilization of routine laboratory tests. Rheumatologists prescribed hydroxychloroquine more frequently than did primary care physicians. The use of nonsteroidal antiinflammatory drugs, cyclooxygenase-2 inhibitors, glucocorticoids, azathioprine, cyclophosphamide, and methotrexate was similar for both groups.
Conclusion
Overall, the utilization of health services and prescription patterns among SLE patients followed by primary care physicians and rheumatologists in Puerto Rico are similar. However, rheumatologists ordered SLE biomarkers of disease activity and prescribed hydroxychloroquine more frequently than did primary care physicians.
PMCID: PMC2735395  PMID: 18646350
Systemic Lupus Erythematosus; Healthcare Utilization; Prescription Pattern; Puerto Rico
10.  Prevalence of systemic lupus erythematosus and associated comorbidities in Puerto Rico 
Objective
To determine the prevalence of systemic lupus erythematosus (SLE) and its associated comorbidities in patients from Puerto Rico using a database from a health insurance company.
Methods
The insurance claims submitted by physicians in 2003 to a health insurance company of Puerto Rico were examined. Of 552,733 insured people, 877 had a diagnosis of SLE (code 710.0) per the International Classification of Diseases, Ninth Revision (ICD-9). Demographic parameters and selected comorbidities were determined. The diagnosis of comorbities was ascertained using the ICD-9 code, the Current Procedural Terminology-4 (CPT-4) code (for disease specific procedures) and/or the Medi-Span Therapeutic Classification System (for disease specific pharmacologic treatment). Fisher exact test and Chi-square were used to evaluate differences between SLE patients groups.
Results
The mean age was 42.0 ± 13 and the female to male ratio was 12.5:1. The overall prevalence of SLE was 159 per 100,000 individuals. The prevalence for females was 277 per 100,000 women and for males it was 25 per 100,000 men. The most common comorbidities were high blood pressure (33.7%), osteopenia/osteoporosis (22.2%), hypothyroidism (19.0%), diabetes mellitus (11.6%) and hypercholesterolemia (11.6%). Overall, high blood pressure, diabetes mellitus, hypercholesterolemia, and coronary artery disease were more prevalent in SLE patients older than 54 years. Osteopenia/osteoporosis was more prevalent in women than in men.
Conclusions
The prevalence of SLE in Puerto Rico is very high. High blood pressure, diabetes mellitus, hypercholesterolemia, hypothyroidism and osteopenia/osteoporosis are common comorbidities in these patients. Identification and management of these comorbidities are critical for optimal medical care to this population.
doi:10.1097/RHU.0b013e318124a8af
PMCID: PMC3581330  PMID: 17762454
Systemic lupus erythematosus; prevalence; comorbidities; Puerto Rico
11.  Outcome and Predictors of Kidney Disease Progression in Puerto Ricans with Systemic Lupus Erythematosus Initially Presenting with Mild Renal Involvement 
Objectives
The aims of this study were to determine the outcome and predictors of renal disease progression in Puerto Ricans with systemic lupus erythematosus (SLE) initially presenting mild renal involvement.
Methods
A retrospective cohort of 61 SLE patients (per American College of Rheumatology classification) with mild renal involvement was studied. Mild renal disease was defined as glomerular filtration rate (GFR) ≥ 90 ml/min in the presence of proteinuria (> 0.25g/day, but < 3.5 g/day), hematuria, and/or urinary cellular casts. Demographic parameters, clinical manifestations, serologic markers, comorbidities, pharmacologic treatments, disease activity and damage accrual were determined at onset of renal disease. Factors associated with renal disease progression were evaluated using recurrent event survival analysis.
Results
Of 61 patients, 55(90.2%) were women. The mean [standard deviation (SD)] age at renal onset was 29(11.2) and the mean (SD) follow-up period was 5.1(3.4) years. Thirty-eight patients had a decline in GFR: Thirty-two had a mild decline (GFR = 60–89 ml/min), five developed moderate to severe renal insufficiency (GFR = 15–59 ml/min), and one evolved to end-stage renal disease (GFR< 15 ml/min). In the Cox model, low C4 levels and proteinuria > 0.5g/day were associated with an earlier decline in GFR.
