natriuretic-peptide--brain and Arthritis--Rheumatoid

There is evidence that rheumatoid arthritis (RA) is associated with higher overall and cardiovascular (CV) morbidity and mortality as compared with general population. Increased prevalence of traditional risk factors and chronic inflammation, that has been recognized as independent CV risk factor, may play an important role in atherosclerosis and subsequently ischemic heart disease development. However, myocardial dysfunction as a result of chronic inflammation and secondarily myocardial fibrosis markedly participates on heart failure development. Proinflammatory cytokines, such as C-reactive protein, tumor necrosis factor alpha (TNFα), interleukins 1 and 6, that are markedly increased in RA, play a role in the acceleration of atherosclerosis as well as myocardial fibrosis development. Several studies documented that increased CV risk was associated with seropositivity, disease activity score, citrullination, and duration of RA. Early detection of heart dysfunction is based on echocardiographic detection of diastolic dysfunction resulting from myocardial inflammation and fibrosis. Some studies showed also higher prevalence of left ventricular systolic dysfunction and increased prevalence of cardiac arrhythmias as compared to non-RA population. There are still controversies on the impact of NT-proBNP in predicting cardiac impairment in RA patients. Some authors consider it to be a sensitive noninvasive predictor of subclinical CV disease in these patients and also a predictor of all-cause mortality independently on traditional CV risk factors. However, the correlation with parameters of cardiac function was confirmed only in a few studies. The impact of biological treatment on progression of atherosclerosis and heart failure is still controversial and seems to be not harmful in young patients with normal left ventricular function. The effect of biologics, especially anti-TNFα drugs, is probably related to the cardiac function before treatment. Larger prospective clinical, echocardiographic, and magnetic resonance studies are needed.

Topics: Antibodies, Blocking; Arthritis, Rheumatoid; Biomarkers; Cardiovascular Diseases; Fibrosis; Humans; Immunotherapy; Inflammation; Inflammation Mediators; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Tumor Necrosis Factor-alpha

Owing to the selective inhibition of PGI2 synthesis, treatment with COX-2 inhibitors constitutes a potential risk for the increased occurrence of thrombotic cardiovascular incidents and of the first-time occurrence or a deterioration in pre-existing heart failure. Elderly patients, particularly those with a history of ischemic heart disease, hypertension or heart failure, are at risk. One key indication for selective COX-2 inhibitors is the chronic treatment of patients suffering from rheumatoid arthritis or osteoarthritis. However, these patients have an excess cardiovascular mortality, which relates particularly to cardiovascular incidents or heart failure. The use of nonselective antiphlogistic drugs and COX-2 inhibitors is associated with a higher potential risk in these patient groups. In essence, more than 80 million patients worldwide were treated with rofecoxib up to its voluntary withdrawal. The high number of patients who are still being treated with COX-2 inhibitors or for whom the use of COX-2 inhibitors is planned justifies the use of a biochemical marker which, as a screening instrument, is initially designed to recognize the patients who are "ill" despite the lack of symptoms. In asymptomatic patients with NT-proBNP levels below the cut-off, high-risk patients require further work-up. Recognition of these risk factors is easily accomplished considering the case history and the results of an established cardiovascular risk score (e.g. PROCAM score). These risk patients should then also be referred for intensive diagnostic work-up. On the other hand, symptomatic patients or those with high NT-proBNP levels should primarily be referred for more extensive cardiovascular diagnosis before a decision is taken concerning the use of COX-2 inhibitors. As an integral part of this extensive work-up the determination of NT-proBNP can help to improve the accuracy of diagnosis and prognostic assessment. With the exception of patients showing symptoms of an unstable coronary heart disease, imminent cerebral ischemia, uncontrolled arterial hypertension or decompensated heart failure, the use of a COX-2 inhibitor is possible provided special caution is exercised. Termination of treatment is advisable if there is a clinical deterioration of specific symptoms or signs in those patients (product information). Follow-up with NT-proBNP (monitoring) can be helpful in detecting imminent cardiac decompensation at an earlier stage in order to take suitable countermea

Topics: Aged; Algorithms; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Biomarkers; Cardiovascular Diseases; Clinical Medicine; Contraindications; Cyclooxygenase Inhibitors; Humans; Lactones; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Osteoarthritis; Peptide Fragments; Risk Assessment; Sulfones

To determine the change in established biomarkers of cardiovascular (CV) risk, namely, total cholesterol/high-density lipoprotein cholesterol ratio (TC/HDL-C), N-terminal pro-brain natriuretic peptide (NT-proBNP) and insulin resistance (IR) in patients with early RA treated with two different treat-to-target strategies.. Fasting glucose, lipids, insulin and NT-proBNP were measured at baseline, weeks 26 and 78 in 79 DMARD-naïve RA patients, free of CV disease, as part of a double-blind randomized controlled trial of MTX with either infliximab (IFX) or methylprednisolone as induction therapy. Homeostasis model assessment-estimated IR (HOMA-IR) (glucose*insulin/405) was used to measure IR. Multiple imputation was employed, and linear regression analyses were adjusted for baseline values.. Changes in DAS44-CRP did not differ between the treatment arms at weeks 26 and 78. Mean TC/HDL-C, HOMA-IR and NT-proBNP improved in both groups at weeks 26 and 78, although change in NT-proBNP was not statistically significant at week 78. Changes in TC/HDL-C and NT-proBNP were similar between treatment arms, but HOMA-IR values in the IFX + MTX arm were 42% lower than those treated with MTX + methylprednisolone at week 78 (P = 0.003); the difference remained significant after adjustment for baseline BMI, ACPA positivity, smoking status and intramuscular glucocorticoid use (P = 0.007).. When implementing a treat-to-target approach, treatment of early RA was associated with improvement in TC/HDL-C, HOMA-IR and NT-proBNP, and a greater long-term improvement in HOMA-IR was seen in those treated with IFX.. EU Clinical Trials Register, http://www.clinicaltrialsregister.eu, Eudract-2005-005013-37; ISRTCNregisrty, http://www.isrctn.com, ISRCTN48638981.

Topics: Adult; Aftercare; Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Biomarkers; Blood Glucose; Cardiovascular Diseases; Cholesterol, HDL; Diabetes Complications; Double-Blind Method; Early Diagnosis; Female; Glucocorticoids; Humans; Infliximab; Insulin; Insulin Resistance; Lipid Metabolism; Male; Methotrexate; Methylprednisolone; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Surveys and Questionnaires; Treatment Outcome; Young Adult

Observational associations between inflammation and cardiovascular disease are interesting, but randomised experimental data are lacking. We investigated the effect of the IL-6 receptor blocker tocilizumab on N terminal pro B type natriuretic peptide (NT-proBNP) and high sensitivity troponin T (hsTnT) in rheumatoid arthritis (RA) patients.. A post-hoc study was performed in a subset of patients with moderate to severe RA participating in a randomised controlled trial. The effect of tocilizumab on cardiac biomarkers was determined using stored serum (baseline and 24 weeks) in recipients of tocilizumab (8 mg/kg every 4 weeks plus DMARDs; n = 225) or placebo (every 4 weeks plus DMARDs; n = 132).. Median NT-proBNP and hsTnT concentrations at baseline were 100 pg/ml and 5.7 pg/ml, respectively. NT-proBNP decreased in both study arms (median at 24 weeks 77 pg/ml in the placebo arm, 79 pg/ml in the tocilizumab arm; p<0.001 for the decrease in both arms), and decreased to a similar extent comparing study arms (tocilizumab effect: -5.5%, p=0.55). hsTnT also decreased in both study arms (median at 24 weeks 3.1 pg/ml in the placebo arm, 4.4 pg/ml in the tocilizumab arm; p<0.001 for the decrease in both arms). The extent of the reduction in hsTnT was greater in the placebo group (tocilizumab effect: +23.3%, p=0.002). Change in NT-proBNP, but not hsTnT, correlated modestly with change in CRP (r = 0.17, p=0.013).. These data argue against a rapid preferential benefit of IL-6 blockade on these specific surrogate markers of cardiovascular risk, but may be consistent with a general cardiovascular benefit of improved RA treatment. CLINICAL TRIALS.. NCT00106574.

