Tebeb Gebretsadik

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.

Amino-terminal fragment of the prohormone brain-type natriuretic peptide in rheumatoid arthritis

OBJECTIVEnIncreased concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with cardiovascular morbidity and mortality, but little is known about their relationship to chronic inflammation. Patients with rheumatoid arthritis (RA) have chronic inflammation, increased arterial stiffness, and accelerated coronary atherosclerosis. This study was undertaken to test the hypothesis that NT-proBNP concentrations are elevated in patients with RA and are associated with coronary artery calcification and markers of inflammation.nnnMETHODSnIn 159 patients with RA (90 with early RA and 69 with longstanding RA) without heart failure and 88 control subjects, serum concentrations of NT-proBNP, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFalpha) were measured and coronary calcification was assessed. Associations between NT-proBNP levels and the other parameters were investigated.nnnRESULTSnNT-proBNP concentrations were elevated in patients with longstanding RA (median 142.8 pg/ml [interquartile range 54.8-270.5]) and those with early RA (median 58.1 pg/ml [interquartile range 19.4-157.6]) compared with controls (18.1 [3.2-46.0]) (P < 0.001). In patients with RA, NT-proBNP concentrations were associated with age (rho = 0.35, P < 0.001), levels of IL-6 (rho = 0.33, P < 0.001), TNFalpha (rho = 0.23, P = 0.003), and C-reactive protein (CRP) (rho = 0.21, P = 0.01), coronary calcium score (rho = 0.30, P < 0.001), systolic blood pressure (rho = 0.30, P < 0.001), and disease activity (rho = 0.29, P < 0.001). After adjustment for age, race, and sex, the associations between NT-proBNP concentrations and disease activity, TNFalpha, IL-6, and CRP remained significant, but those with systolic blood pressure and coronary calcium score were attenuated.nnnCONCLUSIONnNT-proBNP concentrations are increased in patients with RA without clinical heart failure and may indicate subclinical cardiovascular disease and a chronic inflammatory state.

Health Literacy, Physician Trust, and Diabetes-related Self-care Activities in Hispanics with Limited Resources

Background. Hispanics with diabetes often have deficits in health literacy (HL). We examined the association among HL, psychosocial factors, and diabetes-related self-care activities. Methods. Cross-sectional analysis of 149 patients. Data included patient demographics and validated measures of HL, physician trust, self-efficacy, acculturation, self-care behaviors, and A1c. Results. Participants (N=60) with limited HL were older and less educated, and had more years with diabetes compared with adequate HL participants (N=89). Limited HL participants reported greater trust in their physician, greater self-efficacy, and better diet, foot care, and medication adherence. Health literacy status was not associated with acculturation or A1c. In adjusted analyses, HL status remained associated with physician trust, and we observed a notable but nonsignificant trend between HL status and medication adherence. Discussion. Lower HL was associated with greater physician trust and better medication adherence. Further research is warranted to clarify the role of HL and physician trust in optimizing self-care for Hispanics.

Objectives, design and enrollment results from the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure Study (INSPIRE)

BackgroundRespiratory syncytial virus (RSV) lower respiratory tract infection (LRI) during infancy has been consistently associated with an increased risk of childhood asthma. In addition, evidence supports that this relationship is causal. However, the mechanisms through which RSV contributes to asthma development are not understood. The INSPIRE (Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure) study objectives are to: 1) characterize the host phenotypic response to RSV infection in infancy and the risk of recurrent wheeze and asthma, 2) identify the immune response and lung injury patterns of RSV infection that are associated with the development of early childhood wheezing illness and asthma, and 3) determine the contribution of specific RSV strains to early childhood wheezing and asthma development. This article describes the INSPIRE study, including study aims, design, recruitment results, and enrolled population characteristics.Methods/designThe cohort is a population based longitudinal birth cohort of term healthy infants enrolled during the first months of life over a two year period. Respiratory infection surveillance was conducted from November to March of the first year of life, through surveys administered every two weeks. In-person illness visits were conducted if infants met pre-specified criteria for a respiratory illness visit. Infants will be followed annually to ages 3-4 years for assessment of the primary endpoint: wheezing illness. Nasal, urine, stool and blood samples were collected at various time points throughout the study for measurements of host and viral factors that predict wheezing illness. Nested case-control studies will additionally be used to address other primary and secondary hypotheses.DiscussionIn the INSPIRE study, 1952 infants (48% female) were enrolled during the two enrollment years and follow-up will continue through 2016. The mean age of enrollment was 60 days. During winter viral season, more than 14,000 surveillance surveys were carried out resulting in 2,103 respiratory illness visits on 1189 infants. First year follow-up has been completed on over 95% percent of participants from the first year of enrollment.With ongoing follow-up for wheezing and childhood asthma outcomes, the INSPIRE study will advance our understanding of the complex causal relationship between RSV infection and early childhood wheezing and asthma.

