Longitudinal trajectories of albuminuria and risk of subclinical and clinical heart failure, atrial fibrillation, and coronary heart disease: the MESA study

AIMS: We examined whether trajectories of urine albumin-creatinine ratio (UACR) over 5- and 10-year periods were associated with subclinical and clinical heart failure (HF), heart failure subtypes, atrial fibrillation (AF), and coronary heart disease (CHD). METHODS: We modelled 5-year UACR trajectories in 5,581 participants (mean age 61.7 years) from the Multi-Ethnic Study of Atherosclerosis using latent class mixed modelling across baseline, Exam 2, and Exam 3 (2000-2005). A separate sample of 4,343 participants with UACR measured at baseline, Exam 5, and at least one intermediate exam (2000-2012) was used for 10-year trajectory modelling. Cox proportional hazards models were used to assess associations between UACR trajectories and clinical endpoints. Linear regression analyses examined associations between UACR trajectories and N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT), as well as myocardial fibrosis assessed by cardiac MRI T1 mapping. RESULTS: Three distinct trajectory groups were identified for each time window. In the 5-year model, the "sustained medium to high" group, and in the 10-year model, the "rapid rise" group (each ∼8%) had 1.5- to 3.7-fold higher risks of HF, HF subtypes, composite of HF/death, AF, and CHD. Most of these associations were independent of baseline UACR levels and remained significant even among individuals with normoalbuminuria at baseline. After censoring for interim AF or CHD, associations persisted for HF and HFpEF, but not HFrEF. These groups also exhibited elevated NT-proBNP, hs-TnT, native T1, and extracellular volume fraction. CONCLUSION: Progressive UACR increases identify individuals at elevated cardiovascular risk, particularly for HF.