Effects of Renin-Angiotensin System Inhibitors on Atrial Mechanics Parameters in Patients with Metabolic Syndrome.

INTRODUCTION: Metabolic syndrome (MS) is associated with abnormalities in atrial mechanics, atrial remodeling, and an increased risk of heart rhythm disorders. One of the most commonly used approaches to the prevention of cardiac remodeling in arterial hypertension is the administration of renin-angiotensin system (RAS) inhibitors. Therefore, this study aimed to investigate the effects of RAS inhibitors on atrial mechanics parameters in patients with MS. METHODS AND MATERIALS: This longitudinal observational study included 55 patients with hypertension and MS, as defined by the ATP III criteria. The patients were evaluated at the start of antihypertensive treatment with an RAS inhibitor. The patients' clinical characteristics, chosen pharmacological treatment, and transthoracic echocardiography findings were recorded at baseline and 6 months thereafter. A student's dependent sample t-test was used for comparisons between groups. Pearson correlation was used to evaluate the relationships between variables. RESULTS: Patients with MS had higher peak atrial longitudinal strain (PALS) values at 6 months than at baseline. Meanwhile, systolic strain and peak late strain rates were lower at follow-up than at baseline. The different antihypertensive treatments had comparable effects on the PALS changes during the follow-up period. Higher high-density lipoprotein levels at baseline were correlated with changes in PALS. CONCLUSION: The administration of RAS inhibitors improved atrial mechanics parameters in the early stages of antihypertensive management in MS.

Risk Factors of Muscle Wasting in Women with Rheumatoid Arthritis: Relevance of the Persistent Failure of Conventional Combination Therapy.

Background: Muscle wasting, also known as myopenia, is frequent in rheumatoid arthritis (RA). To date, it is still unknown if the failure of pharmacologic therapies increases the risk of myopenia in RA. Objective: To identify if treatment failure with conventional synthetic DMARDs (csDMARDs) constitutes an independent risk factor of muscle wasting in women with RA. Methods: This was a cross-sectional study. We included 277 women with RA. Assessments in RA patients included: clinical, epidemiological, and therapeutic variables. The skeletal muscle index (SMI) was estimated by DXA, and myopenia was diagnosed if they had an SMI < 5.45 kg/m2. Multivariable logistic regression models identified risk factors of myopenia. Results: Muscle wasting was observed in 28.2% of patients with RA. The risk factors of myopenia in RA were menopausal (OR: 4.45, 95% CI: 1.86 to 10.64) and failure of combined therapy with csDMARDs (OR: 2.42, 95% CI: 1.15 to 5.07). The increased body mass index was protective (OR:0.81, 95% CI: 0.75 to 0.87). Conclusions: Around one of four patients with RA presented muscle wasting. Muscle wasting is related to treatment failure of combined csDMARDs; other factors influencing the presence of muscle wasting is being postmenopausal, whereas, the body mass index was a protective factor.

Therapeutic response to leflunomide in combo therapy and monotherapy is associated to serum teriflunomide (A77 1726) levels.

There is a significant rate of therapeutic failure in rheumatoid arthritis (RA) patients treated with leflunomide (LEF). This study investigates the utility values of teriflunomide levels (A77 1726) in identifying RA patients who remained with moderate or severe disease activity after the treatment with LEF. In this cross-sectional study, we compared: (a) RA patients who achieved a DAS28-ESR ≤ 3.2, and (b) RA patients who maintained a DAS28-ESR > 3.2 after treatment. ROC curves determined the cut-off of A77 1726 with the better performance to identify patients achieving a DAS28-ESR ≤ 3.2. Of the 115 patients treated with LEF, 69 (60%) remained with moderate/severe disease activity and 46 (40%) achieved low disease activity/remission. Higher A77 1726 levels showed a negative correlation with DAS28-ESR (r = - 0.42, p < 0.001) and other parameters of disease activity. We obtained the following utility values with the cut-off of A77 1726 > 10 µg/mL to identify RA patients who achieved a DAS28-ESR ≤ 3.2: sensitivity of 91.31%; specificity of 73.91%; positive predictive value of 70.00%; and negative predictive value of 92.73%. Serum A77 1726 discriminated between RA patients who remained with moderate/severe disease activity despite the treatment with LEF both as monotherapy and LEF as combo therapy.

Functional disability is related to serum chemerin levels in rheumatoid arthritis.

Adipokines, especially chemerin, can interact with cytokines and other molecules in inflammation. To date, there is insufficient information regarding a possible correlation between functional disability and chemerin and other pro-inflammatory molecules in rheumatoid arthritis (RA). To identify the association of functional disability with serum chemerin and other pro-inflammatory molecules, including other adipokines, cytokines and E-selectin, in patients with RA. Cross-sectional study. Assessment: disease activity (DAS28-ESR) and functional disability (HAQ-DI). We compared the adipokines (chemerin, leptin, adiponectin, resistin, and visfatin), cytokines (TNF-α, IL-6, IL-1ß, and IL-18) and E-selectin levels between RA with functional disability and RA non-disabled patients. Of 82 patients with RA, 43 (52%) had functional disability. The RA with functional disability group had higher chemerin (140 vs. 112 ng/mL, p = 0.007) than the non-disabled RA group. Chemerin correlated with the HAQ-DI (rho = 0.27, p = 0.02) and DAS28-ESR (rho = 0.21, p = 0.05). Severe activity correlated with IL-6 (rho = 0.33, p = 0.003) and E-selectin (rho = 0.23, p = 0.03) but not with disability. No other pro-inflammatory molecules correlated with HAQ-DI. High chemerin levels were associated with functional disability in RA, whereas no other molecules correlated with loss of function. These results encourage further studies assessing new roles of chemerin as a marker of impairment in RA.

