Parental Stroke Associated With 3-Fold Increased Risk for Stroke in Offspring

Emma Hitt, PhD

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Learn more March 31, 2010 — Parental stroke before the age of 65 years is associated with a 3-fold increased risk for stroke in offspring, according to new data from the Framingham Heart Study.

These findings suggest that "a reliable family history can serve as a 'poor man's genetic risk score' providing a simple, aggregate estimate of an individual's genetic risk," lead author Seshadri Sudha Seshadri, MD, with Boston University in Massachusetts, told Medscape Neurology.

The results are published in the March 23 issue of Circulation.

Inconsistent Results

According to the researchers, previous study results suggest that stroke risk ranges from a "doubling of risk in the offspring to no observed impact of parental history of stroke."

To further investigate the issue, Dr. Seshadri and colleagues used data from the Framingham study offspring cohort. The analysis included 3443 offspring of the original Framingham cohort who had not had a stroke at baseline and who had parental stroke status verified by the age of 65 years. All offspring attended required examinations and were followed up for up to 8 years.

A total of 106 parental strokes were documented by the age of 65 years, and 128 strokes were documented in the offspring. Of the strokes, 74 and 106 among the parents and offspring, respectively, were ischemic.

On multivariate analysis and after adjusting for conventional stroke risk factors, parental stroke was associated with an increased risk for incident stroke of the same type (hazard ratio [HR], 2.79; 95% confidence interval [CI], 1.68 – 4.66; P < .001) and for ischemic stroke (HR, 3.15; 95% CI, 1.69 – 5.88; P < .001).

Similar findings were observed in the offspring regardless of parental sex.

According to Dr. Seshadri, physicians should recognize that if one or both of a person's parents had a stroke before they turned 65 years old, their stroke risk is 3 times that of others.
"She or he should make it a point to check for and address modifiable risk factors, such as a higher blood pressure, smoking, and low levels of physical activity," she said.

Dr. Seshadri noted that more studies are required to understand which specific genes underlie stroke risk. "Framingham and collaborating studies identified 1 gene called NINJ2, and the findings were published in April 2009 in an article in the New England Journal of Medicine, but there is a lot more that needs to be done," she said (N Engl J Med. 2009;360:1718-1728).

Environment vs Genes

Ralph L. Sacco, MD, with the University of Miami, Miller School of Medicine, in Florida and president-elect of the American Heart Association, noted that prior studies have been inconsistent in documenting the importance of family history of stroke as a risk factor for stroke.

“Although there are many environmental determinants of stroke, such as smoking, physical inactivity, and diet, we also know that various factors are under genetic as well as environmental control, such as hypertension, diabetes, high cholesterol, and obesity,” he said. “The beauty of the Framingham Study is the long term in-person observation across multiple generations of family members,” he added.

According to Dr. Sacco, researchers continue to identify new genetic markers that may provide better clues to the specific genetic factors that increase risk. “This may also help in the discovery of new mechanisms that cause stroke and provide insights into new treatments,” he said.

The study was not commercially funded. Dr. Seshadri and Dr. Sacco have disclosed no relevant financial relationships.

Circulation. 2010;121:1304-1312.