Conclusions
The majority of SLE Puerto Rican patients initially presenting with mild renal involvement had a decrease in GFR after an average of five years of kidney disease, although most had a mild dysfunction. Low C4 levels and proteinuria were predictors of an earlier decline in GFR. The awareness of these factors may contribute to early identification of individuals at risk of renal deterioration.
doi:10.1097/RHU.0b013e31821c020a
PMCID: PMC3569025  PMID: 21617555
systemic lupus erythematosus; lupus nephritis; proteinuria; hypocomplementemia; Puerto Ricans; Hispanics
12.  Disease Activity and Damage are not Associated with Increased Levels of Fatigue in Systemic Lupus Erythematosus Patients from LUMINA LXVII, a Multiethnic Cohort 
Arthritis and rheumatism  2009;61(9):1179-1186.
Objective
To determine the factors associated with increased levels of fatigue over the course of the disease in systemic lupus erythematosus (SLE) patients from LUMINA (Lupus in Minorities: Nature versus Nurture), a longitudinal multiethnic cohort.
Methods
Patients with SLE (American College of Rheumatology revised and updated criteria), age ≥16 years, disease duration ≤ 5 years at entry into the cohort (T0), of Hispanic (Texan or Puerto Rican), African America or Caucasian ethnicity, were studied. The association between socioeconomic-demographic, health behaviors, behavioral and psychological, functional and clinical characteristics and fatigue was examined using generalized estimating equations to account for the longitudinal nature of the data.
Results
Five-hundred and fifteen patients (~91% female) contributed 2,609 visits to these analyses; there were: 93 (18.1%) Texan Hispanics, 101 (19.6%) Puerto Rican Hispanics, 169 (32.8%) African Americans, and 152 (29.5%) Caucasians; the patients mean (SD) age and follow up time were 37.2 (12.0) and 4.7 (3.2) years, respectively. Variables associated with increased levels of fatigue in the multivariable analyses were Caucasian ethnicity, the presence of constitutional symptoms(fever, weight loss), higher levels of pain, of abnormal illness-related behaviors and of helplessness (p’s between 0.0018 and <0.0001).
Conclusions
The presence of pain, abnormal illness-related behaviors, helplessness and constitutional manifestations were associated with increased levels of fatigue; however, lupus specific measures, such as disease activity and damage were not. Interventions aimed at decreasing fatigue need to take into account these findings.
doi:10.1002/art.24649
PMCID: PMC2748186  PMID: 19714612
13.  TIME to SEIZURE OCCURRENCE and DAMAGE in PROFILE, a MULTIETHNIC SLE COHORT 
Lupus  2008;17(3):177-184.
SUMMARY
The objective of this study was to determine risk factors predicting seizures and damage due to seizures in a multi-ethnic systemic lupus erythematosus (SLE) cohort (PROFILE) which includes SLE patients (n=1295) from five different US institutions. Only patients with seizures after SLE diagnosis (incident) were included in the analyses of clinical seizures, 80/1295, 6.2%; but all patients (prevalent and incident) in the analyses of damage due to seizures 51/1295, 3.9%. We examined socioeconomic-demographic, clinical and genetic variables predictive of clinical seizures and damage from seizures by Cox Proportional Hazard Ratios (HR) and 95% Confidence Intervals (CI). Independent predictors of a shorter time to occurrence of clinical seizures were younger age (HR=1.0; 95% CI 0.9–1.0), having Hispanic-Texan ethnicity (HR=2.7; 95% CI 1.3–5.7) or African-American ethnicity (HR=1.8; 95% CI 1.0–3.1, and the prior occurrence of a cerebrovascular accident [CVA] (HR=3.3; 95% CI 1.6–7.1) or an episode of psychosis (HR=2.4; 95% CI 1.1–5.0), while the prior occurrence of photosensitivity (HR=0.5; 95% CI 0.3–0.9).was the only independent predictor of a longer time to the clinical occurrence of seizures Independent predictors of a shorter time to occurrence of damage due to seizures were younger age (HR=1.0 95% CI 0.9–1.0), male gender (HR=2.4; 95% CI 1.1–5.4), and the occurrence of a prior CVA (HR=2.7; 95% CI 1.0–7.0 or an episode of psychosis (HR=4.7; 95% CI 2.3–9.9). No allele from the candidate genes examined (HLA-DRB1, HLA-DQB1, FCGR2A, FCGR3A, or FCG3B) predicted clinical seizures or damage due to seizures.
doi:10.1177/0961203307086639
PMCID: PMC2787620  PMID: 18372357
14.  Possible Protective Effect of Hydroxychloroquine on Retarding the Occurrence of Integument Damage in Lupus: Data from LUMINA, a Multiethnic Cohort 
Arthritis care & research  2010;62(3):393-400.