Topics: Aged; Antibodies, Monoclonal, Humanized; Arthritis, Rheumatoid; Biomarkers; Cardiovascular Diseases; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, Interleukin-6; Troponin T

To study the influence of anti-tumor necrosis factor-α (TNF-α) treatment on echocardiographic measures and concentrations of endothelin 1 (ET-1), interleukin 6 (IL-6), and amino-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in a cohort of 23 female patients with rheumatoid arthritis (RA).. We recruited 23 patients (mean age 51.3 ± 1.55 yrs) with RA resistant to treatment with disease-modifying antirheumatic drugs and average disease duration of 7.1 ± 1.0 years who had been selected to start treatment with the anti-TNF-α antagonist infliximab. Transthoracic echocardiographic examinations were performed before the first infusion and repeated after 1 year of treatment. Data for age, sex, RA disease activity by Disease Activity Score (DAS28) and echocardiographic data, NT-proBNP, IL-6, ET-1, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and other routine laboratory data were collected before treatment and after 1 year.. Twelve months of treatment with infliximab resulted in reduction of RA activity (i.e., reduction of DAS and acute-phase reactants). There was increased left ventricle ejection fraction, from 58.5% before treatment to 63% after. Treatment with infliximab also resulted in significant reduction of ET-1 (1.26 fmol/ml before treatment vs 0.43 fmol/ml after), IL-6 (58.46 pg/ml vs 3.46 pg/ml), and NT-proBNP (43.06 fmol/ml vs 14.78 fmol/ml). These reductions were observed after just 4 months of treatment and remained significant until the termination of the study.. In patients with RA, treatment with infliximab contributed significantly to increase in left ventricular ejection fraction. Improvement of cardiac function was shown by conventional echocardiography; there was reduction of biochemical markers of heart failure.

Topics: Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Rheumatoid; Cohort Studies; Female; Heart Failure; Humans; Infliximab; Middle Aged; Natriuretic Peptide, Brain; Stroke Volume; Ultrasonography; Ventricular Dysfunction, Left

Patients with rheumatoid arthritis (RA) are at increased risk of heart failure and vascular events. Small increases in circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with an increased risk of a cardiovascular event, and high levels signal left ventricular dysfunction. Data on the effects of tumour necrosis factor alpha(TNFalpha) blocking agents on circulating NT-proBNP levels in patients with active RA are lacking but may be informative.. 171 consecutive patients with RA (28-joint disease activity score >3.2) without congestive heart failure (NYHA class III or IV) were scheduled to receive adalimumab once every 2 weeks. Serum NT-proBNP concentrations were measured simultaneously on stored baseline and 16-week samples. Paired sample t tests were used to observe differences in biomarkers before and after adalimumab administration. Correlations between the biomarkers and changes in circulating log NT-proBNP levels were evaluated with the Pearson test and multivariable linear regression analyses of correlates were performed (forward selection procedure).. Circulating levels of NT-proBNP decreased significantly after 16 weeks of adalimumab administration (median NT-proBNP 83.0 pg/ml vs 69.5 pg/ml, p=0.004). Changes in NT-proBNP levels were associated with changes in pulse pressure (r=0.18, p=0.02), systolic blood pressure (r=0.16, p=0.04) and erythrocyte sedimentation rate (r=0.18, p=0.02). On multivariable analysis, changes in pulse pressure and erythrocyte sedimentation rate remained independently associated with changes in circulating NT-proBNP levels.. These observations show that blocking TNFalpha in patients with RA without evident heart failure decreases NT-proBNP levels by about 18%. This suggests no treatment-induced deterioration in cardiac function and a potential cardiovascular risk benefit.

Topics: Adalimumab; Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Biomarkers; Blood Pressure; Blood Sedimentation; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Factors; Tumor Necrosis Factor-alpha

Several biomarkers of cardiovascular function are found to be increased in rheumatoid arthritis (RA), with some suggesting a relationship with disease activity and improvement with adequate anti-rheumatic treatment. Promising biomarkers include N-terminal pro-brain natriuretic peptide (NT-proBNP) and the soluble receptor form of advanced glycation end-products (sRAGE). The objective of this study was to investigate associations between NT-proBNP and sRAGE levels and markers of inflammation and disease activity in early RA patients and their changes during (effective) anti-rheumatic treatment.. Data from 342 consecutive early RA patients participating in the 'Parelsnoer' cohort were used. At baseline and after 6 months' disease activity, NT-proBNP and sRAGE levels were assessed.. After 6 months, NT-proBNP decreased from 83 pmol/L (mean) at baseline to 69 pmol/L at follow-up (p < 0.001), while sRAGE increased from 997 pg/mL to 1125 pg/mL (p < 0.001). A larger decrease in erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) was associated with larger changes in NT-proBNP and sRAGE. For every point decrease in ESR, there was a 1.7-point decrease in NT-proBNP and a 2.2-point increase in sRAGE. For CRP, these values were 1.7 and 2.7, respectively (p < 0.001).. Suppressing inflammation, independently of achieving remission, increases sRAGE levels and decreases NT-proBNP levels significantly. Whether this translates into a decrease in incident cardiovascular disease remains to be elucidated.

Topics: Arthritis, Rheumatoid; Biomarkers; C-Reactive Protein; Humans; Inflammation; Natriuretic Peptide, Brain

Diastolic dysfunction (DD) is more prevalent in patients with rheumatoid arthritis (RA) compared to the general population. However, its evolution over time and its significant clinical predictors remain uncharacterized. We report on baseline and prospective changes in diastolic function and its associated RA and cardiovascular (CV) predictors.. In this study, 158 RA patients without clinical CV disease (CVD) were enrolled and followed up at 4 to 6 years, undergoing baseline and follow-up echocardiography to assess for DD, as well as extensive characterization of RA disease activity and CV risk factors. Novel measures of myocardial inflammation and perfusion were obtained at baseline only. Using baseline and follow-up composite DD (E/e', Left Atrial Volume Index (LAVI) or peak tricuspid regurgitation (TR) velocity; ≥ 1 in top 25%) as the outcome, multivariable regression models were constructed to identify predictors of DD.. DD was prevalent in RA patients without clinical heart failure (HF) (40.7% at baseline) and significantly progressed on follow-up (to 57.9%). Baseline composite DD was associated with baseline RA disease activity (Clinical Disease Activity Index; CDAI) (OR 1.39; 95% CI 1.02-1.90; p=0.034). Several individual diastolic parameters (baseline E/e' and LAVI) were associated with troponin-I and brain natriuretic peptide (BNP). Baseline and follow-up composite DD, however, were not associated with myocardial inflammation, myocardial microvascular dysfunction, or subclinical atherosclerosis.. DD is prevalent in RA patients without clinical HF and increases to >50% over time. Higher RA disease activity at baseline predicted baseline composite DD. Future longitudinal studies should explore whether adverse changes in diastolic function lead to clinical HF and are attenuated by disease-modifying antirheumatic drugs (DMARDs).

