1. Neuro-Hormonal vs Structural Hypertension why they require different approaches
Paul A. Sobotka
Chief Medical Officer
Rox Medical, Inc.

2. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
Employee
Consultant
Rox Medical, Inc.
Cibiem, Inc.

3. Structural verses Neuro Hormonal Hypertension
Structural HTN
Neuro-Hormonal HTN
Adapted from Physiology; Berne & Levy

4. Elastic Fibers are Terminally Differentiated After the age of 50, HTN is principally Structural
Systolic BP
Diastolic BP
Of course we have known this for 2 decades- the bp and pulse pressure rise with age, and about the age of 50 something not so mysterious develops- pulse pressure widens= the hallmark of changes in underlying causes of hypertension
Burt. Hypertension 1995;25:313

5. Renal Sympathetic Activity Declines with Age
Indeed Murray Esler published in 1986 the contribution of renal sympthatic activity to hypertension as a function of age and he observed that renal sympathetic drive falls as patients get older, which implies that renal neuro or renal sympathetic drive is less and less a contributing factor to hypertension in aging. A similar graphic can be made for MSNA and age, which shows that aging is associated with hypertension in a mechanism other than sympthatetic drive.
Esler et.al., J Cardiovasc Pharmacol, 1986

6. The aorta is meant to buffer each heart beat The Windkessel Function of the Aorta

7. Even a small amount of compliance dramatically reduces peak pressure
Non compliance and pistol shot arterial wave forms

8. Loss of Aortic Elasticity Increases Volume Sensitivity
Aging, ISH
Volume Sensitivity
Circumferential STRESS
N/cm2
Circumferential STRAIN
(aortic distension)

9. Loss of Aortic Elastance

10. Treatment of Structural Hypertension Reduce Effective Arterial Volume
Circumferential STRESS
N/cm2
Circumferential STRAIN
(aortic distension)

11. Reduction of Arterial Volume with Diuretics
2.4% of total body water is arterial (42l water in a 70kg adult);
To reduce effective arterial volume by 1 liter, a diuretic must remove 25% circulating volume;
Restoring Windkessel with diuretics inherently activates RAA and is associated with systemic AE.
adapted by Cevasco M and Dunlap ME 

12. Loss of Aortic Elasticity Increases Pulse Wave Velocity
Avolio et al; Circ:1983

13. Young Compliant Arteries
Young compliant arteries : Normal PW velocity (8 m/sec)
Diastole
Systole

14. Elderly Stiff Arteries
Elderly stiff arteries with ISH : Increased PW velocity (12 m/sec)
Systole
Ventricular-vascular mismatch The reflected wave increases central SBP during late systole:

15. Futility of Targeting Peripheral Vascular Resistance
The model is open to room air, as if all PVR is eliminated

16. Physiology Profile Hypertension
Structural HTN
Age > 60y
Pulse Pressure > 60 mmHg
Pulse Wave Velocity elevated (>10m/s)
Treatment targeting functional etiology will be less or not effective in reducing bp (which does not mean that they may not have clinical benefits)
RDN (EuroIntervention May;11(1):110-6)
Medications

17. 75% of Uncontrolled HTN is Structural 68% Uncontrolled Hypertension > 65 years
patients are over 50yr
% Uncontrolled
Isolated
Systolic
Htn
Isolated
Systolic Htn
aka,
‘Structural
Hypertension’
Sys/Dias
Htn
As we look at which patients are struggling most with control of their hypertension, it is the older patients, over age 50yrs who comprise 85% of the uncontrolled hypertension patients. They are as adherent to medications, but are getting less relief or effect. This is because their hypertension has fundamentally changed to predominantly Isolated Systolic Hypertension or Structural Hypertension do to arterial and aortic stiffening.
Isolated
Diastolic
Htn
Franklin et al, Hypertension 2001

18. Experience with catheter-based renal denervation
Ott, ESH 2015
Experience with catheter-based renal denervation
BP responce after renal denervation (RDN) is heterogenous
Ewen et al, Hypertension 2015;65:193-9)

19. 75% of Uncontrolled HTN is Structural 68% Uncontrolled Hypertension > 65 years
patients are over 50yr
% Uncontrolled
Isolated
Systolic
Htn
Isolated
Systolic Htn
aka,
‘Structural
Hypertension’
Sys/Dias
Htn
As we look at which patients are struggling most with control of their hypertension, it is the older patients, over age 50yrs who comprise 85% of the uncontrolled hypertension patients. They are as adherent to medications, but are getting less relief or effect. This is because their hypertension has fundamentally changed to predominantly Isolated Systolic Hypertension or Structural Hypertension do to arterial and aortic stiffening.
Isolated
Diastolic
Htn
Franklin et al, Hypertension 2001

20. Mechanical Solution for Structural Hypertension
Consider the Rox Coupler a mechanical solution to a structural etiology- retrospective analysis of outcomes with the coupler based on presence of ISH
Effect of the ROX coupler implantation in subgroups of
Combined hypertension: SBP > 140 and DBP > 90 mmHg
Isolated Systolic Hypertension: SBP > 140 and DBP < 90 mmHg
C Ott et al. J Am Heart Assoc Dec 21. 5(12)

21. Office systolic BP reduction (mmHg)
Ott, ESH 2015
Office blood pressure reduction after 6 months
CH ISH
Office systolic BP reduction (mmHg)
after 6 months
p = 0.572*
*even after adjustement (age, baseline office systolic BP): CH/ISH has no impact on office BP reduction (p=0.910).

22. Ambulatory systolic BP reduction (mmHg)
Ott, ESH 2015
Ambulatory blood pressure reduction after 6 months
CH ISH
Ambulatory systolic BP reduction (mmHg)
after 6 months
p = 0.672*
*even after adjustement (age, baseline ambulatory systolic BP): CH/ISH has no impact on office BP reduction (p=0.720).

23. Mechanical solutions for structural hypertension: Immediate BP reduction (-28/-15 mmHg)
Systolic BP
( mmHg )
~72
~60
Diastolic BP
( mmHg )
Eliminates the possibility of placebo, sham or Hawthorne effects