Objective
To determine the features predictive of time-to-integument damage in patients with systemic lupus erythematosus (SLE) from a multiethnic cohort (LUMINA).
Methods
SLE LUMINA patients (n=580), age ≥16 years, disease duration ≤5 years at baseline (T0), of African American, Hispanic and Caucasian ethnicity were studied. Integument damage was defined per the SLICC damage index (scarring alopecia, extensive skin scarring and skin ulcers lasting at least six months); factors associated with time-to-its occurrence were examined by Cox proportional univariable and multivariable (main model) hazards regression analyses. Two alternative models were also examined; in model 1 all patients, regardless of when integument damage occurred (n=94), were included; in model 2 a time-varying approach (GEE) was employed.
Results
Thirty-nine (6.7%) of 580 patients developed integument damage over a mean (SD) total disease duration of 5.9 (3.7) years and were included in the main multivariable regression model. After adjusting for discoid rash, nailfold infarcts, photosensitivity and Raynaud’s phenomenon (significant in the univariable analyses), disease activity over time [Hazard ratio (HR)=1.17; 95% Confidence interval (CI) 1.09–1.26)] was associated with a shorter time-to-integument damage whereas hydroxychloroquine use (HR=0.23, 95% CI 0.12–0.47) and Texan-Hispanic (HR=0.35; 95% CI 0.14–0.87) and Caucasian ethnicities (HR=0.37; 95% CI 0.14–0.99) were associated with a longer time. Results of the alternative models were consistent with those of the main model albeit in model 2 the association with hydroxychloroquine was not significant.
Conclusions
Our data indicate that hydroxychloroquine use is possibly associated with a delay in integument damage development in patients with SLE.
doi:10.1002/acr.20097
PMCID: PMC3202433  PMID: 20391486
Integument; skin; lupus; LUMINA Hispanics; African Americans; damage; hydroxychloroquine
15.  Factors predictive of thrombotic events in LUMINA, a multi-ethnic cohort of SLE patients (LXXII) 
Rheumatology (Oxford, England)  2010;49(9):1720-1725.
Objective. Thrombosis is an important cause of morbidity and mortality in SLE. We have explored the factors associated with time to the occurrence of thrombotic events in SLE patients to expand our cohort’s previous observations.
Method. SLE patients (ACR criteria), age ≥16 years, disease duration ≤5 years at enrolment (T0), African-American, Hispanic (Texan or Puerto Rican) or Caucasian ethnicity, from LUMINA, a longitudinal cohort, were studied. An event was defined as the presence of arterial or venous thrombosis. Time to the first thrombotic event was examined by univariable and multivariable (MV) Cox models adjusting for pertinent baseline clinical and socio-demographic variables.
Results. A total of 643 patients were studied; mean (s.d.) age was 36.4 (12.6) years and disease duration at T0 was 1.4 (1.3) years; 90% were female. After T0, 81 (12.6%) patients had developed a thrombotic event. In the MV model, age [hazard ratio (HR) = 1.06; 95% CI 1.03, 1.08; P < 0.0001], health insurance (HR = 0.53; 95% CI 0.30, 0.94; P = 0.029), smoking (HR = 1.85; 95% CI 1.01, 3.40; P = 0.048), damage (T0) (HR = 1.44; 95% CI 1.20, 1.71; P < 0.0001), aPL (HR = 2.12; 95% CI 1.19, 3.76; P = 0.011) and glucocorticoid (highest dose) (HR = 1.01; 95% CI 1.01, 1.02; P < 0.0001) were significant.
Conclusions. Age, poverty, smoking, damage accrual, aPL and higher doses of glucocorticoids were independently associated with a shorter time to the first thrombotic event; health insurance had a protective effect. Acting upon modifiable risk factors at the personal (smoking, high-dose glucocorticoids) and societal (poverty, health insurance) levels may prevent these events and improve the long-term outcome of SLE patients.
doi:10.1093/rheumatology/keq140
PMCID: PMC2948827  PMID: 20498010
Systemic lupus erythematosus; Thrombotic events; Risk factors
16.  Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L) 
Annals of the Rheumatic Diseases  2007;66(9):1168-1172.
