Interrelations between albuminuria, electrocardiographic left atrial abnormality, and incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort

Highlights

• Impact of combination of albuminuria and ECG left atrial abnormality (ECG-LAA) on atrial fibrillation (AF) risk is unknown.

• Concomitant presence of albuminuria and ECG-LAA is associated with a greater risk of AF than each predictor in isolation.

• Only Black individuals with concomitant albuminuria and ECG-LAA have a higher risk of incident AF.

• These findings raise the possibility of a differential mechanistic pathway to AF according to race-ethnicity.

Abstract

Background

The objective of the study was to examine the joint associations of albuminuria and electrocardiographic left atrial abnormality (ECG-LAA) with incident atrial fibrillation (AF) and whether this relationship varies by race.

Methods

This analysis included 6670 participants free of clinical cardiovascular disease (CVD), including atrial fibrillation (AF), from the Multi-Ethnic Study of Atherosclerosis. ECG-LAA was defined as P-wave terminal force in V1 [PTFV1] >5000 μV × ms. Albuminuria was defined as urine albumin-creatinine ratio (UACR) ≥30 mg/g. Incident AF events through 2015 were ascertained from hospital discharge records and study-scheduled electrocardiograms. Cox proportional hazard models were used to examine the association of “no albuminuria + no ECG-LAA (reference)”, “isolated albuminuria”, “isolated ECG-LAA” and “albuminuria + ECG-LAA” with incident AF.

Results

Over a median follow-up of 13.8 years, 979 incident cases of AF occurred. In adjusted models, the concomitant presence of ECG-LAA and albuminuria was associated with a higher risk of AF than either ECG-LAA or albuminuria in isolation (HR (95% CI): 2.43 (1.65–3.58), 1.33 (1.05–1.69), and 1.55 (1.27–1.88), respectively (interaction p-value = 0.50). Effect modification by race was observed with a 4-fold greater AF risk in Black participants with albuminuria + ECG-LAA (HR (95%CI): 4.37 (2.38–8.01) but no significant association in White participants (HR (95% CI) 0.60 (0.19–1.92) respectively; (interaction p-value for race x albuminuria-ECG-LAA combination = 0.05).

Conclusions

Concomitant presence of ECG-LAA and albuminuria confers a higher risk of AF compared to either one in isolation with a stronger association in Blacks than Whites.

Introduction

Albuminuria is an independent risk factor for cardiovascular disease (CVD), heart failure (HF), atrial fibrillation (AF), and CVD mortality [[1], [2], [3], [4]], and higher urine albumin creatinine ratio (UACR) is associated with increased renal and CVD risk even with preserved estimated glomerular filtration rate (eGFR) [5]. Therefore, the European Society of Cardiology (ESC) on CVD risk prevention recommends measuring albuminuria and eGFR as part of the routine assessment as the incorporation of albuminuria to CVD risk score resulted in the reclassification of individuals with albuminuria to very high CVD risk, especially in those with chronic kidney disease (CKD) [6,7]. With the approval of newer drugs that reduce the progression of albuminuria with resultant clinical benefits [8,9], identifying risk factors that modify the association of albuminuria with outcomes may identify high-risk populations that would especially benefit from these therapies. Although the association of albuminuria with AF is well established [3], partly due to left atrial (LA) and left ventricular (LV) remodeling [10,11], it is unknown whether this association is modified by markers of LA remodeling. One well-known marker of LA abnormality (LAA) is an abnormal P-terminal force in V1 (PTFV1), which has been associated with an increased risk of poor outcomes such as AF, mortality, and cardioembolic stroke [[12], [13], [14]]. As early detection of albuminuria represents a scalable and cost-effective tool to detect and prevent CVD outcomes [7], exploring its association and interaction with abnormal PTFV1, an intermediate marker between risk factors and AF [13], derived from another ubiquitous and cost-effective tool of electrocardiogram (ECG), may reveal a feasible route for identifying high-risk populations. Further, while Black individuals have a higher prevalence of albuminuria and abnormal PTFV1 than White individuals [12,15], it is unknown whether these are involved in the Black-White difference in AF risk as well. Therefore, we proposed to examine the association and interaction between albuminuria defined as UACR ≥30 mg/g, and ECG-LAA defined as abnormal PFTV1 (>5000 μV × ms) with incident AF stratified by race using data from the Multiethnic study of Atherosclerosis (MESA).