352 OLAS: Olmesartan/Amlodipine vs Olmesartan/Thiazide FJ Martinez-Martin et al enzyme inhibitor in the OLAS study, these treatment strategies are generally similar, and our results suggest that the different effects on inflammatory mediators could contribute to the results shown in ACCOMPLISH. Blockade of the renin–angiotensin system has anti-inflammatory actions and, in parti- cular, olmesartan has been shown to reduce CRP, TNF-a, IL-6 and monocyte chemotactic protein-1 in the EUropean Trial on Olmesartan and Pravastatin in Inflammation and Atherosclerosis (EUTOPIA).39 Am- lodipine also has anti-inflammatory properties,13 whereas hydrochlorothiazide elicits microinflamma- tion and increases the circulating levels of CRP.31 The clinical relevance of these findings is, however, not yet established. The PROBE design may introduce investigator bias but has been validated in many hypertension trials to date, and reflects usual clinical practice more closely than a randomized controlled design.40 Another limitation of the present study is a small, not significant but consistent difference in blood pressure (1.5/0.8 mm Hg lower in the OA group). However, a post hoc analysis did not find a significant correlation between this difference and the observed changes in metabolic and inflamma- tion parameters. In conclusion, both the olmesartan/amlodipine and olmesartan/hydrochlorothiazide combinations were effective and well tolerated in this study, but the effects on metabolic and inflammatory markers and on new-onset T2DM were possibly more favourable for the combination containing the CCB. The impressive results of the ACCOMPLISH trial on hard CV endpoints have not been explained, but our study may be hypothesis-generating and stimulate further research that may eventually elucidate the BP-independent protection afforded by the renin– angiotensin system blocker/CCB combination. What is known about topic K Non-diabetic hypertensive patients with metabolic syndrome (MetS) have a higher cardiovascular risk than similar patients without MetS. They are also at high risk of developing type 2 diabetes (T2DM). K Renin-angiotensin system (RAS) blockers, i.e. angiotensin- converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), improve insulin sensitivity and reduce the risk of developing T2DM. K Thiazide diuretics decrease insulin sensitivity and increase the incidence of T2DM, whereas calcium channel blockers (CCBs) have a neutral effect. What this study adds K This study shows that antihypertensive combination therapy with an ARB plus either amlodipine or hydrochlorothiazide is well tolerated and effective in reducing BP and markers of both renal and CV risk in obese non-diabetic patients with MetS. K The study also shows that ARB + CCB combination therapy has possibly more favourable effects on metabolic and inflammatory markers and on new-onset T2DM than an ARB + hydrochlorothiazide combination in this patient population. These effects were independent of thiazide- induced hypokalaemia and BP reductions. Journal of Human Hypertension Conflict of interest Francisco Javier Martinez-Martin has received lec- ture fees from Daiichi-Sankyo, Pfizer, Menarini, Chiesi, Takeda and others and also grant funding from Pfizer and Chiesi, but none directly related to this study. The authors have no other relevant affiliations or financial involvement with any entity with a financial interest or conflict related with the subject of this article. Acknowledgements The authors gratefully acknowledge the altruistic collaboration of the nurses and auxiliary personnel in our Hypertension Clinic, and also of the laboratory personnel. The authors would also like to thank Jo Bentley (inScience Communications, a Wolters Kluwer business), whose services were funded by Daiichi-Sankyo, for editing this manuscript for English language. This study was supported by a grant from the Fundacio´n Canaria COMLP #01501008. References 1 Barrios V, Escobar C, Caldero´ n A, Llisterri JL, Alegrı´a E, Mun˜ iz J et al. Prevalence of the metabolic syndrome in patients with hypertension treated in general practice in Spain: an assessment of blood pressure and low- density lipoprotein cholesterol control and accuracy of diagnosis. J Cardiometab Syndr 2007; 2: 9–15. 2 Schillaci G, Pirro M, Vaudo G, Gemelli F, Marchesi S, Porcellati C et al. Prognostic value of the metabolic syndrome in essential hypertension. J Am Coll Cardiol 2004; 43: 1817–1822. 3 Liu SJ, Guo ZR, Hu XS, Wu M, Chen FM, Kang GD et al. Risks for type-2 diabetes associated with the metabolic syndrome and the interaction between impaired fasting glucose and other components of metabolic syndrome the study from Jiangsu, China of 5 years follow-up. Diabetes Res Clin Pract 2008; 81: 117–123. 4 Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta- analysis. Lancet 2007; 369: 201–207. 5 Bakris GL. Combined therapy with a calcium channel blocker and an angiotensin II type 1 receptor blocker. J Clin Hypertens 2008; 10: 27–32. 6 Mancia G, Laurent S, Agabiti-Rosei E, Ambrosioni E, Burnier M, Caulfield MJ et al. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. Blood Press 2009; 18: 308–347. 7 Bakris G, Molitch M, Hewkin A, Kipnes M, Sarafidis P, Fakouhi K, Bacher P, Sowers J. STAR investigators. differences in glucose tolerance between fixed-dose antihypertensive drug combinations in people with metabolic syndrome. Diabetes Care 2006; 29: 2592–2597. 8 Kintscher U, Bramlage P, Paar WD, Thoenes M, Unger T. Irbesartan for the treatment of hypertension in patients with the metabolic syndrome: a sub analysis of the Treat to Target post authorization survey. Prospective observational, two-armed study in 14 200 patients. Cardiovasc Diabetol 2007; 6: 12.