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Genetics and Lifestyle Additive for Cardiovascular Risk

Sue Hughes

July 02, 2018

A poor genetic cardiovascular risk profile and poor lifestyle behaviors are additive in terms of risk for future cardiovascular
events, a new study suggests.

"If you have both poor genes and a bad lifestyle you have double trouble," senior author, Pim van der Harst, MD, University
of Groningen, the Netherlands, commented to Medscape Medical News.

The study was published online in JAMA Cardiology on June 27.

"We know genes play a role in cardiovascular risk and we also know lifestyle has an effect, but we didn't know how these
two things affected each other," van der Harst explained.

"Until now, genetics have generally been left out of lifestyle studies on cardiovascular risk," he added. "We wanted to look at
whether lifestyle changes will help people with a poor genetic profile or if are they just out of luck. And if you have good
genes can you engage in poor behaviour and still live happily ever after."

What they found was that good lifestyles lower risk in all genetic risk categories to about the same relative extent, he said.
An ideal lifestyle approximately halves the risk for atrial fibrillation (AF), hypertension, and stroke across all genetic risk
categories.

"However, in absolute terms, this will be of more benefit to those at highest genetic risk," he said. "If you have an absolute
risk of 10 in 100 and improving lifestyle reduced this by 30%, then your risk falls to 7 in 100, which is a meaningful
improvement.

"But if you start with an absolute risk of only 1 in 100, then reducing this by 30% gives you a risk of 0.7 in 100, which is not
that much different. So we will spend money most effectively by concentrating our resources on high-risk patients."

UK Biobank Cohort Study

For the study, the researchers analyzed data on 339,003 unrelated white individuals of British descent aged 40 to 70 years
from the UK Biobank cohort study. All participants had genotype and matching genetic data, which were used to calculate a
polygenic risk score. They had also provided information on lifestyle and other potentially health-related aspects through
extensive baseline questionnaires, interviews, and physical measurements.

American Heart Association criteria for definitions of healthy lifestyle behaviors were used. Overall lifestyle was
subsequently categorized into ideal (having at least three ideal lifestyle factors), poor (having at least three poor lifestyle
factors), or intermediate (all other combinations).

Genetic risk was categorized as low (quintile 1), intermediate (quintiles 2 to 4), or high (quintile 5). Within each genetic risk
group, the risks for incident events associated with ideal, intermediate, or poor combined health behaviors and factors were
investigated and compared with risks of low genetic risk and ideal lifestyle.

During the 6-year follow-up, 3.0% of the cohort developed coronary artery disease, 2.1% developed atrial fibrillation, 0.9%
developed stroke, 4.8% developed hypertension, and 1.4% developed diabetes.

Results showed that genetic risk and lifestyle were independent predictors of incident events, and there were no interactions
for any outcome.

The researchers note that the effects of lifestyle on disease development were the strongest for diabetes. And while ideal
lifestyle reduced the risk for incident diabetes in all genetic risk groups, poor lifestyle was associated with a 15-fold higher
risk in the high genetic risk group.

Compared with ideal lifestyle in the low genetic risk group, poor lifestyle was associated with a hazard ratio of up to 4.54 for
coronary artery disease, 5.41 for AF, 4.68 for hypertension, 2.26 for stroke, and 15.46 for diabetes in the high genetic risk
group.

"There have always been people who have smoked all their life and were fine and people refer to them and think they will
also be okay," van der Harst commented. "But our results show that even if your genetic risk is very low, your bad lifestyle
can still have a detrimental effect."

For example, he notes, if someone has a low genetic risk for AF and a poor lifestyle, then their risk for AF is about the same
as having a high genetic risk and an ideal lifestyle.
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Targeting High Genetic Risk

van der Harst noted that while the relative reduction in risk associated with healthy lifestyle is similar across all genetic risk
groups, those at high genetic risk derive a greater absolute benefit. "They have more to gain so they should be targeted for
lifestyle intervention first."

"Our results suggest that when we are doing risk prediction we need to be aware of both genetic and lifestyle risk," he
added. "We are moving towards personalized risk assessment. I believe in the future everyone will have genetic tests and
we then then target interventions toward the highest risk.

He envisions people having a "genetic passport" and will be able to program in the effect of certain lifestyle changes to see
how this affects their risk of cardiovascular disease. "That would be very motivational, and would help with shared decision
making on lifestyle and medication choices."

"I think it is fair to tell people that if they have high genetic risk then they need to take extra care in terms of lifestyle," he
said. "People often copy their peers in lifestyle behavior, but if a teenager knows he is at a high genetic cardiovascular risk
and that not smoking can bring that down in a meaningful way, then that is a powerful reason for him to resist following his
peers on this behavior.

"We need to single out those at high risk and emphasize the harms of unhealthy lifestyle behaviors, especially to them,
while at the same time keep up the message that a healthy lifestyle is good for all," he concluded.

Individual coauthors were supported by grants from the Marie Sklodowska-Curie Individual Fellowship and the Netherlands
Organisation for Scientific Research. The authors have disclosed no relevant financial relationships.

JAMA Cardiol. Published online June 27, 2018. Abstract.

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Cite this article: Genetics and Lifestyle Additive for Cardiovascular Risk - Medscape - Jul 02, 2018.

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