Effect of Long-Term Allopurinol Therapy on Left Ventricular Mass Index in Patients with Ischemic Heart Disease; A Cross-Sectional Study

Vascular Health and Risk Management Dovepress open access to scientific and medical research Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 27.91.139.62 on 02-Jul-2020 For personal use only. Open Access Full Text Article ORIGINAL RESEARCH Effect of Long-Term Allopurinol Therapy on Left Ventricular Mass Index in Patients with Ischemic Heart Disease; A Cross-Sectional Study This article was published in the following Dove Press journal: Vascular Health and Risk Management Manal M Alem 1 Sarah R Aldosari 2 Alhassna A Alkahmous 2 Adam S Obad 2 Nagy M Fagir 3 Bandar S Al-Ghamdi 2,3 1 Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; 3Heart Centre, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia Background: Left ventricular hypertrophy (LVH), as assessed by measurement of left ventricular mass (LVM), is one of the most important cardiovascular risk factors. It is commonly present in patients with ischemic heart disease (IHD), irrespective of the level of blood pressure; recently, oxidative stress has been shown to be an important factor in its development. The question then arises: can this risk factor be modified by antioxidant treatment (e.g., with allopurinol, a xanthine oxidase inhibitor)? Methods: This is an observational study with a cross-sectional design which explored the association between long-term (>12 months) allopurinol therapy and LV mass index (LVMI) as well as geometry in patients generally receiving standard treatments for IHD. The primary endpoint was LVMI measurement (by 2D-echocardiography) and secondary endpoints included the association of allopurinol use with LV function (ejection fraction), blood pressure, glycemic control, and lipid profile. Results: Ninety-six patients on standard anti-ischemic drug treatment (control group) and 96 patients who were additionally taking allopurinol (minimum dose 100 mg/day) were enrolled. Both groups were matched for age, sex, height, and co-morbidities, but poorer kidney function in the allopurinol group required further sub-group analysis based on renal function. Allopurinol treatment was associated with the lowest LVMI in the patients with normal serum creatinine (median LVMI; 70.5 g/m2): corresponding values were 76.0 and 87.0 in the control group with, respectively, normal and elevated serum creatinine, and 89.5 in the allopurinol group with elevated serum creatinine (P=0.027). In addition, allopurinol was associated with better glycemic control (HbA1c) with a difference of 0.8% (95% CI; 1.3, 0.2) (P=0.004) as compared with control patients. Conclusion: In our population, treatment with allopurinol (presumably because of its antioxidant properties) has shown a tendency to be associated with smaller LVM in IHD patients with normal serum creatinine, along with better glycemic control. Keywords: IHD, LVMI, left ventricular geometry, allopurinol, glycemic control, HbA1c, Saudi Arabia Introduction Correspondence: Manal M Alem Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, PO Box 1982, Dammam 31441, Saudi Arabia Email 539 submit your manuscript | www.dovepress.com Vascular Health and Risk Management 2019:15 539–550 DovePress © 2019 Alem et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://doi.org/10.2147/VHRM.S226009 Powered by TCPDF (www.tcpdf.org) Cardiovascular disease is the most common cause of death worldwide and ischemic heart disease (IHD) is the principal culprit. The Framingham Heart study (1970) established the left ventricular hypertrophy (LVH) as one of the most important risk factors for ischemic heart disease and mortality in a cohort of 5127 men and women over 14 years of follow-up.1 Electrocardiography was initially used for the detection of LVH, but this was replaced by echocardiographic techniques that allowed reliable, Dovepress Vascular Health and Risk Management downloaded from https://www.dovepress.com/ by 27.91.139.62 on 02-Jul-2020 For personal use only. Alem et al accurate, and non-invasive estimation of left ventricular mass (LVM). Echocardiographic measurements were then obtained in a cohort of 3220 men and women participating in the Framingham Heart study and were followed for 4 years to establish the prognostic value of LVM beyond traditional cardiovascular risk factors.2 Left ventricular (LV) geometric patterns were later found to possess an independent prognostic significance, with concentric hypertrophy having the worst prognosis, followed by eccentric hypertrophy, concentric remodeling, and normal geometry.3,4 In patients with IHD, left ventricular hypertrophy is an essential and common pathological finding irrespective of incident hypertension.5 In fact, its occurrence in this population carries an adverse impact on survival that is significantly greater than that of multivessel disease or LV systolic dysfunction.6 Another cardiovascular risk factor that has been significantly associated with LVM is serum uric acid, such association was studied mostly in hypertensive population7–11 with sex-related differences,9,10 and in general population studies12–14 with a wide range of serum uric acid concentration. More recent research has built up that oxidative stress and reactive oxygen species (ROS) (e.g., superoxide (O−2), hydroxyl radical (•OH), and hydrogen peroxide (H2O2)) creating nitroso-redox imbalance and mediate the development of LVH and remodeling.15 Xanthine oxidoreductase or xanthine oxidase (XO) is an enzyme system that is primarily responsible for uric acid production as the terminal product of purine metabolism contributes to the generation of ROS and oxidative stress. This raises the possibility that an “old” class of drugs, i.e., the xanthine oxidase inhibitors, might be repositioned among cardiovascular prevention strategies. The xanthine oxidase inhibitor drug, allopurinol, has shown antioxidant properties and prevented cardiac hypertrophy and remodeling in both animal models16–18 and clinical studies19–21 in addition to uric acid reduction. Since, concomitant allopurinol therapy is commonly added to standard anti-ischemic drug regimens in patients with IHD, due to hyperuricemia or gout. We sought via this cross-sectional study to explo (...truncated)