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. A ..
WCH - Prevalence
WCH can account for up to 40-50% of the overall hypertensive population
HT FU 16 years
P < 0.0001
0.35
0.30
HT
0.25
FU 16 years
P < 0.0001
77 (19.7%)
WCH
21 (5.4%)
WCH
53 (6.4%)
0.02
0.00 0 2 4 6 8 10 12 14
NT
2 4 6 8 10 12 14
0.00 0 20
16
18
20
Years
Years
In a number of studies CV risk increased Greater risk of new onset DM / established HT / LVH Out-of-office BP values higher than in true normotensives Beneficial effects of antihypertensive treatment never addressed by randomized trials
Patients with WCH well represented in several trials demonstrating the beneficial effects of treatment
Increased nighttime blood pressure or nondipping profile for prediction of cardiovascular outcomes. Review article
Our
the phenotype of isolated nocturnal hypertension is better associated with CV target organ damage and 'hard end points' as compared with the nondipping pattern
Tsioufis
C, et al.
Comparative prognostic role of nighttime blood pressure and nondipping profile on renal outcomes.
These
findings underline the importance of nocturnal BP phenotypes, retrieved by ambulatory BP measurements, on age-dependent progressive kidney function decline and question whether, to what extent and in whom the reduced nocturnal BP or reverse nondipping BP profile to a normal pattern will be of benefit C, et al Am J Nephrol 2011;33:277-88
Tsioufis
Rothwell
Zhang
11-Year Increase in Risk of CV Death for 10 mmHg Increase in SBP at Different Baseline SBP Values
5
4 3
4.5
2.4
2 1 0
0.9 0.6
2.0
120
130
140
Baseline SBP (mmHg) Sega, Facchetti, Bombelli, Corrao, Grassi, Mancia, Circulation 2005; 111: 1777-1783
ROC Curve Areas (AUC) for Prediction of CV Events by Different SBPs and SBP Combinations (PAMELA)
Sensitivity
1.0
0.9 0.8 0.7 0.6 0.5 0.76 0.742 Clinic 0.742 Clinic + 24h 0.753 * Clinic + Home 0.762 All three 0.764 Ref 0.5 0.6 0.7 0.8 0.9 0.78
Clinic AUC
0.80
Clinic + Home
Clinic + 24h
0.762 0.753
*
0.764
0.4
0.3 0.2 0.1 0 0 0.1 0.2 0.3 0.4
0.74
*
AUC
0.72 1.0
1-Specificity
P significant vs: *
0.70
Absolute values and differences between clinic and ambulatory BP at baseline and with different targets with treatment
160 130 S
139.0 14.8
Baseline (n = 422)
128.3 125.5 13.7 13.9
mmHg
100
D
70 40 5
80.3 9.3 75.0 9.3
72.4 8.6
Clinic Day
74.3 8.9 71.8 8.6 68.9 8.2
71.5 8.4 70.7 8.2 68.6 7.9
67.9 8.3
68.9 7.3
66.8 6.8
24h
from clinic
Day 24h Day 24h
from clinic
Day 24h Day 24h
from clinic
Day 24h
-0.8
+2.3
from clinic
+0.6 +1.0
Day 24h
-0.8
-1.1
mmHg
-2.5
-2.0
Day 24h
-2.9
Day 24h
-5 -10 -15
-3.5
-13.5
( +)
18,7
( -)
(+)
7,4
20% 10 (10% 5) .
Not the lower the better but the earlier the better
ONTARGET: Adjusted risk of outcome events achieved by SBP divided into deciles.
H =130 mmHg J
INVEST Study
JACC 2009;54(20):1827-34
INVEST Study
JACC 2009;54(20):1827-34
1. 2.
3.
<< >>
-INVEST-ACTION-Syst-Eur:
J ( 70-80mmHg)
(, YAK, ) .
BP Goals of Treatment
On the basis of current data, it may be prudent to recommend lowering BP within the range of 130-139 / 80-85 mmHg in all HTs, and possibly close to lower values in this range
Mancia et al., ESH Task Force, J Hypertens 2009; 27: 2121
WHO/ISH (2003)
NICE (2006) ESH/ESC (2003/2007) ESH Reappraisal (2009) JACC (2011, Elderly) NICE (2011) JNC 8
exists in clinical practice. In clinical practice no drug is ALWAYS 1st choice and no drug is
NEVER 1st choice.
antihypertensive treatment trials) should move more and more towards an INDIVIDUALIZED treatment approach.