Cystatin C, Renal Function, and Atherosclerosis in Rheumatoid Arthritis

Objective. We examined the hypothesis that cystatin C, a novel marker of renal function, is elevated in rheumatoid arthritis (RA) and is associated with inflammation and coronary atherosclerosis. Methods. We measured serum cystatin C, creatinine, tumor necrosis factor-α and interleukin 6 concentrations, coronary artery calcium score (CACS), and Modified Diet in Renal Disease estimated glomerular filtration rate in 167 patients with RA and 91 controls. Results. Cystatin C was higher in RA patients [median (IQR) 1.16 (0.99–1.35) mg/l] than controls [1.01 (0.90–1.19) mg/l; p < 0.001] and correlated positively with erythrocyte sedimentation rate (p < 0.001), C-reactive protein (p = 0.01), 28-joint Disease Activity Score (p = 0.006), and Framingham risk score (FRS; p = 0.02). Cystatin C was correlated with CACS (p < 0.001) in RA, but this was not significant after adjustment for age, race, sex, and FRS (p = 0.44). Conclusion. Cystatin C concentrations are higher in RA than controls and may reflect inflammation and undetected subclinical renal dysfunction. Cystatin C provides information regarding the risk of atherosclerosis in RA, but this is not independent of the information provided by conventional cardiovascular risk factors.

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]u2009mg/l vs. 0.89 [IQR: 0.76–0.99]u2009mg/l; pu2009<u20090.001 after adjustment for age, race, sex and MDRD-eGFR). Cystatin C was significantly associated with SLICC (pu2009=u20090.04), erythrocyte sedimentation rate (ESR) (pu2009=u20090.02), TNF-α (pu2009=u20090.008) and IL-6 (pu2009=u20090.01) after adjustment for age, race, and sex. Cystatin C was not significantly correlated with coronary calcium score in SLE (rho=0.096, pu2009=u20090.31) and the association remained non-significant after adjustment for age, race, sex, and Framingham risk score (pu2009=u20090.99). 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.

Metabolic control and bone health in adolescents with type 1 diabetes

BackgroundAdults with type 1 diabetes (T1D) have decreased bone mineral density (BMD) and increased fracture risk, yet the etiologies remain elusive. Early detection of derangements in bone biomarkers during adolescence could lead to timely recognition. In adolescents with T1D, we evaluated the relationships between metabolic control, BMD, and bone anabolic and turnover markers.MethodsCross-sectional study of 57 adolescent subjects with T1D who had HbA1c consistently ≥ 9% (Poor Control, PC n = 27) or < 9% (Favorable Control, FC n = 30) for two years prior to enrollment. Subjects had T1DM for at least three years and were without diabetes complications, known celiac disease, or other chronic diseases.ResultsThere were no differences between HbA1c groups in BMD, components of the IGF system, or 25-hydroxyvitamin D status. The prevalence of 25-hydroxyvitamin D abnormalities was similar to that seen in the general adolescent population. Few patients met the recommended dietary allowance (RDA) for vitamin D or calcium.ConclusionsThese data provide no evidence of association between degree of metabolic control and BMD in adolescents with T1D. Adolescents with T1D have a high prevalence of serum 25-hydroxyvitamin D abnormalities. Longitudinal studies are needed to evaluate the predictive value of vitamin D abnormalities on fracture risk.