Objective
In patients with systemic lupus erythematosus (SLE), hydroxychloroquine prevents disease flares and damage accrual and facilitates the response to mycophenolate mofetil in those with renal involvement. A study was undertaken to determine whether hydroxychloroquine also exerts a protective effect on survival.
Methods
Patients with SLE from the multiethnic LUMINA (LUpus in MInorities: NAture vs nurture) cohort were studied. A case‐control study was performed within the context of this cohort in which deceased patients (cases) were matched for disease duration (within 6 months) with alive patients (controls) in a proportion of 3:1. Survival was the outcome of interest. Propensity scores were derived by logistic regression to adjust for confounding by indication as patients with SLE with milder disease manifestations are more likely to be prescribed hydroxychloroquine. A conditional logistic regression model was used to estimate the risk of death and hydroxychloroquine use with and without the propensity score as the adjustment variable.
Results
There were 608 patients, of whom 61 had died (cases). Hydroxychloroquine had a protective effect on survival (OR 0.128 (95% CI 0.054 to 0.301 for hydroxychloroquine alone and OR 0.319 (95% CI 0.118 to 0.864) after adding the propensity score). As expected, the propensity score itself was also protective.
Conclusions
Hydroxychloroquine, which overall is well tolerated by patients with SLE, has a protective effect on survival which is evident even after taking into consideration the factors associated with treatment decisions. This information is of importance to all clinicians involved in the care of patients with SLE.
doi:10.1136/ard.2006.068676
PMCID: PMC1955128  PMID: 17389655
17.  Protective Effect of Hydroxychloroquine on Renal Damage in Patients with Lupus Nephritis: Data from LUMINA, a Multiethnic U.S. Cohort 
Arthritis and rheumatism  2009;61(6):830-839.
Objective
To assess if hydroxychloroquine can delay renal damage development in lupus nephritis patients.
Methods
Lupus nephritis patients (n=256) from LUMINA (n=635), a multiethnic cohort of African Americans, Hispanics and Caucasians, age ≥16 years, disease duration ≤5 years at baseline (T0) were studied. Renal damage was defined per the SLICC Damage Index (≥1 of the following lasting at least six months: estimated/measured glomerular filtration rate <50%, 24-hour proteinuria ≥3.5 g and/or end-stage renal disease, regardless of dialysis or transplantation). Patients with renal damage before T0 were excluded (n=53). The association between hydroxychloroquine use and renal damage (as defined, or omitting proteinuria) was estimated using Cox proportional regression analyses adjusting for potentially confounders. Kaplan-Meier survival curves based on hydroxychloroquine intake or World Health Organization (WHO) Class glomerulonephritis were also derived.
Results
Sixty-three (31.0%) of 203 patients developed renal damage over a mean (standard deviation) disease duration of 5.2 (3.5) years. The most frequent renal damage domain item was proteinuria. Hydroxychloroquine-takers (79.3%) exhibited a lower frequency of WHO Class IV glomerulonephritis, lower disease activity and received lower glucocorticoid doses than non-takers. After adjusting for confounders, hydroxychloroquine was protective of renal damage occurrence in full (HR=0.12; 95% CI 0.02-0.97; p=0.0464) and reduced (HR=0.29; 95%CI 0.13-0.68; p=0.0043) models. Omitting proteinuria provided comparable results. The cumulative probability of renal damage occurrence was higher in hydroxychloroquine non-takers and in WHO Class IV glomerulonephritis (p<0.0001).
Conclusions
After adjusting for possible confounding factors the protective effect of hydroxychloroquine in retarding renal damage occurrence in SLE is still evident.
doi:10.1002/art.24538
PMCID: PMC2898742  PMID: 19479701
18.  Predictors of cardiovascular damage in patients with systemic lupus erythematosus: data from LUMINA (LXVIII), a multiethnic US cohort 
Rheumatology (Oxford, England)  2009;48(7):817-822.
Objective. To determine the features predictive of atherosclerotic cardiovascular damage in patients with SLE.
Methods. SLE LUMINA (LUpus in MInorities: NAture vs nurture) patients (n = 637), aged ⩾16 years, disease duration ⩽5 years at baseline (T0), of African–American, Hispanic and Caucasian ethnicity were studied. Atherosclerotic cardiovascular damage was defined by the following items of the SLICC Damage Index (SDI) cardiovascular domain: angina or coronary artery by pass surgery, myocardial infarction and/or congestive heart failure; factors associated with its occurrence were examined by univariable and multivariable regression analyses.
