Resistant hypertension: NECESIDADES PARA INICIAR UN PROGRAMA DE DENERVACION

Luis M Ruilope

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

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.

EXCLUSION OF

PSEUDORESISTANCE

• THE ROLE OF ABPM AND

HBPM IN THE CORRECT

DIAGNOSIS OF

RESISTANT

HYPERTENSION

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)

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%

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 CVD0

5

10

15

20

25

30

35

True RH

I-O RHp<0.001

p<0.001

%

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

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

WHY DOES RH DEVELOP?

• IS THIS A PHENOTYPE?

• IS IT THE CONSEQUENCE OF MAINTAINEDLY UNCONTROLLED BLOOD PRESSURE LEVELS?

“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

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)

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

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.

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

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

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