Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Frailty and the relationship between blood pressure and mortality in elderly patients with type 2 diabetes (Zwolle Outpatient Diabetes project Integrating Available Care-34) Kornelis J.J. van Hateren a , Steven H. Hendriks a , Klaas H. Groenier a,b , Stephan J.L. Bakker c , Henk J.G. Bilo a,c,d , Nanne Kleefstra a,c,e , and Gijs W.D. Landman a,f Objective: We aimed to investigate whether adjustment for frailty influences the relationship of blood pressure with mortality in elderly patients with type 2 diabetes mellitus (T2DM). Methods: Patients aged 60 years and older (n ¼ 858) were selected from a prospective observational cohort study of primary care patients with T2DM. Frailty was defined as a score less than 80 on the subscale ‘physical functioning’ of the RAND-36 questionnaire. After median follow-up for 14 years, multivariate Cox regression analyses were performed to evaluate the association between blood pressure and (cardiovascular) mortality. Analyses were performed in strata according to the frailty level (‘physical functioning’ score <80 and 80) and were repeated for patients older than 75 years. Results: Frailty was highly prevalent in our study population; 629 out of 858 patients (73%) fulfilled the criterion. For patients aged at least 60 years, the hazard ratios (95% confidence interval) of a 10 mmHg increase in SBP and DBP for cardiovascular mortality in nonfrail patients were 1.38 (1.15–1.68%) and 1.60 (1.07–2.37%), respectively. No relationship was observed for frail patients. For the oldest frail elderly, the hazard ratios of SBP and DBP for all-cause mortality were 0.92 (0.87–0.98%) and 0.83 (0.73–0.93%), respectively. For the oldest nonfrail elderly, a positive relationship between SBP and all-cause mortality was observed. Conclusions: Frailty modifies the relationship between blood pressure and mortality in elderly patients with T2DM. Higher blood pressure was related to increased cardiovascular mortality in nonfrail patients, even in the oldest elderly, and to lower all-cause mortality in frail patients. Keywords: blood pressure, diabetes mellitus type 2, elderly, mortality, observational studies Abbreviations: T2DM, type 2 diabetes mellitus; ZODIAC, Zwolle Outpatient Diabetes project Integrating Available Care INTRODUCTION A lthough numerous randomized controlled trials have investigated the effects of blood pressure low- ering on a variety of end points in patients with type 2 diabetes mellitus (T2DM), only the Action in Diabetes and Vascular disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study performed a sub- analysis for the oldest elderly (>75 years) [1]. This subanal- ysis showed beneficial effects of the blood pressure- lowering intervention with respect to cardiovascular mortality. However, the generalizability of the results from this subanalysis has been questioned, as only relatively healthy patients were included [2]. Observational studies have shown that there appears to be an absence or even an inverse relationship between blood pressure and mortality in elderly patients with T2DM, even after adjustment for a measure of heart failure [3–5]. The level of frailty has been postulated as an explaining factor. Frailty can be defined as the vulnerability of a patient to a sudden change in health status after a minor illness, which increases the risk of adverse health outcomes [6]. Physical functioning, measured with walking speed, influences the relationship between mortality and blood pressure [7]. A positive relationship between blood pressure and mortality was observed among the fast walkers, whereas no relationship was observed among slow walkers. We aimed to investigate whether adjustment for a measure of frailty, derived from the RAND-36 questionnaire, would influence the inverse Journal of Hypertension 2015, 33:1162–1166 a Diabetes Centre, Isala, Zwolle, b Department of General Practice, c Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, d Department of Internal Medicine, Isala, e Langerhans Medical Research Group, Zwolle and f Department of Internal Medicine, Gelre Hospital, Apeldoorn, The Netherlands Correspondence to Kornelis J.J. van Hateren, MD, PhD, Diabetes Centre, Isala, P.O. Box 10400, 8000 GK Zwolle, The Netherlands. Tel: +31 38 4242518; fax: +31 38 4243367; e-mail: k.j.j.van.hateren@isala.nl Received 1 October 2014 Revised 28 January 2015 Accepted 28 January 2015 J Hypertens 33:1162–1166 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI:10.1097/HJH.0000000000000555 1162 www.jhypertension.com Volume 33  Number 6  June 2015 Original Article