ACC’s Valve Staging Tool Reveals Silent Disease is Common in the Elderly

Asymptomatic valvular heart disease (VHD) is common in older adults and may be a marker of increased risk of cardiovascular events, according to an analysis from the community-based ARIC study.

Nearly 40% of the participants in their 70s, who have been followed since middle age with screenings that include echocardiography, met criteria that put them in an at-risk stage for valve dysfunction. Moreover, nearly one in five patients had “progressive valvular disease”—a harbinger of more-severe disease to come.

“This concept of valvular heart disease stages has been around now for 6 or 7 years,” senior study author Amil M. Shah, MD, MPH (Brigham and Women’s Hospital, Boston, MA), told TCTMD. “To our knowledge, this paper is the one of the first quantifications of the prevalence of those stages in an older, at-risk population.”

The four-stage classification intended to capture the progression of VHD was included in guidelines issued jointly by the American College of Cardiology (ACC) and the American Heart Association (AHA) in 2014, and later revised in 2020. The stages include at-risk for valve dysfunction (stage A), progressive valvular dysfunction (stage B), severe asymptomatic valve dysfunction (stage C), and severe symptomatic valve dysfunction (stage D).

In this new study, published online December 16, 2022, in Circulation, the researchers found that compared with no VHD, having one of the stages, even stage A, was associated with a greater risk of all-cause death, heart failure (HF), atrial fibrillation (AF), and CAD that increased in prevalence with higher VHD stage.

“We don't know if those adverse outcomes are driven by the valve necessarily, but it does suggest that clinicians should be treating aggressively for prevention with all appropriate approaches for cardiovascular risk reduction in those individuals,” Shah said.

Robert Bonow, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), a member of the writing committee that created the guidelines, commenting on the paper for TCTMD, said despite the fact that the researchers adjusted for possible confounders, the interpretation of the findings is clouded by the fact that older patients have other things going on that may explain some of these outcomes.

“In the group who were in stages C and D, where you have severe aortic stenosis, it's not surprising those patients may have a higher mortality that is related to the valve disease,” Bonow said. “But even in that group, 23% had a prior MI and 27% had heart failure.”

For patients at stage A, he added, the study isn’t convincing that aortic sclerosis alone increases mortality risk.

Staging and Progression Followed

Shah and colleagues, led by Khaled Shelbaya, MD, MSc (Brigham and Women’s Hospital), examined data on 6,118 adults (mean age 76; 42% male; 22% Black) who enrolled in the Atherosclerosis Risk in Communities (ARIC) study from four communities in the United States between 1987 and 1989 when they were middle-aged. The data pertinent to this study were the echocardiograms collected between 2011 and 2013 as part of study protocol visit 5 compared with those collected between 2018 and 2019 as part of protocol visit 7. Aortic stenosis, aortic regurgitation, mitral stenosis, and mitral regurgitation stage were defined according to the VHD guidelines.

At visit 5, 39% had stage A, 17% had stage B, and 1.1% had stage C/D disease, and 0.7% had undergone a valve replacement. Compared with those who did not have a valve disease stage, those who did were more likely to have hypertension, diabetes, chronic kidney disease, CAD, MI, HF, stroke, and AF. They also had higher systolic BP and higher concentrations of biomarkers of myocardial stress (NT-proBNP) and injury (high-sensitivity troponin T).

In terms of disease severity, 15% of patients had stage A aortic stenosis, 4.1% had stage B aortic stenosis (3.8% mild, 0.3% moderate), 0.3% had stage C asymptomatic severe aortic stenosis, and 0.4% had stage D symptomatic severe aortic stenosis. Approximately one-third of patients had stage A mitral regurgitation, which was predominantly mild.

At 6.6 years of follow-up, all stages of VHD were associated with increased risk of death, HF, AF, and CAD. Compared with no VHD, the hazard ratio for mortality was 1.3 (95% CI 1.1-1.4) for stage A, 1.5 (95% CI 1.3-1.7) for stage B, and 3.0 (95% CI 2.2-4.2) for stage C/D.

Over the study period, the prevalence of freedom from any VHD stage decreased from 43% to 24%. The prevalence of stage A decreased from 39% to 31% and the prevalence of stage C/D increased from 1.1% to 7.3%. The stage C/D increases also were observed for those with aortic stenosis and mitral regurgitation. No significant changes were seen in prevalence rates for stage B VHD.

Slowly Progressing Disease or Problem?

Bonow said an important contribution of the study is delineating disease progression, which he noted was fairly slow in stage A patients, who progressed from aortic sclerosis to clinically significant stenosis at a rate of < 1% per year over the follow-up period.  

“So, on the one hand it suggests that aortic sclerosis alone, which is creating a murmur in a valve, may not be a disease that is going to progress a whole lot in older age. And yet, if you look at the outcomes, even the at-risk people in stage A have a worse outcome than the people with no valve problem,” he added. “To me, it gets back to the idea that there are comorbidities in these older patients . . . and [a question of] whether the valve disease is causative or is just a marker of people who are sicker at a given age.”

Bonow noted that the study does not include information on primary indication and type of aortic or mitral valve interventions. Importantly, he said, it also suffers from significant missing data, which is “somewhat of a concern,” particularly if it contributed to over- or underestimating rates of progression.

Among ARIC participants who were alive, 30% didn’t attend visit 7, and another 429 who did attend visit 7 didn’t have an echocardiogram done.

“Attrition over time is an issue and that tends to increase as participants get older and it’s not really surprising. We did try to account for that using statistical approaches like inverse-probability weighting, but obviously those are not perfect,” Shah said. “My interpretation, particularly with respect to progression, where attrition is a significant limitation, is that we know that the attrition is not random and the individuals who are sicker are more likely to not show up.”

As such, he believes that the attrition likely led to underestimating rates of progression.