Graciela S. Alarcón

Renal damage is the most important predictor of mortality within the damage index: data from LUMINA LXIV, a multiethnic US cohort

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 > or =16 years, disease duration < or =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.

Angiotensin-converting enzyme inhibitors delay the occurrence of renal involvement and are associated with a decreased risk of disease activity in patients with systemic lupus erythematosus—results from LUMINA (LIX): a multiethnic US cohort

OBJECTIVE To examine if angiotensin-converting enzyme (ACE) inhibitor use delays the occurrence of renal involvement and decreases the risk of disease activity in SLE patients. METHODS SLE patients (Hispanics, African Americans and Caucasians) from the lupus in minorities: nature vs nurture (LUMINA) cohort were studied. Renal involvement was defined as ACR criterion and/or biopsy-proven lupus nephritis. Time-to-renal involvement was examined by univariable and multivariable Cox proportional hazards regression analyses. Disease activity was examined with a case-crossover design and a conditional logistic regression model; in the case intervals, a decrease in the SLAM-R score >or=4 points occurred but not in the control intervals. RESULTS Eighty of 378 patients (21%) were ACE inhibitor users; 298 (79%) were not. The probability of renal involvement free-survival at 10 yrs was 88.1% for users and 75.4% for non-users (P = 0.0099, log rank test). Users developed persistent proteinuria and/or biopsy-proven lupus nephritis (7.1%) less frequently than non-users (22.9%), P = 0.016. By multivariable Cox proportional hazards regression analyses, ACE inhibitors use [hazard ratio (HR) 0.27; 95% CI 0.09, 0.78] was associated with a longer time-to-renal involvement occurrence whereas African American ethnicity (HR 3.31; 95% CI 1.44, 7.61) was with a shorter time. ACE inhibitor use (54/288 case and 254/1148 control intervals) was also associated with a decreased risk of disease activity (HR 0.56; 95% CI 0.34, 0.94). CONCLUSIONS ACE inhibitor use delays the development of renal involvement and associates with a decreased risk of disease activity in SLE; corroboration of these findings in other lupus cohorts is desirable before practice recommendations are formulated.

Predictors of cardiovascular damage in patients with systemic lupus erythematosus: data from LUMINA (LXVIII), a multiethnic US cohort

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 >or=16 years, disease duration <or=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.

Associated factors and impact of myocarditis in patients with SLE from LUMINA, a multiethnic US cohort

OBJECTIVE To examine the factors associated with myocarditis and its impact on disease outcomes in SLE patients. METHODS SLE patients aged > or = 16 yrs, disease duration < or = 5 yrs from LUMINA (LUpus in Minorities: NAture vs nurture), a multiethnic US cohort, were studied. Myocarditis was defined as per the category 3 of the pericarditis/myocarditis item of the SLAM-Revised (SLAM-R). Patients with concurrent pericardial involvement were excluded. Patients with myocarditis were compared with those without myocarditis or its sequelae in the preceding year. The association between myocarditis and baseline variables (T(0)) was first examined. The impact of myocarditis on disease activity over time (SLAM-R), damage accrual [SLICC Damage Index (SDI)] at last visit (T(L)) and mortality was evaluated. RESULTS Fifty-three of the 496 patients studied had myocarditis. African American ethnicity [Odds ratio (OR) = 12.6; 95% CI 1.6, 97.8] and SLAM-R at diagnosis (OR = 1.1, 95% CI 1.0, 1.1) were significantly and independently associated with myocarditis. Myocarditis did not predict disease activity over time, but approached significance as a predictor of SDI at T(L) in multivariable analyses P = 0.051. Kaplan-Meier curves indicated that myocarditis was associated with shorter survival (log-rank = 4.87, P = 0.02), particularly in patients with > or = 5 yrs disease; however, myocarditis was not retained in the Cox proportional hazards regression model. CONCLUSIONS Ethnicity and disease activity at diagnosis were associated with the occurrence of myocarditis in SLE. Myocarditis did not significantly impact on disease activity over time, but impacts some on damage accrual and survival, reflecting overall the more severe disease those patients experience.

Factors predictive of thrombotic events in LUMINA, a multi-ethnic cohort of SLE patients (LXXII)

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 cohorts previous observations. METHOD SLE patients (ACR criteria), age >or=16 years, disease duration <or=5 years at enrollment (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.

Impact of immigration on the clinical expression of systemic lupus erythematosus: a comparative study of Hispanic patients residing in the USA and Mexico

OBJECTIVE To compare the socio-economic characteristics, clinical features and health-related quality of life in Hispanic SLE patients residing in Mexico and in the Southwest USA (Mexican and Texan, herein). METHODS Mexican and Texan SLE patients (fulfilling ACR criteria) participating in separate longitudinal outcome studies were evaluated. Texan patients were randomly chosen to match total disease duration with the Mexican patients. Cross-sectional data for the Mexican patients were obtained by a US-trained investigator who had previously participated in data collection for the cohort to which the Texan patients belonged. Socio-economic and -demographic characteristics, clinical characteristics, disease activity (with SLAM-Revised), damage accrual (with SLICC/ACR Damage Index) and self-reported function (with Short Form-36) were compared between the two groups. RESULTS Seventy Mexican patients were matched with either one or two Texan patients (n = 94) for a total of 164 patients. Mexican patients were younger. In age-adjusted analyses, the Mexican patients were more educated, had better health-related quality of life and overall less systemic SLE manifestations. Mexican patients were exposed more frequently to AZA. CONCLUSIONS Texan patients had more severe disease than the Mexican patients. In multivariable analyses, Texan Hispanic ethnicity was significantly associated with high disease activity, but significance was not reached for damage. The discrepant findings observed between these two Hispanic groups of SLE patients may reflect socio-economic or biological factors. Given the global phenomenon of immigration, rheumatologists should be aware of the overall course and outcome of immigrant SLE patients if undesirable outcomes are to be prevented.