348 OLAS: Olmesartan/Amlodipine vs Olmesartan/Thiazide FJ Martinez-Martin et al Patients who had already been uptitrated to the maximum treatment doses but still had SBP 4160 mm Hg were removed from the study. In all patients with fasting glycaemia 45.6 mmol l 1 but o7 mmol l 1 at any visit after the first, a standard oral glucose tolerance test was performed within the following 10 days. New-onset T2DM was diagnosed in patients with fasting glycaemia X7 mmol l 1 or 120 min post-load glycaemia 411.1 mmol l 1, in the absence of clinical signs of type 1 or secondary diabetes mellitus, according to the current World Health Organization guidelines.17 Weight, height, waist circumference, fasting plas- ma glucose and insulin, lipid profile (that is, total cholesterol, high-density lipoprotein-cholesterol and triglycerides), creatinine, sodium, potassium, bilirubin, aminotransferases, high-sensitivity-CRP, and urinary albumin and creatinine (in early morning samples) were measured by standard clinical procedures. Heart rate and BP were mea- sured according to current guidelines,6 using a validated semi-automatic device (OMRON 705P), in the morning (between 08:30 and 11:30) after 5 min of rest in a sitting position with the back supported; patients were advised to avoid smoking and caffeinated drinks 30 min before the measure- ment. The values for BP and heart rate obtained at each visit were the average of two measurements separated by at least 2 min; a third reading was obtained if there was a difference of 5 mm Hg or 5 beats per minute between the two readings. Plasma TNF-a was measured using a commercial enzyme-linked immunosorbent assay (ARCUS Bio- logicals, Modena, Italy); plasma adiponectin, ICAM- 1, VCAM-1 and interleukins-1b, -6 and -8 were also measured with a commercial enzyme-linked immu- nosorbent assay (LINCO Research Inc., MO, USA). The insulin resistance index (IRI) was estimated by the homeostasis model assessment formula:18 IRI ¼ fasting plasma insulin fasting plasma glucose/ 135, with insulin in pmol l 1 (1 mU per l ¼ 6.00 pmol l 1) and glucose in mmol l 1. Compliance was assessed by returned pill counts and tolerance by questionnaire. An intention-to-treat analysis was performed in all patients who received at least one dose of study medication and had a subsequent efficacy observa- tion. All analyses were specified a priori, except where otherwise indicated. All calculations were performed using the statistical software SPSS 15.0 (SPSS Inc., Chicago, IL, USA) for Microsoft Win- dows, including logistic regression modelling. The sample size was calculated with the assumption (based on a pilot trial) of a 25% difference in the means between the groups for most of the main variables (namely IRI, adiponectin, TNF-a, IL-1b, IL-6, ICAM-1, and VCAM-1), and a 40% variation coefficient within the groups, yielding 54 patients per group for a 90% statistical power with a ¼ 0.05. Assuming a 10% patient loss, a sample size of 60 per group was required. However, the study could be Journal of Human Hypertension underpowered for the secondary objective (new- onset T2DM), as we did not have enough informa- tion to calculate an adequate sample size. The data are presented as mean±s.d., with 95% confidence intervals for differences as appropriate. Changes from baseline and between groups in BP, heart rate and laboratory parameters were evaluated using a Student’s t-test for paired or unpaired data, or analysis of variance, as appropriate. Categorical variables were compared using the w2 or the Fisher’s exact tests, as appropriate. The survival analysis for new-onset T2DM was performed using the Kaplan–Meier model followed by the log-rank test. The standard Pearson model was used for correla- tion analysis. All statistical tests were two-tailed and a P-value of o0.05 was considered statistically significant. Results Enrolment for this trial began in May 2005, includ- ing a 6-month, 8-patient pilot trial to check for feasibility and to confirm the sample size calcula- tion. A total of 256 patients were screened, of whom 120 were randomized. At baseline, the mean age was 59.3±8.1 years, 55% of patients were female, and the mean body mass index was 31.2±3.7 kg m 2. There were 60 patients in each group. The flowchart of the study is shown in Figure 2. Of the 120 patients randomized, 31 (25.8%) had received previous antihypertensive treatment; 17 in the OA group and 14 in the OH group. None had received combination treatment and all had a SBP 4140 mm Hg; three had received a thiazide diuretic, two a b-blocker, nine a CCB (seven dihydropyridi- nic, two non-dihydropyridinic), nine an angioten- sin-converting enzyme inhibitor, seven an ARB and Figure 2 Flowchart of the OLAS study. Doses are mg per day. A, amlodipine; D, doxazosin; H, hydrochlorothiazide; O, olmesartan; OGTT, oral glucose tolerance test; SBP, systolic blood pressure; T2DM, type 2 diabetes mellitus.