Declaration of conflict of interest

Declaration of conflict of interest

Prevalence and main features of resistant hypertension in Central and Eastern Europe: data from the G. Brambilla 1, G. Seravalle 2, R. Cifkova 3, C. Farsang 4, S. Laurent 5, H. K. Narkiewicz 6, J. Redon 7, M. Bombelli 1,G. Mancia 1, G. Grassi 1 1 Clinica Medica, University of Milano-Bicocca, Ospedale San Gerardo dei Tintori, Monza, Milan, Italy; 2 Istituto Auxologico Italiano, Ospedale San Luca, Milan, Italy; 3 Institute of Clinical and Experimental Medicine, Prague, Czech Republic; 4 Cardiometabolic Department, St Imre Teaching Hospital, Budapest, Hungary; 5 Pharmacology Department, Hopital Europeen Georges Pompidou, Paris, France; 6 Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland; 7 Internal Medicine, Hospital Clinico, University of Valencia, Valencia, Spain.

Resistant Hypertension 27 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, HeagertyAM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, StruijkerBoudier HA, Zanchetti A. J Hypertens 27;25:115-187 Hypertension is usually defined resistant or refractory to treatment when a therapeutic plan that has included attention to lifestyle measures and the prescription of at least three drugs (including a diuretic) in adeguate doses has failed to lower systolic and diastolic blood pressure to goal

Prognosis of Resistant Hypertension In the unadjusted analysis, patients with resistant hypertension were significantly more likely to suffer the combined outcomes of death, MI, CHF, stroke or CKD (18.% vs. 13.5%%, p<.1, unadjusted HR 1.54, 95% CI 1.4-1.69). Following multivariable adjustment including baseline patient demographics, comorbidities, study site, and year of study entry, resistant hypertension was associated with increased risk of adverse CV outcomes (HR 1.47, 95% CI 1.33-1.62, p<.1) Daugherty SL, et al. Circulation 212; published online February 29, 212.

Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, White A, Cushman WC, White W, Sica D, Ferdinand K, Giles TD, Falkner B, Carey RM. Hypertension. 28;51:143-19 Resistant Hypertension

Resistant Hypertension Prevalence of Resistant Hypertension in the United States, 23 28 Persell SD. Hypertension 211; 57: 176-18 Uncontrolled and apparent treatment resistant hypertension in the United States, 1988-28 Egan Bm, Zhao Y, Axon Rn, Brzezinski WA, Ferdinand KC. Circulation 211;124:146-158 Clinical features of 8295 patients with resistant hypertension classified on the basis of ambulatory blood pressure monitoring de la Sierra A, Segura J, Benegas JR, Gorostidi M, de la Cruz JJ, Amario P, Oliveras A, Ruilope LM Hypertension 211; 57: 898-92. Incidence and prognosis of resistant hypertension in hypertensive patients Daugherty SL, Powers D, Magid DJ, Tavel HM, Masoudi FA, Margolis KL, O Connor PJ, Selby JV, Ho M Circulation 212; published online February 29, 212.

Aim of the study Evaluate the prevalence and clinical characteristic of resistant hypertension in the population of the BP-CARE study (9 european eastern countries)

Blood Pressure Control Rate and Cardiovascular Risk Profile (BP-CARE) Latvia Belarus Czech Republic Slovakia Ukraine Romania Bosnia Serbia Albania 1 February to 3 March 28 9 countries involved About 8 doctors involved (General practitioners and specialists) 7923 patients enrolled Data collection form: - Personal history - Demographic parameters - Anthropometric parameters - Drug history - Values of blood pressure - Glycemic and lipid profile (last 12 months) - Laboratory Tests (last 12 months) 4738 G Grassi G, et al. Eur Heart J 211

Prevalence of resistant hypertension in a BP-CARE subpopulation n=1312 n=521 n=423 Non compliant (n=7) Non compliant and WCH (n=34) WCH (n=64) n=368 True Resistant Hypertension (atrh) (n=255, 19.4%) HT controlled BP 14/9 mmhg HT uncontrolled BP > 14/9 mmhg, and N of drugs < 3 or N of drugs > 3 (without diuretic) Resistant Ht BP > 14/9 mmhg, and N of drugs 3 (with diuretic), or N of drugs 4 (with diuretic).

Demographic and anthropometric variables Years % Kg/m 2 Cm * 8 1 4 12 6 4 2 8 6 4 2 3 2 1 1 8 6 4 2 Age Gender (M) BMI WC Controlled HT Uncontrolled HT TRH

Hemodynamic parameters mmhg 2 * mmhg 12 * bpm 1 * 18 16 1 8 14 12 8 6 1 6 8 4 6 4 4 2 2 2 SBP DBP HR Controlled HT Uncontrolled HT TRH

Pharmacologic treatments a.u. 5 % 1 4 3 2 1 Number of drugs 9 8 7 6 5 4 3 2 1 ACE-i B-B AT2 Ca-A D Other Use of different class of antihypertensive drugs Controlled HT Uncontrolled HT TRH

Resistant Hypertension and comorbidities % 7 6 * Controlled Ht Uncontrolled HT TRH 5 4 3 2 * * 1 OB Central OB DM Renal disease

Resistant Hypertension and comorbidities % 7 6 5 Controlled HT Uncontrolled HT TRH 4 3 2 * 1 * CHD CHF STROKE TIA

Metabolic profile mg/dl mg/dl mg/dl 3 25 2 15 1 5 Total Cholesterol 8 6 4 2 32 28 16 24 14 2 12 16 1 8 12 6 8 4 4 2 mg/dl HDL Cholesterol Triglycerides Glycaemia Controlled HT Uncontrolled HT TRH 18

Renal Function ml/min/1.73m 2 12 * 1 8 6 4 2 egfr (MDRD) Controlled HT Uncontrolled HT TRH

Conclusion The present study provides evidence that the prevalence of TRH in Central and Eastern european countries is superimposable to that of western Europe and USA. It also shows 1) the very high cardiovascular risk profile of TRH and 2) the high association of this condition with overweight, obesity, diabetes, renal failure and a history of previous cardiovascular events.

RHT and BP values at diagnosis % 6 5 4 * Controlled HT Uncontrolled HT TRH 3 2 1 Stage 1 HT Stage 2 HT Stage 3 HT ISH