Guideline recommended treatment to targets of cardiovascular risk is inadequate in patients with inflammatory joint diseases.

OBJECTIVES: Patients with inflammatory joint diseases (IJD) have an increased risk of cardiovascular disease (CVD). Our goal was to examine indications for, and use of, lipid-lowering therapy (LLT) and antihypertensive treatment (AntiHT) in patients with IJD. Furthermore, to investigate the frequency of low-density lipoprotein cholesterol (LDL-c) and blood pressure (BP) goal attainment among IJD patients. METHODS: The cohort was derived from the NOrwegian Collaboration on Atherosclerosis in patients with Rheumatic joint diseases (NOCAR). Indications for AntiHT were: systolic/diastolic BP ≥ 140/90 mm Hg, self-reported hypertension or AntiHT. CVD risk was estimated by the systematic coronary risk evaluation (SCORE) algorithm. LDL-c goals were <2.6 mmol/L in case of diabetes, total cholesterol > 8 mmol/L or a SCORE estimate ≥ 5%, and <1.8 mmol/L for those with established CVD or SCORE ≥ 10%. Comparisons across IJD entities were performed using age and sex adjusted logistic regression. RESULTS: In total, 2277 patients (rheumatoid arthritis: 1376, axial spondyloarthritis: 474, psoriatic arthritis: 427) were included. LLT and AntiHT were indicated in 36.1% and 52.6% of the patients, of whom 37.6% and 47.0% were untreated, respectively. LDL-c and BP targets were obtained in 26.2% and 26.3%, respectively. Guideline recommended treatment and/or corresponding treatment targets were not initiated or obtained in approximately 50%. Rheumatoid arthritis patients were particularly likely to be undertreated with LLT, whereas hypertension undertreatment was most common in psoriatic arthritis. CONCLUSIONS: Inadequate CVD prevention encompasses all the three major IJD entities. The unmet need for CVD preventive measures is not only prevalent in RA, but exists across all the major IJD entities.

Discrepancies in risk age and relative risk estimations of cardiovascular disease in patients with inflammatory joint diseases.

OBJECTIVE: The European guidelines on cardiovascular disease (CVD) prevention advise use of relative risk and risk age algorithms for estimating CVD risk in patients with low estimated absolute risk. Patients with inflammatory joint diseases (IJD) are associated with increased risk of CVD. We aimed to estimate relative risk and risk age across IJD entities and evaluate the agreement between 'cardiovascular risk age' and 'vascular age models'. METHODS: Using cross-sectional data from a nationwide project on CVD risk assessment in IJD, risk age estimations were performed in patients with low/moderate absolute risk of fatal CVD. Risk age was calculated according to the cardiovascular risk age and vascular age model, and risk age estimations were compared using regression analysis and calculating percentage of risk age estimations differing ≥5years. RESULTS: Relative risk was increased in 53% and 20% had three times or higher risk compared to individuals with optimal CVD risk factor levels. Furthermore, 20-42% had a risk age ≥5years higher than their actual age, according to the specific risk age model. There were only minor differences between IJD entities regarding relative risk and risk age. Discrepancies ≥5years in estimated risk age were observed in 14-43% of patients. The largest observed difference in calculated risk age was 24years. CONCLUSION: In patients with low estimated absolute risk, estimation of relative CVD risk and risk age may identify additional patients at need of intensive CVD preventive efforts. However, there is a substantial discrepancy between the risk age models.

Cardiovascular disease risk profiles in inflammatory joint disease entities.

BACKGROUND: Patients with inflammatory joint diseases (IJD) have increased risk of cardiovascular disease (CVD). Our aim was to compare CVD risk profiles in patients with IJD, including rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) and evaluate the future risk of CVD. METHODS: The prevalence and numbers of major CVD risk factors (CVD-RFs) (hypertension, elevated cholesterol, obesity, smoking, and diabetes mellitus) were estimated in patients with RA, axSpA and PsA. Relative and absolute risk of CVD according to Systematic Coronary Risk Evaluation (SCORE) was calculated. RESULTS: In total, 3791 patients were included. CVD was present in 274 patients (7.2%). Of those without established CVD; hypertension and elevated cholesterol were the most frequent CVD-RFs, occurring in 49.8% and 32.8% of patients. Patients with PsA were more often hypertensive and obese. Overall, 73.6% of patients had a minimum of one CVD-RF, which increased from 53.2% among patients aged 30 to <45 years, to 86.2% of patients aged 60 to ≤80 years. Most patients (93.5%) had low/moderate estimated risk of CVD according to SCORE. According to relative risk estimations, 35.2% and 24.7% of patients had two or three times risk or higher, respectively, compared to individuals with no CVD-RFs. CONCLUSIONS: In this nationwide Norwegian project, we have shown for the first time that prevalence and numbers of CVD-RFs were relatively comparable across the three major IJD entities. Furthermore, estimated absolute CVD risk was low, but the relative risk of CVD was markedly high in patients with IJD. Our findings indicate the need for CVD risk assessment in all patients with IJD.

Rapid Anti-Inflammatory Effects of Gonadotropin-Releasing Hormone Antagonism in Rheumatoid Arthritis Patients with High Gonadotropin Levels in the AGRA Trial.

OBJECTIVES: Gonadotropin-releasing hormone (GnRH) and pituitary gonadotropins, which appear to be proinflammatory, undergo profound secretory changes during events associated with rheumatoid arthritis (RA) onset, flares, or improvement e.g. menopausal transition, postpartum, or pregnancy. Potential anti-inflammatory effects of GnRH-antagonists may be most pronounced in patients with high GnRH and gonadotropin levels. Therefore, we investigated the efficacy and safety of a GnRH-antagonist, cetrorelix, in RA patients with high gonadotropin levels. METHODS: We report intention-to-treat post hoc analyses among patients with high gonadotropin levels (N = 53), i.e. gonadotropin levels>median, from our proof-of-concept, double-blind AGRA-study (N = 99). Patients with active longstanding RA, randomized to subcutaneous cetrorelix (5mg days1-2; 3mg days 3-5) or placebo, were followed through day 15. Only predefined primary and secondary endpoints were analyzed. RESULTS: The primary endpoint, Disease Activity Score of 28-joint counts with C-reactive protein (DAS28-CRP), improved with cetrorelix compared with placebo by day 5 (-1.0 vs. -0.4, P = 0∙010). By day 5, more patients on cetrorelix achieved at least a 20% improvement in the American College of Rheumatology scale (44% vs. 19%, P = 0.049), DAS28-CRP≤3.2 (24% vs. 0%, P = 0.012), and European League against Rheumatism 'Good-responses' (19% vs. 0%, P = 0.026). Tumor necrosis factor-α, interleukin-1ß, interleukin-10, and CRP decreased with cetrorelix (P = 0.045, P = 0.034, P = 0.020 and P = 0.042 respectively) compared with placebo by day 15. Adverse event rates were similar between groups. CONCLUSIONS: GnRH-antagonism produced rapid anti-inflammatory effects in RA patients with high gonadotropin levels. GnRH should be investigated further in RA. TRIAL REGISTRATION: ClinicalTrials.gov NCT00667758.