Topics: Arthritis, Rheumatoid; Cardiovascular Diseases; Diastole; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Prospective Studies; Ventricular Dysfunction, Left

Patients with rheumatoid arthritis (RA) are 1.5 times more likely to develop cardiovascular disease (CVD) attributed to chronic inflammation. A decrease in inflammation in patients with RA is associated with increased low-density lipoprotein (LDL) cholesterol. This study was undertaken to prospectively evaluate the changes in lipid levels among RA patients experiencing changes in inflammation and determine the association with concomitant temporal patterns in markers of myocardial injury.. A total of 196 patients were evaluated in a longitudinal RA cohort, with blood samples and high-sensitivity C-reactive protein (hsCRP) levels measured annually. Patients were stratified based on whether they experienced either a significant increase in inflammation (an increase in hsCRP of ≥10 mg/liter between any 2 time points 1 year apart; designated the increased inflammation cohort [n = 103]) or decrease in inflammation (a decrease in hsCRP of ≥10 mg/liter between any 2 time points 1 year apart; designated the decreased inflammation cohort [n = 93]). Routine and advanced lipids, markers of inflammation (interleukin-6, hsCRP, soluble tumor necrosis factor receptor II), and markers of subclinical myocardial injury (high-sensitivity cardiac troponin T [hs-cTnT], N-terminal pro-brain natriuretic peptide) were measured.. Among the patients in the increased inflammation cohort, the mean age was 59 years, 81% were women, and the mean RA disease duration was 17.9 years. The average increase in hsCRP levels was 36 mg/liter, and this increase was associated with significant reductions in LDL cholesterol, triglycerides, total cholesterol, apolipoprotein (Apo B), and Apo A-I levels. In the increased inflammation cohort at baseline, 45.6% of patients (47 of 103) had detectable circulating hs-cTnT, which further increased during inflammation (P = 0.02). In the decreased inflammation cohort, hs-cTnT levels remained stable despite a reduction in inflammation over follow-up. In both cohorts, hs-cTnT levels were associated with the overall estimated risk of CVD.. Among RA patients who experienced an increase in inflammation, a significant decrease in routinely measured lipids, including LDL cholesterol, and an increase in markers of subclinical myocardial injury were observed. These findings highlight the divergence in biomarkers of CVD risk and suggest a role in future studies examining the benefit of including hs-cTnT for CVD risk stratification in RA.

Topics: Aged; Apolipoprotein A-I; Apolipoproteins B; Arthritis, Rheumatoid; Asymptomatic Diseases; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Female; Heart Disease Risk Factors; Heart Diseases; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Receptors, Tumor Necrosis Factor, Type II; Risk Assessment; Triglycerides; Troponin T

The high prognostic significance of the concentration of the N-terminal - pro-B-type natriuretic peptide (NT-proBNP) in the development of cardiovascular diseases (CVD) was identified for rheumatoid arthritis (RA) and general populations.. to investigate the significance of NT-proBNP level in patients (pts) with RA with the ineffectiveness and/or intolerance of basic anti - inflammatory therapy; compare the level of NT-proBNP with atherosclerotic lesion of the brachiocephalic arteries (BCA), traditional risk factors and inflammatory markers.. The investigation enrolled 28 pts (24women/4men) with the lack of efficacy/resistance and/or intolerance of basic anti - inflammatory drugs (DMARDs); median age was 55 [46; 61] years, median disease duration 114 [60; 168] month; DAS28 6,2 [5.1; 7.0]; SDAI 35.0[23.9; 51.0], CDAI 30.0[21.0; 42.0], serum positivity for rheumatoid factor (RF) (100%)/anti - cyclic citrullinated peptide antibodies (ACCP) (86%). The study did not include RA pts with congestive heart failure. High incidence of traditional risk factors was found in RA pts: arterial hypertension - in 75%, dyslipidemia - 61%, smoking - 17%, overweight - 61%, family history of cardiovascular diseases - 36%, hypodynamia - 68%. Coronary artery disease was diagnosed in 11% RA pts. Lack of efficacy of 3 or more DMARDs was found in 46% of pts, intolerance to previous therapy with DMARDs - in 54% pts. 47% were receiving methotrexate (20 [18; 25] mg/week), 11% - leflunomide, 7% - sulfasalazine, 46% - glucocorticoids, 75% - non - steroidal anti - inflammatory drugs. The control group consisted of 20 healthy donors, comparable to pts by age and sex. Serum levels of of NT-proBNP were measured using electrochemiluminescence method Elecsys proBNP II (Roche Diagnostics, Switzerland). The determination of the intima - media thickness (IMT) BCA were assessed from duplex scanning. Atherosclerotic lesion of BCA was assessed by the presence of atherosclerotic plaque (IMT ≥1.2 mm).. NT-proBNP concentrations in RA pts proved to be higher (78.7 [41.4; 101.3] pg/ml) than those in the control group (55.3 [36.6; 67.3] pg/ml, p100 pg/ml - 1 group (n=6) and ≤100 pg/ml - 2 group (n=22). Groups of RA pts did not differ in gender, age, activity of RA, frequency of detection of traditional risk factors. Atherosclerotic lesion of the BCA was detected in 3 (50%) pts of the 1 group and in 8 (36%) pts of the 2 group (p>0.05). In RA pts the level of NT-proBNP correlated with age (r=0.39; p.. Выявлена высокая прогностическая значимость концентрации N-концевого фрагмента предшественника мозгового натрийуретического пептида В-типа (N-terminal fragment of brain natriuretic peptide progenitor, NT-proBNP) в развитии сердечно - сосудистых заболеваний (ССЗ) при ревматоидном артрите (РА) и в общей популяции. Цель: уточнить значение NT-proBNP у больных РА с неэффективностью и/или непереносимостью базисной противовоспалительной терапии, сопоставить уровень NT-proBNP с атеросклеротическим поражением брахиоцефальных артерий (БЦА), традиционными факторами риска (ТФР) ССЗ и маркерами воспаления. Материалы и методы. Обследовано 28 пациентов с РА (24 женщины и 4 мужчин) с неэффективностью и/или непереносимостью базисных противовоспалительных препаратов (БПВП); медиана возраста составила 55 [46; 61] лет; продолжительность болезни - 114 [60; 168] мес; DAS28 - 6,2 [5,1; 7,0] балла; SDAI - 35,0 [23,9; 51,0], CDAI - 30,0 [21,0; 42,0]. Все больные были серопозитивны по ревматоидному фактору (РФ), 86% - по антителам к циклическому цитруллинированному пептиду (АЦЦП). Внесуставные проявления выявлялись у 54% больных. На момент включения в исследование 47% больных получали метотрексат (медиана дозы 20,2 [18; 25] мг/нед), 11% - лефлуномид, 7% - сульфасалазин, 46% - глюкокортикоиды, 75% - нестероидные противовоспалительные препараты. У 46% пациентов отмечена неэффективность 3 и более БПВП, у 54% - непереносимость предшествовавшей терапии БПВП. В исследование не включались пациенты с РА, имеющие хроническую сердечную недостаточность. У больных РА обнаружена высокая частота ТФР: артериальная гипертензия - у 75%, дислипидемия - 61%, курение - 17%, избыточная масса тела - 61%, отягощенная наследственность по ССЗ - 36%, гиподинамия - 68% больных. Ишемическую болезнь сердца диагностировали у 11% пациентов. Контрольную группу составили 20 здоровых доноров, сопоставимых с больными по возрасту и полу. Концентрацию NT-proBNP определяли в сыворотке крови методом электрохемилюминесценции (Roche Diagnostics, Швейцария). Всем пациентам проведено дуплексное сканирование экстракраниального отдела БЦА с определением толщины комплекса интима - медиа (КИМ). Атеросклеротическое поражение БЦА оценивали по наличию атеросклеротической бляшки (толщина КИМ≥1,2 мм). Результаты. У пациентов с РА выявлены более высокие уровни NT-proBNP (78,7 [41,4; 101,3] пг/мл) по сравнению с группой здорового контроля (55,3 [36,6; 67,3] пг/мл, p100 пг/мл - 1-я группа (n=6) и ≤100 пг/мл - 2-я группа (n=22). Группы

Topics: Antirheumatic Agents; Arteries; Arthritis, Rheumatoid; Atherosclerosis; Biomarkers; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

Patients with rheumatoid arthritis (RA) have an excess risk of cardiovascular (CV) disease (CVD). The objective of the study was to compare CV risk profile in female and male RA patients with low disease activity.. The study group consisted of 70 RA patients with continuous low disease activity and no CVD (54 women, 16 men) and 33 healthy controls of comparable age. The groups were assessed for blood pressure, serum amino-terminal pro-brain natriuretic peptide (NT-proBNP), carotid intima media thickness (cIMT), electrocardiography, ejection fraction (EF), and diastolic dysfunction (DD).. Significantly higher burden of atherosclerosis, as revealed by higher cIMT, was found in males [0.93 (0.2) mm] vs females [0.80 (0.2) mm]. The risk of 10-year CVD was significantly higher in men than in women with RA. High/very high risk of fatal CVD was found in 62.5% of male patients. Males were significantly more often current/ex-smokers and had lower HDL-cholesterol and higher atherogenic index. There were no significant differences in NT-proBNP, QTc duration, and parameters of EF and DD.. In RA patients with continued low disease activity, a higher burden of atherosclerosis was found in males than in females. The data suggest a significant impact of traditional CV risk factors.

