Free fatty acids are associated with metabolic syndrome and insulin resistance but not inflammation in systemic lupus erythematosus.

Free fatty acids (FFAs) are implicated in the pathogenesis of insulin resistance and atherosclerosis. Inflammatory cytokines promote lipolysis and increase FFAs, a cause of endothelial dysfunction and increased atherosclerosis risk. We hypothesized that increased inflammation is associated with increased FFAs, resulting in insulin resistance and atherosclerosis in patients with systemic lupus erythematosus (SLE). We measured clinical variables, serum FFAs, homeostasis model assessment for insulin resistance (HOMA), inflammatory cytokines, markers of endothelial activation, cholesterol concentrations and coronary artery calcium in 156 patients with SLE and 90 controls. We compared FFAs in patients with SLE and controls using Wilcoxon rank sum tests and further tested for the independent association between FFAs and disease status with adjustment for age, race and sex using multivariable regression models. We assessed the relationship between FFAs and continuous variables of interest using Spearman correlation and multivariable regression analysis. Levels of FFAs were higher in patients with SLE than controls (0.55 mmol/l (0.37-0.71) vs 0.44 mmol/l (0.32-0.60), P = 0.02). Levels of FFAs remained significantly higher among patients with SLE after adjustment for age, race and sex (P = 0.03) but not after further adjustment for body mass index (P = 0.13). FFA levels did not differ according to the usage of current immunosuppressive medications in univariate and adjusted analysis (all P > 0.05). Among patients with SLE, concentrations of FFAs were higher among those with metabolic syndrome compared to those without (0.66 mmol/l (0.46-0.81) vs 0.52 mmol/l (0.35-0.66), P < 0.001). FFAs were positively correlated with insulin resistance (HOMA) (rho = 0.23, P = 0.004, P adjusted = 0.006) and triglyceride levels (rho = 0.22, P = 0.01, P adjusted = 0.004). FFAs were not associated with inflammatory cytokines (IL-6, TNF-α) (all P > 0.05) but were positively associated with levels of E-selectin (rho = 0.33, P = < 0.001, P adjusted = 0.001) and ICAM-1 (rho = 0.35, P < 0.001, P adjusted = 0.001). FFAs were correlated with coronary artery calcium score (rho = 0.20, P = 0.01) but this was attenuated after adjustment for age, race and sex (P = 0.33). From our study we concluded that FFAs are elevated in patients with SLE, particularly those with metabolic syndrome. FFAs in patients with SLE are not associated with markers of generalized inflammation but are associated with insulin resistance and markers of endothelial activation.

Cystatin C is associated with inflammation but not atherosclerosis in systemic lupus erythematosus.

BACKGROUND: Even mild renal impairment is associated with increased atherosclerosis and cardiovascular mortality. Cystatin C, a novel measure of renal function, is more sensitive than conventional creatinine-based measures for the detection of subtle renal impairment. Increased cystatin concentrations are also associated with cardiovascular risk, independently of conventional measures of renal function. This study examined the hypothesis that cystatin C is elevated in systemic lupus erythematosus (SLE) and is associated with coronary atherosclerosis. METHODS: Serum cystatin C, creatinine, tumor necrosis factor (TNF)-α, interleukin (IL)-6, coronary artery calcium score (CACS), Framingham risk score (FRS), Modified Diet in Renal Disease estimated glomerular filtration rate (MDRD-eGFR), and other clinical parameters were measured in 118 patients with SLE and 83 control subjects. The independent association between concentrations of cystatin C and SLE was evaluated using multivariable linear regression models, and the relationship between renal measures and coronary calcium was assessed with multivariable proportional odds logistic regression models. RESULTS: Cystatin C, but not other measures of renal function, was significantly higher in patients with SLE than in controls (1.09 [interquartile range, IQR: 0.85-1.28] mg/l vs. 0.89 [IQR: 0.76-0.99] mg/l; p < 0.001 after adjustment for age, race, sex and MDRD-eGFR). Cystatin C was significantly associated with SLICC (p = 0.04), erythrocyte sedimentation rate (ESR) (p = 0.02), TNF-α (p = 0.008) and IL-6 (p = 0.01) after adjustment for age, race, and sex. Cystatin C was not significantly correlated with coronary calcium score in SLE (rho=0.096, p = 0.31) and the association remained non-significant after adjustment for age, race, sex, and Framingham risk score (p = 0.99). CONCLUSIONS: Cystatin C was higher in patients with SLE than in control subjects even after adjustment for conventional measures of renal function. Cystatin C was significantly correlated with several markers of inflammation in SLE but was not associated with coronary atherosclerosis. Subtle renal dysfunction does not appear to be directly associated with accelerated atherosclerosis in SLE.

