QTc prolongation, increased NT-proBNP and pre-clinical myocardial wall remodeling in excessive alcohol consumers: The SABPA study

Highlights

• Alcohol abuse is one of the most significant contributors to cardiovascular diseases (CVD).

• Alcohol metabolism and tolerance differ between ethnicities.

• Ethnic-specific γ-GT cut-points elucidate pre-clinical structural alterations.

• Alcohol consumption and electrical and biochemical modifications are linked to CVD.

Abstract

Alcohol contributes greatly to vascular and structural modifications. Due to differences in the metabolism and tolerance of alcohol between ethnic groups, the manner of these modifications may differ. We investigated the association between alcohol consumption – measured via ethnic-specific gamma glutamyl transferase (γ-GT) cut-points – and markers of cardiac perfusion, electrical activity, and pre-clinical structural alterations. A South African target population study was performed in a bi-ethnic cohort (n = 405). Alcohol consumption was determined according to previously defined ethnic-specific γ-GT cut-points, where γ-GT ≥ 19.5 U/L and γ-GT ≥ 55 U/L indicated excessive alcohol consumption in Caucasians and Africans, respectively. Ambulatory 24-h blood pressure and electrocardiograms (ECG), 10-lead ECG left ventricular hypertrophy (LVH), ischemic events, N-terminal pro-brain natriuretic peptide (NT-proBNP), and QTc prolongation were assessed. Fasting blood samples were obtained. A poorer cardio-metabolic profile and mean 24-h hypertensive and ECG-LVH values were evident in high γ-GT groups of both ethnicities, when compared to their low counterparts. The African high γ-GT group reported a higher intake of alcohol and presented significant increases in NT-proBNP (p < 0.001), QTc prolongation (p = 0.008), and ischemic events (p = 0.013). Regression analyses revealed associations between ECG-LVH and NT-proBNP, QTc prolongation, ischemic events, and SBP, in the African high γ-GT group exclusively. High alcohol consumers presented delayed electrical conduction in the heart accompanied by ECG-LVH, ischemic events, and increased vaso-responsiveness, predominantly in Africans. Ultimately, increased left ventricular distension on a pre-clinical level may elevate the risk for future cardiovascular events in this population.

Introduction

South Africa has recently been rated as one of the countries with the highest hypertension prevalence rates, with alcohol abuse being one of the most significant contributors to hypertension, especially in Africans (Lloyd-Sherlock, Beard, Minicuci, Ebrahim, & Chatterji, 2014). Prospective data from the SABPA study revealed that 66.0% of African participants met the criteria for hypertension, based on ambulatory blood pressure monitoring during a 3-year follow-up. In comparison, only 39.2% of the Caucasian participants were classified as hypertensive (Hamer et al., 2015). In a recent study conducted by our group, it was evident that alcohol consumption and dependence are greater in the SABPA African cohort, due to its utilization as a possible coping strategy in a psycho-socially demanding environment (Oosthuizen, Malan, Scheepers, Cockeran, & Malan, 2016). The metabolism and tolerance of alcohol also vastly differs between African and Caucasian individuals from South Africa (Malan et al., 2014, Oosthuizen et al., 2016, van Deventer et al., 2015). Specific gamma glutamyl transferase (γ-GT) cut-points associated with 24-h hypertension have been developed accordingly (Oosthuizen et al., 2016). To further explore the detrimental effect of excessive alcohol consumption between ethnicities – regardless of the presence of fatty liver disease and oxidative stress (Hastedt et al., 2013, Tsai et al., 2012) – these ethnic-specific γ-GT cut-points may be utilized to determine the degree of alcohol consumption and associated risk markers pertaining to cardiac perfusion as well as electrical and structural alterations.

The electrocardiogram (ECG) is the recommended tool for assessing the presence of left ventricular hypertrophy (LVH) in hypertensive subjects (Piepoli, et al., 2016). The corrected QT (QTc) interval represents the flow of electrical current through the ventricles (Levine et al., 2008). QTc prolongation is associated with ventricular arrhythmias, ischemic events, and LVH. Therefore, alterations in the QTc segment may be associated with excessive alcohol consumption (Malan et al., 2012, Mayet et al., 1996). Additionally, modifications in biochemical markers may also be reflective of such alterations.

NT-proBNP is produced by the cardiomyocytes during diastole to promote vasodilation in the periphery (Ravassa et al., 2015). Elevated levels of NT-proBNP have been associated with pre-clinical hemodynamic and structural modifications and have been observed in heart failure, arrhythmias, ischemia, and LVH (Andrade et al., 2011, Glick et al., 2013, Ravassa et al., 2015, Volpe et al., 2014, Zhou et al., 2012). Elevated levels of cardiac stress markers, NT-proBNP and cardiac troponin T (cTnT), have been observed in Africans when compared to Caucasians (Van Vuren, Malan, von Känel, Cockeran, & Malan, 2016). These elevated levels of NT-proBNP have additionally been linked to an increased cardiovascular disease risk in Africans (Van Vuren et al., 2016). Increased levels of NT-proBNP may be present in high alcohol consumers to alleviate the increased peripheral resistance and cardiac workload. These alterations, however, have not yet been investigated between ethnicities.

Consequently, we aim to use these previously defined ethnic-specific γ-GT cut-points to address the lack of data regarding alcohol consumption, cardiac stress markers, and their collective association with pre-clinical structural alterations in a South African bi-ethnic cohort. We hypothesize that 1) QTc prolongation and elevated levels of NT-proBNP will be evident in African and Caucasian high alcohol consumers, and 2) that QTc prolongation and NT-proBNP elevation will be associated with pre-clinical structural wall remodeling and ischemic events in African high alcohol consumers specifically.