Topics: Arthritis, Rheumatoid; Blood Pressure; Cardiovascular Diseases; Cardiovascular System; Carotid Intima-Media Thickness; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Assessment; Risk Factors; Sex Characteristics; Stroke Volume

Current validated cardiovascular (CV) risk estimates were developed in populations with relatively stable levels of inflammation, whereas patients with rheumatoid arthritis (RA) routinely experience significant changes in inflammation. This study was undertaken to test whether changes in inflammation affect estimated CV risk as measured using validated population-based risk calculators.. Participants in a prospective RA cohort who experienced a decrease or an increase of ≥10 mg/liter in the C-reactive protein (CRP) level at 2 consecutive time points 1 year apart (CRP decrease group and CRP increase group, respectively) were included in this study. We estimated 10-year CV risk using the following calculators: Framingham Risk Score, 2013 American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease Risk Score, Reynolds Risk Score (RRS), and QRISK2. Of these calculators, only the RRS includes a variable addressing the CRP level. Paired t-tests were performed to compare risk scores at baseline and 1-year follow-up. We calculated the correlations between the changes in risk scores and changes in pro-B-type natriuretic peptide (pro BNP), a surrogate marker of CV risk.. One hundred eighty RA patients were included in the study (mean age 57.8 years, 84% female, 80% seropositive). Of the calculators studied, only the RRS was sensitive to changes in inflammation; an increase in inflammation was associated with increased estimated CV risk (P < 0.0001), and only the RRS was correlated with changes in proBNP (r = 0.17, P = 0.03).. Our data showed no significant change in CV risk estimated using validated general population CV risk calculators except for the RRS. These findings suggest that CV risk may be modulated by changes in inflammation in RA, which is not typically considered when using existing CV risk calculators.

Topics: Arthritis, Rheumatoid; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Assessment; Risk Factors; Time Factors

To prospectively investigate the effect of tocilizumab (TCZ) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), as a predictor of congestive heart failure (CHF) in patients with active rheumatoid arthritis (RA).. Seventy patients with RA (median age 59 years, 86% female) free of cardiovascular disease were treated with TCZ and followed for 24 weeks. The NT-proBNP levels were measured at baseline and week 24. Thirty healthy controls were included for comparison of normal NT-proBNP levels with those of RA patients.. The NT-proBNP level was significantly higher in patients with RA than in controls (median 42.5 pg/mL vs 109.0 pg/mL, p < 0.001). NT-proBNP levels decreased by 63% over the 24 weeks of TCZ treatment. Multiple linear regression analysis indicated that the percentage change in the NT-proBNP level was significantly associated with that of the Simplified Disease Activity Index (β = 0.356, p = 0.014), even after adjusting for the levels of rheumatoid factor, duration of RA, age, and anti-cyclic citrullinated peptide antibody.. TCZ decreased the NT-proBNP level in patients with RA without preceding cardiovascular disease and CHF. TCZ may have a cardioprotective effect in those with active RA.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Arthritis, Rheumatoid; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

Common carotid artery intima-media thickness (CIMT), as measured by ultrasound, has utility in stratification of the accelerated cardiovascular risk seen in rheumatoid arthritis (RA); however, the technique has limitations. Carotid magnetic resonance imaging (MRI) is emerging as a useful research tool in the general population, but has yet to be applied in RA populations. Our objectives were to describe the utility of carotid artery MRI (carotid-MRI) in patients with RA in comparison to healthy controls and to describe the association with RA disease phenotype.. Sixty-four patients with RA and no history of cardiovascular (CV) disease/diabetes mellitus were assessed for RA and CV profile, including homeostasis model assessment-estimated insulin resistance (HOMA-IR) and N-terminal pro-brain natriuretic peptide (NT-proBNP). All underwent carotid-MRI (3 T), and were compared to 24 healthy controls. Univariable analysis (UVA) and multivariable linear regression models (MVA) were used to determine associations between disease phenotype and carotid-MRI measures.. There were no significant differences in carotid arterial wall measurements between patients with RA and controls. Wall and luminal volume correlated with 10-year CV risk scores (adjusted as per 2017 European League Against Rheumatism (EULAR) guidance); rho = 0.33 (p = 0.012) and rho = 0.35 (p = 0.008), respectively, for Joint British Societies-2 risk score. In UVA, carotid-MRI volumetric measures predominantly were associated with traditional CV risk factors including age, ever-smoking and HOMA-IR (p < 0.05). Lower body mass index was associated with wall maximum thickness (r = - 0.25 p = 0.026). In MVA, age was independently associated with wall volume (B 1.13 (95% CI 0.32, 1.93), p = 0.007) and luminal volume (B 3.69 (95% CI 0.55, 6.83, p = 0.022), and RA disease duration was associated with luminal volume (B 3.88 (95% CI 0.80, 6.97), p = 0.015).. This study demonstrates the utility of carotid-MRI in RA, reporting an association between three-dimensional measures in particular and CV risk scores, individual traditional CV risk factors and RA disease duration. Carotid-MRI in RA is a promising research tool in the investigation of CVD.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Blood Sedimentation; C-Reactive Protein; Cardiovascular Diseases; Carotid Artery, Common; Carotid Intima-Media Thickness; Female; Humans; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Reproducibility of Results; Risk Factors; Severity of Illness Index

Myocardial dysfunction and heart failure (HF) are increased in rheumatoid arthritis (RA), yet there are few studies of the myocardium in RA.. RA patients with no known heart disease or risk factors underwent gadolinium-enhanced cardiac magnetic resonance imaging (MRI). Images were assessed for left-ventricular (LV) structural and functional parameters and for myocardial late gadolinium enhancement (LGE; an indicator of myocardial fibrosis) and T2-weighted imaging (an indicator of active inflammation). We modeled the associations between RA characteristics and N-terminal pro-brain natriuretic protein (NT-proBNP) levels with LGE and T2-weighted imaging. We also assessed whether LGE and/or T2-weighted imaging were associated with abnormal LV structure or dysfunction.. A total of 60 RA patients were studied. LGE was present in 19 (32%) and T2-weighted imaging in 7 (12%), 5 of whom also had LGE. After adjustment for relevant confounders, higher odds of LGE with each swollen joint (odds ratio [OR] 1.87, P = 0.008), each log unit higher C-reactive protein level (OR 3.36, P = 0.047), and each log unit higher NT-proBNP (OR 20.61, P = 0.009) were found. NT-proBNP was also significantly higher (135%) among those with T2-weighted imaging than in those without T2-weighted imaging or LGE. Higher LV mass index and LV mass:end diastolic volume ratio were observed in those with T2-weighted imaging than in those with no myocardial abnormalities and in those with LGE without T2-weighted imaging; however, ejection fraction was not reduced in those with either LGE or T2-weighted imaging.. These data suggest that cardiac MRI findings indicating myocardial inflammation/fibrosis are correlated with RA disease activity and alterations in myocardial structure known to precede clinical HF.