Novel cardiovascular risk prediction models in patients with systemic lupus erythematosus.

Women with systemic lupus erythematosus (SLE) have increased risk for coronary heart disease (CHD) which is underestimated by the Framingham risk score (FRS). We hypothesized that new risk scores that include inflammation or vascular age in the risk calculation would better identify women with SLE at risk for CHD, particularly in those with subclinical coronary atherosclerosis. We calculated the FRS and Reynolds risk score (RRS) in 121 women with SLE and 65 age-matched female controls; coronary age-modified risk scores (camFRS, camRRS) were calculated using coronary age derived from the coronary artery calcium (CAC) score. Risk scores were compared in SLE and controls, and in SLE patients with and without CAC. Although CAC was present in 21 SLE patients (17%) and four controls (6%) (p = 0.033); the FRS, camFRS, RRS, and camRRS, did not differ significantly among SLE and controls (p > 0.05), but were all significantly higher in SLE patients with CAC compared with those without (p < 0.001 for all). The camFRS (8%, p = 0.016) but not camRRS (5%, p = 0.221) assigned significantly more SLE patients to a category of ≥ 10% risk than conventional FRS (1%) and RRS (2%). The RRS was of limited use but coronary age may improve CHD risk prediction in SLE.

Preventing glycaemic relapse in recently controlled type 2 diabetes patients: a randomised controlled trial.

AIMS/HYPOTHESIS: After achieving glycaemic control, many type 2 diabetic patients relapse to clinically significant levels of hyperglycaemia. We sought to determine the optimal frequency of telephone contact by nurse practitioners that was necessary to prevent glycaemic relapse. METHODS: This parallel, randomised controlled trial ran from June 2002 to February 2006 at an academic medical centre, studying 164 type 2 diabetic patients who had recently achieved glycaemic control. Participants were randomly assigned by sequential, concealed, computer-generated allocation to a 2 year maintenance strategy consisting of: (1) routine follow-up (n = 54); (2) routine follow-up and quarterly telephone contact (n = 55); or (3) routine follow-up and monthly telephone contact (n = 55). Blinding was not possible. The primary outcome was cumulative incidence of glycaemic relapse, defined as an increase in HbA(1c) of > or =1%; all participants were analysed. Cumulative incidence and prevalent proportions were compared. Weight change and hypoglycaemia were also assessed. RESULTS: All participants randomised were included in the analyses. The study was completed by 90% of participants and intervention fidelity was high. At 24 months, the cumulative incidence of relapse was 41%. At 12 months, prevalent proportions of relapse were 20%, 14% and 15% for control, quarterly contact and monthly contact, respectively. At 24 months, they were 25%, 21% and 29%, respectively. There was no statistically significant difference in cumulative incidence or prevalent proportions of relapse among the study arms. Adverse events did not differ between study arms. CONCLUSIONS/INTERPRETATION: This first randomised controlled trial to test an intervention to prevent glycaemic relapse found that regularly scheduled telephone contact by a nurse practitioner was no more effective than routine follow-up care in preventing glycaemic relapse.

Oxidative stress in systemic lupus erythematosus: relationship to disease activity and symptoms.

