Relationship between increased left atrial volume and microvascular complications in patients with type 2 diabetes
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.
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Patients
We initially recruited 180 white consecutive outpatients with type 2 diabetes, who regularly attended our diabetes clinic during a period of 18 months. For the current study, we excluded patients with: (1) a prior history of IHD (myocardial infarction, angina, coronary revascularization), chronic HF, LV systolic dysfunction (i.e., LV ejection fraction < 45%), moderate-to-severe heart valve diseases, paroxysmal or persistent atrial fibrillation and atrial flutter; (2) a prior history of cirrhosis,
Results
Of the 157 patients included in the study (mean age 68.9 years, mean HbA1c 7.3% and mean duration of disease 14.5 years), 51 patients had nephropathy (32 with abnormal albuminuria alone and 19 with eGFR < 60 ml/min/1.73 m2 and/or abnormal albuminuria), 24 patients had retinopathy (19 with non-proliferative and 5 with proliferative or laser-treated diabetic retinopathy) and 22 patients had lower-extremity sensory neuropathy. Overall, 67 (42.7%) patients had one or more of these microvascular
Discussion
This cross-sectional study is the first to specifically examine the relationship between increasing LAVI values and microvascular complications (singly or in combination) in type 2 diabetic patients with preserved LV systolic function and free from IHD (as ascertained by clinical history and stress myocardial perfusion scintigraphy).
The major finding of our study is that type 2 diabetic patients with LAVI ≥ 32 ml/m2 had a remarkably higher prevalence of diabetic retinopathy, nephropathy
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Diabetic microvascular complications are associated with left atrial structural alterations in asymptomatic type 2 diabetes patients: A cross-sectional study
2023, Journal of Diabetes and its ComplicationsBurden of Microvascular Disease and Risk of Atrial Fibrillation in Adults with Type 2 Diabetes
2022, American Journal of MedicineCitation Excerpt :Additionally, most of the prior studies were not focused on individuals with type 2 diabetes.18,19 Our results are in agreement with prior reports of a positive association between microvascular disease and left atrial volume, a predictor of atrial fibrillation.20,21 Our findings also corroborate those from prior reports observing an increased risk of atrial fibrillation among individuals with kidney disease.9,18,19
Longer diabetes duration reduces myocardial blood flow in remote myocardium assessed by dynamic myocardial CT perfusion
2018, Journal of Diabetes and its ComplicationsCitation Excerpt :Coronary microvascular dysfunction might be an early marker of atherosclerosis because it precedes clinically apparent coronary artery disease.2 Previous studies showed that hemoglobin A1c (HbA1c), neuropathy,3 left atrial volume,4 epicardial adipose tissue,5 or aortic distensibility6 are related with microvascular dysfunction in diabetic patients. Especially, longer duration of diabetes could be a strong predictor for worse microvascular dysfunction.7
Left ventricular systolic dysfunction predicts long-term major microvascular complication outcomes in type 1 diabetes. The Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood onset diabetes
2018, Journal of Diabetes and its ComplicationsCitation Excerpt :Previous data have also cross-sectionally, linked the presence of diabetic microvascular complications with abnormal heart structure and function independent of existing hypertension and atherosclerotic CAD.8, 9 Recently, Bonapace et al. reported cross-sectional associations between increased left atrial volume index and microvascular complications (albuminuria, overt nephropathy, diabetic retinopathy and peripheral sensory neuropathy), whether individually or in combination9 in patients with type 2 diabetes. Similarly, in a cohort of 531 Mexican Americans with type 2 diabetes, a dose-dependent relation was observed between the severity of retinopathy and abnormal myocardial structure and function, including decreased LVEF.8
Early impairment in left ventricular longitudinal systolic function is associated with an increased risk of incident atrial fibrillation in patients with type 2 diabetes
2017, Journal of Diabetes and its ComplicationsCitation Excerpt :It is reasonable to assume that impaired LSSYS is the most early marker of disease related to coexisting coronary microvascular dysfunction and subclinical atherosclerosis that involve both the left ventricle and the left atrium, and that predisposes to the development of fibrotic changes that favor myocardial electrical instability and subsequent development of AF. In fact, the existence of an atrial diabetic cardiomyopathy paralleling an LV diabetic cardiomyopathy, irrespective of coexisting loading conditions, was also recently suggested (Bonapace et al., 2015; Kadappu et al., 2012). Our study has some important limitations that should be mentioned.
Evaluation of the association between diabetic retinopathy and the incidence of atrial fibrillation: A nationwide population-based study
2016, International Journal of CardiologyCitation Excerpt :Diabetes is associated with LA enlargement and dysfunction independent of hypertension or diastolic dysfunction [14]. Furthermore, a more severe grade of DR is associated with worse cardiac structural changes, including an increased LA dimension and increased left ventricular mass [13,15]. Considering that atrial structural remodeling is a well-known substrate for AF development, the presence and severity of DR can increase the risk of AF by LA structural remodeling.
Funding Sources: GT is supported in part by grants from the University School of Medicine of Verona, Verona, Italy.
Disclosures: The authors have no potential conflicts of interest to disclose.