Study finds that healthy lifestyle can offset genetic risk

Study finds that healthy lifestyle can offset genetic risk

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Even people with a high genetic risk for stroke may be able to offset it by adopting a healthy lifestyle, a new study says, Image credit: Specker/Vedfelt/Getty Images.
  • Researchers investigated how cardiovascular health interacts with a high genetic risk for stroke.
  • They found that optimal cardiovascular health reduces the lifetime risk of stroke among those with a high genetic risk.
  • Basic lifestyle interventions, such as following a healthy diet, exercising, and not smoking cigarettes, partially offset this risk.

Stroke is the second leading cause of death worldwide and a major cause of disability and dementia. In the United States, adults aged 25 and over have a lifetime risk of stroke of around 24{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809}.

Both genetic and environmental factors influence stroke risk. Managing cardiometabolic risk factors and promoting healthy lifestyle behavior are frontline strategies for improving cardiovascular health and decreasing stroke risk.

Recent genome-wide association studies have identified multiple risk variants for stroke and have enabled the development of genetic risk scores that predict stroke incidence.

It has been unclear whether improving cardiovascular health may offset the genetic risk for stroke.

Recently, however, researchers found that maintaining optimal cardiovascular health can partially offset a high genetic risk for stroke, reducing a person’s overall lifetime stroke risk.

The study appears in the Journal of the American Heart Association.

“The public message is clear,” Dr. Tatjana Rundek, professor of neurology and public health sciences at the University of Miami, not involved in the study, told Medical News Today.

“Regardless of the potential of harboring ‘bad’ genetic risk, improving cardiovascular health should be the most important priority for public health. Promoting ideal cardiovascular health should start at an early age, and many of us believe that we should start with a healthy diet and exercise at birth,” she noted.

For the study, the researchers analyzed data from 11,568 middle-aged adults who were stroke-free at baseline, and followed them for an average of 28 years.

Their lifetime risk of stroke was estimated from levels of genetic risk based on a validated stroke polygenic risk score and levels of cardiovascular health according to the American Heart Association’s “Life’s Simple 7,” which are now revised and updated to “Life’s Essential 8.”

The initial “Life’s Simple 7” recommendations are:

  • cholesterol control
  • blood pressure control
  • blood glucose control
  • physical activity
  • healthy diet
  • no smoking
  • maintaining a healthy body mass index (BMI).

Participants were assessed for “Life’s Simple 7” at the start of the study from a mix of self-reported and clinically-assessed measures.

Over the follow-up period, 1,138 participants were diagnosed with stroke. Of these, 14{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} had a low genetic risk, 41.7{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} had an intermediate genetic risk, and 44.3{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} a high genetic risk.

The researchers further noted that participants who scored low on “Life’s Simple 7” experienced 56.8{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of stroke events, whereas those with optimal “Life’s Simple 7” measures experienced 6.2{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of strokes.

Altogether, they found that participants with the highest genetic risk and lowest “Life’s Simple 7” scores had the highest lifetime risk of stroke at 24.8{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809}.

They further found that across all polygenic risk score categories, those with an optimal “Life’s Simple 7” score had a 30-43{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} lower lifetime risk of stroke than those with an inadequate “Life’s Simple 7” score.

This, they noted, corresponded to 6 additional years of stroke-free life in those with the highest genetic risk.

Prof. Lu Qi, distinguished chair and professor in the Department of Epidemiology at Tulane University School of Public Health and Tropical Medicine, not involved in the study, told MNT:

“‘Life’s Simple 7’ [has] been related to lower genetic risks of cardiovascular diseases including stroke in previous studies. It is not surprising the optimal ‘Life’s Simple 7’ score is associated with a lower genetic variation associated stroke risk.”

When asked how “Life’s Simple 7” might reduce genetic stroke risk.

Prof. Rundek said that “[t]he exact mechanism by which the combined risk/ lifestyle factors and genetic factors affect the risk for stroke is unknown and likely complex.”

“One way of explaining how ideal cardiovascular health — ‘Life’s Simple 7’ — can reduce genetic stroke risk is to think about genetic susceptibility to stroke risk in the presence of deleterious ‘Life’s Simple 7’ factors, because certain genes could be expressed only when activated by the presence of environmental factors or poor ‘Life’s Simple 7’ [scores for] cardiovascular health,” she noted.

“If we reduce these environmental factors and achieve ideal ‘Life’s Simple 7’ cardiovascular health [score] — stroke risk genes that we potentially harbor — would not be expressed to do harm and contribute to increased stroke risk,” added Prof. Rundek.

The researchers concluded that maintaining optimal cardiovascular health can partially offset a high genetic risk for stroke.

