The most common heart valve disease in the world

A new, large population-based study of men over 45 years of age indicates that insulin resistance may be an important risk factor for the development of the world’s most common heart valve disease – aortic stenosis (AS).

Published today in a peer-reviewed journal Annals of medicineThese findings are believed to be the first to highlight this previously unrecognized risk factor for the disease.

It is hoped that demonstrating the link between AS and insulin resistance – when cells do not respond effectively to insulin and the body produces more than necessary to maintain normal glucose levels – will open up new possibilities for preventing the disease.

Aortic stenosis is a devastating heart disease. It causes the aortic valve to narrow, restricting blood flow from the heart. Over time, the valve thickens and stiffens, causing the heart to work harder to effectively pump blood throughout the body. If this problem is not addressed, it can gradually cause damage that can lead to life-threatening complications such as heart failure.

Symptoms, which include chest pain, fatigue, shortness of breath and heart palpitations, can take years for AS sufferers to overcome. 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 gender, high blood pressure, smoking and diabetes.

Insulin resistance, which often develops many years before the onset of type 2 diabetes, occurs when cells do not respond effectively to insulin, the hormone responsible for regulating blood glucose levels. In response, the body produces more insulin to maintain normal glucose levels, leading to elevated levels of insulin in the blood (hyperinsulinemia).

In the current study, researchers analyzed data from 10,144 Finnish men aged 45 to 73 years, all initially free of AS, participating in the Metabolic Syndrome in Men (METSIM) study. At the beginning of the study, the researchers measured several biomarkers, including those associated with hyperinsulinemia and/or insulin resistance. After a mean follow-up of 10.8 years, 116 men (1.1%) were diagnosed with AS.

The team identified several biomarkers associated with insulin resistance – such as fasting insulin, 30- and 120-minute insulin, proinsulin and serum C-peptide – that were associated with an increased risk of AS. 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 aortic valve disease.

The researchers then used advanced statistical techniques to isolate key biomarker profiles, identifying two distinct patterns indicating 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 of Kuopio University Hospital in Finland.

“Because insulin resistance is common in Western populations, managing metabolic health may represent a new approach to reducing AS risk and improving cardiovascular health in aging populations. “Future research is now warranted to determine whether improving insulin sensitivity through measures such as weight control and exercise may help prevent this disease.”

The main advantages of this study include the large population cohort and long follow-up period. However, its limitations include its exclusive focus on men and the relatively small number of AS cases, which may limit the generalizability of the results to other populations.

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