DECLARATION OF CONFLICT OF INTEREST. None to declare

Transcription

1 DECLARATION OF CONFLICT OF INTEREST None to declare

2 Sympathetic nerve traffic, insulin resistance and baroreflex control of circulation in patients with resistant hypertension Gino Seravalle Marco Volpe Federica Ganz Laura Magni Gianmaria Brambilla Raffaella Dell Oro Simone Muraro Michele Bombelli Giuseppe Mancia Guido Grassi 572 GS European Society of Cardiology - Paris 2011

3 2007 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 2007;25: 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. 2008;51: Resistant hypertension is defined as the failure to achieve goal blood pressure in patients who are on optimal doses of three or more antihypertensive medications, ideally one of which is a diuretic 573 GS

4 Prevalence of TRUE resistant hypertension Prevalence of Resistant Hypertension in the United States, Stephen D. Persell Hypertension 2011; 57: The prevalence of resistant hypertension is unknown. Using data from the National Health and Nutrition Examination Survey from 2003 through 2008, nonpregnant adults with hypertension were classified as resistant if their blood pressure was 140/90 mm Hg and they reported using antihypertensive medications from 3 different drug classes or drugs from 4 antihypertensive drug classes regardless of blood pressure. Among US adults with hypertension, 8.9% (SE: 0.6%) met criteria for resistant hypertension. This represented 12.8% (SE: 0.9%) of the antihypertensive drug treated population. adults with resistant hypertension were more likely to be older, to be non- Hispanic black, and to have higher body mass index (all P<0.001). They were more likely to have albuminuria, reduced renal function, and self-reported medical histories of coronary heart disease, heart failure, stroke, and diabetes mellitus (P<0.001). Most (85.6% [SE: 2.4%]) individuals with resistant hypertension used a diuretic. Of this group, 64.4% (SE: 3.2%) used the relatively weak thiazide diuretic hydrochlorothiazide.. Cardiovascular diseases, diabetes mellitus, obesity, and renal dysfunction were all common in this population. 574 GS

5 Pathophysiological mechanisms in resistant hypertension Less nocturnal dipping Endothelial dysfunction Gene variations Insulin resistance Aldosterone 575 GS Yugar-Toledo JC et al DNACell Biol 2011 Mar 27; Quinaglia T et al J Human Hypertens, advanced publication May 2011 Pimenta E et al J Hypertens 2007;25:2131-7; Calhoun D et al Int J Hypertens 2011:837817

6 Aim of the study Aim of this study was to evaluate the neuroadrenergic profile and its relationship with metabolic/humoral patterns in patients with resistant hypertension 576 GS

7 Methods Population 8 Resistant Hypertensives (RHT; 6 M/2 F; age 61.8 ± 2.9 yrs) 13 Essential Hypertensives (EHT; 9 M/4 F; age 59.7 ± 2.3 yrs) 9 Healthy subjects (C; 7 M/2 F; age 60.0 ± 2.4 yrs) Parameters OSA/sleepiness Berlin questionnaire, Epworth Sleepiness Scale anthropometric: weight, BMI, WC echocardiographic: LVMI, LVEF metabolic Fasting glycaemia e insulinemia HOMA index 24-h ambulatory BP monitoring Spacelabs not invasive beat-to-beat BP Finapres heart rate EKG respiration rate pneumotachograph plasma aldosterone RIA muscle sympathetic nerve traffic Baroreflex sensitivity microneurography, peroneal nerve i.v. infusion vasoactive drugs 577 GS

8 (kg/m 2 ) (b/min) (mmhg) Anthropometric and haemodynamic parameters BMI HR BP S D 15 C EHT RHT 50 C EHT RHT 60 C EHT RHT P < GS

9 (bs/min) (bs/100hb) Sympathetic nerve traffic MSNA MSNA C EHT RHT C EHT RHT 20 P < 0.05; P < GS

10 Question Which mechanisms are responsible for the adrenergic overdrive of resistant hypertension? 1. Aspecific 2. Humoral 3. Metabolic 4. Reflex 580 GS

11 Question: Which mechanisms are responsible for the adrenergic overdrive of resistant hypertension? 1. Aspecific Different degree of BP load Different degree of TOD P < GS

12 (mmhg) Question: Which mechanisms are responsible for the adrenergic overdrive of resistant hypertension? 1. Aspecific Different degree of BP load Different degree of TOD h Daytime Night-time 150 S D 60 C EHT RHT C EHT RHT C EHT RHT P < GS

13 (mmhg) (g/m 2 ) Question: Which mechanisms are responsible for the adrenergic overdrive of resistant hypertension? 1. Aspecific Different degree of BP load Different degree of TOD h Daytime Night-time S LVMI D C EHT RHT C EHT RHT C EHT RHT 50 C EHT RHT P < GS

14 (ng/dl) Question: Which mechanisms are responsible for the adrenergic overdrive of resistant hypertension? 2. Humoral ALDO C EHT RHT P < GS

15 Question: Which mechanisms are responsible for the adrenergic overdrive of resistant hypertension? 3. Metabolic HOMA index C EHT RHT P < GS

16 Correlations between adrenergic and metabolic/humoral factors r Aldo vs MSNA 0.38 HOMA vs MSNA P < EHT RHT EHT RHT 584 GS

17 Question: Which mechanisms are responsible for the adrenergic overdrive of resistant hypertension? 4. Reflex 585 GS

18 Baroreflex Control of HR and MSNA in EHT and RHT HR (b/min) 9 MSNA (%i.a.) MAP (mmhg) <0.05 vs C C EHT RHT 1667 G

19 ΔMSNA (%i.a.)/δmap (mmhg) ΔHR (b/min)/δmap (mmhg) Question: Which mechanisms are responsible for the adrenergic overdrive of resistant hypertension? 4. Reflex Baroreflex sensitivity 0 C EHT RHT 0 C EHT RHT <0.05 vs C 585 GS

20 Conclusions These preliminary findings provide evidence that resistant hypertension is characterized by a marked sympathetic activation, greater for magnitude than that seen in non resistant essential hypertension. They also suggest that in resistant hypertension the adrenergic overdrive: - is not linked to sleep apnoea - is related to insulin resistance and to plasma aldosterone levels - is not influenced by reflex control mechanism that appears to be preserved Implication The greater sympathetic activation seen in resistant hypertension represents the pathophysiological background for the clinical use of renovascular denervation 586 GS

21