Systemic lupus erythematosus is associated with increased cardiovascular morbidity and mortality, and vitamin D deficiency is common in this patient population. However, the relationship between circulating vitamin D levels and long-term outcomes in SLE has remained unclear. To address this gap, the investigators examined whether serum 25-hydroxyvitamin D (25[OH]D) levels were associated with mortality and major cardiovascular events, including stroke, myocardial infarction, and angina requiring bypass procedures.
The analysis was based on data from the Hopkins Lupus Cohort, which began routinely measuring 25(OH)D levels every three months in 2009. The researchers evaluated vitamin D levels at different time points—baseline, the average level over the previous year, and the most recent measurement—and assessed their association with both mortality and cardiovascular outcomes.
Two complementary approaches were used: a prospective analysis focusing on events occurring after the first vitamin D measurement, and a lifetime analysis that also included events prior to cohort enrollment. All statistical models accounted for potential confounders such as age, sex, race, and body mass index.
The following were the key findings:
- The prospective analysis included 1,768 patients with over 11,000 person-years of follow-up.
- Patients with vitamin D levels below 20 ng/mL had the poorest clinical outcomes.
- Individuals entering the cohort with 25(OH)D levels under 20 ng/mL had more than twice the risk of death compared with those with levels of 30–39 ng/mL.
- The risk of cardiovascular events was nearly three times higher in the vitamin D–deficient group.
- Low vitamin D levels were significantly associated with an increased risk of angina or the need for bypass surgery.
- An elevated risk of myocardial infarction was observed in patients with low vitamin D levels, although this did not reach statistical significance.
- Stroke risk was not significantly associated with vitamin D levels.
- Lifetime analysis reinforced the overall findings from the prospective analysis.
- A U-shaped relationship was identified between vitamin D levels and myocardial infarction risk, indicating potential harm at both low and very high levels.
- This U-shaped pattern was consistent with previous findings from the same research group on adverse pregnancy outcomes in SLE.
- No clear association was found between mortality or cardiovascular risk and recent or average vitamin D levels over the prior year.
- The findings raise questions about the effectiveness of vitamin D supplementation alone in modifying long-term cardiovascular risk once deficiency is established.
Overall, the findings suggest that an initial vitamin D level below 20 ng/mL may serve as an indicator of increased mortality and cardiovascular risk in patients with SLE. While the results do not establish causality, they underscore the importance of early risk stratification and warrant further research into the role of vitamin D in the long-term management of systemic lupus erythematosus.
Reference:
Assawasaksakul T, Fava A, Goldman D, Magder LS, Petri M. 25-Hydroxyvitamin D levels are associated with mortality and cardiovascular events in systemic lupus erythematosus. Ann Rheum Dis. 2025 Nov 11:S0003-4967(25)04452-8. doi: 10.1016/j.ard.2025.10.013. Epub ahead of print. PMID: 41224553.
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