Presentación del Dr. Luis Miguel Ruilope Urioste, del Hospital Universitario 12 de Octubre de Madrid, durante la I Reunión de Denervación Renal de la Sección de Hemodinámica y Cardiología Intervencionista (SHCI) de la Sociedad Española de Cardiología (SEC), celebrada del 29 al 30 de enero de 2014.

1. Resistant hypertension:
NECESIDADES PARA INICIAR UN
PROGRAMA DE DENERVACION
Luis M Ruilope

2. GRADES OF BP AS DEFINED BY CURRENT GUIDELINES
• OPTIMAL BP < 120/80 mmHg
• NORMAL BP 120-129/80-84 mmHg
• HIGH-NORMAL BP 130-139/85-89 mmHg
• GRADE 1 HYPERTENSION 140-159/90-99 mmHg
• GRADE 2 HYPERTENSION 160-179/100-109 mmHg
• GRADE 3 HYPERTENSION > 180/110 mmHg
• ISH > 140/< 90 mmHg
• RESISTANT HYPERTENSION
• MALIGNANT HYPERTENSION

4. Other definitions
• Controlled hypertension (<140/90 mmHg)
requiring 4 or more drugs can be
considered as resistant while refractory
hypertension should be that present in
patients requiring 5 or more drugs in the
absence of adequate control.
Calhoun D et al, Circulation 2008.

5. EXCLUSION OF
PSEUDORESISTANCE
• THE ROLE OF ABPM AND
HBPM IN THE CORRECT
DIAGNOSIS OF
RESISTANT
HYPERTENSION

6. Frequency of Resistant Hypertension
in Treated Hypertensives: Spain
de la Sierra A et al. Hypertension. 2011;57:898-902.
Treated Patients With
Hypertension
Resistant Hypertension
(12.2% of total
treated population)
True resistant
hypertension
(7.6% of total treated
population)
White-coat
hypertension
(4.6% of total treated
population)

7. Proportion of patients diagnosed as
having Refractory hypertension with
normal ABPM values
• Daytime BP < 135/85 mmHg
– 44.1%
• 24-hour BP < 130/80 mmHg
– 37.5%
• Nighttime BP < 120/70 mmHg
– 31.8%

8. TOD and CVD in patients with True (24-h BP
> 130 and/or 80 mmHg) or isolated-office
(24-h BP < 130/80 mmHg) Refractory
hypertension
TOD CVD
0
5
10
15
20
25
30
35
True RH
I-O RH
p<0.001
p<0.001
%

9. Incidence of RH in new hypertensives
• In new hypertensives, 2% present with RH after
18 months of pharmacological therapy
• Development of RH is followed by a 50% increase
in risk of suffering CV events or death
• It takes place after similar duration of arterial
hypertension. There must be a factor accelerating
CV and probably renal damage in RH.
Daugherty et al, Circulation 2012
Pimenta & Calhoun, Circulation 2012

10. FACILITATORS OF BP UNRESPONSIVENESS TO
STANDARD THERAPY
• Clinical inertia
• Poor compliance
• Inadequate diet (salt)
• Inadequate and late use of combinations
• Primary aldosteronism (10-12%)
• Inadequate control of SNS activity
• BP variability
• OSA
• Diabetes and obesity
• CKD
• Progression of arterial disease due to an inadequate BP
control
Solini a & Ruilope LM. Nat Rev Cardiol 2013

11. WHY DOES RH DEVELOP?
• IS THIS A PHENOTYPE?
• IS IT THE CONSEQUENCE OF
MAINTAINEDLY
UNCONTROLLED BLOOD
PRESSURE LEVELS?

12. “neurogenic hypertension”
- 10% of RH patients could
constitute a phenotype
characterized by an increased
heart rate and high levels of
plasma aldosterone
David Calhoun, ISH, Sydney, 2012

13. Dzau et al. Circulation 2006;114:2850–70
Mancia et al. J Hypertens 2007;25:1105–87
Risk factors lead to increasing risk of organ damage
and clinical events: The cardio-renal continuum
● The risk associated with maintainedly elevated BP is greatly
magnified by other CV risk factors, e.g.:
– Hyperlipidaemia
– Diabetes
– LVH
– CKD
– Increased arterial stiffness
● The presence of such risk factors initiates pathological events and
processes like oxidative stress and endothelial dysfunction which
ultimately lead to overt organ damage and failure
● BP can become unresponsive as a consequence of the
maladaptation of the vessels (increase in peripheral resistances and
arterial stiffness)

14. Exclude
Pseudoresistance
Identify and Reverse
Contributing Lifestyle
Factors
Discontinue or Minimize
Interfering Substances
Screen for Secondary
Causes of HT
Pharmacologic
approach:
# adherence
Diagnostic and Treatment
Algorithm of RH
Schmieder 2012

15. Schmieder RE, Redon J, Grassi G, Kjeldsen SE, Mancia G, Narkiewicz, Parati
G, Ruilope L, van der Borne P, Tsioufis C. ESH POSITION PAPER: RENAL
DENERVATION-AN INTERVENTIONAL THERAPY OF RESISTANT
HYPERTENSION. J HYPERTENS (IN PRESS)
• Hypertensive patients are elegible for RDN if
they have treatment resistant hypertension
defined by office SBP >= 160 mmHg (150
mm Hg if type 2 diabetes) despite treatment
with 3 or more drugs og different types in
adequate doses, including one diuretic, which
is equivalent to stage 2 or 3 hypertension.
• Patients should be evaluated by a
hypertension specialist.

16. RESULTS ADEQUATE
INTERVENTION IN RH
• N=197 RH patients with SBP > 160 mmHg
• ABPM normal in 108 (pseudoresistant)
• Spironolactone administered to 75 good
response in 60 (80%)
• Remaining 29 (14 intolerant to spiro), 18
responded to other combinations
• 11 (12.3%) were denervated
Fontela A et al, Rev Esp Cardiol 2012

17. True resistant HTN non responders to spironolactone
Δ Office BP (final vs baseline)
Post-Spironolactone Post-Aliskiren 300 mg
+3 mmHg
-9 mmHg*
-30
-25
-20
-15
-10
-5
0
5
Office Diastolic BP
P< 0.004
+1 mmHg
-28 mmHg*-30
-25
-20
-15
-10
-5
0
5
Office Systolic BP
P<0.005
*p<0.05 for differences between post- and pre-aliskiren therapy
Segura J.et al., J Am Soc Hypertension 2011

18. CONCLUSIONS
1- RH IS A PREVALENT PROCCESS
2- ADEQUATE INTERVENTION DEFINES
AND CONTROL THE MAJORITY OF CASES
3- IDEALLY THREE PARTNERS INTERVENE IN
THE PROCCESS: PRIMARY CARE,
HYPERTENSIOLOGIST AND INTERVENTIONIST
4- RDN IS REQUIRED IN 10-15% OF THE
CASES