Several Factors Linked to Subsequent Events After TIA, Minor Stroke

A number of factors related to demographics, medical history, and an index TIA or minor stroke foretell a greater risk of a subsequent stroke and may be used to identify patients who require closer follow-up over the long term, a systematic review and meta-analysis shows.

While there weren’t any unexpected factors associated with long-term stroke risk, a novel aspect of the analysis, led by Faizan Khan, PhD (University of Calgary, Canada), was the estimation of population attributable fractions (PAFs) to highlight those that were most impactful.

Having a minor stroke rather than a TIA as the index event was the most important nonmodifiable factor associated with subsequent stroke, with a PAF of 28.0%. Key modifiable factors included hypertension, smoking, and three stroke subtypes—those caused by cardioembolism, large-artery atherosclerosis, and small-vessel disease (PAFs 11.1% to 19.3%).

“There’s a limited capacity to follow or closely monitor all patients with TIA or minor stroke,” Khan told TCTMD. “So given the knowledge that these patients have a high long-term stroke risk, I think our findings can really help identify and narrow down on patients who really could benefit from aggressive stroke prevention measures and . . . that can help allocate scarce healthcare resources to those who would benefit the most.”

He added that knowing which factors have the highest PAFs can help guide interventions to lower risk of future events.

Relevant for Population Health

This new study, published online last week in Circulation, follows on another from this research group released last year, showing that risk of a subsequent stroke continues to accrue after a minor stroke or TIA over at least 10 years of follow-up.

“Not all patients with TIA or minor stroke will have an enduring stroke risk that will necessitate ongoing risk-reduction measures,” Khan said, adding that there may be subsets of patients who have an especially high risk that could benefit from closer monitoring and more aggressive secondary prevention efforts.

The current systematic review and meta-analysis was designed to reveal the factors that might be used to define such high-risk groups. The researchers examined data from 28 cohort studies with a total of 86,810 patients with TIA or minor stroke (NIHSS score ≤ 5) followed for at least 1 year. Median patient age was 69 years, and the median percentage of male participants was 57%.

There’s a limited capacity to follow or closely monitor all patients with TIA or minor stroke. Faizan Khan

Numerous demographic factors and aspects of medical history were associated with long-term risk of stroke with a high certainty of evidence. Older patients (adjusted HR 1.04 per year; 95% CI 1.02-1.05) and men (adjusted HR 1.25; 95% CI 1.15-1.36) were more likely to have a subsequent event. In addition, smokers and those with atrial fibrillation, diabetes, hypertension, ischemic heart disease, and a history of stroke/TIA before the index event were at greater risk (adjusted HRs 1.29 to 1.70).

Moreover, several variables assessed around the time of the index event were prognostic of a future stroke: ABCD² score ≥ 4, acute infarct on neuroimaging, diffusion-weighted imaging (DWI)-positive lesions, minor stroke as the index event, aphasia or dysarthria, paresis, and stroke caused by cardioembolism, large-artery atherosclerosis, or small-vessel disease (adjusted HRs 1.45 to 2.19).

When considering all these factors, PAFs ranged from a low of 3.8% for atrial fibrillation to a high of 28.0% for having a minor stroke versus a TIA as the index event.

Overall, “there were no surprises in the factors that came out to be predictive,” Khan said, noting, however, that the inclusion of PAFs in the analysis “has relevance from a population health or population impact perspective.”

Correct Index Diagnosis Important

That having a minor stroke was associated with such a large PAF indicates that “it’s really important to make the correct diagnosis when you’re evaluating these patients,” Khan said. “It’s important to be thorough and rule out any sort of stroke mimics because identification of a minor stroke, which is having a visible infarct on brain imaging, will dictate . . . how aggressive you will be in your secondary stroke prevention measures.”

Senior author Michael Hill, MD (University of Calgary), underscored the fact that in many parts of the world, stroke patients are not typically followed by a stroke specialist over the long term. Factors assessed around the time of the index event may help determine who gets closer follow-up moving forward, with higher-risk patients getting the most attention, he suggested.

From that perspective, quantifying a patient’s risk using the PAF information, rather than simply recognizing that they are at higher risk, is useful, he indicated.

“People don’t think about the quantitative aspects of risk. They think about qualitative things—hypertension’s bad, high cholesterol’s bad, diabetes is bad, but by how much?” Hill said, adding that the PAF information in the current study, though nuanced, “provides a real addition to the literature.”