Suppression of inflammation reduces endothelial microparticles in active systemic lupus erythematosus.

BACKGROUND: In a prospective observational study, we investigated whether patients with active systemic lupus erythematosus (SLE) had higher indices of endothelial damage and dysfunction than healthy controls and whether improved disease control was associated with improvement in these indices. METHODS: Twenty-seven patients with active SLE (four or more American College of Rheumatology (ACR) criteria) and 22 age-matched controls were assessed. Endothelial microparticles (EMPs; CD31+/annexin V+/CD42b-) were quantified using flow cytometry. Brachial artery flow-mediated dilatation (FMD) was measured using automated edge-tracking software. Twenty-two patients had a second assessment at a median (IQR) of 20 (16, 22) weeks after initiating new immunosuppressive therapy. RESULTS: SLE patients had a median (IQR) baseline global British Isles Lupus Assessment Group Disease Activity Index (BILAG-2004) score of 14 (12, 22). CD31+/annexin V+/CD42b- EMPs were higher (157 548/ml (59 906, 272 643) vs 41 025(30 179, 98 082); p=0.003) and endothelial-dependent FMD was lower (1.63% (-1.22, 5.32) vs 5.40% (3.02, 8.57); p=0.05) in SLE patients than controls. CD31+/annexin V+/CD42b- EMPs correlated inversely with FMD (%) (r(2) -0.40; p=0.006). At follow-up, the median (IQR) change in global BILAG-2004 score was -11 (-18, -3). CD31+/annexin V+/CD42b- EMP levels were reduced (166 982/ml (59 906, 278 775 vs 55 655(29 475, 188 659; p=0.02) and FMD had improved (0.33% (-2.31, 4.1) vs 3.19% (0.98, 5.09); p=0.1) at the second visit. CONCLUSIONS: Active SLE is associated with evidence of increased endothelial damage and endothelial dysfunction, which improved with suppression of inflammation. Better control of active inflammatory disease may contribute to improved cardiovascular risk in patients with SLE.

Cardiovascular risk factors in inflammatory arthritis.

PURPOSE OF REVIEW: To assess factors that promote atherogenesis and cardiovascular disease (CVD) in rheumatoid arthritis (RA). Also, to determine how control of inflammation with conventional and biological antirheumatic drugs affects cardiovascular risk. RECENT FINDINGS: An excess risk of CVD occurs early in the RA disease course and indeed may predate disease onset. Inflammation is a key driver of CVD risk as it adversely affects body composition, glucose handling and lipid function, especially the atheroprotective role of high-density lipoprotein. Therapies for RA, especially hydroxychloroquine and methotrexate (MTX) have positive effects on cardiovascular risk factors such as glycaemic control and reverse cholesterol transport. MTX and antitumour necrosis factor-alpha drugs also appear to have beneficial effect on CVD event risk, although the data on MTX appears more consistently to favour such a benefit. SUMMARY: Future work needs to understand which aspects of the inflammatory state contribute most to CVD risk and whether specific anti-inflammatory agents, either alone or in combination, afford maximal CVD protection in RA.

Risk factors for coronary heart disease in connective tissue diseases.

Atherosclerosis and cardiovascular disease risk is enhanced in certain connective tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic vasculitis and antiphospholipid syndrome. The reason for this accelerated process is likely to be multifactorial. Traditional risk factors are more prevalent in some of these patient groups compared with the general population (e.g. smoking in RA and hypertension in SLE). However, these factors do not fully explain that enhanced risk. Chronic inflammation associated with these disorders as well as some specific autoantibodies have been shown to contribute to this increased risk although their role remains controversial. The role of therapies is unclear and while steroids may exacerbate metabolic risk factors, the anti-inflammatory effects of traditional and more novel biological therapies may reduce overall cardiovascular risk in these populations. We recommend proactive screening for modifiable cardiovascular risk factors in patients with these conditions.