Harvard Health Letter

Does stroke risk begin with the stork?

Early life exposures, including those in the womb, may increase stroke risk later in life.

When we think about the risk factors for having a heart attack or stroke, the rogues' gallery includes poor eating habits, being overweight, having high blood pressure or elevated LDL cholesterol levels, and, of course, smoking. As adults, many of us fight the good fight against these risk factors in hopes of staving off cardiovascular calamity. Countless studies show that if we follow through, the efforts pay off, although obviously there are no guarantees. Unknown risk factors, and those that experts are less certain about, may have harmful effects, even as we dutifully work at minimizing the certified ones. And genetic predisposition can certainly trump even the most sterling health habits.

Also out of our control are all the exposures we experience in childhood — or even earlier, as developing fetuses in the womb. The notion of early-life exposures resulting in disease much later on is quite familiar. Was anyone really surprised by study results reported in 2009 that children exposed to secondhand smoke are more likely to develop lung cancer than those who aren't? But, as a rule, we don't think of tracing strokes (or heart attacks) back to when we were wee things or in utero. Yet there are some tantalizing clues that groundwork for our cardiovascular troubles is laid early in life and not simply a matter of adult behaviors and genetic inheritance. For example, Harvard researchers believe that early-life exposures of some kind may help explain one of the great riddles of American epidemiology, the Stroke Belt.

The Stroke Belt

Strokes occur when the blood supply to the brain is cut off by a clot in an artery or when an artery breaks open, so blood spills into the brain. Either way, it's serious business. Year after year, stroke comes after heart attack and cancer on the list of the leading causes of death in the United States.

In the southeastern part of the country, stroke cuts an even larger swath through the population. Residents of North Carolina, South Carolina, Georgia, Alabama, Mississippi, Arkansas, and Tennessee (Louisiana sometimes is included, too) are 20% to 50% more likely to die from a stroke than those who live elsewhere in the country. This Stroke Belt, as it has come to be called, has existed since at least the 1940s, and the excess mortality isn't confined to any one group: men, women, blacks, and whites from the region are more likely than other Americans to die from stroke.

Researchers have poked around in the data for decades, trying to tease out explanations for the geographic difference. Socioeconomic status, access to medical care, more people in those states having traditional stroke risk factors like high blood pressure or diabetes — none of these characteristics adequately explains the greater number of fatal strokes.

Several years ago, M. Maria Glymour, an assistant professor at the Harvard School of Public Health, started investigating whether the Stroke Belt mystery could be solved by looking at early-life exposures, not just snapshots of the risk profiles of adults. In a 2007 paper cleverly titled "Is the 'stroke belt' worn from childhood?" she and her colleagues found that people who lived in the Stroke Belt as children were 25% more likely to have a stroke in adulthood than those who had never lived there, and that their risk was actually a bit higher than people who lived in the region as both children and adults.

In 2009, Glymour reported findings from a follow-up study that used a larger database, which puts the statistics on a firmer footing. The gist of the results was similar. This time, though, people with "double exposure" — birth and adulthood in the Stroke Belt — had the highest stroke mortality rate. Still, people born in the Southeast who moved away seemed to lug the Stroke Belt risk with them, although the risk was greater for whites than for blacks. If you're interested in reading more about this study, we've posted some details on our Web site at www.health.harvard.edu/healthextra.

Low birthweight an explanation

The Stroke Belt isn't the only geographic "hot spot" for stroke mortality that can't be explained by differences in genes or lifestyle. British researchers have also found higher stroke mortality rates in certain parts of northern England and in Wales.

The question that comes to mind is perhaps the most important one: what exactly are the exposures early in life that might increase our stroke risk later on? British researchers have zeroed in on low birthweight, poverty, and poor maternal health and nutrition as likely suspects. It's possible that our circulatory systems are affected in subtle ways by what we ate as children, undocumented environmental exposures, even psychological stresses. In utero exposures may affect how blood vessels develop or change the inflammatory response in enduring ways, so strokes are more easily triggered and atherosclerotic plaque in arteries more abundant. There are any number of possibilities — and no firm answers.

This research into the prenatal and childhood origins of stroke doesn't mean we should give up on cardiovascular disease prevention in adults. Far from it. Depending on our childhoods, we may need to try even harder. But it is another reason to think of adult lifestyle changes as risk reducers and a way to improve the odds, not as efforts that will wipe the slate clean.