Bojana Stamenkovic

Prevalence and factors associated with left ventricular dysfunction in the EULAR Scleroderma Trial and Research group (EUSTAR) database of patients with systemic sclerosis

Objectives: To measure the prevalence of, and factors associated with, left ventricular (LV) dysfunction in systemic sclerosis (SSc). Methods: The EUSTAR database was first searched. A case-control study of a patient subset was then performed to further identify independent factors associated with LV dysfunction by simple and multiple regression. Results: Of 7073 patients, 383 (5.4%) had an LV ejection fraction (EF) of <55%. By multiple regression analysis, age, sex, diffuse cutaneous disease, disease duration, digital ulcerations, renal and muscle involvement, disease activity score, pulmonary fibrosis and pulmonary arterial hypertension were associated with LV dysfunction. In the second phase, 129 patients with SSc with LVEF <55% were compared with 256 patients with SSc with normal LVEF. Male sex (OR 3.48; 95% CI 1.74 to 6.98), age (OR 1.03; 95% CI 1.01 to 1.06), digital ulcerations (OR 1.91; 95% CI 1.05 to 3.50), myositis (OR 2.88; 95% CI 1.15 to 7.19) and use of calcium channel blockers (OR 0.41; 95% CI 0.22 to 0.74) were independent factors associated with LV dysfunction. Conclusion: The prevalence of LV dysfunction in SSc is 5.4%. Age, male gender, digital ulcerations, myositis and lung involvement are independently associated with an increased prevalence of LV dysfunction. Conversely, the use of calcium channel blockers may be protective.

Erectile dysfunction is frequent in systemic sclerosis and associated with severe disease: a study of the EULAR Scleroderma Trial and Research group

IntroductionErectile dysfunction (ED) is common in men with systemic sclerosis (SSc) but the demographics, risk factors and treatment coverage for ED are not well known.MethodThis study was carried out prospectively in the multinational EULAR Scleroderma Trial and Research database by amending the electronic data-entry system with the International Index of Erectile Function-5 and items related to ED risk factors and treatment. Centres participating in this EULAR Scleroderma Trial and Research substudy were asked to recruit patients consecutively.ResultsOf the 130 men studied, only 23 (17.7%) had a normal International Index of Erectile Function-5 score. Thirty-eight per cent of all participants had severe ED (International Index of Erectile Function-5 score ≤ 7). Men with ED were significantly older than subjects without ED (54.8 years vs. 43.3 years, P < 0.001) and more frequently had simultaneous non-SSc-related risk factors such as alcohol consumption. In 82% of SSc patients, the onset of ED was after the manifestation of the first non-Raynauds symptom (median delay 4.1 years). ED was associated with severe cutaneous, muscular or renal involvement of SSc, elevated pulmonary pressures and restrictive lung disease. ED was treated in only 27.8% of men. The most common treatment was sildenafil, whose efficacy is not established in ED of SSc patients.ConclusionsSevere ED is a common and early problem in men with SSc. Physicians should address modifiable risk factors actively. More research into the pathophysiology, longitudinal development, treatment and psychosocial impact of ED is needed.

Mapping and predicting mortality from systemic sclerosis

Objectives To determine the causes of death and risk factors in systemic sclerosis (SSc). Methods Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. Results We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. Conclusion Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients’ survival.

Validation of the osteoporosis quality of life questionnaire QUALEFFO-41 for the Serbian population

