Το µεταβολικό σύνδροµο σχετίζεται µε υψηλό επίπεδο διέγερσης του συµπαθητικού νευρικού συστήµατος και αυξηµένη αρτηριακή σκληρότητα σε ασθενείς µε ανθεκτική υπέρταση Κ.Δηµητριάδης, Κ.Τσιούφης, Θ.Καλός, Λ.Νικολοπούλου, Ι.Λιατάκης, Ε.Κούτρα, Ε.Ηλιάκη, Σ.Γαλανάκος, Δ.Τούσουλης Α Πανεπιστηµιακή Καρδιολογική Κλινική, Ιπποκράτειο Νοσοκοµείο Αθηνών
Increased sympathetic activity in hypertension Severe hypertensives Mild to moderate hypertensives normotensives Grassi G, Exp Physiol 2009 Tsioufis C. International J Hypertension 2011
MS and MSNA in hypertension Grassi G, et al. Diabetologia 2005; 48: 1359
Methods investigating SNS Baroreceptor function Heart rate variability Catecholamines MSNA Regional catecholamine spillover
Microneurography 17 June 1966 a meeting of the Scandinavian EEG society in Copenhagen by Vallbo AB and Hagbarth KE
Aortic PWV as predictor of CV events Carotid-to-femoral PWV is predictor of cardiovascular events in hypertension the relationship of stiffness with events is continuous the cut-off point of >12 m/sec is proposed >10 m/sec in a recent consensus
Aim of the study To assess the effect of metabolic syndrome (MS) on muscle sympathetic nerve activity (MSNA) and arterial stiffness in patients with resistant hypertension (RHT)
Study data Study population: Subjects with RHT hypertension that referred to the hypertension clinic of our institution for BP evaluation and management Exclusion criteria: Secondary hypertension Pseudo RHT Atrial fibrillation or major cardiac arrhythmias DM on insulin therapy Established cardiovascular /renal disease at baseline Significant valvular disease Significant systemic illness/terminal disease Unwilling to sign informed consent
Study population We investigated 36 RHT patients (mean age 59 years, 24 males, office blood pressure (BP)=178/93 mmhg, under 4.3±0.6 drugs)
Definition MS (ATP III) 1. abdominal obesity: waist circumference (measured at the midpoint between the bottom of the rib cage and the top of iliac crest from patients at minimal respiration) >102 cm in men and >88 cm in women; 2. hypertriglyceridaemia: serum triglycerides >150 mg/dl; 3. low high-density lipoprotein (HDL) cholesterol: <40 mg/dl in men and <50 mg/dl in women; and 4. impaired glucose metabolism: high fasting blood glucose 100 mg/dl.
MSNA technique
Procedures: c-f PWV estimation computerized method, by a validated device (Complior SP ) online recording and calculation of c-f PWV 2 different PWV tracings recorded simultaneously Time delay between rapid upstroke of c-f artery pulse waves 5 consecutive measurements obtained and averaged
Parameter Clinical characteristics RHT RHT P with MS without MS (n=20) (n=16) Age at baseline (years) 59±9 58±10 NS Male (%) 62.5 70 NS Body mass index (kg/m 2 ) 31.8±1.2 26.1±0.9 <0.05 Waist circumference (cm) 109.2±5.4 94.8±9.1 0.001 Current smokers (%) 38 35 NS Type 2 diabetes (%) 43 10 <0.001
Antihypertensive therapy Parameter RHT with MS RHT without MS P (n=16) (n=20) Number of drugs 4.3±0.5 4.2±0.5 0.667 ACE inhibitors/arbs/dri (%) 100 100 -- Aldosterone antagonists (%) 36 38 0.609 Beta-blockers (%) 82 84 0.544 CCBs (%) 100 100 -- Diuretics (%) 100 100 -- Oral sympatholytics (%) 28 31 0.600
Office and ambulatory data Parameter RHT with MS RHT without MS P (n=16) (n=20) Office systolic BP (mmhg) 185±16 172±13 <0.05 Office diastolic BP (mmhg) 97±12 92±10 <0.05 Office HR (bpm) 78±2 75±4 NS 24h systolic BP (mmhg) 153±12 146±11 <0.05 24h diastolic BP (mmhg) 88±11 82±8 <0.05 24h ambulatory HR (bpm) 76±4 73±6 NS
Renal and metabolic profile Parameters RHT with MS (n=16) Patients without MS (n=20) P Glucose (mg/dl) 130.9±12 94.3±11 <0.05 Insulin (µιu/ml) 11.8±0.7 8.3±0.5 <0.05 Creatinine (mg/dl) 1±0.3 0.96±0.3 NS egfr (ml/min/1.73m 2 ) 75.3±19.2 77.4±17.1 NS Triglycerides (mg/dl) 188±112 116±103 <0.05 HDL cholesterol (mg/dl) 42±11 60±9 <0.05 LDL cholesterol (mg/dl) 164±32 138±39 <0.05
Echocardiography data Parameter RHT with MS RHT without MS P (n=16) (n=20) Left atrial diameter (mm) 43.0 ± 3.1 42.4 ± 4.1 NS IVSTd (mm) 12.7 ± 1.6 11.3± 1.2 <0.05 LVPWTd (mm) 12.5 ± 1.1 11.2± 1.4 <0.05 LVEF (%) 63.1± 5.2 61.7 ± 3.4 NS LV mass/body surface area (g/m 2 ) 132.2± 17.1 123.6 ± 16.2 0.001 Mitral inflow E/A ratio 0.72 ± 0.20 0.9± 0.17 <0.05
MSNA and PWV data Parameter RHT with MS RHT without P (n=16) MS (n=20) PWV (m/sec) 11.8± 0.7 9.2± 0.9 <0.001 MSNA (bursts/min) 55.1±1.9 44.3±2.1 <0.05 MSNA (bursts per 100 heartbeats) 82.1 ±2.5 73.3± 2.1 <0.05 Respiratory rate (breaths/min) 19.3 ±1.3 19±1.7 NS
Characteristic MSNA recording in a resistant hypertensive patient with MS 58 bpm 58 bpm Raw Raw MSNA Integrated MSNA Integrated MSNA MSNA: 81 bursts per 100 heart beats
MSNA recording in a resistant hypertensive patient without MS 58 bpm Raw MSNA Integrated MSNA MSNA: 60 bursts per 100 heart beats
PWV (m/ sec) PWV and MSNA levels in study groups p<0.001 MSNA (bursts/100 heartbeats) p<0.001 MS No MS MS No MS
Additional analysis Analysis in the non-dm patients (27 patients) confirmed the higher MSNA and PWV related to MS PWV was related to office and ambulatory systolic BP (r=0.245 and 0.224 respectively p<0.05) MSNA was associated with waist circumference (r=0.36, p=0.004) and office systolic BP (r=0.36, p<0.05)
Limitations Small number of patients Lack of control/healthy group No norepinephrine estimation/ssna Lacking analysis of baroreflex response data Effects of multiple drugs on sympathetic drive
Συµπεράσµατα Στην ανθεκτική υπέρταση το µεταβολικό σύνδροµο σχετίζεται µε υψηλά επίπεδα MSNA και καρωτιδο-µηριαίας ΤΣK Τα ευρήµατα αυτά υποστηρίζουν ότι η παρουσία του µεταβολικού συνδρόµου επιβαρύνει περαιτέρω την υπερδραστηριότητα του συµπαθητικού νευρικού συστήµατος και την αρτηριακή σκληρότητα στους ασθενείς µε ανθεκτική υπέρταση
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