Relationship between increased left atrial volume and microvascular complications in patients with type 2 diabetes

Abstract

Aims

We assessed whether left atrial volume index (LAVI) was associated with the presence of microvascular complications in patients with type 2 diabetes, and whether this association was independent of hemodynamic and non-hemodynamic factors.

Methods

We studied 157 consecutive outpatients with type 2 diabetes with no previous history of ischemic heart disease, chronic heart failure and valvular diseases. A transthoracic echocardiography and myocardial perfusion scintigraphy were performed in all participants. Presence of microvascular complications was also recorded.

Results

Overall, 51 patients had decreased estimated glomerular filtration rate and/or abnormal albuminuria, 24 had diabetic retinopathy, 22 had lower-extremity sensory neuropathy, and 67 (42.7%) patients had one or more of these microvascular complications (i.e., combined endpoint). After stratifying patients by LAVI, those with LAVI ≥ 32 ml/m² had a greater prevalence of microvascular complication, lower left ventricular (LV) ejection fraction, higher LV mass index and higher E/e’ ratio than those with LAVI < 32 ml/m². Logistic regression analyses revealed that microvascular complications (singly or in combination) were associated with increased LAVI, independently of age, sex, diabetes duration, hemoglobin A1c, hypertension, LV-ejection fraction, LV mass index and the E/e’ ratio.

Conclusions

These results indicate that microvascular diabetic complications are associated with increased LAVI in well-controlled type 2 diabetic patients with preserved systolic function and free from ischemic heart disease, independently of multiple potential confounders.

Introduction

Several epidemiological studies have demonstrated that type 2 diabetes is a powerful risk factor for cardiovascular diseases (CVDs), including the development of heart failure (HF) (Seshasai et al., 2011).

The mechanisms leading to the increased risk of HF in people with type 2 diabetes remain uncertain and are likely multifactorial. Possible pathogenic factors include coronary atherosclerosis, hypertension and other established CVD risk factors. However, a number of studies have suggested that type 2 diabetes may affect cardiac structure and function, independent of established CVD risk factors, consistent with the presence of a distinct diabetic cardiomyopathy (Boudina and Abel, 2007, Fang et al., 2004, Galderisi et al., 1991, Rubler et al., 1972). Efforts to understand risk factors contributing to the increased burden of HF in people with type 2 diabetes are critical in reducing the morbidity and mortality attributed to this disease.

Left atrial (LA) enlargement is thought to be a sensitive marker of chronic left ventricular (LV) diastolic dysfunction (Tsang, Barnes, Gersh, Bailey, & Seward, 2002) and provides prognostic information incremental to both clinical parameters and conventional measures of LV function in various pathological conditions (Abhayaratna et al., 2006). The Framingham Heart Study investigators reported that after multivariable adjustment, LA enlargement was a strong predictor of incident stroke in men and mortality in both sexes (Benjamin, D’Agostino, Belanger, Wolf, & Levy, 1995). Other investigators reported that LA volume index (LAVI) ≥ 32 ml/m² was independently associated with an increased incidence of CVD and HF in a cohort of elderly individuals with preserved LV systolic function (Takemoto et al., 2005, Tsang et al., 2003). Again, increased LAVI predicted independently the risk of CVD mortality in patients with acute myocardial infarction (Moller et al., 2003), in those with dilated cardiomyopathy (Rossi et al., 2002), in those with chronic HF and preserved systolic function (Rossi et al., 2006, Rossi et al., 2014), and in patients with chronic kidney disease (Hee et al., 2014).

For several years, most studies in type 2 diabetes were focused mainly on LV structural and functional abnormalities (Fang et al., 2003, Galderisi, 2006, Jarnert et al., 2008, Poulsen et al., 2010, Shishehbor et al., 2003). In recent years, however, there has been a growing scientific interest in exploring the functional and structural changes of the LA as well as the prognostic impact of LA enlargement on CVD outcomes in this patient population (Kadappu et al., 2012, Poulsen et al., 2013, Tadic and Cuspidi, 2015).

Recent data from the Atherosclerosis Risk in Communities study also demonstrated an independent association between diabetic retinopathy and the development of HF in patients with type 2 diabetes without a history of CVD (Cheung et al., 2008). Additionally, Aguilar et al. (2009) reported that more severe diabetic retinopathy was associated with both increased LAVI and increased LV mass, independently of age, sex, glycemic control, hypertension and previous ischemic heart disease (IHD).

To our knowledge, there is a paucity of published data regarding the relationship of the most important microvascular complications (retinopathy, nephropathy and peripheral neuropathy) with LAVI in patients with type 2 diabetes without overt IHD.

Thus, the aim of this study was to assess whether LAVI as measured by echocardiography was associated with the presence of microvascular complications in a large sample of type 2 diabetic patients free from IHD, and whether this association was independent of relevant hemodynamic and non-hemodynamic factors.