BackgroundVertebral fractures could lead to reduced physical, social and mental functioning, and loss of personal independence. Therefore, during the treatment of osteoporosis, it has become necessary to examine the changes in everyday functioning, well-being and health related quality of life (HRQOL). To that effect, this study aims to translate, culturally adapt, and validate the Serbian version of Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41) for patients with vertebral fractures.MethodsNine female patients with osteoporosis participated in the pre-validation study. A validation, case–control study included two groups of female patients: one that consisted of 50 female patients with osteoporosis, and with at least one vertebral fracture, and another one that consisted of 50 control patients with osteoporosis but without fractures. They completed the QUALEFFO-41 and the EuroQol group questionnaire with five dimensions (EQ-5D) twice within a month. The validation study examined internal consistency, concurrent validity, test-retest reliability, sensitivity and specificity.ResultsDuring the pre-validation study, three of the items in the QUALEFFO-41 were slightly changed. Afterwards, during the validation study, the statistically significant differences (adjusted for: age, duration of menopause, current employment and marital status) in the mean values of all domains and total scores between the groups were noted. For the case group, the internal consistency of the QUALEFFO-41 domains and of total questionnaire was above 0.70. The test-retest reliability was tested by the intraclass correlation coefficients (ICC) that were in range 0.87 – 0.96 for the case, and 0.15 – 0.83 for the control group. Correlations between the total scores of the QUALEFFO-41 and the EQ-5D health state value, for both groups were negative and statistically significant (r = -0.78, p<0.001 and r = -0.73, p<0.001, respectively). The QUALEFFO-41 had a better prediction of the value of HRQOL of cases compared to the generic questionnaire EQ-5D (the AUC difference was 0.099, p = 0.013).ConclusionsThe Serbian QUALEFFO-41 version is reliable, valid, sensitive and predictive for examinations of HRQOL in patients with prevalent vertebral fractures and can be used in further studies.

Nailfold capillary abnormalities in erectile dysfunction of systemic sclerosis: a EUSTAR group analysis

OBJECTIVE The objective of this study was to analyse an association between nailfold capillary abnormalities and the presence and severity of erectile dysfunction (ED) in men with SSc. METHODS A cross-sectional analysis of the prospective European League Against Rheumatism (EULAR) Scleroderma Trial and Research database was performed. Men with SSc were included if they had undergone nailfold capillaroscopy and simultaneous ED assessment with the 5-item International Index for Erectile Function (IIEF-5). RESULTS Eighty-six men met the inclusion criteria. Eight men (9.3%) had not had sexual intercourse and could not be assigned an IIEF-5 score. Sixty-nine of the 78 men (88.5%) with an IIEF-5 score had nailfold capillary abnormalities, of whom 54 (78.3%) suffered from ED. Nine men (11.5%) had no nailfold capillary abnormalities, of whom six (66.7%) had ED (P = 0.44). ED was more frequent in older men (P = 0.002) and in men with diffuse disease (P = 0.06). Men with abnormal capillaroscopy had a higher median EULAR disease activity than men without (P = 0.02), a lower diffusing capacity of the lung (P = 0.001) and a higher modified Rodnan skin score (P = 0.04), but mean IIEF-5 scores did not differ [15.7 (S.D. 6.2) vs 15.7 (S.D. 6.3)]. IIEF-5 scores did not differ between men with early (n = 12), active (n = 27) or late (n = 27) patterns (IIEF-5 scores of 17.9, 16.3 and 14.7, respectively). There were no differences in the prevalence of early, active and late capillaroscopy patterns between men with or without ED. CONCLUSION Neither the presence or absence of abnormal capillaroscopy findings nor the subdivision into early, active and late patterns is associated with coexistent ED in SSc.

Monocyte chemoattractant protein-1 as a marker of systemic lupus erythematosus: an observational study

There is a pivotal need for new markers to be tested in every day clinical practice for systemic lupus erythematosus (SLE) and lupus nephritis (LN). The levels of monocyte chemoattractant protein-1 (MCP-1) in the serum and urine of 72 SLE patients (27 with LN and 45 without LN involvement) and 30 healthy individuals were studied to establish their clinical significance. The SLE Disease Activity Index (SLEDAI) was used to establish the disease activity. Urine and serum MCP-1 was determined using the sandwich enzyme immunosorbent assay. Urinary, but not serum MCP-1, positively correlated with proteinuria (r = 0.839; p < 0.001) and negatively correlated with glomerular filtration, evaluated using the modification of diet in renal disease (MDRD) formula (r = − 0.293; p < 0.05), and with C3 complement component in active LN patients (r = − 0.519, p = 0.019). Both serum and urinary MCP-1 demonstrated a positive correlation with SLEDAI (r = 0.318; p < 0.01 and r = 0.431; p < 0.001). We also demonstrated that the levels of serum and urinary MCP-1 were significantly higher in patients with SLE compared to healthy controls, regardless of the disease activity and renal involvement. We recommend MCP-1 measurement in the routine laboratory follow-up of the SLE patients.

