Download Advancements in Blood Pressure Management

Advancements in Blood Pressure Management
New technology for better management of anti-hypertension medications and
improved assessment of cardiovascular risk
For over 100 years, physicians have relied on the systolic and diastolic pressures measured with a brachial cuff
sphygmomanometer to manage their patients. However, blood pressure in the brachial artery can be very different from
the pressure at the heart, and numerous recent studies have shown that blood pressure at the heart explains the effects of
anti-hypertensive drugs and predicts clinical outcomes significantly better than brachial pressure. Today, new technology
allows the noninvasive measurement of the central blood pressure with the same fidelity as a pressure catheter placed in the
ascending aorta, without the associated costs and risks. The predictive superiority of central blood pressure over brachial
blood pressure is primarily due to the closer proximity of the ascending aorta to important target organs such as the
heart, brain, and kidney.
Three aspects of central blood pressure are especially important:
• Individual variability in the difference between central and brachial pressures can be significant
and clinically important.
• Central pressures cannot be reliably inferred from brachial pressures.
• Medications may have significantly different effects on brachial blood pressure than on central blood pressure.
Noninvasive Central Blood Pressure Measurement
Central systolic blood pressure cannot be estimated from the brachial systolic value. McEniery et al. reported a study of
over 10,000 adults aged 18 to 101 years whose individual brachial systolic pressures ranged from 100 to 200mmHg1.
They found individual variability between brachial and central systolic pressures ranged from as few as 2-3mmHg to approximately 30mmHg. The variations decreased with age, but even in the oldest adults averaged approximately 10mmHg.
Central pulse pressure also showed a large degree of variability. In addition, central pulse pressure increased continually
over the age range while brachial pulse pressure declined up to age 60 and then increased as individuals aged further1.
Because of such individual variability, central pressure cannot reliably inferred from brachial pressure measurement.
The SphygmoCor XCEL System derives the central aortic pressure waveform using a standard blood pressure cuff.
The pressure oscillations in a partially-inflated cuff are analyzed to produce the central aortic pressure waveform.
As in previous tonometer-based SphygmoCor systems, generalized transfer functions are used to derive the central aortic
pressure waveform and corresponding indices (Figure 1). The SphygmoCor XCEL was cleared by the US Food and Drug
Administration as substantially equivalent to previously validated SphygmoCor systems2. The procedure can be conducted
in the office setting with minimal training and is quick, easy to perform, painless and reproducible.
Figure 1: An example of two patients with the same brachial
systolic/diastolic pressures (144/90), but significantly different
central systolic pressures (122/90 and 136/90).
Left panel – peripheral waveform
Right panel – central aortic waveform.
Central Blood Pressure and Medication Effectiveness
Several recent studies have demonstrated that individuals with the same brachial pressure can have a significantly
different central pressure and that differential clinical outcomes can be explained by these differences in central pressures.
One example is the Conduit Artery Function Evaluation (CAFE) Study which demonstrated that elevated central systolic
and pulse pressure are associated with a higher risk of cardiovascular events and renal impairment, even though brachial
pressures were the same in the different study cohorts3. A later study by Kampus et al. showed that individuals treated
to the same target brachial pressure had different central systolic and pulse pressures and different left ventricular mass
effects4. Different classes of antihypertensive medications can have different effects on the central pressure values5.
In general, vasoactive medications have a more beneficial impact on central blood pressure than non-vasoactive drugs6,7.
Arterial vasodilators promote relaxation of vascular smooth muscle cells, delaying the return of the reflected wave and
reducing systolic augmentation8. As can be seen from Table 1, the effect on central pressure of different classes of
vasoactive drugs varies by class7. In addition an individual’s response can vary, even within the same class of drugs.7
Class
Central Systolic Pressure
Augmentation Index
Arterial Stiffness
ACE inhibitors
Angiotension-receptor blockers
Beta-blockers (non-vasoactive)
Calcium-channel blockers
Diuretics
Nitrates
Table 1: Comparative Effects of Antihypertensive Medications on Central Hemodynamic Indices
Central Blood Pressure, Cardiovascular Risk, and Hypertension
Numerous studies in both healthy and diseased subjects have consistently demonstrated that elevated central blood
pressure is independently associated with increased cardiovascular events and is superior to brachial pressure as
a predictor of those events. In a report from the Strong Heart Study, a multi-year NIH-funded study, Roman et al.
reported that in 2,405 individuals central pulse pressures were more strongly predictive of cardiovascular events,
independent of brachial pressures9. Specifically, when central pulse pressure equals or exceeds 50mmHg, the risk
of cardiovascular disease increases by nearly 70%; in individuals younger than 60 years, the increase was 150%.