Oxidative stress may play a role in the pathogenesis of systemic lupus erythematosus (SLE). We examined the hypothesis that oxidative stress was associated with indices of lupus disease activity and severity of symptoms. Urinary F2 isoprostane excretion, a validated marker of oxidative stress, was measured in 95 patients with SLE and 103 healthy controls. Outcome measures included SLEDAI and SLICC scores, the modified health assessment questionnaire, the fatigue severity scale (FSS), and visual analogue scales (VAS) for fatigue, pain and overall disease activity. F2 isoprostane excretion was compared in patients and controls, and its relationship with clinical variables in SLE examined. F2 isoprostane excretion did not differ significantly among patients with lupus (2.7 +/- 2.3 ng/mg Cr) and control subjects (2.2 +/- 1.4 ng/mg Cr) (P = 0.70). In patients with lupus, F2 isoprostane concentrations were independently associated with higher patient reported disease activity (VAS) (OR = 1.52, P = 0.01), fatigue (FSS, OR = 1.52, P = 0.03) and lower quality of life (OR = 0.73, P = 0.05), but not with objective markers or inflammation or disease activity. In conclusion, F2 isoprostane excretion is associated with patient-reported symptoms in SLE but not with measures of inflammation, SLEDAI or SLICC. Oxidative stress may contribute to debilitating symptoms such as fatigue in SLE.

Congestive heart failure with preserved systolic function in a statewide sample of community hospitals.

BACKGROUND: The importance of congestive heart failure (CHF) in patients with preserved left ventricular systolic function is increasingly recognized, but most studies have been conducted at a single, usually academic, medical center. The aim of this study was to determine the prognosis, readmission rate, and effect of ACE inhibitor therapy in a Medicare cohort with CHF and preserved systolic function. METHODS AND RESULTS: We examined a statewide, random sample of 1,720 California Medicare patients hospitalized with an ICD-9 diagnosis of CHF confirmed by a decreased left ventricular ejection fraction (EF) or chest radiograph from July 1993 to June 1994 and January 1996 to June 1996. Among the 782 patients with confirmed CHF and an in-hospital left ventricular EF measurement, 45% had reduced systolic function (ReSF) (EF < 40%) and 55% had preserved systolic function (PrSF) (EF > 40%). The PrSF group had a lower 1-year mortality rate but similar hospital readmission rates for both CHF and all causes. In patients with ReSF, ACE inhibitor treatment was associated with a lower mortality rate (P =.04) and a trend toward a lower CHF readmission rate (P =.13). In contrast, ACE inhibition therapy was associated with neither a lower rate of mortality nor CHF readmission in PrSF patients (P =.61 and.12, respectively). In multivariate analyses treatment with ACE inhibitors in PrSF patients was not associated with either a reduction in mortality (hazard ratio, 1.15; 95% CI, 0.79-1.67) or CHF readmission (hazard ratio, 1.21; 95% CI, 0.92-1.58). CONCLUSIONS: CHF with PrSF seems to be associated with high mortality and morbidity rates, but ACE inhibitors may not produce comparable benefit in this group as in patients with ReSF.

Is screening mammography effective in elderly women?

PURPOSE: Screening mammography is effective in reducing breast cancer mortality in women between the ages of 50 and 69 years. We sought to determine whether older women who undergo screening mammography have a decreased risk of metastatic breast cancer. SUBJECTS AND METHODS: We studied 690,993 women aged 66 to 79 years who were California Medicare beneficiaries from January 1992 to December 1993, and who chose the fee-for-service plan. Health Care Financing Administration part B billing records were used to determine the use of screening mammography. The extent of breast cancer (in situ, local, regional, or metastatic) was ascertained for the 6,767 women who were diagnosed with the disease in 1993, using data from the California State Cancer Registry. For each type (extent) of breast cancer, the relative risk (RR) and 95% confidence (CI) of developing breast cancer was estimated by dividing the risk of its development in screened women by the risk in women who were not screened. RESULTS: A total of 46% of women had mammography during the 2-year study period. In situ, local, and regional breast cancer were more likely to be detected among women who underwent screening mammography. For example, the relative risk of detecting local breast cancer in screened women was 3.3 (95% CI: 3.1 to 3.5). The risk of detecting metastatic breast cancer, on the other hand, was significantly reduced among women aged 66 to 79 years who underwent screening mammography (RR = 0.57, 95% CI: 0.45 to 0.72). CONCLUSION: Screening mammography is associated with a decreased risk of detecting metastatic breast cancer among elderly women. Public health recommendations need to weigh the benefit of screening elderly women against the cost and potential harm from screening and treating early lesions that may have no effect on mortality.

