People with a genetic predisposition for more abdominal fat may be at a greater risk of having a stroke, a study found.
However, the researchers also report that increased blood sugar levels, considered a risk factor for the development of stroke, appear not to influence its occurrence.
Their study, “Mendelian randomization study of obesity and cerebrovascular disease,” was published in the journal Annals of Neurology.
Obesity is a well-recognized risk factor for stroke, which occurs when the blood supply to part of the brain is interrupted or reduced. However, it remains to be understood how obesity affects the molecular processes of stroke — meaning whether or not excess weight is the actual cause of the condition.
Genome-wide association studies (GWAS) enable researchers to search all genes in an individual’s cells for small variations that occur more frequently in people with a particular disease. Scientists then use these data to pinpoint genes that may contribute to the risk of developing a certain disorder.
Using updated GWAS data for body fat distribution, obesity, and stroke, investigators at the Massachusetts General Hospital and their collaborators assessed how different cerebrovascular disease subtypes are affected by obesity traits. The team also sought to clarify which obesity parameter — waist-to-hip ratio (WHR) or body mass index (BMI) — best explains any increase in the risk of stroke.
The researchers further assessed the contribution of systolic blood pressure and blood glucose levels — both previously identified as possible mediators of obesity. Systolic blood pressure, the first number in the typical measurement, indicates how much pressure the blood is exerting against the artery walls when the heart beats.
The results revealed that genetic predisposition to higher BMI did not increase the risk of cerebrovascular disease. According to the team, not taking into account factors such as muscle mass and fat distribution may make BMI “a relatively poor biological tool for examination of causal pathways in disease.”
The risk for large artery ischemic stroke — a blood clot blocking a blood vessel in the brain — increased by 75% for each 10% increase in WHR, which is a measurement of waist circumference divided by hip circumference. Likewise, a similar increase in WHR was associated with a 57% greater risk for small vessel ischemic stroke and a 197% increase in the likelihood of having intracerebral hemorrhage.
Increased WHR also led to greater changes in white matter, which is made of nerve fibers.
Adjusting for genetic determinants of BMI did not alter these results, the researchers found.
Nearly 10% of the effect of WHR on ischemic stroke was mediated by systolic blood pressure. In contrast, blood sugar levels did not alter the risk of having ischemic stroke.
“Abdominal adiposity may trigger causal pathological processes, partially independent from blood pressure and totally independent from glucose levels, that lead to cerebrovascular disease,” the scientists said.
“Potential targets of these pathological processes could represent novel therapeutic opportunities for stroke,” they added.
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