Serum chemerin levels: A potential biomarker of joint inflammation in women with rheumatoid arthritis.

BACKGROUND: Chemerin has a potential role in perpetuating inflammation in autoimmune diseases. Nevertheless, to date, there is no conclusive information on whether high chemerin levels increase the severity of rheumatoid arthritis (RA). Therefore, this study evaluated whether serum chemerin is a biomarker of disease activity in RA patients. METHODS: Study design: cross-sectional. The assessment included clinical and laboratory characteristics, body mass index (BMI) and fat mass. The severity of the disease activity was identified according to the DAS28-CRP index as follows: A) RA with a DAS28-CRP≤2.9 (remission/mild activity) and B) RA with a DAS28-CRP>2.9 (moderate/severe activity). Serum chemerin concentrations were measured by ELISA, and ≥103 ng/mL was considered a high level. Logistic regression analysis was applied to determine whether high chemerin levels were associated with disease activity in RA after adjusting for confounders. Multiple regression analysis was performed to identify variables associated with chemerin levels. RESULTS: Of 210 RA patients, 89 (42%) subjects had moderate/severe disease activity and had higher serum chemerin levels than patients with low disease activity or remission (86 ± 34 vs 73± 27; p = 0.003). Serum chemerin correlated with the number of swollen joints (r = 0.15; p = 0.03), DAS28-CRP (r = 0.22; p = 0.002), and C-reactive protein levels (r = 0.14; p = 0.04), but no correlation was observed with BMI and fat mass. In the adjusted logistic regression analysis, high chemerin levels (≥103 ng/mL) were associated with an increased risk of moderate/severe disease activity (OR: 2.76, 95% CI 1.35-5.62; p = 0.005). In the multiple regression analysis, after adjusting for potential confounders, serum chemerin levels were associated with higher DAS28-CRP (p = 0.002). CONCLUSIONS: Higher chemerin levels increased the risk of moderate and severe disease activity in RA. These results support the role of chemerin as a marker of inflammation in RA. Follow-up studies will identify if maintaining low chemerin levels can be used as a therapeutic target.

Genotypic Analyses of the Sclerostin rs851056 and Dickkopf rs1569198 Polymorphisms in Mexican-Mestizo Postmenopausal Osteoporosis: A Case-Control Study.

Background: The Wnt/ß catenin pathway promotes bone mineralization stimulating proliferation, differentiation, and survival of osteoblasts; it also inhibits osteoclast differentiation and osteocyte activity. Sclerostin (SOST) and Dickkopf 1 (DKK1) are Wnt/ß catenin pathway inhibitors. Genetic variability in the expression of SOST and DKK1 might be involved in the development of postmenopausal osteoporosis (OP). Aim: To determine whether the SOST rs851056 and DKK1 rs1569198 polymorphisms are associated with OP in Mexican-Mestizo postmenopausal women. Materials and Methods: Two hundred and eighty Mexican-Mestizo postmenopausal women were assessed for their bone mineral density by dual-energy X-ray absorptiometry (DXA). Patients were classified as OP or non-OP. Genomic DNA was extracted from peripheral blood leukocytes. Genetic polymorphisms were analyzed by quantitative polymerase chain reaction using TaqMan probes. Results: The frequency of OP was 40% among the study population. Osteoporotic patients were older (p < 0.001), had a higher frequency of smoking (p = 0.01), and lower body mass index (p < 0.001) compared with the non-osteoporotic patients. The genotypic frequencies of the rs851056 locus of the SOST gene were GG 19%, GC 45%, and CC 35%, whereas the genotypic frequencies of the rs1569198 locus of the DKK1 gene were GG 15%, GA 40%, and AA 44%. In relation to rs851056 locus of the SOST gene, no differences were observed between the OP and non-OP cohorts in the frequencies of the GC polymorphism (48.7% vs. 43.1%). Similarly, analyses of the DKK1 rs1569198 does not demonstrate differences in the GA genotypic frequencies between the OP and non-OP cohorts (42.5% vs. 38.9%). Conclusion: Polymorphisms SOST rs851056 and DKK1 rs1569198 polymorphisms are not associated with OP in Mexican-Mestizo postmenopausal women.

Utility of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as biomarker to predict therapeutic response to methotrexate in rheumatoid arthritis.

The objective of this study was to investigate the usefulness of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in predicting short-term therapeutic response to methotrexate (MTX) in rheumatoid arthritis (RA). Patients with active RA, with Disease Activity Score-28 joints (DAS-28) >3.2, starting oral MTX, were included. We measured at baseline, 3 and 6 mo: DAS-28, Health Assessment Questionnaire-Disability Index (HAQ-DI), patient's perception of disease severity, morning stiffness and pain, as well as modifications in sTREM-1 levels. A reduction in DAS-28 > 1.2 at 3 or 6 mo was considered adequate response. A significant decrease in DAS-28 was observed at 3 and 6 mo. HAQ-DI also decreased at 3 and 6 mo. No significant changes were observed in sTREM-1 levels at 3 or 6 mo. Using as cut-off a baseline value of sTREM-1 levels > 390 pg/ml, we obtained low values of sensitivity (61.5%), specificity (59.3%), positive predictive value (59.3%) and negative predictive value (61.5%) for adequate response to MTX at 3 mo. We found no clinical value of sTREM-1 levels in predicting therapeutic response to MTX in RA. Further studies should evaluate if sTREM-1 levels are predictive for other outcomes, including higher structural damage or good response to biologics.