Topics: Adult; Aged; Arthritis, Rheumatoid; C-Reactive Protein; Contrast Media; Endomyocardial Fibrosis; Female; Gadolinium DTPA; Heart; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Risk Factors

Topics: Arthritis, Rheumatoid; Cardiovascular Diseases; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, Interleukin-6; Risk Factors; Troponin T

To determine N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with early rheumatoid arthritis (RA) before the use of disease-modifying antirheumatic drugs (DMARDs); to compare NT-proBNP values with traditional risk factors (TRF), cardiovascular diseases (CVD), inflammatory markers, and left ventricular (LV) diastolic dysfunction (DD).. The investigation enrolled 74 patients with a valid RA diagnosis (the 2010 ACR/EULAR criteria), 56 (74%) women, median (Me) age, 54 years; disease duration, 7 months; seropositive for IgM rheumatoid factor (87%) and/or anti-cyclic citrullinated peptide antibodies (100%) with no history of the use of DMARDs and glucocorticosteroids. Duplex scanning and echographic findings were used to assess TRF for CVD and carotid artery atherosclerosis (CAA) in all the patients with early RA prior to therapy. An E/A ratio was used as a criterion for LVDD.. NT-proBNP concentrations in patients with early RA proved to be higher than those in the control group (p<0.0001). Higher-than-normal NT-proBNP levels were seen in 36 (49%) patients. The patients with early RA and elevated NT-proBNP values were older and had a higher body mass index (BMI) than those with normal NT-proBNP levels. Those with elevated NT-proBNP concentrations were more frequently found to have CAA, coronary calcification, and coronary heart disease; their intima-media thickness was also larger and C-reactive protein (CRP) levels higher than in those with normal NT-proBNP values. There were correlations between NT-proBNP levels and erythrocyte sedimentation rate, CRP, simplified disease activity index, and clinical disease activity index. Multivariate analysis revealed that chronic heart failure (CHF), CAA, CRP and low-density lipoprotein (LDL) levels, and BMI correlated with NT-proBNP concentrations. LVDD was detected in 35 (48%) patients with early RA. The level of NT-proBNP in patients with DD was higher than in those without DD. Higher-than-normal NT-proBNP values were observed in 23 (65%) and 12 (32%) patients with and without LVDD, respectively. The optimal NT-proBNP level for CHF detection was equal to 237.4 pg/ml (86% sensitivity and 85% specificity); the area under the ROC curve was 0.879.. Just at the early disease stage, the patients are noted to have a high NT-proBNP level that is influenced by higher BMI, low LDL levels, CAA, CHF, and high CRP values. In the patients with early RA, the diagnostically significant NT-proBNP concentration for CHF detection was higher (237 pg/ml) than in those without RA (125 pg/ml). The patients with early RA should undergo NT-proBNP determination, LVDD screening, correction of TRF for CVD, atherosclerosis treatment, and remission achievement.. Цель исследования. Определить уровень N-концевого натрийуретического пептида (NT-proBNP) у больных ранним ревматоидным артритом (РА) до назначения базисных противовоспалительных препаратов (БПВП), сопоставить уровень NT-proBNP с традиционными факторами риска (ТФР), сердечно-сосудистыми заболеваниями (ССЗ), маркерами воспаления и диастолической дисфункцией (ДД) миокарда левого желудочка (ЛЖ). Материалы и методы. В исследование включили 74 пациента с достоверным диагнозом РА (критерии ACR/EULAR, 2010), 56 (74%) женщин, медиана (Ме) возраста 54 года, длительности заболевания 7 мес; серопозитивные по ревматоидному фактору класса IgM (87%) и/или антителам к циклическому цитруллинированному пептиду (100%) без опыта приема БПВП и глюкокортикостероидов. Оценка ТФР развития ССЗ, атеросклероза сонных артерий (АСА) по данным дуплексного сканирования и эхокардиография проведены у всех пациентов с ранним РА до начала терапии. В качестве критерия ДДЛЖ использовали соотношение Е/А. Результаты. Концентрация NT-proBNP у больных ранним РА оказалась выше, чем в группе контроля (р<0,0001). У 36 (49%) больных РА уровень NT-proBNP превышал норму. Пациенты с ранним РА и повышенным уровнем NT-proBNP были старше, обладали более высоким индексом массы тела (ИМТ), чем больные РА с нормальным уровнем NT-proBNP. При повышенном уровне NT-proBNP чаще, чем при нормальном, выявлялись АСА, кальциноз коронарных артерий, ИБС, а также была больше толщина комплекса интима-медиа слева, выше уровень С-реактивного белка (СРБ). Выявлены корреляции между уровнем NT-proBNP и СОЭ, СРБ, SDAI, CDAI. По данным многофакторного анализа, с уровнем NT-proBNP коррелируют наличие ХСН, уровень СРБ, наличие АСА, уровень ЛПНП, ИМТ. ДДЛЖ выявлена у 35 (48%) пациентов с ранним РА. Уровень NT-proBNP у больных с ДД выше, чем у пациентов без ДД. У 23 (65%) с ДДЛЖ и у 12 (32%) больных без ДДЛЖ уровень NT-proBNP превышал норму. Оптимальный уровень NT-proBNP для выявления ХСН равен 237,4 пг/мл (чувствительность 86%, специфичность 85%), площадь под ROC-кривой 0,879. Заключение. У пациентов с РА уже на ранней стадии заболевания отмечается высокий уровень NT-proBNP, на повышение которого влияют увеличение ИМТ, низкий уровень ЛПНП, наличие АСА, ХСН, высокий уровень СРБ. У пациентов с ранним РА диагностически значимый уровень NT-proBNP для выявления ХСН выше (237 пг/мл), чем у пациентов без РА (125 пг/мл). У пациентов с РА необходимо уже на ранней стадии заболевания определять уровень NT-proBNP, проводить скрининг ДДЛЖ и ко

Topics: Arthritis, Rheumatoid; Cardiovascular Diseases; Carotid Intima-Media Thickness; Comorbidity; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Ventricular Dysfunction, Left

To measure concentrations of high-sensitivity cardiac troponin (HS-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with rheumatoid arthritis (RA) and to examine correlates.. The plasma concentrations of HS-cTnT and NT-proBNP were measured in consecutive patients with RA and compared to values obtained from age-matched and sex-matched healthy controls.. We included 236 unrelated patients with RA (192 females, 57 ± 13 yrs) and 213 controls (170 females, 55 ± 15 yrs). Seventy-one patients with RA were free of cardiovascular (CV) risk factors. HS-cTnT and NT-proBNP concentrations were significantly higher in the total cohort of patients with RA (p = 0.03 and p < 0.0001, respectively) and in the subgroup free of CV risk factors (p = 0.02 and p < 0.0001, respectively) compared to controls. In addition, both the total cohort of patients with RA and the subgroup free of CV risk factors were more likely to have levels above the cutoff concentrations of HS-cTnT (p = 0.003 and p = 0.007, respectively) and NT-proBNP (p = 0.0001 and p < 0.0001, respectively) than controls. Patients with RA and increased C-reactive protein (CRP) levels had higher HS-cTnT (p = 0.03) and NT-proBNP (p = 0.02) concentrations. HS-cTnT levels positively correlated with the 28-joint Disease Activity Score (DAS28-CRP; r = 0.2, p = 0.020). Multivariate logistic regression analysis indicated that increased HS-cTnT levels were independently associated with a DAS28-CRP > 5.1 (OR 11.8; 95% CI 1.6-35.5) and a body mass index > 30 kg/m(2) (OR 2.7; 95% CI 1.3-5.5).. HS-cTnT and NTproBNP are increased in patients with RA, independent of CV risk factors. The association between HS-cTnT, NT-proBNP, and CRP, together with the correlation between HS-cTnT and disease activity, support the link between myocardial injury/dysfunction and inflammation.

