A large new population
study of men over 45 indicates insulin resistance may be an important risk
factor for the development of the world’s most common heart valve disease –
aortic stenosis (AS).
Published in the peer-reviewed journal Annals of Medicine, the findings are believed to be the first to highlight this previously
unrecognized risk factor for the disease.
It is hoped that by demonstrating this
link between AS and insulin resistance – when cells fail to respond effectively
to insulin and the body makes more than necessary to maintain normal glucose
levels – new avenues for the prevention of the disease could open.
Aortic stenosis is a debilitating heart
condition. It causes a narrowing of the aortic valve, restricting blood flow
out of the heart. Over time, the valve thickens and stiffens, making the heart
work harder to pump blood effectively around the body. If not addressed, this
can gradually cause damage that can lead to life-threatening complications,
such as heart failure.
People living with AS can take years to
develop symptoms, which include chest pain, tiredness, shortness of breath and
heart palpitations. Some may never experience symptoms, but may still be at
risk of heart failure and death. Previously identified risk factors for AS
include age, male sex, high blood pressure, smoking and diabetes.
Insulin resistance, which often develops
years before the onset of type 2 diabetes, occurs when cells fail to respond
effectively to insulin, the hormone responsible for regulating blood glucose
levels. In response, the body makes more insulin to maintain normal glucose
levels – leading to elevated blood insulin levels
(hyperinsulinemia).
In the current study, researchers
analysed data from 10,144 Finnish men aged 45 to 73 years old, all initially
free of AS, participating in the Metabolic Syndrome in Men (METSIM) Study. At
the start of the study, the researchers measured several biomarkers, including
those related to hyperinsulinemia and/or insulin resistance. After an average
follow-up period of 10.8 years, 116 men (1.1%) were diagnosed with AS.
The team identified several biomarkers
related to insulin resistance – such as fasting insulin, insulin at 30 minutes
and 120 minutes, proinsulin, and serum C-peptide – that were associated with
increased AS risk. These biomarkers remained significant predictors of AS, even
after adjusting for other known risk factors, such as body mass index (BMI) and
high blood pressure, or excluding participants with diabetes or an aortic valve
malformation.
The researchers then used advanced
statistical techniques to isolate key biomarker profiles, identifying two
distinct patterns that indicate insulin resistance as a predictor of AS,
independent of other cardiovascular risk factors, such as age, blood pressure,
diabetes, and obesity.
“This novel finding highlights that
insulin resistance may be a significant and modifiable risk factor for AS,”
says lead author Dr Johanna Kuusisto, from the Kuopio University Hospital, in
Finland.
“As insulin resistance is common in
Western populations, managing metabolic health could be a new approach to
reduce the risk of AS and improve cardiovascular health in aging populations.
Future studies are now warranted to determine whether improving insulin
sensitivity through measures such as weight control and exercise can help
prevent the condition.”
The major strengths of this study
include its large population-based cohort and long follow-up period. However,
its limitations include the sole focus on male subjects and the relatively
small number of AS cases, which may limit the generalizability of the findings
to other populations.
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