Long-term prognosis and causes-specific mortality in incident aortic stenosis - a Swedish nation-wide cohort study

Background

Aortic stenosis (AS) is the most common valvulopathy requiring intervention (1, 2), an increasingly important cause of morbidity and mortality in Sweden. While progress has been made in improved diagnosis, earlier referral and broader indications for valve interventions (3), it is unclear how this translates into survival benefit. In addition, detailed knowledge of the major causes of death, place of death, and rates of autopsy verification in AS is limited.

Purpose

To quantify long-term all-cause and cardiovascular mortality in individuals with incident AS compared with matched population controls, and to characterize detailed cause-of-death patterns.

Methods

All individuals aged ≥50 years with incident aortic stenosis were identified from the Swedish National Patient Register using ICD codes. Individuals with AS were matched on sex and year of birth to individuals without valvulopathies. Baseline comorbidities, aortic valve interventions (time-updated), socioeconomic variables, vital status and causes of death were identified through linkage with other registers. The primary outcomes were all-cause mortality and cardiovascular mortality. Secondary outcomes included detailed cause-specific mortality, place of death, and autopsy verification rates. Survival was assessed using Kaplan–Meier estimates and using Cox proportional hazards models.

Results

Among the 432 848 individuals (83 041 with AS and 349 807 without), the mean age was 76 years. Individuals with AS were older than comparators and had more comorbidities. During a mean follow-up time of 6,6 years, 192 467 (44.5%) deaths were recorded. Crude all-cause and cardiovascular mortality rates were substantially higher among individuals with AS (Figure 1). After multivariable adjustment for age, sex, comorbidities, and time-updated valve interventions, AS was associated with a more than two-fold increased risk of all-cause mortality (HR 2.63, 95% CI 2.60–2.67) and a more than three-fold of cardiovascular mortality (HR 3.59, 95% CI 3.52–3.66). Older age, male sex, and higher comorbidity burden were independently associated with increased mortality, while aortic valve intervention was associated with improved survival.

Cardiovascular disease was the leading cause of death in both groups, followed by malignancy, while in the third position were respiratory disease (for AS individuals) and psychiatric disorders (for comparators) (Figure 2). Individuals with AS were more likely to die in hospital and underwent autopsy more frequently.

Conclusions

Individuals with aortic stenosis remain at increased risk of all-cause and cardiovascular mortality compared with general population. Although cardiovascular disease and malignancy were the leading causes of death in both groups, individuals with AS exhibited a substantially higher proportion of cardiovascular and respiratory deaths, and more frequent in-hospital death, indicating a persistent prognostic burden.Figure 1Figure 2