Cardiovascular Mortality in Systemic Lupus Erythematosus

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Lupus nephritis a risk factor for some, but not all, cardiovascular outcomes in study of patients with SLE.
Lupus nephritis a risk factor for some, but not all, cardiovascular outcomes in study of patients with SLE.

In a study designed to assess the role of lupus nephritis (LN) as an overall risk factor for various cardiovascular (CV) outcomes in patients with systemic lupus erythematosus (SLE), researchers found an elevated risk of myocardial infarction (MI) and CV mortality (CVM), but not stroke, in patients with SLE and LN compared with patients with SLE absent LN. Results were published ahead of print January 3, 2017, in Rheumatology.1

SLE is associated with excess CV morbidity and mortality resulting from conventional cardiovascular disease (CVD) risk factors in addition to SLE-related risk and treatment factors. However, the contribution of LN to CVD in patients with SLE has been incompletely characterized.

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For the study, the research team analyzed multiple Danish administrative data sources linked by the unique numerical identifier all Danish citizens receive at birth or upon immigration. The investigators calculated hazard ratios (HR) to assess the risk of MI, stroke, and CVM in patients with SLE relative to population controls and to compare those CVD risks in patients with SLE with and without LN.

Results showed an HR for MI of 2.2 (95% CI, 1.4-3.4) and 18.3 (95% CI, 5.1- 65.0) in patients with SLE without LN and with LN, respectively, compared with matched population controls, representing an 8-fold increase in the risk of MI in the presence of LN (HR = 8.5; 95% CI, 2.2-33.0; P =.002). The HR for CVM was 1.6 (95% CI, 1.1-2.5) and 7.8 (95% CI, 3.0-20.0) in SLE patients without LN and with LN, respectively, compared with matched population controls, representing a more than 4-fold increased risk of CVM (HR: 4.9; 95% CI, 1.8-13.7; P =.002) with LN. No significant association between LN and stroke risk was found (HR: 1.9; 95% CI, 0.9-4.4; P =.115).

In an email interview, lead investigator Marie-Louise Hermansen, MD, told Rheumatology Advisor that the study's results may not be applicable to all patients with SLE. “We did not have access to data on specific details of ethnicity in the registers used. However, in 2011, 92% of the Danish population was composed of white individuals and this composition of ethnicity is probably reflected in the study population as well,” she stated.

“It is well known that a higher proportion of African Americans, Asians, and Hispanics than white patients are developing LN. Further, white patients tend to have a less severe disease course of LN than other ethnic groups. It is reasonable to assume that there are also factors related to ethnicity that might influence the risk of cardiovascular morbidity and cardiovascular mortality in patients with LN. At least this is the case in the general population where more African Americans are affected by cardiovascular disease than other ethnic groups. Thus, extrapolation to populations outside Denmark should be done with caution.”

Summary and Clinical Applicability

When asked about the implications of the study for clinical practice, Dr Hermansen noted that her team's results echo similar studies in which findings of excess CVD risk suggest that systematic screening for CVD risk factors be considered in all patients with SLE. “Our results also indicate that the subgroup of SLE patients with LN should be acknowledged as having a particularly high risk of cardiovascular events during both early and later phases of their disease course,” she added. 

“Consequently, physicians should consider screening this subgroup for cardiovascular risk factors and cardiovascular disease more closely.”

Study Limitations 

  • The Danish National Patient Register lacks information on patients' clinical characteristics, including a lack of biochemical information, which prevented the authors from investigating both traditional and disease-specific CV risk factors. 

  •  Lack of medication data prevented analysis on the impact of medications on risk of CV events. 

  • The small number of patients in some subgroups, particularly men, resulted in less statistical power in the results. 

Reference

Hermansen M-L, Lindhardsen J, Torp-Pedersen C, Faurschou M, Jacobsen S. The risk of cardiovascular morbidity and cardiovascular mortality in systemic lupus erythematosus and lupus nephritis: a Danish nationwide population-based cohort study [published online January 4, 2017]. Rheumatol Oxf Engl. doi:10.1093/rheumatology/kew475

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