Results. Forty-three (6.8%) of 637 patients developed cardiovascular damage over a mean ± s.d. total disease duration of 6.6 ± 3.6 years. Nearly 90% of the patients were women with a mean ± s.d. age of 36.5 (12.6) years; all ethnic groups were represented. By multivariable analyses, after adjusting for the cardiovascular manifestations present, age [odds ratio (OR) = 1.06; 95% CI 1.03, 1.09], male gender (OR = 3.57; 95% CI 1.35, 9.09) SDI at baseline (OR = 1.28; 95% CI 1.09, 1.50) and CRP levels [highest tertile (OR = 2.63; 95% CI 1.17, 5.91)] were associated with the occurrence of cardiovascular damage, whereas the number of years of education was negatively associated with such outcome (OR = 0.85; 95% CI 0.74, 0.94).
Conclusions. Our data suggest that atherosclerotic cardiovascular damage in SLE is multifactorial; traditional (age, gender) and disease-related factors (CRP levels, SDI at baseline) appear to be important contributors to such an occurrence. Tight control of the inflammatory process must be achieved to prevent it.
doi:10.1093/rheumatology/kep102
PMCID: PMC2722811  PMID: 19454606
Lupus; Cardiovascular; Atherosclerosis; Damage; Ethnicity; C-reactive protein
19.  Renal damage is the most important predictor of mortality within the damage index: data from LUMINA LXIV, a multiethnic US cohort 
Rheumatology (Oxford, England)  2009;48(5):542-545.
Objective. Damage accrual in SLE has been previously shown to be an independent predictor of mortality. We sought to discern which SLICC Damage Index (SDI) domains are the most important predictors of survival in SLE.
Methods. SLE patients (ACR criteria), age ⩾16 years, disease duration ⩽5 years at enrolment, of African–American, Hispanic or Caucasian ethnicity were studied. Disease activity was assessed using the SLAM-Revised (SLAM-R) at diagnosis. Damage was ascertained using the SDI at the last visit. The SDI domains associated with time to death (and interaction terms) were examined by univariable and multivariable Cox proportional hazards regression analyses; those significant in the multivariable analyses were added to the final two models (with and without poverty) that included other variables known to be associated with shorter survival.
Results. A total of 635 SLE patients were studied of whom 97 (15.3%) have died over a mean (s.d.) total disease duration of 5.7 (3.7) years. Patients were predominantly women [570 (89.8%)]; their mean (s.d.) age was 36.5 (12.6) years; 126 (19.8%) had developed renal damage, 62 (9.3%) cardiovascular, 48 (7.8%) pulmonary and 34 (5.4%) peripheral vascular damage. When excluding poverty from the multivariable model, the renal domain of the SDI was independently associated with a shorter time to death (hazard ratio = 1.65; 95% CI 1.03, 2.66).
Conclusions. The renal domain of the damage index is associated with a shorter time to death when poverty, a strong predictor of this outcome, is removed from the model. Preventing renal damage in lupus patients has long-term prognostic implications.
doi:10.1093/rheumatology/kep012
PMCID: PMC2722801  PMID: 19233884
Lupus; Renal damage; Mortality; Survival; Cohort; Ethnicity; SLICC damage index
20.  Factors Associated with Arterial Vascular Events in PROFILE: A Multiethnic Lupus Cohort 
Lupus  2009;18(11):958-965.
Summary
The objective of this study was to determine the factors associated with the occurrence of arterial vascular events in a multiethnic systemic lupus erythematosus (SLE) cohort. The PROFILE cohort, comprised of SLE patients (n=1,333) of defined ethnicity from five different U.S. institutions, was studied to determine demographic, clinical and biological variables associated with vascular events. An arterial vascular event (first episode) was either a myocardial infarction, angina pectoris and/or a vascular procedure for myocardial infarction, stroke, claudication and/or evidence of gangrene. Patient characteristics were analyzed by univariable and multivariable Cox proportional hazards regression analyses. One-hundred twenty-three (9.8%) patients had at least one incident arterial event. Age at cohort enrollment (HR= 1.04, 95% CI 1.03-1.06), smoking (HR= 2.20, 95% CI 1.40-3.46), and the CRP2* C alleles (HR= 1.91, 95%CI 1.04-3.49) were associated with a shorter time-to-the occurrence of arterial vascular events. Some clinical manifestations of disease activity were associated with a shorter time-to-occurrence [psychosis (HR= 2.21, 95% CI 1.10-4.44), seizures (HR= 1.85, 95% CI 1.00-3.24) and anemia (HR= 1.83, 95% CI 1.02-3.31)], but others were not [arthritis (HR= 0.32, 95% CI 0.18-0.58)]. In conclusion, older patients, especially in the context of a predisposing environmental factor (smoking) and severe clinical manifestations, are at higher risk of having arterial vascular events. The genetic contribution of the variation at the CRP locus was not obscured by demographic or clinical variables. Awareness of these factors should lead to more effective management strategies of patients at risk for arterial vascular events.
