Elevated biological age acceleration (BAA) may be a viable predictor of all-cause mortality in patients with moderate-to-severe aortic valve stenosis, emphasizing the need for early intervention in this patient population.

Xinxue Liao, MD, PhD, chief physician and professor in the Department of Cardiovascular Medicine at The First Affiliated Hospital at Sun Yat-Sen University in Guangzhou, China, and colleagues conducted a prospective cohort study that examined the link between BAA and all-cause mortality in patients with moderate-to-severe aortic valve stenosis. This study, according to the researchers, is the first to investigate the correlation between elevated BAA and greater all-cause mortality in this patient population.

The study findings appeared in The Journal of the American College of Cardiology-Asia.

Compared with mild aortic valve stenosis, moderate and severe aortic valve stenosis showed significantly worse clinical outcomes and a higher risk for mortality, the study team explained. Previous research revealed extremely high 5-year mortality rates of 56% and 67% for moderate and severe aortic valve stenosis cases, respectively.

For cardiometabolic multimorbidity, stroke, and all-cause mortality in patients with ischemic heart disease and cerebrovascular disorders, BAA has shown strong predictive ability. However, in patients with moderate-to-severe aortic valve stenosis, its capability has been inconclusive, the researchers said.

In a cohort of 559 patients selected in the ARISTOTLE study, BAA was measured via clinical biomarkers based on the Klemera-Doubal-method biological age and PhenoAge algorithms. The association between BAA and mortality was also evaluated.

“Our findings demonstrate that BAA, based on blood biomarkers and clinical measurements, exhibits a significant positive relationship with increased all-cause mortality risk in this patient population,” the study authors wrote. “Moreover, incorporation of BAA into the conventional risk factor model provides substantial incremental predictive capacity for all-cause mortality.”

Variability in Progression

Compared with conventional thinking that aortic stenosis is a progressive disease that worsens gradually, it seems that certain factors related to biological aging may cause an accelerated progression of disease and mortality in some patients, said Sibi Krishnamurthy, MD, interventional and structural cardiologist at NYU Langone Health in New York City. “Even though aortic stenosis is one of the most common valvular abnormalities we deal with, there is still significant variability in its progression among patients.”

Current guidelines, Krishnamurthy noted, recommend assessing patients with moderate-to-severe aortic valve stenosis anywhere from every 6 months to 1- to 2-year intervals.

“While this is an observational study, it does suggest that some patients may need shorter screening intervals based on their biological vs chronological age,” he said. “It emphasizes that physicians follow established guidelines but allows for some modifications in clinical practice to fit individual patient profiles.”

The study coincides with a growing body of literature highlighting the importance of biological aging for the progression of aortic stenosis specifically and cardiovascular outcomes generally, explained Matthew Tomey, MD, cardiologist at Mount Sinai Fuster Heart Hospital in New York City.

“The research reinforces the importance of recognizing biological aging, which is sometimes conceptualized as frailty, in patients with aortic stenosis,” Tomey said. “A person with a chronological age of 75 can be biologically older than another person of the same age. This matters when examining patient longevity.”

The strong link between elevated levels of BAA and greater all-cause mortality risk stressed the importance of effecting more proactive interventions for patients with elevated BAA, the researchers said. “Unlike chronological age, BA is potentially modifiable through effective targeted interventions, including intensive management of hypertension and blood glucose levels,” they wrote. “In addition, accumulating evidence has suggested that regular physical exercise can help lower blood pressure and improve renal function.”

Tomey noted that there is a rich opportunity through basic, translational, and clinical research to understand the contribution of biological aging to the pathogenesis of aortic stenosis and many other human diseases. “Beyond prognostication, if we can elucidate mechanisms of aging, we may open new doors to prevention, therapy, and longevity,” he said.

Liao reported having no financial disclosures relevant to the study. Tomey reported having no financial interests to disclose. Krishnamurthy reported having no financial interests to disclose. Martta Kelly is a medical journalist who lives in the metropolitan New York area.