Researchers have identified insulin resistance as an independent risk factor for aortic stenosis, according to a study published in the Annals of Medicine.
Investigators followed 10,144 Finnish men for nearly 11 years and found that multiple biomarkers reflecting insulin resistance were significantly associated with incident aortic stenosis (AS), even after adjusting for traditional cardiovascular risk factors like age, obesity, and hypertension.
The study documented 116 new cases of AS (1.1%) during the follow-up period. Subjects who developed AS showed significantly higher levels of fasting plasma insulin, proinsulin, and C-peptide, as well as elevated 30-minute and 120-minute post-glucose challenge insulin levels compared with those who did not develop AS. The Matsuda index, a measure of insulin sensitivity, showed a protective effect with a hazard ratio of 0.68.
Using principal component analysis, researchers identified three distinct clusters of risk factors. The insulin resistance component showed a hazard ratio of 1.37 (95% CI, 1.09-1.73) for developing AS, while a component reflecting age and blood pressure showed a hazard ratio of 1.77 (95% CI, 1.45-2.17). A third component comprising C-reactive protein and HbA1c showed no significant association with AS.
The association between insulin resistance markers and AS remained significant even after excluding patients with diabetes or those with congenitally malformed aortic valves, suggesting insulin resistance may be particularly important in the development of AS in patients with normal tricuspid valves. While diabetes increased AS risk, the study found that impaired fasting glucose and impaired glucose tolerance did not.
The study's lead author, Maija Sohlman, and colleagues from the University of Eastern Finland conducted their research as part of the Metabolic Syndrome in Men (METSIM) Study. The median age of participants who developed AS was 62 years.
Given the prevalence of insulin resistance in Western populations, the authors suggest that measures improving insulin sensitivity, such as weight control and exercise, might prove effective in AS prevention, though they note this requires further study.
Previous research has established various risk factors for AS, including age, male sex, elevated low-density lipoprotein cholesterol, lipoprotein(a), hypertension, smoking, and diabetes. This study is the first large-scale prospective investigation to demonstrate insulin resistance as an independent risk factor.
The study's strengths included its large population-based cohort, comprehensive baseline characterization of participants, and extensive biomarker analysis. The researchers noted limitations, including the inclusion of only male subjects and a relatively small number of incident AS cases.
The findings align with recent research showing that hyperinsulinemia can lead to activation and differentiation of valvular interstitial cells, potentially explaining the mechanistic link between insulin resistance and AS development.
Without intervention, severe AS carries a 70-80% risk of death within five years. Current treatment options are limited to aortic valve replacement, either through traditional open-heart surgery or transcatheter aortic valve replacement (TAVR).
No potential conflict of interest was reported by the authors.
