Low Vitamin D Linked to Higher Mortality and Cardiovascular Risk among Lupus Patients: Study
USA: A long-term prospective cohort study has found that lupus patients with low vitamin D — specifically low 25-hydroxyvitamin D levels — at enrollment had significantly worse outcomes. Over an average follow-up of 6 years, these patients experienced twice the risk of all-cause mortality and three times the risk of major cardiovascular events, highlighting the importance of monitoring and managing vitamin D levels in lupus care.
A new analysis from the Johns Hopkins Lupus Cohort, published in Annals of the Rheumatic Diseases, provides compelling evidence that vitamin D status plays a meaningful role in long-term outcomes among individuals with systemic lupus erythematosus (SLE). Led by Theerada Assawasaksakul and colleagues from Johns Hopkins University, the study evaluated whether different measures of 25-hydroxyvitamin D (25[OH]D) — including baseline, recent, and annual mean values — were linked to mortality and cardiovascular complications such as stroke, myocardial infarction, and angina or coronary bypass.
The cohort began routine quarterly vitamin D testing in 2009, giving researchers a unique opportunity to track levels longitudinally and relate them to clinical events. The prospective arm of the study included 1,768 patients, accounting for more than 11,300 person-years of follow-up.
Findings showed a clear pattern:
- Patients with vitamin D deficiency (<20 ng/mL) at cohort entry had the highest rates of mortality and cardiovascular events.
- Compared to those with baseline levels of 30–39 ng/mL, severely deficient patients had over twice the risk of death (HR 2.05).
- These patients also had nearly three times the risk of major cardiovascular events (HR 2.98).
- The link between low vitamin D and myocardial infarction alone was not statistically significant.
- However, the risk of angina or requiring coronary bypass surgery was significantly higher (HR 3.53).
In addition to the main prospective findings, the researchers conducted a lifetime analysis that included events occurring before participants joined the cohort. This broader look supported the same overall trend, with an interesting U-shaped relationship emerging for myocardial infarction risk — a pattern the investigators noted had also appeared in their earlier work on pregnancy outcomes in SLE.
Notably, mean vitamin D levels over the last year and the most recent single measurement did not show a significant association with outcomes. This raises important questions about whether vitamin D supplementation, often initiated after deficiency is detected, is sufficient to modify long-term cardiovascular or mortality risk. According to the authors, the results highlight that baseline vitamin D status — potentially reflecting cumulative deficiency over years — may be more influential than short-term improvements following supplementation.
The study adds to growing evidence that cardiovascular disease continues to be a major concern in lupus care, and it highlights the potential role of vitamin D as a marker of risk. While the findings do not establish causation or confirm that correcting vitamin D deficiency can change outcomes, they point to the value of routine monitoring and early intervention.
"As clinicians continue to search for modifiable factors that could improve long-term prognosis in lupus, these results suggest that attention to vitamin D levels at the time of diagnosis or early in disease management may be particularly important," the authors concluded.
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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