Insulin Resistance is Associated with Increased Concentrations of NT-proBNP in Rheumatoid Arthritis: IL-6 as a Potential Mediator

We examined the hypothesis that insulin resistance (IR) decreases circulating concentrations of N-terminal (NT)-probrain natriuretic peptide (BNP). Obesity, despite being a risk factor for heart failure (HF), is paradoxically associated with lower concentrations of BNP, a marker of myocardial stress. Low BNP in obesity is postulated to be due to IR; however, it has been difficult to define the role of IR independent of obesity. IR in rheumatoid arthritis (RA) is increased, independent of obesity, thus allowing potential mechanistic insights into the relationship between IR and BNP. We measured demographic factors, traditional cardiovascular risk factors, body mass index (BMI), markers of inflammation (interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor α (TNFα)), NT-proBNP, and IR by the homeostatic model assessment (HOMA) in 140 patients with RA and 82 control subjects. Patients with heart failure and coronary artery disease were excluded. We used multiple linear regression models to examine the relationship between HOMA and NT-proBNP in RA and controls and in RA alone, the additional effect of inflammation. As previously reported, NT-proBNP concentrations were higher in RA (median 80.49xa0pg/mL, IQR (23.67–167.08xa0pg/mL)) than controls (17.84xa0pg/mL (3.28–36.28xa0pg/mL)) (Pu2009<u20090.001), and the prevalence of IR, defined by HOMAu2009>u20092.114, was higher among RA than controls (53xa0% vs. 15xa0%, Pu2009>u20090.001). HOMA was positively correlated with NT-proBNP (rhou2009=u20090.226, Pu2009=u20090.007) in RA, but not in controls (rhou2009=u2009−0.154, Pu2009=u20090.168). In a multivariable model adjusted for age, race, and sex, we found that increasing HOMA was statistically associated with increasing NT-proBNP concentrations in RA (Pu2009=u20090.001), but not controls (Pu2009=u20090.543) (P for interactionu2009=u20090.036). In RA subjects, when IL-6 was further included in the model, IL-6 (Pu2009=u20090.0014), but not HOMA (Pu2009=u20090.43), remained significantly associated with NT-proBNP, suggesting that IL-6 may be mechanistically involved in the relationship between IR and NT-proBNP in RA. We conclude that in patients with RA, insulin resistance is associated with higher, rather than the expected lower, concentrations of NT-proBNP and that this may be related to increased IL-6.

High-sensitivity cardiac troponin-I is elevated in patients with rheumatoid arthritis, independent of cardiovascular risk factors and inflammation.

Objectives We examined the hypothesis that cardiac-specific troponin-I (cTn-I), a biomarker of myocardial injury, is elevated in patients with rheumatoid arthritis (RA). Background RA patients have an increased incidence of heart failure (HF). Chronic myocardial injury in RA may be a mechanism for the development of HF. Methods We compared cTn-I concentrations measured by high-sensitivity immunoassay in 164 patients with RA and 90 controls, excluding prior or active heart failure. We examined the relationship between cTn-I concentrations and cardiovascular risk factors, inflammation, and coronary artery calcium score (CACS), a measure of coronary atherosclerosis. Results cTn-I concentrations were 49% higher in patients with RA (median 1.15 pg/mL [IQR 0.73–1.92] than controls (0.77 pg/mL [0.49–1.28](P<0.001). The difference remained statistically significant after adjustment for demographic characteristics (Pu200a=u200a0.002), further adjustment for cardiovascular (CV) risk factors (Pu200a=u200a0.004), inflammatory markers (Pu200a=u200a0.008), and in a comprehensive model of CV risk factors and inflammatory markers (Pu200a=u200a0.03). In patients with RA, cTn-I concentrations were positively correlated with age (rhou200a=u200a0.359), Framingham risk score (FRS) (rhou200a=u200a0.366), and systolic blood pressure (rhou200a=u200a0.248 (all P values ≤0.001)), but not with measures of inflammation or RA drug therapies. cTn-I was significantly correlated with CACS in RA in univariate analysis, but not after adjustment for age, race, sex and FRS (Pu200a=u200a0.79). Further model adjustments for renal function and coronary artery disease confirmed the significance of the findings. Conclusion High-sensitivity cTn-I concentrations are elevated in patients with RA without heart failure, independent of cardiovascular risk profile and inflammatory markers. Elevated troponin concentrations in RA may indicate subclinical, indolent myocardial injury.

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%) (pu2009=u20090.033); the FRS, camFRS, RRS, and camRRS, did not differ significantly among SLE and controls (pu2009>u20090.05), but were all significantly higher in SLE patients with CAC compared with those without (pu2009<u20090.001 for all). The camFRS (8%, pu2009=u20090.016) but not camRRS (5%, pu2009=u20090.221) assigned significantly more SLE patients to a category ofu2009≥u200910% risk than conventional FRS (1%) and RRS (2%). The RRS was of limited use but coronary age may improve CHD risk prediction in SLE.