natriuretic-peptide--brain and Osteoarthritis

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

we investigated whether higher concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) predicts cardiovascular adverse events (CV-AEs) in patients with osteoarthritis treated with antiinflammatory drugs.. NT-proBNP was measured in baseline samples from 433 patients enrolled in a prospective randomized study designed to test the therapeutic effect of a novel metalloproteinase inhibitor. We monitored CV-AEs and retrospectively investigated their relationship to the concomitant use of selective cyclooxygenase-2 inhibitors (coxibs), traditional nonsteroidal antiinflammatory drugs (tNSAIDs), and glucocorticoids. CV-AEs included myocardial infarction, stroke, new or worsening of preexisting arterial hypertension, congestive heart failure, and several less severe CV-AEs.. we observed 82 mild to serious CV-AEs during an observational period of 200 days. The risk of such events was 1.95-fold higher in patients who were taking tNSAIDs, glucocorticoids, or coxibs (i.e., any inhibitor) and who had NT-proBNP concentrations > or = 100 ng/L than in patients taking any inhibitor who had NT-proBNP values <100 ng/L (P < 0.05). Patients taking coxibs (alone or in addition to tNSAIDs or glucocorticoids) with baseline NT-proBNP values > or = 100 ng/L had a 7.41-fold higher risk for CV-AEs than those with baseline values <100 ng/L (P < 0.01). Patients who were taking 2 or more antiinflammatory drugs and had NT-proBNP values > or = 100 ng/L had a 3.74-fold higher risk for CV-AEs than those with NT-proBNP values <100 ng/L (P < 0.05). An NT-proBNP value <100 ng/L was associated with negative predictive values of >85% across all treatment groups.. NT-proBNP may be a useful marker for anticipating cardiovascular risk associated with the use of antiinflammatory drugs for osteoarthritis.

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Cardiovascular Diseases; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Metalloproteases; Middle Aged; Natriuretic Peptide, Brain; Osteoarthritis; Peptide Fragments; Pilot Projects; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Assessment

Osteoarthritis (OA) is associated with higher cardiovascular mortality risk. High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are well-characterized prognostic cardiac markers. We aimed to describe the changes in biomarkers measured one year apart in a cohort of 347 subjects with OA who underwent hip or knee replacement surgery in 1995/1996 and to analyze the prognostic value of repeated measurements for long-term mortality. During a median follow-up of 19 years, 209 (60.2%) subjects died. Substantial changes in cardiac biomarkers, especially for NT-proBNP, and an independent prognostic value of NT-proBNP for long-term mortality were found for both baseline measurement concentration (hazard ratio (HR) 1.32, 95% confidence interval (CI) (1.13-1.55)) and follow-up measurement concentration (HR 1.39, 95% CI 1.18-1.64) (all HR per standard deviation increase after natural log-transformation). Baseline concentrations were correlated with follow-up concentrations of NT-proBNP and no longer showed prognostic value when included simultaneously in a single model (HR 1.08, 95% CI 0.86-1.37), whereas the estimate for the one-year measurement remained robust (HR 1.31, 95% CI 1.04-1.66). Therefore, no significant additional benefit of repeated NT-proBNP measurements was found in this cohort, facilitating the use of a single NT-proBNP measurement as a stable prognostic marker.

Topics: Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Biomarkers; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Osteoarthritis; Peptide Fragments; Prognosis; Proportional Hazards Models; Risk Factors; Troponin T

The purpose of this study was describe the cardiovascular phenotype of the aneurysms-osteoarthritis syndrome (AOS) and to provide clinical recommendations.. AOS, caused by pathogenic SMAD3 variants, is a recently described autosomal dominant syndrome characterized by aneurysms and arterial tortuosity in combination with osteoarthritis.. AOS patients in participating centers underwent extensive cardiovascular evaluation, including imaging, arterial stiffness measurements, and biochemical studies.. We included 44 AOS patients from 7 families with pathogenic SMAD3 variants (mean age: 42 ± 17 years). In 71%, an aortic root aneurysm was found. In 33%, aneurysms in other arteries in the thorax and abdomen were diagnosed, and in 48%, arterial tortuosity was diagnosed. In 16 patients, cerebrovascular imaging was performed, and cerebrovascular abnormalities were detected in 56% of them. Fifteen deaths occurred at a mean age of 54 ± 15 years. The main cause of death was aortic dissection (9 of 15; 60%), which occurred at mildly increased aortic diameters (range: 40 to 63 mm). Furthermore, cardiac abnormalities were diagnosed, such as congenital heart defects (6%), mitral valve abnormalities (51%), left ventricular hypertrophy (19%), and atrial fibrillation (22%). N-terminal brain natriuretic peptide (NT-proBNP) was significantly higher in AOS patients compared with matched controls (p < 0.001). Aortic pulse wave velocity was high-normal (9.2 ± 2.2 m/s), indicating increased aortic stiffness, which strongly correlated with NT-proBNP (r = 0.731, p = 0.005).. AOS predisposes patients to aggressive and widespread cardiovascular disease and is associated with high mortality. Dissections can occur at relatively mildly increased aortic diameters; therefore, early elective repair of the ascending aorta should be considered. Moreover, cerebrovascular abnormalities were encountered in most patients.

Topics: Adolescent; Adult; Aged; Aneurysm; Aortic Aneurysm, Thoracic; Aortic Dissection; Aortography; Cardiovascular Diseases; Cause of Death; Cerebrovascular Disorders; Chromosome Aberrations; Cohort Studies; Female; Genes, Dominant; Genomic Structural Variation; Humans; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Male; Middle Aged; Natriuretic Peptide, Brain; Osteoarthritis; Peptide Fragments; Phenotype; Pregnancy; Smad3 Protein; Survival Analysis; Syndrome; Vascular Stiffness; Young Adult

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