Low Vitamin D Linked to More Severe Stroke, Poor Outcomes

Susan Jeffrey

February 13, 2015

NASHVILLE, TENNESSEE — Low vitamin D levels are associated with larger brain infarct volume and worse outcomes in patients with ischemic stroke, a new study shows.

Researchers found that patients with vitamin D levels below 30 ng/mL had infarcts two-fold larger than those with higher levels and had a higher risk for functional dependence at 3 months.

These findings, if replicated in further studies, "provide the impetus for yet other studies to come where you could think of scenarios where you have cases who have a very high risk for developing stroke that you might then select for supplementation," lead author Nils Henninger, MD, senior study author and assistant professor of neurology and psychiatry at University of Massachusetts Medical School in Worcester, concluded.

The new findings were presented here at the International Stroke Conference (ISC) 2015.

Role in Brain Health?

Population-based studies have shown a link between low vitamin D and stroke. Vitamin D affects stroke risk factors, such as hypertension and diabetes, which can in turn increase stroke risk, or cause the stroke to be more severe, Dr Henninger noted. "Recently there has been some data coming out that vitamin D somehow directly affects the stroke risk and the outcome of the stroke," he said.

How vitamin D could affect stroke severity isn't clear, "but understanding this I think is important because it may provide the rationale to use vitamin D supplementation to reduce stroke risk in select patients," he said. Previous studies of vitamin D supplementation have not been successful, suggesting that patient selection may be key.

In this study, the researchers investigated whether there is a link between low vitamin D levels, measured by 25(OH)D concentration, and subsequent infarct volume, or whether it relates to functional outcome at 3 months after the stroke.

Other questions included whether any effect of vitamin D levels differed between stroke subtypes, and whether the time of vitamin D measurement might affect that relationship.

They retrospectively analyzed consecutive patients with acute ischemic stroke that were evaluated from January 2013 to January 2014 at their tertiary referral center. All patients (n = 96) had MRI-proven acute ischemic stroke; the median age was 73 years, and 45% of patients were women. Vitamin D levels were drawn within 12 months of stroke.

Demographic factors associated with normal vitamin D levels, defined as greater than 30 ng/mL among these patients, were older age, having had an embolic stroke, having atrial fibrillation, and no tobacco use or alcohol abuse.

Multivariable linear and logistic regression analyses were used to test whether vitamin D is an independent predictor of infarct volume and poor 90-day outcome (modified Rankin Scale [mRS] score >2).

They found that patients with a low vitamin D level had twice the infarct volume of those with normal levels, about 17 vs 8 mL (P = .01). The relationship was similar by stroke subtype, with a significant association for lacunar strokes (P = .001) but a nonsignificant trend for nonlacunar strokes (P = .072).

The relationship between vitamin D and infarct size was most significant among patients who had their levels measured within 2 weeks of the stroke, showing a 4-fold increase in diffusion-weighted lesion volume for those with low vitamin D vs those with normal levels (P = .05). When the levels were measured more remotely, more than 2 weeks before the stroke, no significant relationship was found between vitamin D levels and infarct volume.

Finally, patients with low serum concentrations of 25(OH)D were more likely to have a mRS score greater than 2, indicating at least some functional dependence. The risk for poor 90-day outcome increased almost two-fold for every 10-ng/mL decrease in vitamin D, he noted.

Risk for Poor 90-Day Outcome After Stroke

Variable Odds Ratio (95% Confidence Interval) P Value
Vitamin D status (per 10 ng/mL) 2.11 (1.00 - 4.42) .048


The study has some limitations, he noted. They cannot, for example, determine causality. "Is vitamin D really the culprit, causing all the effects we noticed or maybe it's an innocent bystander, a sentinel, maybe even a biomarker of global health status," Dr Henninger said.

In addition, the study was small, and because it was a retrospective analysis, vitamin D was measured at the discretion of the treating physician. Further, the researchers have few data on lifestyle factors among these patients.

"Though causality remains to be proven, our results highlight the need to further explore vitamin D as a promising biomarker for cerebral ischemic vulnerability and potential target for stroke prevention," the authors conclude.

Although it is too early to advocate vitamin D supplementation for stroke prevention, there are reasons to measure levels and, if they are low, to consider supplementation, including bone health, Dr Henninger said. He does this in his own practice. "However, what I don't want to advocate is just unjudicious supplementation. It is in fact possible to have too high levels, which become toxic, so more is not always better."

Intuitive Sense

Jose Biller, MD, professor and chair of neurology at the Loyola University Chicago Stritch School of Medicine, Illinois, moderated a press conference here where these results were presented.

"Prior studies have shown that low vitamin D levels increase cardiovascular risk," Dr Biller told Medscape Medical News.

"Actually, low vitamin D levels have been reported to double the risk of stroke (in women)," he noted. "Moreover, low vitamin D levels have been associated with an increased risk of poststroke hip fractures."

More recently, low vitamin D levels in children have been associated with subclinical atherosclerosis in adults. "A priori, it makes intuitive sense to maintain adequate vitamin D levels in these patients," he concluded.

The study received no outside funding. The authors have disclosed no relevant financial relationships.

International Stroke Conference (ISC) 2015. Abstract W MP62. Presented February 11, 2015.


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