QTc prolongation, increased NT-proBNP and pre-clinical myocardial wall remodeling in excessive alcohol consumers: The SABPA study
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.
Section snippets
Study design
This sub-study forms part of an observational, cross-sectional study: the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study, which was conducted between late summer and late autumn of 2008 and then again in 2009, to avoid seasonal variations (Malan, Hamer, Frasure-Smith, Steyn, & Malan, 2015). Ethical number: NWU-00036-07-S6.
Research participants
The study sample was composed of urban African and Caucasian, male and female teachers (n = 409) from the North-West Province, South Africa, aged
Results
Significant differences existed between ethnic and γ-GT cut point groups, independent of a priori covariates for γ-GT, (F(1,405); 35.6; p = 0.010); NT-proBNP (F(1,405); 32.3; p = 0.009); QTc (F(1,405); 404.16; p = 0.013). According to previously defined γ-GT cut-points (Oosthuizen et al., 2016), no significant interactions were found between gender groups within the same ethnicities (F(1,405); 35.32; p = 0.061).
Discussion
The novelty of this study entails the use of ethnic-specific alcohol cut-points in the determination of alcohol-consumption related alterations in the cardiac perfusion, electrical activity, and structure in a South African, bi-ethnic population. Overall, we demonstrated that ECG-LVH as well as the prevalence of ischemic events were associated with both QTc prolongation and increased NT-proBNP levels, predominantly in African excessive alcohol consumers. This also implies increased
Recommendations and limitations
Due to the nature of this study (cross-sectional analyses), no causal mechanisms could be determined and/or verified. This study is limited to the SABPA teachers' cohort and is not representative of other working environments. It also is recommended that hair samples be used to establish chronic alcohol abuse more accurately, due to such samplings' direct reflection of alcohol abuse per se, and not the indirect effect of alcohol on the induction of liver enzymes. This will also ensure the
Conclusion
In conclusion, we were able to demonstrate the association between perfusion, electrical conduction, and myocardial structural alterations in an excessive alcohol consumers' cohort, especially in Africans. The aftermath of increased vascular resistance resulting in cardiac structural modifications and hemodynamic alterations might increase the African population's risk for CVD as well as the risk for the Caucasian population, as additionally supported by the RaVL amplitude. The following
Conflicts of interest
The authors declare no conflict of interest.
Acknowledgments
The author acknowledges all who assisted in obtaining the data and blood samples. The present study was partially funded by the National Research Foundation, South African Medical Research Council, ROCHE Diagnostics, North-West University (Potchefstroom Campus), North-West Department of Education South Africa, as well as the Metabolic Syndrome Institute, France. Any opinion, findings, and conclusions or recommendations expressed in this material are those of the author(s) and therefore the
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