Cardiac amyloidosis risk across ethnoracial and clinical subgroups: a five-year national study

Cardiac amyloidosis is underdiagnosed. Amyloid deposits cause progressive diastolic dysfunction of a nondilated ventricle. Among the main subtypes, transthyretin amyloidosis (ATTR) affects 1 in 2,000 people, while light-chain (AL) amyloidosis is increasing in prevalence. Early identification of risk factors and prompt intervention may prevent severe complications. This study aimed to identify the risk factors for developing cardiac amyloidosis and its associated morbidity and mortality.

This retrospective cohort study used the National Inpatient Sample (2016-2020) to examine patients hospitalized with cardiac amyloidosis identified by ICD-10 codes. Over 50 risk factors, including hematologic, rheumatologic, and renal conditions, were evaluated as possible contributors. Predictors of cardiac amyloidosis and mortality were analyzed by demographic group. Inclusion required a primary or secondary diagnosis. Multiple logistic regression, adjusted for age, sex, and comorbidities, assessed associations. The primary outcome was cardiac amyloidosis; the secondary outcome was in-hospital mortality.

There were 23,119 patients with cardiac amyloidosis. The mean age was 72.23 years, and 58% were male. Hereditary transthyretin amyloidosis (OR 215.89, 95% CI: 176.17-264.56) and familial Mediterranean fever (OR 111.99, 95% CI: 72.39-173.24) showed the strongest associations, both statistically significant (P<0.001). Additional risk factors included hematologic conditions, such as multiple myeloma (OR 15.31), Waldenström's macroglobulinemia (OR 6.99), and MGUS (OR 4.45), all P<0.001. Renal conditions such as chronic kidney disease (OR 1.83), end-stage renal disease (OR 2.76), and renal transplant (OR 2.4), and rheumatologic conditions such as Sjögren's syndrome (OR 2.04) and sarcoidosis (OR 1.69) were also significant (all P<0.001). By demographics, Black race (OR 2.52, P<0.001), Asian race (OR 1.11, P = 0.034), and older age (OR 1.05, P<0.001) were associated with increased risk. Notably, asthma, diabetes, and obesity were not linked to cardiac amyloidosis. In-hospital mortality increased with ESRD (OR 2.4), multiple myeloma (OR 1.41), and older age (OR 1.015).

Hereditary transthyretin amyloidosis, familial Mediterranean fever, and Black race were the strongest risk factors, while end-stage renal disease and multiple myeloma correlated with higher in-hospital mortality. ICD-10-based diagnoses may limit accuracy. This stresses the need for improved risk stratification and targeted screening.