When asked about the study’s limitations, Prof. Qi noted that as the study was observational in nature, it is “limited for causal inference.”

Prof. Christie M. Ballantyne, chief of Cardiology at Baylor University, also not involved in the study, further pointed out that:

“The data in African Americans was not robust, and other racial and ethnic groups, such as Hispanic, South Asian, and East Asian, were not well-represented in this study. Additional studies in other populations are needed to optimize the polygenic risk scores to be more useful in clinical practice for all of our patients.”

Prof. Rundek added that “[i]t may be hard to achieve and maintain ideal ‘Life’s Simple 7’ cardiovascular [score] if there is a strong individual genetic susceptibility to stroke risk [which includes] an increased risk of hypertension and other ‘Life’s Simple 7’ factors.”

“In addition, there are certain genetic markers — rare alleles — that are not included in polygenic risk scores as they contribute to risk by only a small amount. However, they may have a cumulative effect if present within an individual. […] How changes in ‘Life’s Simple 7’ factors over time affect genetic risk is also an interesting question. All of these would need to be carefully investigated in future studies,” she explained.

Genetic link between COVID-19 and Alzheimer’s identified

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A new study finds a genetic bridge between Alzheimer’s and COVID-19. Nor Hasen/EyeEm/Getty Images
  • In a new study, scientists have identified a genetic link between the development of Alzheimer’s and severe COVID-19 outcomes.
  • The study also identifies the same immune system changes in both diseases.
  • Targeting specific “risk” genes could lead to future treatments for Alzheimer’s disease and COVID-19.

Alzheimer’s disease is the most common form of dementia, a syndrome where cognitive function declines progressively over time.

According to the World Health Organization (WHO), over 55 million people live with dementia worldwide, and doctors diagnose 10 million new cases each year. Around 60–70{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809} of these are Alzheimer’s cases.

Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.

“While Alzheimer’s is primarily characterized by a harmful buildup of amyloid protein and tangles in the brain, there is also extensive inflammation in the brain that highlights the importance of the immune system in Alzheimer’s,” explains Dr. Dervis Salih.

Dr. Salih is a senior research associate in neurodegenerative disease at University College London (UCL).

In previous work by UCL, genetic studies revealed that different genes can alter the risk of developing Alzheimer’s disease. These “risk genes” change how microglia, or immune cells of the brain, respond to amyloid protein and tangles.

Scientists have focused on a subpopulation of microglia cells known as interferon response microglia (IRM), which increase with age and in response to amyloid proteins.

IRM cells respond to interferon proteins that the body releases to fight viral infections, such as SARS-CoV-2.

According to Dr. Rosa Sancho, head of research at Alzheimer’s Research UK, “Fairy early in the pandemic, people with dementia emerged as a group at particular risk of severe COVID-19.”

The current findings, published in the journal Brain, build on previous work by Dr. Salih.

The new study, led by Naciye Magusali, a doctoral candidate at UCL, focused on the genotyping of 2,547 human DNA samples. Of these, 1,313 were from people with a diagnosis of Alzheimer’s disease, and 1,234 were from controls without Alzheimer’s.

The authors identified a variant of the interferon-stimulated gene oligoadenylate synthetase 1 (OAS1) that can increase the risk of developing Alzheimer’s disease by an estimated 11–22{cfdf3f5372635aeb15fd3e2aecc7cb5d7150695e02bd72e0a44f1581164ad809}.

Scientists have also shown that OAS1, which regulates inflammatory proteins, contributes to the genetic risk associated with severe COVID-19 outcomes.

According to the current study, cells treated to mimic the effects of COVID-19 showed a lower expression of OAS1.

Dr. Salih explains: “The variant in OAS1 associated with disease is lowering OAS1 expression. This supports the idea that people with lower levels of OAS1 are more likely to show a chronic cytokine response or ‘cytokine storm.’”

The work shows that the body needs OAS1 to reduce the amount of inflammation-causing proteins. According to Dr. Salih:

“We see in […] microglial cells that OAS1 is suppressing pro-inflammatory function of cells in response to elevated levels of interferon.”

These findings show the importance of inflammation in both the progression of Alzheimer’s disease and the severity of COVID-19.

Speaking about the new research, Dr. Sancho points out that “[w]e don’t know whether the effects of this risk gene could influence long-term neurological consequences of COVID-19 or whether COVID-19 […] increases the risk of dementia later in life.”

Dr. David Strain, a senior clinical lecturer at the University of Exeter in the United Kingdom, comments: “It does add important information as to the pathogenesis of the more severe presentations of COVID-19 and will hopefully be able to shed further light on potential treatment options or even personalized preventive medicine.”

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