doi:10.1177/0961203309104862
PMCID: PMC2846757  PMID: 19762396
21.  Systemic Lupus Erythematosus in a Multiethnic US Cohort (LUMINA): LXI. Value of C-Reactive Protein as a Marker of Disease Activity and Damage 
The Journal of rheumatology  2008;35(12):2355.
Objective
To determine whether C-reactive protein (CRP) measured by a high sensitivity (hs) assay is a surrogate marker of disease activity and damage in systemic lupus erythematosus (SLE).
Methods
Five hundred eighty-eight patients with SLE participating in a multiethnic cohort (Hispanic, African American, and Caucasian) were studied. Disease activity was measured with the Systemic Lupus Activity Measure-Revised (SLAM-R) and damage with the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI). hs-CRP was measured by immunometric assay. Disease activity and hs-CRP were measured at enrollment and damage accrual at last visit. The association of hs-CRP with the SLAM-R and SDI was examined by univariable (Pearson's correlation) and multivariable (linear regression) analyses. The association of hs-CRP and each individual domain of the SLAM-R and SDI was examined by Spearman's correlation.
Results
hs-CRP was associated with the SLAM-R in the univariable (r = 0.35, p < 0.001) and multivariable (t = 7.11, coefficient ß = 0.27, p < 0.001) analyses. It also correlated with the constitutional, eye, pulmonary, gastrointestinal, neuromotor, and laboratory domains of the SLAM-R. hs-CRP was associated with the SDI (r = 0.12, p = 0.004) in the univariable analysis but not in the multivariable analysis. When the individual domains of the SDI were analyzed, hs-CRP correlated with the renal, pulmonary, cardiovascular, musculoskeletal, and diabetes domains.
Conclusion
hs-CRP was associated with disease activity but not with overall damage accrual; however, it correlated with specific domains of the damage index. hs-CRP may be useful to monitor the course of the disease and predict its intermediate outcome, but longitudinal studies with serial hs-CRP measurements are necessary to define its clinical value.
doi:10.3899/jrheum.080175
PMCID: PMC2818030  PMID: 19004040
SYSTEMIC LUPUS ERYTHEMATOSUS; DISEASE ACTIVITY; C-REACTIVE PROTEIN; DISEASE DAMAGE
22.  Complement receptor 2 polymorphisms associated with systemic lupus erythematosus modulate alternative splicing 
Genes and immunity  2009;10(5):457-469.
Genetic factors influence susceptibility to systemic lupus erythematosus (SLE). A recent family-based analysis in Caucasian and Chinese populations provided evidence for association of single-nucleotide polymorphisms (SNPs) in the complement receptor 2 (CR2/CD21) gene with SLE. Here we confirmed this result in a case-control analysis of an independent European-derived population including 2084 patients with SLE and 2853 healthy controls. A haplotype formed by the minor alleles of three CR2 SNPs (rs1048971, rs17615, rs4308977) showed significant association with decreased risk of SLE (30.4% in cases vs. 32.6% in controls, P = 0.016, OR = 0.90 [0.82-0.98]). Two of these SNPs are in exon 10, directly 5′ of an alternatively spliced exon preferentially expressed in follicular dendritic cells (FDC), and the third is in the alternatively spliced exon. Effects of these SNPs as well as a fourth SNP in exon 11 (rs17616) on alternative splicing were evaluated. We found that the minor alleles of these SNPs decreased splicing efficiency of exon 11 both in vitro and ex vivo. These findings further implicate CR2 in the pathogenesis of SLE and suggest that CR2 variants alter the maintenance of tolerance and autoantibody production in the secondary lymphoid tissues where B cells and FDCs interact.
doi:10.1038/gene.2009.27
PMCID: PMC2714407  PMID: 19387458
Alternative splicing; systemic lupus erythematosus; complement receptors; single-nucleotide polymorphisms; B cells; follicular dendritic cells
23.  Features Associated With, and the Impact of, Hemolytic Anemia in Patients With Systemic Lupus Erythematosus: LX, Results From a Multiethnic Cohort 
Arthritis and rheumatism  2008;59(9):1332-1340.
