Left ventricular size and function in patients with systemic lupus erythematosus associate with lupus anticoagulant: An echocardiographic follow-up study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with increased risk of cardiac dysfunction. The pathophysiological mechanisms are poorly understood, and prognostic markers are warranted. PURPOSE: We aimed to identify SLE-characteristics associated with measures of cardiac size and function during a five-year follow-up. METHODS: We included 108 patients with SLE: 90% females, mean age 46 ± 13 years, median disease duration 14 (range 7-21) years. We performed blood sampling for potential biomarkers as well as a standard echocardiography at baseline and at a 5-year follow-up. To investigate associations with baseline and prospective 5-year changes in echocardiographic parameters, we performed multivariate regression analyses of SLE-related baseline variables (clinical disease activity, lupus nephritis, chronic kidney disease, anti-cardiolipin and/or anti-beta-2 glycoprotein I antibodies, and lupus anticoagulant (LAC)) and adjusted for traditional risk factors. RESULTS: During follow-up, diastolic function regressed in two out of five echocardiographic measures (E/A ratio 1.4 ± 0.5 vs. 1.3 ± 0.5, p = 0.002; tricuspid regurgitation peak velocity 2.0 ± 0.6 vs. 2.2 ± 0.4 mmHg, p < 0.001). Left ventricular (LV) end-diastolic volume index increased (43.7 ± 13.9 vs. 52.5 ± 15.7 mL/m2, p < 0.001). Left and right ventricular systolic function remained stationary. LAC was associated with inferior diastolic function: lower E/A ratio (p = 0.04) and higher E/e' ratio at baseline (p = 0.04) and increased left ventricular atrial volume index during follow-up (p = 0.01). LAC was further associated with LV dilatation during follow-up (p = 0.01). CONCLUSION: Presence of LAC was associated with measures of diastolic function as well as progressive LV dilatation during the 5-year follow-up. Thus, LAC might be a predictor of cardiac dysfunction in SLE patients. LAC is known to have implications for the microvascular circulation, but the clinical significance of the present findings is yet to be elucidated.

Early development of tendinopathy in humans: Sequence of pathological changes in structure and tissue turnover signaling.

Overloading of tendon tissue with resulting chronic pain (tendinopathy) is a common disorder in occupational-, leisure- and sports-activity, but its pathogenesis remains poorly understood. To investigate the very early phase of tendinopathy, Achilles and patellar tendons were investigated in 200 physically active patients and 50 healthy control persons. Patients were divided into three groups: symptoms for 0-1 months (T1), 1-2 months (T2) or 2-3 months (T3). Tendinopathic Achilles tendon cross-sectional area determined by ultrasonography (US) was ~25% larger than in healthy control persons. Both Achilles and patellar anterior-posterior diameter were elevated in tendinopathy, and only later in Achilles was the width increased. Increased tendon size was accompanied by an increase in hypervascularization (US Doppler flow) without any change in mRNA for angiogenic factors. From patellar biopsies taken bilaterally, mRNA for most growth factors and tendon components remained unchanged (except for TGF-beta1 and substance-P) in early tendinopathy. Tendon stiffness remained unaltered over the first three months of tendinopathy and was similar to the asymptomatic contra-lateral tendon. In conclusion, this suggests that tendinopathy pathogenesis represents a disturbed tissue homeostasis with fluid accumulation. The disturbance is likely induced by repeated mechanical overloading rather than a partial rupture of the tendon.

Myocardial fibrosis associates with lupus anticoagulant in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that carries increased risk of cardiovascular disease; however, the underlying pathophysiological mechanisms remain poorly understood. We aimed to investigate the prevalence and degree of myocardial fibrosis in SLE patients and associated disease characteristics. Forty-nine SLE patients (89% female, mean age 52 ± 13 years, median disease duration 19 (11-25) years) and 79 sex-and age-matched healthy controls were included. CMR with T1 mapping was performed on SLE patients and healthy controls. Fifty-one SLE patients received gadolinium contrast for the evaluation of late gadolinium enhancement (LGE) and extra cellular volume (ECV). Multiple linear regression analyses were performed to investigate the association between markers of myocardial fibrosis on CMR (LGE, T1, ECV) and SLE-related variables [clinical disease activity, lupus nephritis, chronic kidney disease, anti-cardiolipin and/or anti-beta-2 glycoprotein I antibodies, and lupus anticoagulant (LAC)] with adjustment for traditional risk factors. T1 values were elevated in SLE patients compared to healthy controls (1031 ± 36 ms vs. 1019 ± 25 ms, p = 0.01). LGE was present in 20% of SLE patients who received gadolinium contrast. On multivariable analysis, LAC was associated with LGE in SLE patients (ß = 3.87, p = 0.02). Neither T1 nor ECV associated with SLE disease characteristics; however, there was a trend towards an association between LAC and T1 (ß = 16.9, p = 0.08). SLE patients displayed signs of myocardial fibrosis on CMR that were associated with the presence of LAC. These findings support the pathophysiological understanding of LAC as a mediator of microvascular and subsequent myocardial dysfunction.