---
, ACEI, ARB ACEI, ARB BB, ACEI, ARB BB, BB, CA ACEI, ARB Diuretics, BB, ACEI,
ARB,Antialdost.ant
BP-Lowering Regimens Based on Different Drug Classes and Total Major CV Events in Younger and Older Patients
No. of events/patients Difference in SBP/DBP (mmHg) 1st listed 2nd listed ACEI vs D or BB Age < 65 819/ 9448 Age 65 1795/10783 CA vs D or BB Age < 65 1165/20358 Age 65 2653/21204 ACEI vs CA Age < 65 548/ 5130 Age 65 1583/ 8170 ARB vs others Age < 65 183/ 742 Age 65 438/ 3167 Risk ratio (95%CI) Risk ratio (95%CI) P for homogeneity
1066/12012 2525/14429 1430/23236 3363/24981 568/ 4919 1608/ 8140 204/ 722 487/ 3171
1.05 (0.96-1.14) 1.01 (0.95-1.06) 1.06 (0.98-1.14) 1.02 (0.97-1.06) 0.91 (0.78-1.06) 0.98 (0.92-1.05) 0.89 (0.75-1.05) 0.91 (0.81-1.02)
2.0
Individual treatment can (regretfully) not apply to all patients Need for genetic/other markers of treatment efficacy(BP reduction/improvement of OD/event prevention )and safety in individuals
Effects on metabolic risk factors Effects on organ damage Presence / absence of diabetes / MS Presence / absence of CKD Presence / absence of CVD
Other disorders limiting particular drug use Cost of drugs 24h BP coverage Once-a-day administration Favorable side effect profile Previous patients experience with drug class
Ratio of observed to expected incremental blood pressure-lowering effects* of adding a drug or doubling the dose according to the class of drug (n = 11000, 42 studies)
Incremental SBP reduction ratio of observed to expected additive effects
1.5
1.04 (0.88-1.20) 1.00 (0.76-1.24) 0.89 (0.69-1.09) 1.01 (0.90-1.12) 1.16 (0.93-1.39)
1.0
0.5
0.19 (0.08-0.30)
Adding a drug from another class (on average standard doses) Doubling dose of same drug (from standard dose to twice standard)
0.22 (0.19-0.25)
0.20 (0.14-0.26)
0.0
Thiazide
Betablocker
ACEinhibitor
All classes
* The expected incremental effect is the incremental blood pressure reduction of the added (or doubled drug), assuming an additive effect and allowing for the smaller reduction from 1 drug (or dose of 1 drug) given the lower pretreatment blood pressure because of the other
1980s
1990s2000s
ACE inhibitor/thiazide
ACEI / CA
Syst-Eur Syst-China INVEST ASCOT STAR ACCOMPLISH
CA / D
FEVER ELSA VALUE HOT
ARB / D
LIFE SCOPE RENAAL TRANSCEND
ARB / CA
RENAAL (?)
CA / BB
HOT (2nd used)
Diuretic
ACE inhibitors
Mancia et al., J Hypert 2009; 27: 2121
Effects of Persistence or Adherence with Antihypertensive Drug Therapy on the Reduction in Hazard Ratio of Coronary (n = 6665) and Cerebrovascular (n = 5351) Outcomes in 242.594 Patients Persistence category
0
Adherence level
0 -10 -20 -30 -40
Continuing use
Low
Intermediate
High
-16% -21%
-24%-23%
-37% -36%
-50 -50
Estimates are adjusted for gender, age, initial antihypertensive regimen, number of different classes of antihypertensive medications dispensed during FU, use of other drugs during FU, and categories of Charlson comorbidity index score. * At least 1 episode of no prescription coverage for > 90 days
Corrao, Parodi, Nicotra, Zambon, Merlino, Cesana, Mancia, J Hypert 2011; 29: 610-618
New devices
CPAP Deep brain stimulation Device guided respiration Brainstem neurovascular decompression Renal artery stending Rheos device
Renal denervation
Pathophysiological substrate of
activated renal sympathetic fibers in the pathogenesis of hypertension
Severe hyprertensives
normotensives
SNS
Kidney
HTN
..The renal sympathetic nerves probably serve as the critical link between the sympathetic nervous system and the kidney in hypertension.
DiBona, Curr
Mechanoreceptors chemoreceptors
CV mortality risk
8 6 4 2 0
1X risk 8X risk
4X risk 2X risk
115/75
135/85
155/95
175/105
SBP/DBP (mmHg)
Lewington et al. Lancet 2002;360:190313
*Individuals aged 4069 years
Severe
Resistant hypertension
Current indications
office BP 160 systolic or 100 mmHg diastolic (150/95 mmHg in type 2 diabetes) despite
Resistant Hypertension
Diagnosis
Diet
Drugs Devices
Second step:
Optimize antihypertensive treatment with at least 3 (or better 4) tolerated drugs including a diuretic and an antialdosterone drug (if clinically possible, e.g after reevaluating renal function and the potential risk of hyperkaliemia) Check for effective BP control using ABPM before giving indication for RDN
Schmieder,.........Tsioufis. J Hypertens. 2012;30:837-841.
Exclusion criteria
Clinical eGFR<45 mL/min per 1.73 m 2 DM-I history of a recent MI, unstable angina, or a cerebrovascular accident within 6 months, Pregnacy Anatomical History of renal artery intervention (balloon angioplasty or stenting) Renal artery irregularities (stenosis >30%, aneurusm) multiple renal arteries (>20mm in diameter) main renal arteries of less than 4 mm in diameter or less than 20 mm in length
Straightforward procedure
goal
Centres should be specialized in the management of hypertension (ie ESH Hypertension Excellence Centers) with at least one hypertension expert being actively involved in the treatment and screening process. The interventions are performed by interventional cardiologists or angiologists who have been trained in performing this specific intervention and who are qualified to manage potential complications such as acute dissection of renal arteries by stent implantation Appropriate expertise could be assumed in centres with >25 renal interventions per year. Centers should enter their data into large registries to ensure proper quality control and to allow for an analysis of the procedural success acutely and at long-term follow up. Eur Heart J April 2013
Pain? Changes in renal haemodynamics? Electrical stimulation at ostium of each renal artery?
Treatment Procedure
Only the next days/weeks post procedure Renal Noradrenaline spillover MSNA BP reduction
Re-evaluation and implementation of current eligibility criteria (anatomical and clinical) for RSD therapy
Patients eligibility for RSD confirmed Specialized catheterization laboratory Center for RSD
RSD therapy
Future Medicine
Personalized Medicine