Objective
To examine the clinical and genetic correlates of hemolytic anemia and its impact on damage accrual and mortality in systemic lupus erythematosus (SLE) patients.
Methods
SLE patients (American College of Rheumatology [ACR] criteria) of Hispanic (Texan or Puerto Rican), African American, and Caucasian ethnicity from the LUMINA (LUpus in MInorities, NAture versus nurture) cohort were studied. Hemolytic anemia was defined as anemia with reticulocytosis (ACR criterion). The association between degrees of hemolytic anemia and socioeconomic/demographic, clinical, pharmacologic, immunologic, psychological, and behavioral variables was examined by univariable and multivariable (proportional odds model) analyses. Genetic variables (FCGR and Fas/Fas ligand polymorphisms) were examined by 2 degrees of freedom test of association and Cochran-Armitage trend tests. The impact of hemolytic anemia on damage accrual and mortality was examined by multivariable linear and Cox regression analyses, respectively.
Results
Of 628 patients studied, 90% were women, 19% were Texan Hispanic, 16% were Puerto Rican Hispanic, 37% were African American, and 28% were Caucasian. Sixty-five (10%) patients developed hemolytic anemia at some time during the disease course, 83% at or before diagnosis. Variables independently associated with degrees of hemolytic anemia were African American ethnicity, thrombocytopenia, and the use of azathioprine. Hemolytic anemia was associated with damage accrual after adjusting for variables known to affect this outcome; however, hemolytic anemia was not associated with mortality.
Conclusion
The association of hemolytic anemia with thrombocytopenia suggests a common mechanism in their pathophysiology. Hemolytic anemia is an early disease manifestation and is associated with African American ethnicity and the use of azathioprine; it appears to exert an impact on damage but not on mortality.
doi:10.1002/art.24020
PMCID: PMC2760833  PMID: 18759263
24.  Time to Renal Disease and End-Stage Renal Disease in PROFILE: A Multiethnic Lupus Cohort 
PLoS Medicine  2006;3(10):e396.
Background
Renal involvement is a serious manifestation of systemic lupus erythematosus (SLE); it may portend a poor prognosis as it may lead to end-stage renal disease (ESRD). The purpose of this study was to determine the factors predicting the development of renal involvement and its progression to ESRD in a multi-ethnic SLE cohort (PROFILE).
Methods and Findings
PROFILE includes SLE patients from five different United States institutions. We examined at baseline the socioeconomic–demographic, clinical, and genetic variables associated with the development of renal involvement and its progression to ESRD by univariable and multivariable Cox proportional hazards regression analyses. Analyses of onset of renal involvement included only patients with renal involvement after SLE diagnosis (n = 229). Analyses of ESRD included all patients, regardless of whether renal involvement occurred before, at, or after SLE diagnosis (34 of 438 patients). In addition, we performed a multivariable logistic regression analysis of the variables associated with the development of renal involvement at any time during the course of SLE.
In the time-dependent multivariable analysis, patients developing renal involvement were more likely to have more American College of Rheumatology criteria for SLE, and to be younger, hypertensive, and of African-American or Hispanic (from Texas) ethnicity. Alternative regression models were consistent with these results. In addition to greater accrued disease damage (renal damage excluded), younger age, and Hispanic ethnicity (from Texas), homozygosity for the valine allele of FcγRIIIa (FCGR3A*GG) was a significant predictor of ESRD. Results from the multivariable logistic regression model that included all cases of renal involvement were consistent with those from the Cox model.
Conclusions
Fcγ receptor genotype is a risk factor for progression of renal disease to ESRD. Since the frequency distribution of FCGR3A alleles does not vary significantly among the ethnic groups studied, the additional factors underlying the ethnic disparities in renal disease progression remain to be elucidated.
Fcγ receptor genotype is a risk factor for progression of renal disease to ESRD but does not explain the ethnic disparities in renal disease progression.
Editors' Summary
Background.
