Systemic Lupus Erythematosus, with focus on vascular wall changes, cardiac risk-factor awareness and cardiovascular events
Abstract: Systemic Lupus Erythematosus is an autoimmune disease with a wide range of disease manifestations with respect to severity and magnitude of organ involvement. An increased risk of cardiovascular disease (CVD) compared with the general population causes both morbidity and mortality in SLE patients. Consequently prevention, early detection and treatment of arteriosclerotic manifestations are of high priority for the clinician. The aims in the present thesis focused on identifying non-invasive possible markers associated with atherosclerosis in SLE patients and in comparison with controls. Cardiac risk factor (CRF) awareness among patients, the documentation of these factors in patients records and the adherence to given advice about changing risk factor behaviour was evaluated. Furthermore, the incidence of CVD among SLE patients compared with the general population and matched controls was analysed and predictors of cerebrovascular events evaluated. Arterial stiffness was measured using two methods: firstly, using an ultrasound echo-tracking system it was found that SLE patients without CVD had an increased stiffness of the popliteal artery (p=0.005), and that the diameter of the common carotid artery was increased in SLE patients compared with controls (Paper I). Secondly, the aortic pulse wave velocity (PWV), measured by arterial tonometry, was found to be increased reflecting stiffness (p<0.01). An association between C-reactive protein, and complement component 3 and the increase in PWV was also noted (Paper II). Cutaneous microvascular reactivity was measured using an iontophoretic laser-doppler technique after acetylcholine or nitroprusside stimulation with no difference between SLE patients and controls being found (Paper III). However, patients prescribed anti-malarial treatment had an elevated endothelium independent reactivity (p<0.005). Whilst higher doses of prednisone (?5mg/day) were associated with a decrease in the endothelial dependent reactivity (p<0.05) warfarin treatment increased the endothelial dependent reactivity (p<0.05). A validated questionnaire was used to study CRFs (Paper IV). More than 70% of the patients identified obesity, smoking and hypercholesterolaemia as being very important CRFs. The agreement between medical record documentation and the patients´ own report for hypertension, being overweight and hypercholesterolaemia was moderate (kappa 0.42-0.60) but substantial for diabetes (kappa 0.66). There was a notable difference in the self-reported compliance to advice, with good adherence to prescribed medications but poor adherence to lifestyle changes. An overall elevated risk for myocardial infarction (MI) in SLE patients compared with the general population was demonstrated, i.e.., 2.31 (95%CI 1.34-3.7) which was further raised among middle aged female patients to 8.7 (95%CI 1.1-31.4) (Paper V). In this patient group, the SIR for an MI and/or stroke was 8.00 (95%CI 1.65-23.38). The time to a cardiovascular event (CVE) was significantly shorter among SLE patients compared with matched controls (p<0.001) and predicted by hypertension. An event in a SLE patient was predicted by a high SLEDAI score and the presence of anti-cardiolipin-IgG antibodies (aCL-IgG) when adjusted for age and a previous MI. In conclusion, the arterial vessel walls are stiffer and show signs of early ageing in SLE patients. An association with elevated C-reactive protein levels was also noted. Both endothelium dependent and independent cutaneous microvascular reactivity is influenced by medication. Patients’ knowledge of, and adherence to advice regarding modification of CRFs are in need of improvement. The risk for a CVE, and an MI per se, in female SLE patients is notably elevated and the overall risk for an MI is doubled. The time to a CVE in SLE patients is shorter and predicted by hypertension. In SLE patients an event is also predicted by greater disease activity and presence of aCL-IgG antibodies.
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