Even small cerebrovascular lesions may up increased risk of stroke and death

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - In middle-aged and older black and white adults, small lesions that are typically ignored may actually indicate increased risk of stroke and death, according to new research.

Lesions smaller than 3 mm only, lesions 3 mm or larger only, and white matter hyperintensities may be associated with heightened risk for stroke and death, the study authors reported online July 7 in Annals of Internal Medicine.

Lesions smaller than 3 mm occurring along with those 3 mm or larger carry a particularly striking risk increase, they wrote.

"In prior work, we and others have shown that cerebral small vessel disease is associated with an increased risk of stroke, dementia, and mortality. This study extends prior observations to show that even very small subclinical lesions that would typically be considered incidental and benign, in fact, confer increased risk of poor clinical outcomes," principal investigator Dr. Thomas H. Mosley Jr., professor of geriatrics, gerontology, and neurology at the University of Mississippi Medical Center in Jackson, told Reuters Health by email.

"While we do not fully understand the underlying pathology of these lesions, it appears that they may warrant clinical consideration, perhaps taken into consideration along with one's broader risk factor profile," he said.

"I was not surprised to see that the small lesions were predictive of poor outcomes, but I was surprised by the relative contribution of small compared to larger lesions, particularly with respect to stroke risk, where the small lesions yielded the largest associations," he added.

Dr. Mosley and colleagues used magnetic resonance imaging (MRI) data from 1993 to 1995 to compare the stroke risks associated with subclinical brain lesions smaller than 3 mm only with lesions 3 mm or larger only and with lesions of both sizes occurring together, as well the presence of white matter hyperintensities (WMHs), in a community cohort from the ARIC study.

They examined the data from 1,884 adults between 50 and 73 who underwent MRI, had no prior stroke, and had an average follow-up of 14.5 years.

They evaluated lesions seen on MRI according to size, WMH score (on a scale of 0 to 9), incident stroke, all-cause mortality, and stroke-related mortality, and they estimated hazard ratios with proportional hazards models.

Compared with patients with no lesions, the risk of stroke in those with lesions smaller than 3 mm only tripled (hazard ratio 3.47); in patients with lesions 3 mm or larger only, the risk almost doubled (HR 1.94); and in those with lesions of both sizes, the risk increased more than eightfold (HR 8.59).

For patients with a WMH score of at least 3, the risk of stroke more than doubled (HR 2.14).

The presence of lesions that were all under 3 mm tripled the risk for stroke-related death (HR 3.05), and the presence of lesions of both sizes increased the risk for stroke-related death by almost seven times (HR 6.97).

The authors acknowledged that limitations to their study include the low number of strokes, especially hemorrhagic, and the low number of participants with lesions smaller than 3 mm only or with lesions of both sizes.

Dr. Robert Lada, medical director of neurosciences at Providence Alaska Medical Center in Anchorage, told Reuters Health by email, "This is an interesting study, the strength of which lies in how long the group was followed."

"MRIs in the 1990s used a 1.5-Tesla magnet. Neuroimaging now involves a 3.0-Tesla magnet, which identifies more lesions, potentially overestimating the risk. Further studies with current 3-Tesla imaging and with lower age groups would be interesting," he added

"That patients with smaller lesions were of greater risk for future stroke than those with larger lesions is not what most clinicians have been telling patients," added Dr. Lada, who was not involved in the study.

Dr. Lada questioned whether these findings might "apply to younger patients who demonstrate small nonspecific white matter changes. For example, patients diagnosed with migraines who are found to have 'nonspecific white matter changes' are frequently told that this is a normal finding, but now it potentially poses a risk for stroke."

"With the rapidly aging U.S. population, we can anticipate a large concomitant increase in neurologic diseases," Dr. Mosley said. "The discoveries from this and related work holds the promise of offering better targets for treatment. They may also help identify those at risk from an early age and provide better opportunities to intervene earlier in life, when treatments will have the best chance of being effective."

"Of course, the findings from our observational study will need to be replicated by others before the clinical implications are fully understood," he said.

The National Heart, Lung, and Blood Institute primarily funded this research through support of four coauthors.

SOURCE: http://bit.ly/1M6S75r

Ann Intern Med 2015.

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