Børge G. Nordestgaard, MD, DMSc, on the Relationship Between Obesity and Aortic Valve Stenosis

Genetically increased body mass index (BMI) is causally associated with an increased risk of aortic valve stenosis, according to new research.¹

This conclusion comes after a research team from Denmark evaluated measurements of BMI, waist-hip ratio, and waist circumference, as well as data on 5 genetic variants associated with obesity among 108,211 participants in the Copenhagen General Population Study.

The research team was led by Børge G. Nordestgaard, MD, DMSc, who is chief physician in clinical biochemistry at Copenhagen University Hospital in Herlev, Denmark.

Cardiology Consultant reached out to Dr Nordestgaard for more insights on his team’s findings.

CARDIO CON: Can you tell us more about your study and how it came about?

Børge Nordestgaard: We knew that high BMI measurements were observationally associated with increased risk of aortic valve stenosis. We wondered whether this relationship was causal or whether obesity is only just a marker of disease risk. For this purpose, we examined 108,000 individuals from the Copenhagen General Population Study.

CARDIO CON: Specifically, you and your colleagues found that obesity from human genetics was causally associated with a higher risk of aortic valve stenosis and replacement. How might knowing a patient’s genetic predisposition affect clinical practice in the future? Do you think treatment options will become more personalized?

BN: We used the genetic predisposition for obesity as an aggregate instrument for measured BMI. Our genetic results indicate that the relationship between obesity and risk of aortic valve stenosis is causal. Thus, we can exclude reverse causation where aortic valve stenosis would cause people to gain weight. Knowing a single patient’s genetic predisposition to obesity is not yet of clinical importance; however, improved understanding of genetics that lead to obesity could hypothetically reveal new possible traits for personalized treatment.

CARDIO CON: What knowledge gaps still exist regarding causal risk factors for aortic valve stenosis?

BN: We are now interested in knowing the mechanisms between obesity and aortic valve stenosis. Could lipoproteins play a role? Also, it would be interesting to see studies investigating whether obesity is also associated with aortic valve stenosis progression or severity and not only incidence. 

CARDIO CON: What is the key take-home message from your study for cardiologists?

BN: This is yet another cardiovascular disease in which obesity plays an important causal role. Obesity itself can explain many of the symptoms seen in aortic valve stenosis, so it is important to exclude aortic valve stenosis as the reason for symptoms.

Reference:

1. Kaltoft M, Langsted A, Nordestgaard BG. Obesity as a causal risk factor for aortic valve stenosis. J Am Coll Cardiol. 2020;75(2): 163-176. https://doi.org/10.1016/j.jacc.2019.10.050.