Topics: Adult; Aged; Arthritis, Rheumatoid; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Factors; Severity of Illness Index; Troponin T

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 80.49 pg/mL, IQR (23.67-167.08 pg/mL)) than controls (17.84 pg/mL (3.28-36.28 pg/mL)) (P < 0.001), and the prevalence of IR, defined by HOMA > 2.114, was higher among RA than controls (53 % vs. 15%, P > 0.001). HOMA was positively correlated with NT-proBNP (rho = 0.226, P = 0.007) in RA, but not in controls (rho = -0.154, P = 0.168). 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 (P = 0.001), but not controls (P = 0.543) (P for interaction = 0.036). In RA subjects, when IL-6 was further included in the model, IL-6 (P = 0.0014), but not HOMA (P = 0.43), 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.

Topics: Arthritis, Rheumatoid; Body Mass Index; C-Reactive Protein; Female; Humans; Inflammation; Insulin Resistance; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Tumor Necrosis Factor-alpha

Topics: Aged; Arthritis, Rheumatoid; Biomarkers; Case-Control Studies; Cohort Studies; Female; Humans; Inflammation; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Ventricular Dysfunction, Left

Topics: Arthritis, Rheumatoid; Female; Humans; Male; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Topics: Arthritis, Rheumatoid; Female; Humans; Male; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Tumor necrosis factor alpha (TNF-alpha) plays an important role in the pathogenesis of chronic inflammatory diseases, i.e., rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), and ulcerative colitis (UC). Anti-TNF-alpha strategies are successfully used in their treatment. However, their effect on heart function is still uncertain. The objectives of the study were to examine the acute and long-term effect of infliximab on the heart morphology and function in patients with chronic inflammatory disorders. Thirty-one patients (21 men and 10 women) were included. Ten percent of them were diagnosed with RA, 22.5 % with AS, 22.5 % with CD, and 45 % with UC, respectively. N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) was measured before and immediately after infliximab administration at the beginning of the study and in the sixth and 12th months. Echocardiography was performed at baseline and in the sixth and 12th months. There was a significant increase in NT-proBNP after the first infliximab infusion (88.40 ± 14.09 vs. 95.24 ± 14.28 pg/ml, p = 0.0046) and similar response was detected after each infusion in the sixth and 12th months. Plasma NT-proBNP slightly but not significantly decreased (88.40 ± 14.09 vs. 81.74 ± 23.14 pg/ml, p = 0.583, and 88.40 ± 14.09 vs. 56.83 ± 17.77 pg/ml, p = 0.0576, in the sixth and 12th months, respectively). There were no significant changes in echocardiographic structural and functional parameters of the left ventricle during follow-up. Plasma NT-proBNP mildly but significantly increases immediately after infliximab infusion. However, long-term infliximab administration does not deteriorate both cardiac morphology and function.

Topics: Adult; Antibodies, Monoclonal; Antirheumatic Agents; Arthritis; Arthritis, Rheumatoid; Colitis, Ulcerative; Crohn Disease; Echocardiography; Female; Heart; Heart Diseases; Humans; Inflammatory Bowel Diseases; Infliximab; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Spondylitis, Ankylosing; Time Factors; Young Adult

To determine whether adding C-reactive protein, anti-cyclic citrullinated peptide antibodies, rheumatoid factor, N-terminal pro-brain natriuretic peptide (NT-proBNP), oxidized low-density lipoprotein (ox-LDL), or anti-apolipoprotein A-I (anti-Apo A-I) IgG to the Framingham 10-year cardiovascular (CV) risk score (FRS) could improve its CV prognostic accuracy in rheumatoid arthritis (RA).. We performed an ancillary study derived from a prospective single-center cohort consisting of 118 RA patients without CV disease at baseline. The FRS and the various biomarkers were assessed at enrollment and their prognostic accuracy was determined using receiver operating characteristic (ROC) curve analysis. The incremental predictive ability of biomarkers was assessed using the integrated discrimination improvement (IDI) statistics.. During a median followup period of 9 years, the incidence of CV events was 16%. Both the FRS and 3 of the biomarkers (NT-proBNP, ox-LDL, and anti-Apo A-I) were significant predictors of subsequent CV events (area under the ROC curve [AUC] between 0.68 and 0.73). Anti-Apo A-I was the only biomarker to significantly improve the prognostic ability of the FRS, with AUCs increasing from 0.72 to 0.81 and the IDI improving by 175% (P < 0.001).. Among the biomarkers tested, only anti-Apo A-I significantly improved the FRS predictive ability.

Topics: Aged; Aged, 80 and over; Antibodies, Anti-Idiotypic; Apolipoprotein A-I; Arthritis, Rheumatoid; Biomarkers; Cardiovascular Diseases; Cohort Studies; Female; Follow-Up Studies; Humans; Incidence; Lipoproteins, LDL; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Retrospective Studies; Risk Factors; ROC Curve

The REgistry of Pulmonary Hypertension Associated with Rheumatic Disease (REOPARD) was established in Korea. The baseline data are described from the second year of the registry's operation.. Patients with a connective tissue disease (CTD) who met the modified definition of the WHO group I pulmonary arterial hypertension (PAH) were enrolled. PAH was defined as a systolic pulmonary arterial pressure> 40 mmHg by echocardiography or mean pulmonary arterial pressure> 25 mmHg by right heart catheterization. Hemodynamic parameters and clinical data such as demographics, functional class, underlying disease, organ involvement, laboratory tests and current treatment were recorded.. A total of 321 patients were enrolled during the 2-year study period from 2008 to 2010. The mean age of the patients at registration was 51.9 years and 87.5% were female. Most patients were diagnosed by echocardiography and only 24 patients (7.5%) underwent cardiac catheterization. Exertional dyspnea was present in 63.6% of patients and 31.8% were New York Heart Association class III or IV. Among the patients, systemic lupus erythematosus accounted for 35.3%, systemic sclerosis 28.3%, rheumatoid arthritis 7.8%, overlap syndrome 9.0%, and mixed connective tissue disease 5.9%. There were no significant differences in hemodynamics, functional class, diffusing capacity and N-terminal pro-brain natriuretic peptide levels between the disease subgroups. Treatments consisted of calcium antagonists (57.0%), endothelin antagonists (32.7%), prostanoids (27.1%), phosphodiesterase-5 inhibitors (14.3%) and combinations (37.4%).. Compared with previous studies, the results showed some differences: underlying diseases, functional status and treatments. This may be due to differences in ethnic background and diagnostic methods of our study.

Topics: Adult; Aged; Arthritis, Rheumatoid; Data Collection; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Lupus Erythematosus, Systemic; Male; Middle Aged; Mixed Connective Tissue Disease; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Diffusing Capacity; Registries; Republic of Korea; Retrospective Studies; Rheumatic Diseases; Scleroderma, Systemic

Rheumatoid arthritis (RA) is associated with increased cardiovascular (CV) morbidity and mortality, of which amino-terminal pro-brain natriuretic peptide (NT-proBNP) is a predictor. The objective of the study was to investigate associations between NT-proBNP and age, gender, markers of inflammation, disease activity, and kidney function in RA patients, without co-morbidities potentially influencing NT-proBNP concentration. The study group consisted of 90 patients with RA, without clinically relevant coronary heart disease, hypertension, diabetes, advanced chronic kidney disease. The comprehensive assessment of clinical and laboratory parameters of inflammation, disease activity, and kidney function was performed. Plasma samples were frozen for NT-proBNP analysis. Carotid intima media thickness (cIMT) was determined by high-resolution B-mode ultrasonography. The mean NT-proBNP concentrations were significantly higher in a group of RA patients with high disease activity (DAS28 > 5.1) and in a group of patients with subclinical atherosclerosis diagnosed by cIMT ≥ 0.6 mm. In all RA patients, NT-proBNP correlated positively with the age, C-reactive protein, erythrocyte sedimentation rate, cIMT, tricipital skin fold and negatively with hand-grip strength, hemoglobin, red blood cell count, albumin. In the group of women with RA, we found significant positive correlation between NT-proBNP and cystatin-C. Also, patients with NT-proBNP level ≥ 100 pg/ml had significantly higher cystatin-C than those with lower NT-proBNP. NT-proBNP level, in RA patients without co-morbidities potentially influencing this level, is correlated with age, disease activity markers of inflammation, and subclinical renal impairment. It means that risk of CV disorders is higher in older patients with more active RA.

