Prevention of cardiovascular disease in rheumatoid arthritis.

The increased risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA) has been recognized for many years. However, although the characteristics of CVD and its burden resemble those in diabetes, the focus on cardiovascular (CV) prevention in RA has lagged behind, both in the clinical and research settings. Similar to diabetes, the clinical picture of CVD in RA may be atypical, even asymptomatic. Therefore, a proactive screening for subclinical CVD in RA is warranted. Because of the lack of clinical trials, the ideal CVD prevention (CVP) in RA has not yet been defined. In this article, we focus on challenges and controversies in the CVP in RA (such as thresholds for statin therapy), and propose recommendations based on the current evidence. Due to the significant contribution of non-traditional, RA-related CV risk factors, the CV risk calculators developed for the general population underestimate the true risk in RA. Thus, there is an enormous need to develop adequate CV risk stratification tools and to identify the optimal CVP strategies in RA. While awaiting results from randomized controlled trials in RA, clinicians are largely dependent on the use of common sense, and extrapolation of data from studies on other patient populations. The CVP in RA should be based on an individualized evaluation of a broad spectrum of risk factors, and include: 1) reduction of inflammation, preferably with drugs decreasing CV risk, 2) management of factors associated with increased CV risk (e.g., smoking, hypertension, hyperglycemia, dyslipidemia, kidney disease, depression, periodontitis, hypothyroidism, vitamin D deficiency and sleep apnea), and promotion of healthy life style (smoking cessation, healthy diet, adjusted physical activity, stress management, weight control), 3) aspirin and influenza and pneumococcus vaccines according to current guidelines, and 4) limiting use of drugs that increase CV risk. Rheumatologists should take responsibility for the education of health care providers and RA patients regarding CVP in RA. It is immensely important to incorporate CV outcomes in testing of anti-rheumatic drugs.

New developments in the pathogenesis of articular cartilage calcification.

Articular cartilage, unlike growth plate cartilage, is specialized to not undergo matrix calcification. However, articular cartilage mineralization, in the form of CPPD (chondrocalcinosis) and hydroxyapatite crystals, frequently accompanies and complicates osteoarthritis and aging. Recent work has demonstrated that certain features of growth cartilage development and mineralization are shared in degenerative cartilage. These include chondrocyte proliferation, hypertrophy and increased apoptosis. Moreover, parathyroid hormone related protein (PTHrP), one of the central mediators of endochondral development, is abundant in osteoarthritic cartilage. Cartilage PPi elaboration and cytosolic transglutaminase activity are markedly increased with aging. Only recently have the molecular identities been defined for the chondrocyte inorganic pyrophosphate (PPi)-generating isozymes of the phosphodiesterase nucleotide pyrophosphatase (PDNP) family (including PC-1 and B10), and for transglutaminase in articular cartilage. This review focuses on the evolving understanding of the potential roles, in articular cartilage calcification, of PTHrP, PDNP family enzymes, PPi metabolism, and transglutaminase activity.

Necrotizing vasculitis in Greece: clinical, immunological and immunogenetic aspects. A study of 66 patients.

The clinical spectrum and outcome of necrotizing vasculitis were evaluated in a retrospective study in order to assess: (1) the clinical expression and evolution of the disease; (2) the response to several therapeutic approaches based on major events (organ involvement causing disability or death); (3) the immunogenetic background of patients. Sixty-six Greek patients fulfilling the ACR criteria for the diagnosis of vasculitis entered the study. Thirty-seven were diagnosed with Wegener's granulomatosis (WG), 22 with polyarteritis nodosa (PAN) and seven with Churg-Strauss syndrome (CSS). The demographic characteristics of patients with WG and PAN were similar. Cutaneous manifestations, gastrointestinal and peripheral nervous system involvement occurred more often in patients with PAN, whereas pulmonary and upper respiratory tract involvement, renal, ear abnormalities and fever were more frequent in patients with WG. Muscle weakness and asthma were found exclusively in patients with PAN and CSS, respectively, while the presence of classic-antineutrophil cytoplasmic antibodies (c-ANCA) characterized WG patients. Hepatitis B surface antigen (HBsAg) was found in 22% of PAN patients. No significant differences were detected when comparing the PAN and WG groups with respect to the first major event (log-rank P = 0.50) with and without potential confounders (age, gender, therapy or c-ANCA). For WG patients, a statistically significant difference was found on different routes of administration of cyclophosphamide (oral vs pulse) (P = 0.006). Regarding the HLA antigens, an increased frequency of DR1 (26.9% vs 10.3%, P = 0.057) in WG and the absence of DR3 in patients with PAN and CSS were noted. It appears that although the immunogenetic background and the clinical expression of the diseases differ, the response to treatment as well as the evolution and the survival rate of these patients are similar in the two groups.