Relation between bone density and certain parameters of lipid status in postmenopausal women

The aim of the paper was to examine the relation between bone density and certain parameters of lipid status in postmenopausal women. The research involved 300 women referred to densitometric examination as they belonged to the risk group of postmenopausal women. All the examinees had the following biochemical parameters determined: total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, glycemia, serum Ca and P. Univariate logistic regression analyses showed that each year of age, menopause duration, AH are significantly connected to risk increase for the appearance of osteopenia or osteoporosis. Increase in values of SBP, DBP, cholesterol, LDL and triglyceride are connected with significant risk increase for the appearance of osteopenia or osteoporosis. Patients with AH are connected to 11 times elevated risk for the appearance of osteopenia or osteoporosis, cigarette smoking increased the risk by seven times, physical inactivity even by 52 times, CVD in the family anamnesis by eight times, and osteoporosis in the family anamnesis is connected to the risk by four times. In our research, atherogenic lipoproteins negatively correlate with lumbar bone density. Disturbed lipide status is a risk factor for cardiovascular diseases, but also a risk factor for the appearance of osteoporosis.

Correlation between total cardiovascular risk and bone density in postmenopausal women

The aim of the paper was to examine the correlation between the total risk of cardiovascular events, determined by the SCORE (Systematic Coronary Risk Evaluation) system, and bone density in postmenopausal women. Examinees and method: The research involved 300 postmenopausal women. On the basis of bone density measurements, the participants were divided into three groups: group I — 84 examinees had osteoporosis, group II — 115 examinees had osteopenia, and group III — 101 examinees had normal bone mineral density (BMD). Results: Participants with high SCORE risk were statistically significantly older compared to low-risk women (60±3 vs. 55±5; p<0.001). They had significantly lower BMD and T scores (−1.09±0.94 vs. −2.86±0.63; p<0.001). Elevation of the SCORE risk by 1% caused a BMD decrease of 0.033 g/cm2(0.029 to 0.036 gr/cm2). Multivariate logistic regression analysis showed that the following factors caused a significant increase in the risk of decreasing BMD: every year of life by 20%, menopause duration by 26%, increase in systolic blood pressure (BP) by 1 mm Hg by 7%, increase in SCORE risk by 1% by 5.31 times, physical inactivity by 5.96 times, and osteoporosis in the family history by 3.91 times. Conclusion: Postmenopausal women who are at high risk for cardiovascular diseases have a lower BMD than those who are not at high risk for cardiovascular diseases.

QTc dispersion and Cornell duration product can predict 10-year outcomes in hypertensive patients with left ventricular hypertrophy

Persistent and adequate treatment of patients with arterial hypertension leads to more favorable disease outcome.

Association of the A Allele of the TNF-Alpha-308 G/A Gene Polymorphism with Radiographic Progression in Rheumatoid Arthritis

Summary To examine whether the presence of the rare A allele of the TNF-Alpha-308 G/A gene polymorphism is associated with erosive arthritis and rapid radiological progression of the disease. The examined group included 131 patients with early RA. Using the PCR-RFLP method, the TNF-Alpha-308 G/A gene polymorphism was determined for all patients. In relation to the presence of the A allele of the examined polymorphism, the patients were divided into two subgroups: subgroup A (G/A and A/A genotypes) and subgroup G (G/G genotype). Based on the presence of the destructive changes in joints found in the initial radiographs, the findings were classified as erosive and non-erosive RA. Radiological progression was assessed on the basis of the annual change in the Larsen score – LS (0-200). Group A comprised 62 (47.33%) patients, while group G comprised 69 (52.67%) patients. The presence of cysts and erosions in subgroups A and G was compared before the start of the methotrexate therapy. It was determined that erosions (erosive RA) were statistically significantly more frequent in group A (83.87% of patients) in comparison with group G (44.93% of patients), p < 0,001. Group A patients had a higher value of the Larsen score in relation to the group G both before and after methotrexate was administered for a year (before therapy, LS in group A: 48.58 ± 20.54; in group G 20.73 ± 12.31; p < 0.01; after MTX therapy, LS in group A: 58.32 ± 22.25; in group G 25.35 ± 14.57; p < 0.001). The average value of the annual LS change in group A was statistically significantly greater than the change in group G patients (9.98 ± 4.95 to 5.23 ± 2.72) (p < 0.05). The presence of the A allele of the TNF-Alpha-308 G/A gene polymorphism is associated with the occurrence of early erosive joint changes and more rapid radiological progression of the disease.