Systemic lupus erythematosis (SLE, commonly known as “lupus”) is an illness of many manifestations that appear to result from the immune system attacking components of the body's own cells. One of the unfortunate effects of SLE is kidney damage, which can, in a minority of patients, progress to kidney failure (formally called “end-stage renal disease,” or ESRD). Compared to White Americans, other ethnic groups tend to develop renal complications of lupus more often and with worse outcomes.
Why Was This Study Done?
It is unclear why some people with lupus develop kidney problems. The purpose of this US-based study was to confirm the factors that increase the risk of kidney damage and kidney failure, particularly in racial and ethnic minority patients, and to determine which of these factors accelerate the pace of kidney disease. Knowing these risk factors could allow the development and targeting of interventions, such as screening tests and preventive treatments, to prevent long-term loss of kidney function in patients with lupus.
What Did the Researchers Do and Find?
The researchers measured a number of factors in a multi-ethnic group of 1,008 patients with lupus, almost half of whom had some degree of kidney involvement. They found that those who developed kidney damage after being diagnosed with lupus tended to be younger, to have had lupus for a longer time, and to have experienced more effects of lupus in general than those who did not have kidney involvement. Those who developed kidney problems were also more likely to have been unemployed, to have had fewer years of formal education, and to have had high blood pressure before developing kidney involvement. African-American and Texan Hispanic individuals with lupus were more likely to develop kidney involvement, and tended to develop it more rapidly, than White Americans or Puerto Rican Hispanic ethnicity. Actual kidney failure (ESRD requiring dialysis or kidney transplantation) was more likely to occur among Texan Hispanics with kidney involvement than in the other ethnic groups. Diabetes and high blood pressure were not found to predict ESRD, but people with a particular variant of a protein that helps antibodies bind to cells (know as Fc-gamma receptor IIIa, or FcγRIIIa) were found to be more likely to develop ESRD, and to develop it more quickly.
What Do These Findings Mean?
These results suggest that the emergence and progression of kidney disease in patients with lupus depends on medical, genetic, and socioeconomic factors. Because no single test or intervention can be expected to address all of these factors, those treating patients with lupus must remain aware of the complexity of their patients lives at a variety of levels. In particular, ethnic disparities in the risk of serious kidney disease remain to be addressed.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030396.
MedlinePlus page on lupus
Lupus Foundation of America
American College of Rheumatology pages on lupus
Wikipedia entry on lupus (note: Wikipedia is a free Internet encyclopedia that anyone can edit)
doi:10.1371/journal.pmed.0030396
PMCID: PMC1626549  PMID: 17076550
25.  Two Independent Functional Risk Haplotypes in TNIP1 are Associated with Systemic Lupus Erythematosus 
Arthritis and rheumatism  2012;64(11):3695-3705.
Objective
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and altered type I interferon expression. Genetic surveys and genome-wide association studies have identified more than 30 SLE susceptibility genes. One of these genes, TNIP1, encodes the ABIN1 protein. ABIN1 functions in the immune system by restricting the NF-κB signaling. In order to better understand the genetic factors that influence association with SLE in genes that regulate the NF-κB pathway, we analyzed a dense set of genetic markers spanning TNIP1 and TAX1BP1, as well as the TNIP1 homolog, TNIP2, in case-control sets of diverse ethnic origins.
Methods
We fine-mapped TNIP1, TNIP2, and TAX1BP1 in a total of 8372 SLE cases and 7492 healthy controls from European-ancestry, African-American, Hispanic, East Asian, and African-American Gullah populations. Levels of TNIP1 mRNA and ABIN1 protein were analyzed using quantitative RT-PCR and Western blotting, respectively, in EBV-transformed human B cell lines.
Results
We found significant associations between genetic variants within TNIP1 and SLE but not in TNIP2 or TAX1BP1. After resequencing and imputation, we identified two independent risk haplotypes within TNIP1 in individuals of European-ancestry that were also present in African-American and Hispanic populations. These risk haplotypes produced lower levels of TNIP1 mRNA and ABIN1 protein suggesting they harbor hypomorphic functional variants that influence susceptibility to SLE by restricting ABIN1 expression.
Conclusion
Our results confirmed the association signals between SLE and TNIP1 variants in multiple populations and provide new insight into the mechanism by which TNIP1 variants may contribute to SLE pathogenesis.
doi:10.1002/art.34642
PMCID: PMC3485412  PMID: 22833143

Results 1-25 (49)