Background/Purpose: To study the effect of osteoporosis on major adverse cardiovascular events (MACEs) and mortality in a longitudinal cohort of patients with systemic lupus erythematosus (SLE).

Methods: Patients who fulfilled ≥4 1997 ACR criteria for SLE and participated in a cross-sectional study on osteoporosis in the year 2011 were studied. All patients had a DEXA scan performed between years 2004-2008 and followed by the same team of rheumatologists. The incidence of new MACEs, defined as ischemic vascular events (acute coronary syndrome, stroke, peripheral vascular disease) documented by imaging and angiographic studies, was evaluated. Patients were stratified into 2 groups according to osteoporosis at baseline, defined as a DXA T score of < -2.5 or Z score < -2.0 at the hip, femoral neck or lumbar spine, or having a past history of fragility fractures. The effect of osteoporosis on the incident MACEs and mortality was studied by Cox regression analysis, adjusted for confounding factors.

Results: 383 SLE patients were studied (age at DXA scan 40.5±13 years; 94% women; SLE duration 8.0±7.4 years). Osteoporosis at baseline was present in 105 patients (13 with history of fractures) and 8 patients had osteopenia with past fractures. The demographic characteristics, prevalence of traditional atherosclerotic risk factors and antiphospholipid (aPL) antibodies were not significantly different between those with osteoporosis/fracture (group 1; N=113) and without (group 2; N=270). Group 1 patients were more likely to be using glucocorticoids (79% vs 62%; p=0.002) and mycophenolate mofetil/azathioprine/calcineurin inhibitors (58% vs 48%; p=0.08) but less likely to be treated with hydroxychloroquine (40% vs 51%; p=0.051). Over 153±41 months, 44 new MACEs (acute coronary syndrome [n=19]; ischemic stroke [n=19]; peripheral vascular disease with digital gangrene/amputation [n=6]) developed in 42 patients. The incidence of MACEs was significantly higher in group 1 than group 2 patients (1.59 vs 0.63/100 patient-years; p=0.001). The cumulative risk of MACEs at 3, 5 and 10 years was 6.3%, 11.7%, 14.7%, and 0.4%, 1.9%, 4.7%, respectively, in group 1 and 2 patients (log rank test; p=0.002; univariate HR2.58[1.40-4.74]; p=0.002). In a Cox regression model, osteoporosis/fracture remained an independent risk factor for incident MACEs after adjustment for age, sex, LDL level, atherogenic index, diabetes mellitus, hypertension, past MACE, aPL antibodies, smoking, obesity and the use of medications (immunosuppressives, aspirin/warfarin, statins, vitamin D and bisphosphonates) (HR 2.41[1.25-4.67]; p=0.009). At last follow-up, 62(16%) patients succumbed (MACEs in 8 patients [vascular mortality]). Osteoporosis/fracture was associated with vascular mortality (HR 11.1[1.02-120]; p=0.048) but not with all-cause mortality (HR 1.55[0.89-2.68]; p=0.12) after adjustment for the same covariates in separate models.

Conclusion: Osteoporosis increases the risk of MACEs and vascular mortality in patients with SLE, which is not accounted by traditional vascular risk factors. Elevation of inflammatory cytokines in SLE that are common to bone metabolism and atherosclerotic vascular disease may be responsible.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-osteoporosis-on-major-adverse-cardiovascular-events-maces-and-mortality-in-systemic-lupus-erythematosus-a-longitudinal-study/