Age Differences in Aortic Stenosis

Aortic stenosis (AS) is a significant and growing concern, with a prevalence of 2-3% in individuals aged over 65 years. Moreover, with an aging global population, the prevalence is anticipated to double by 2050. Indeed, AS can arise from various etiologies, including calcific trileaflets, congenital valve abnormalities (e.g., bicuspid and unicuspid valves), and post-rheumatic, whereby each has a distinct influence that shapes the onset and progression of the disease. The normal aortic valve has a trilaminar structure comprising the fibrosa, spongiosa, and ventricularis, which work together to maintain its function. In calcific AS, the disease begins with early calcification starting in high mechanical stress areas of the valve and progresses slowly over decades, eventually leading to extensive calcification resulting in impaired valve function. This process involves mechanisms similar to atherosclerosis, including lipid deposition, chronic inflammation, and mineralization. The progression of calcific AS is strongly associated with aging, with additional risk factors including male gender, smoking, dyslipidemia, and metabolic syndrome exacerbating the condition. Conversely, congenital forms of AS, such as bicuspid and unicuspid aortic valves, result in an earlier disease onset, typically 10-20 years earlier than that observed in patients with a normal tricuspid aortic valve. Rheumatic AS, although less common in developed countries due to effective antibiotic treatments, also exhibits age-related characteristics, with an earlier onset in individuals who experienced rheumatic fever in their youth. The only curative therapies currently available are surgical and transcatheter aortic valve replacement (TAVR). However, these options are sometimes too invasive for older patients; thus, management of AS, particularly in older patients, requires a comprehensive approach that considers age, disease severity, comorbidities, frailty, and each patient's individual needs. Although the valves used in TAVR demonstrate promising midterm durability, long-term data are still required, especially when used in younger individuals, usually with low surgical risk. Moreover, understanding the causes and mechanisms of structural valve deterioration is crucial for appropriate treatment selections, including valve selection and pharmacological therapy, since this knowledge is essential for optimizing the lifelong management of AS.