Relationship between earlier and later mammography screening--California Medicare, 1992 through 1994.

Regular screening mammography is recommended to reduce breast cancer mortality. Although predictors of mammography have been studied, factors that influence adherence to guidelines are less understood. We examined the relationship between an index mammogram and subsequent mammograms among California Medicare beneficiaries. Medicare billing data for 1992, 1993, and 1994 were used to estimate the association between screening mammography in 1992 and subsequent screening in 1993 or 1994. We found that women with a 1992 mammogram were more than twice as likely to have a mammogram in 1993 or 1994 than women without a 1992 mammogram (relative risk = 2.58; 95% confidence interval, 2.57-2.59). This relationship was somewhat stronger for black women compared with white women and increased with age. Although further study of regular screening patterns is needed, these findings provide some evidence that encouraging a single mammogram may lead to continued adherence.

Mammography screening among California Medicare beneficiaries: 1993-1994.

BACKGROUND: Over half of all breast cancer deaths occur among women 65 years of age or older. However, mammography screening decreases with increasing age, despite better survival rates for tumors detected early. METHODS: Health Care Financing Administration data from 1993 and 1994, and 1990 United States Census data were used to assess the impact of race, age, Medicaid coverage, and community-level socioeconomic indices on mammography screening for over 800,000 California Medicare beneficiaries. RESULTS: Women who were African American, older, or had Medicaid coverage were significantly less likely to have a biennial mammogram than their counterparts. Women living in areas with fewer college educated residents, with a higher proportion of Mexican or Asian residents had lower use of mammography. However, African-American and Caucasian women with Medicaid coverage had equally low mammography rates (AOR = 1.01, 95% CI .97-1.04), while African-American women with and without Medicaid had similarly low mammography rates (AOR = .96, 95% CI .92-1.01). CONCLUSIONS: Despite dual coverage, Medicare beneficiaries enrolled in Medicaid had few mammograms. African-American Medicare beneficiaries, with and without Medicaid, had low mammography rates. Intervention efforts should be targeted toward these women.

Hormone replacement therapy and endometrial cancer risk: a meta-analysis.

OBJECTIVE: To assess the association of unopposed estrogen or estrogen plus progestin and the risk of developing endometrial cancer or dying of that disease. DATA SOURCES: A literature search of English-language studies was performed using MEDLINE, a review of bibliographies, and consultations with experts. METHODS OF STUDY SELECTION: We identified 30 studies with adequate controls and risk estimates. DATA EXTRACTION AND SYNTHESIS: Risk estimates were extracted by two authors and summarized using meta-analytic methods. The summary relative risk (RR) was 2.3 for estrogen users compared to nonusers (95% confidence interval [CI] 2.1-2.5), with a much higher RR associated with prolonged duration of use (RR 9.5 for 10 or more years). The summary RR of endometrial cancer remained elevated 5 or more years after discontinuation of unopposed estrogen therapy (RR 2.3). Interrupting estrogen for 5-7 days per month was not associated with lower risk than daily use. Users of unopposed conjugated estrogen had a greater increase in RR of developing endometrial cancer than users of synthetic estrogens. The risk for endometrial cancer death was elevated among unopposed estrogen users (RR 2.7, 95% CI 0.9-8.0). Among estrogen plus progestin users, cohort studies showed a decreased risk of endometrial cancer (RR 0.4), whereas case-control studies showed a small increase (RR 1.8). CONCLUSIONS: Endometrial cancer risk increases substantially with long duration of unopposed estrogen use, and this increased risk persists for several years after discontinuation of estrogen. Although not statistically significant, the risk of death from endometrial cancer among unopposed estrogen users is increased, similar to the increased risk of developing the disease. Data regarding risk for endometrial cancer among estrogen plus progestin users are limited and conflicting.