Topics: Adolescent; Adult; Arthritis, Rheumatoid; Blood Sedimentation; C-Reactive Protein; Cardiovascular Diseases; Cystatin C; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Tunica Intima; Tunica Media; Ultrasonography

Patients with rheumatoid arthritis (RA) are at an increased risk for heart failure and left ventricular diastolic dysfunction (LVDD). B-type natriuretic peptide (BNP) may be useful to screen for LVDD in the general population. We compared the effectiveness of BNP as a screening tool for LVDD in RA and non-RA subjects without cardiovascular disease (CVD).. Study subjects were recruited from population-based samples with and without RA, excluding subjects with CVD. LVDD was assessed by 2-dimensional and Doppler echocardiography and categorized as none, mild, moderate/severe, or indeterminate. Linear regression and proportional odds models evaluated the association between LVDD and BNP, adjusting for age, sex, and body mass index.. Among 231 RA and 1,730 non-RA subjects without CVD, BNP was significantly higher in subjects with moderate/severe LVDD compared to those with no or mild LVDD (P = 0.02 for RA and P < 0.001 for non-RA subjects). More RA subjects had elevated BNP than non-RA subjects (16% versus 9%; P < 0.001). Positive predictive value (25% in RA and 18% in non-RA subjects) and sensitivity (40% in RA and 26% in non-RA subjects) were similarly low in both cohorts, but specificity was significantly lower in RA than in non-RA subjects (89% versus 94%; P = 0.02).. While RA subjects were more likely to have elevated BNP, few RA patients with elevated BNP actually have LVDD. Also, normal BNP levels are less likely to rule out LVDD in RA than in non-RA subjects. Therefore, BNP may be less effective for screening in RA subjects compared to the general population.

Topics: Aged; Arthritis, Rheumatoid; Biomarkers; Case-Control Studies; Diastole; Echocardiography, Doppler; Female; Humans; Linear Models; Logistic Models; Male; Mass Screening; Middle Aged; Minnesota; Natriuretic Peptide, Brain; Odds Ratio; Predictive Value of Tests; Risk Assessment; Risk Factors; Severity of Illness Index; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Function, Left

Patients with arthritis frequently are at increased risk for future cardiovascular (CV) events. We investigated the performance of the cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP) for predicting CV events in patients with arthritis taking chronic nonsteroidal antiinflammatory drugs (NSAID).. We evaluated 2-year CV outcomes in a prospective, nested biomarker study among patients (N = 6273) with rheumatoid arthritis and osteoarthritis treated with NSAID in the MEDAL (Multinational Etoricoxib and Diclofenac Arthritis Long-term) trial. Patients were stratified by quartiles of baseline NT-proBNP and established cutpoints of NT-proBNP and hsCRP.. NT-proBNP demonstrated a strong graded relationship with CV outcomes, including CV death (p for trend < 0.0001), myocardial infarction (MI) (p for trend = 0.02), heart failure (HF) (p for trend < 0.0001), and a composite of thrombotic events (CV death, MI, stroke) or HF (p for trend < 0.0001). Baseline levels of hsCRP were not associated with CV events (CV death/MI/stroke/HF; p for trend = 0.65). NT-proBNP remained strongly predictive of CV events after adjustment for age, sex, diabetes, hypertension, hyperlipidemia, smoking, type of arthritis, body mass index, creatinine clearance, history of CV disease, and hsCRP (CV death/MI/stroke/HF: Q4 vs Q1 hazard ratio 3.53, 95% CI 1.89-6.58). Patients with a NT-proBNP level below 100 pg/ml had a 0.94% rate of thrombotic events or heart failure at 2 years.. NT-proBNP is a simple and robust noninvasive indicator of CV risk in patients with arthritis. Risk stratification based on NT-proBNP may facilitate identification of patients with arthritis who are at low CV risk during chronic NSAID treatment.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Diclofenac; Etoricoxib; Female; Heart Failure; Humans; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Osteoarthritis; Peptide Fragments; Prospective Studies; Pyridines; Retrospective Studies; Risk Factors; Sulfones; Thrombosis; Treatment Outcome

Topics: Aged; Amyloidosis; Antibodies, Antinuclear; Antirheumatic Agents; Arthritis, Rheumatoid; Benzimidazoles; Biphenyl Compounds; Carbazoles; Carvedilol; Drug Therapy, Combination; Dyspnea; Etanercept; Female; Furosemide; Glucocorticoids; Hand; Heart Failure; Humans; Immunoglobulin G; Lung Diseases, Interstitial; Natriuretic Peptide, Brain; Propanolamines; Radiography; Receptors, Tumor Necrosis Factor; Rheumatoid Factor; Ribonucleosides; Scleroderma, Systemic; Spironolactone; Sulfasalazine; Tetrazoles; Treatment Outcome

Cardiovascular (CV) disease, the most common cause of mortality in patients with rheumatoid arthritis (RA), is largely attributable to accelerated atherosclerosis. Carotid intima-media thickness (cIMT) has been approved as a surrogate marker of early atherosclerosis.. The aim of the study was to assess cIMT in RA patients lacking concomitant comorbidities potentially influencing cIMT value.. The study group consisted of 74 RA patients, without diagnosed heart or kidney disease, hypertension, diabetes, obesity, or current smoking (mean age, 46.4 [SD, 10.6] years; range, 19-70 years). Assessment of cIMT was determined by high-resolution B-mode ultrasonography in RA patients and 31 control subjects (mean age, 42.6 [SD, 8.0] years; range, 27-59 years).. The mean maximum cIMT value was significantly greater in RA patients than in control subjects (0.73 [SD, 0.14] vs 0.59 [SD, 0.12] mm; P < 0.0001). In RA patients, cIMT correlated positively with a number of immunological and inflammatory parameters and also with amino-terminal pro-brain natriuretic peptide (NT-proBNP), age, metabolic variables (serum cholesterol, creatinine, cystatin C). In multiple linear regression analysis, significant association was found between cIMT and NT-proBNP and age. Patients without atherosclerosis (cIMT <0.6 mm) were younger and had significantly lower concentrations of NT-proBNP and total cholesterol, as well as higher estimated glomerular filtration rate. The course of RA in patients without atherosclerosis was characterized by shorter disease duration, lower tender joint count, and C-reactive protein.. Values of cIMT were significantly greater in RA compared with control subjects. Features of RA, such as extra-articular manifestations, erosions, high inflammatory parameters, and long disease duration, even in the absence of traditional clinical CV risk factors, were associated with greater cIMT, suggesting an unfavorable CV risk profile.

Topics: Adult; Aged; Arthritis, Rheumatoid; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Carotid Arteries; Case-Control Studies; Cholesterol; Creatinine; Cystatin C; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Severity of Illness Index; Tunica Intima; Tunica Media; Ultrasonography

Patients with rheumatoid arthritis (RA) have a higher mortality than the general population, and this increased mortality is related to demographic and disease variables. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a predictor of mortality both in general and patient populations, but has not been shown to predict mortality in patients with RA. This study examines whether NT-proBNP can further improve the prediction of mortality in RA.. 182 patients with RA of 5-9 years disease duration were comprehensively examined in 1997. Serum samples were frozen and later batch analysed for NT-proBNP levels and other biomarkers. Adjusted univariate and logistic regression analyses were performed with death within the 10-year follow-up period as the dependent variable. Significant predictors were also examined as dichotomised variables.. Mortality was predicted in univariate analyses by the following variables: age, sex, homozygosity for HLA-DRB1 shared epitope alleles, Health Assessment Questionnaire, 28-joint Disease Activity Score (DAS28) and NT-proBNP. A multivariate model with age, sex, DAS28 and NT-proBNP as independent variables showed the greatest discrimination.. NT-proBNP provided incremental information in the prediction of mortality in this cohort of patients with RA.

