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To the Editor,
Al-Thanoon et al. reported that several markers of metabolic syndrome (MetS) were improved by the administration of losartan (50 mg/day) or enalapril (20 mg/day).1 A significant increase in high density lipoprotein cholesterol (HDL-C) was noted only with losartan.1 Some comments may be of interest.
The Losartan Intervention for Endpoint reduction (LIFE) trial included 9,193 hypertensive patients with electrocardiographically documented left ventricular hypertrophy.2 These patients were randomized to losartan or atenolol and followed for 4.7 years. Losartan was superior to atenolol in reducing cardiovascular (CV) and total mortality.2 In this study, losartan blunted the decrease in HDL-C and this was associated with fewer composite endpoints compared with atenolol.3 Also, in the LIFE trial, the rise in serumuric acid (SUA) levels was attenuated by losartan and has been related to CV outcomes.4 Losartan is the only angiotensin II type 1 receptor blocker with a hypouricemic effect.5 SUA levels are raisedin MetS,6 and may predict CV events.7 The decrease in SUA levels by drugs used for vascular disease prevention (e.g. atorvastatin) is associated with a reduced risk of CV events.8 Therefore, it would be useful to know if there were any changes in SUA levels in the Al-Thanoon et al. study.1
Non-alcoholic liver disease (NAFLD) is considered a manifestation of MetS which is also associated with raised SUA levels.9 Even abnormal liver function tests (LFTs) have been linked with increased vascular risk.10 A post hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study included 437 patients with coronary heart disease and moderately elevated (<3 × the upper limit of normal) LFTs [alanine (ALT) and aspartate aminotransferase (AST) activities].11 These patients experienced a greater CV benefit from atorvastatin compared with those with normal AST/ALT activities.11 Therefore, it would be interesting to know whether weight reduction together with antihypertensive treatment was associated with changes in AST/ALT activities in the Al-Thanoonet al. study.1
The weight loss (4.2 and 3.0 kg in the losartan and enalapril group, respectively) was quite marked over this 2 month study.1 Did the patients receive lifestyle advice? Also, it is important to consider that any effects on SUA, HDL-C and LFTs might beweight-related.
References
1. Al-Thanoon ZA, Mahmood IH. Effects of Losartan vs. Enalapril on the Markers of Metabolic Syndrome. Oman Med J 2012 Jan;27(1):27-30.
2. Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, et al; LIFE Study Group. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002 Mar;359(9311):995-1003.
3. Olsen MH, Wachtell K, Beevers G, Dahlöf B, de Simone G, Devereux RB, et al. Effects of losartan compared with atenolol on lipids in patients with hypertension and left ventricular hypertrophy: the Losartan Intervention For Endpoint reduction in hypertension study. J Hypertens 2009 Mar;27(3):567-574.
4. Høieggen A, Alderman MH, Kjeldsen SE, Julius S, Devereux RB, De Faire U, et al; LIFE Study Group. The impact of serum uric acid on cardiovascular outcomes in the LIFE study. Kidney Int 2004 Mar;65(3):1041-1049.
5. Daskalopoulou SS, Tzovaras V, Mikhailidis DP, Elisaf M. Effect on serumuric acid levels of drugs prescribed for indications other than treating hyperuricaemia. Curr Pharm Des 2005;11(32):4161-4175.
6. Tsouli SG, Liberopoulos EN, Mikhailidis DP, Athyros VG, Elisaf MS. Elevated serum uric acid levels in metabolic syndrome: an active component or an innocent bystander? Metabolism 2006 Oct;55(10):1293-1301.
7. Levantesi G, Marfisi RM, Franzosi MG, Maggioni AP, Nicolosi GL, Schweiger C, et al. Uric acid: A cardiovascular risk factor in patients with recent myocardial infarction. Int J Cardiol 2012 Jan 18. [Epub ahead of print]
8. Athyros VG, Mikhailidis DP, Liberopoulos EN, Kakafika AI, Karagiannis A, Papageorgiou AA, et al. Effect of statin treatment on renal function and serum uric acid levels and their relation to vascular events in patients with coronary heart disease and metabolic syndrome: a subgroup analysis of the GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) Study. Nephrol Dial Transplant 2007 Jan;22(1):118-127.
9. Katsiki N, Athyros VG, Karagiannis A, Mikhailidis DP. Hyperuricaemiaand non-alcoholic fatty liver disease (NAFLD): a relationship withimplications for vascular risk? Curr Vasc Pharmacol 2011 Nov;9(6):698-705.
10. Mikhailidis DP, Lioudaki E, Ganotakis ES. Liver enzymes: potential cardiovascular risk markers? Curr Pharm Des 2011 Nov;17(33):3632-3643.
11. Athyros VG, Tziomalos K, Gossios TD, Griva T, Anagnostis P, Kargiotis K,et al; GREACE Study Collaborative Group. Safety and efficacy of long-termstatin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis. Lancet2010 Dec;376(9756):1916-1922.
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