Albuminuria Is Independently Associated With Cardiac Remodeling, Abnormal Right and Left Ventricular Function, and Worse Outcomes in Heart Failure With Preserved Ejection Fraction

Abstract

Objectives To determine the relationship between albuminuria and cardiac structure/function in heart failure with preserved ejection fraction (HFpEF). Background Albuminuria, a marker of endothelial dysfunction, has been associated with adverse cardiovascular outcomes in HFpEF. However, the relationship between albuminuria and cardiac structure/function in HFpEF has not been well studied. Methods We measured urinary albumin-to-creatinine ratio (UACR) and performed comprehensive echocardiography, including tissue Doppler imaging and right ventricular (RV) evaluation, in a prospective study of 144 patients with HFpEF. Multivariable-adjusted linear regression was used to determine the association between UACR and echocardiographic parameters. Cox proportional hazards analyses were used to determine the association between UACR and outcomes. Results The mean age was 66±11 years, 62% were female, and 42% were African-American. Higher UACR was associated with greater left ventricular (LV) mass, lower preload-recruitable stroke work, and lower global longitudinal strain. Higher UACR was also significantly associated with RV remodeling (for each doubling of UACR, RV wall thickness was 0.9 mm higher [95% confidence interval (CI) 0.05–0.14 mm; P=0.001, adjusted P=0.01]) and worse RV systolic function (for each doubling of UACR, RV fractional area change was 0.56% lower [95% CI 0.14–0.98%; P=0.01, adjusted P=0.03]. The association between UACR and RV parameters persisted after excluding patients with macroalbuminuria (UACR > 300 mg/g). Increased UACR was also independently associated with worse outcomes. Conclusions In HFpEF, increased UACR is a prognostic marker and is associated with increased RV and LV remodeling, and longitudinal systolic dysfunction.

Associations of Macro- and Microvascular Endothelial Dysfunction With Subclinical Ventricular Dysfunction in End-Stage Renal Disease

“…(38, 39) Recent work by Shah and colleagues has shown that RV remodeling is an independent prognostic factor in HFpEF; (40) in the same cohort, microalbuminuria (a marker of endothelial dysfunction) was associated with RV remodeling independent of comorbidities and LV mass. (41) To our knowledge, the association of VTI with RV function that we observed has not been demonstrated previously in CKD or non-CKD populations. Notably, the association between VTI and RV dysfunction persists even in the smaller subgroup without self-reported atherosclerotic disease and in the whole group after adjustment for medications.…”

The risk of death associated with proteinuria in heart failure is restricted to patients with an elevated blood urea nitrogen to creatinine ratio

“…Still, the strong relationship between proteinuria and decreased survival has been repeatedly demonstrated in both heart failure with preserved EF and more current HF populations suggesting these results are still relevant in today’s practice. 15, 32 The SOLVD trial was not originally designed to investigate associations between proteinuria and renal function and as such, physicians were not blinded to BUN, creatinine or presence of proteinuria. Moreover, non-neurohormonal factors such as protein catabolism and diet that are known to influence urea absorption may have led to uncontrolled confounding.…”

Association between atrial function assessed by 2D‐speckle tracking echocardiography and albuminuria in patients with type 2 diabetes and coronary artery disease

“…Furthermore, albuminuria is correlated with left ventricular (LV) diastolic dysfunction . The association between albuminuria and LV systolic function has been assessed via two‐dimensional speckle‐tracking echocardiography (2DSTE) in such conditions as DM, hypertension, and heart failure with a preserved ejection fraction . Research has shown a relation between albuminuria and subtly impaired LV systolic function.…”