Topics: Adult; Age Factors; Aged; Arthritis, Rheumatoid; Biomarkers; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Norway; Peptide Fragments; Prognosis; Sex Factors

Rheumatoid arthritis (RA) patients who have active disease with longer disease duration have been reported to have increased risk of cardiovascular events compared to the normal population.. The primary aim of our study is to ascertain the prevalence of significant asymptomatic coronary artery disease (CAD) in Asian RA patients who are in remission using multi-detector computed tomography (MDCT). The secondary aims of our study are the usage of pulse wave velocity and the biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-senstivity C-reactive protein (hs-CRP) to detect subclinical atherosclerosis in RA patients.. We performed a comparative cross-sectional study of 47 RA patients who were in remission with a control group of non-RA patients with a history of atypical chest pain in Sarawak General Hospital from November 2008 to February 2009. All patients underwent 64-slice MDCT, assessment of arterial stiffness using the SphygmoCor test and blood analysis for NT-proBNP and hsCRP.. There were 94 patients in our study with a mean age of 50 +/- 8.8 years. The RA and control patients in each group were matched in terms of traditional CV risk factors. Our RA patients had a median disease duration of 3 years (IQR 5.5). MDCT showed evidence of CAD in nine (19.1%) RA patients and three (6.4%) control patients (P = 0.06). There was no significant association between pulse wave velocity (PWV) and presence of CAD in our RA group. There was no significant correlation between PWV with levels of proBNP or hsCRP in our RA patients.. In our current pilot study with the limitation of small sample size, RA was not associated with an increased risk of CAD in our RA patients who were in remission. Larger studies of CAD in Asian RA patients are needed to confirm our current finding.

Topics: Adult; Arteries; Arthritis, Rheumatoid; Asian People; Asymptomatic Diseases; Biomarkers; C-Reactive Protein; Case-Control Studies; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Elasticity; Female; Humans; Malaysia; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Prevalence; Remission Induction; Risk Assessment; Risk Factors; Tomography, X-Ray Computed; Ultrasonography

Rheumatoid arthritis (RA) is associated with increased incidence cardiac failure. It is yet unclear how much the increased incidence is secondary to ischaemic damage, or whether inflammatory cytokines might have a direct effect on the myocardium.. To establish if patients with active rheumatoid arthritis but no history of cardiac disease have higher serum levels of brain natriuretic peptide (BNP), than patients with less active RA, or disease-free controls.. 90 patients with RA and 31 healthy control subjects were recruited. Each was screened to exclude previous history of cardiac disease. RA disease activity was measured using the DAS28 assessment, and other demographic, physical and laboratory tests performed. Serum BNP levels were measured in all subjects.. There was no difference in the age, percentage females or BMI between the RA and control subjects. Median BNP in the RA patients was 80.0 pg/ml (IQR 38.0-132.0) compared with 48.5 (26.0-86.0) in the control subjects (p=0.017). There was a significant correlation between DAS28 and serum BNP in the RA group, r=0.37, p<0.01. RA patients were divided into three groups according to DAS28 scores. Patients with very active disease (DAS28>5.1) had significantly higher BNP levels than patients with moderately active disease (3.2

Topics: Aged; Arthritis, Rheumatoid; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Regression Analysis; Statistics, Nonparametric

We identified IgG reactive with human cardiac troponin-I (cTnI) in plasma and serum samples (N = 1930) from normal blood donors, and in sample cohorts characterized on the basis of clinical biomarkers associated with cardiac, infectious, and autoimmune diseases. cTnI and brain natriuretic peptide were the biomarkers chosen to reflect myocyte damage or left ventricular dysfunction, respectively. The infectious disease cohorts were serologically positive for antibodies to hepatitis B (natural infection), hepatitis C virus, and Chagas (i.e., T.cruzi). The autoimmune cohorts were represented by samples from diagnosed systemic lupus erythematosus (biomarker: dsDNA) and rheumatoid arthritis (biomarker: rheumatoid factor) subjects. The prevalence of IgG autoantibodies reactive with cTnI was high in the normal donor cohort (95/750, 12.7%). The prevalence in the other sample cohorts was not significantly different from that in the normal blood donors, with the exception of a slight increase in the rheumatoid factor cohort (28/137, 20.4%). The presence of anti-cTnI IgG in highly reactive samples was confirmed by inhibition with the antigen and further by screening with a library of peptides derived from the human cTnI amino acid sequence. Our data suggest that these autoantibodies are polyspecific, encompassing epitopes across the entire cTnI sequence, including the cardiac-specific amino terminal region.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Antibodies, Viral; Arthritis, Rheumatoid; Autoantibodies; Chagas Disease; Child; Cohort Studies; Female; Hepatitis B; Hepatitis C; Humans; Immunoglobulin G; Luminescent Measurements; Lupus Erythematosus, Systemic; Male; Middle Aged; Natriuretic Peptide, Brain; Reproducibility of Results; Troponin I; Young Adult

Disease activity in patients with rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality, of which N-terminal pro-brain natriuretic peptide (NT-proBNP) is a predictor. Our objective was to examine the cross-sectional and longitudinal associations between markers of inflammation, measures of RA disease activity, medication used in the treatment of RA, and NT-proBNP levels (dependent variable).. Two hundred thirty-eight patients with RA of less than 4 years in duration were followed longitudinally with three comprehensive assessments of clinical and radiographic data over a 10-year period. Serum samples were frozen and later batch-analyzed for NT-proBNP levels and other biomarkers. Bivariate, multivariate, and repeated analyses were performed.. C-reactive protein (CRP) levels at baseline were cross-sectionally associated with NT-proBNP levels after adjustment for age and gender (r2 adjusted = 0.23; P < 0.05). At the 10-year follow-up, risk factors for cardiovascular disease were recorded. Duration of RA and CRP levels were independently associated with NT-proBNP in the final model that was adjusted for gender, age, and creatinine levels (r2 adjusted = 0.38; P < 0.001). In the longitudinal analyses, which adjusted for age, gender, and time of follow-up, we found that repeated measures of CRP predicted NT-proBNP levels (P < 0.001).. CRP levels are linearly associated with levels of NT-proBNP in cross-sectional and longitudinal analyses of patients with RA. The independent associations of NT-proBNP levels and markers of disease activity with clinical cardiovascular endpoints need to be further investigated.

Topics: Adult; Aged; Arthritis, Rheumatoid; C-Reactive Protein; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

Increased 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.. In 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.. NT-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.. NT-proBNP concentrations are increased in patients with RA without clinical heart failure and may indicate subclinical cardiovascular disease and a chronic inflammatory state.

Topics: Adult; Age Factors; Aged; Arthritis, Rheumatoid; Biomarkers; Blood Pressure; C-Reactive Protein; Calcinosis; Coronary Artery Disease; Female; Humans; Inflammation; Interleukin-1; Lipids; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Regression Analysis; Severity of Illness Index; Statistics, Nonparametric; Tumor Necrosis Factor-alpha

Topics: Aged; Arthritis, Rheumatoid; Biomarkers; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Osteoarthritis; Peptide Fragments; Prognosis

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Biomarkers; Cardiovascular Diseases; Female; Humans; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain

Topics: Antibodies, Monoclonal; Arthritis, Rheumatoid; Heart Failure; Humans; Infliximab; Infusions, Intravenous; Injections; Insurance, Health, Reimbursement; Medicare; Natriuretic Peptide, Brain; Organizational Policy; Self Administration; Societies, Medical; United States

Topics: Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Rheumatoid; Health Services Misuse; Heart Failure; Humans; Infliximab; Infusions, Intravenous; Insurance, Health, Reimbursement; Natriuretic Agents; Natriuretic Peptide, Brain; United States