The risk for those whose central pulse pressure was less than 50mmHg was statistically the same across all lower
pulse pressures. Thus, in this study, 50mmHg represents a threshold above which the risk of a cardiovascular event
increases dramatically. Brachial pressure did not demonstrate the same threshold for risk. Elevated central pressure
and central pressure indices are also predictive of numerous types of end-organ damage, as well as morbidity and
mortality. The evidence has been reviewed by Nelson et al. in Mayo Clinic Proceedings10.
Several studies have shown that central pressure and central pressure indices can distinguish those individuals who,
although not hypertensive, can be found to have end-organ damage. Just as importantly, brachial pressures could
not make such a distinction. In a study of 1,169 participants, Booysen et al. reported that the classes of normal vs.
high normal brachial blood pressure did not distinguish those with or without end-organ damage11. However, when
the same group was divided according to normal vs. high normal central systolic pressure, the groups with and
without such damage could be identified. Also, Kaess, in a report from the Framingham Heart Study, showed
that central pressure augmentation index predicted the development of hypertension in those who were originally
normotensive12. Brachial pressure measurements were not predictive of the development of arterial stiffness,
a major indicator of end-organ damage. Conversely, a European study of 354 young and middle age people
with untreated Stage 1 hypertension showed that those with low central systolic pressure (<125mmHg) were at
significantly less risk of requiring antihypertensive medication than those with high central systolic pressure13.
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Figure 2: The blood pressure waveform is
comprised of two waves – a forward traveling
wave (dark blue) and a reflected wave (red).
The two add together to form the blood pressure waveform. In young, compliant arteries
the pressure waves travel slowly so that the
reflected wave returns during diastole (2a).
As the arteries stiffen with disease or age, the
wave speed increases, the magnitude of the
reflected wave increases, and the reflected
wave
returns during systole (2b). The result,
Aortic
Aortic
asIncreased
shown
in 2c, is 1) a decrease in myocardial
Increased
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Pressure
perfusion pressure, 2) an increase in left
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LV Load
ventricular afterload, and 3) an increase
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inDecreased
central
pulse
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in
in pressure.
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While blood pressure is most often characterized
in terms of simply a maximum (systolic) and a
minimum (diastolic) pressure, it is actually a
continuous wave made up of the summation
of pressure waves generated by the heart’s
contraction and the pressure reflected back
toward the heart from the peripheral arterial tree
as the outgoing wave meets branches or other
sources of impedance mismatch. The interaction
of these two waves is strongly affected by the
speed of the transmitted and reflected waves – the
faster the wave travels, the less separation there is
between the two. The primary determinant of the
wave speed is arterial stiffness. The central pressure waveform, especially during systole, differs
in various parts of the arterial tree if, for example,
the reflected wave occurs earlier or later in the
cardiac cycle (Figure 2).
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Waveform physiology overview
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A number of clinically important central pressure indices
can be derived from the central
waveform captured using
Bloodpressure
Pressure
Blood Pressure
Wave Form
Wave Form
the SphygmoCor System, including central systolic, central diastolic and central pulse pressure (Figure 3). Additionally,
Wave
Wave
augmentation pressure (AP), the increase in systolicReflectived
pressure
due to early return of the Reflectived
reflected
wave, and augmentation
index (AIx), the ratio of augmentation pressure to the central pulse pressure expressed as a percentage, are also provided.
Forward Wave
Forward Wave
Systole
Diastole
The SphygmoCor System provides age and gender-specific reference rangesSystole
based
on overDiastole
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healthy, normotensive
adults, ages 18 – 90 years old.
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Reports generated by the SphygmoCor System
display patient
demographicSystole
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criteria, measures of
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central blood pressure, AP, and AIx (Figure 4). Additionally, central systolic pressure, CPP, AP and AIx parameters are
displayed on the continuum of normal reference range values based on age and gender. The patient’s SphygmoCor
Reference Age, an estimate of the patient’s vascular age based on values derived during the assessment, is also displayed.
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PP = Pulse Pressure
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AP = A
ugmentation Pressure, the contribution
of the reflected wave to the pulse pressure
Alx = AP/PP
Alx = AP/PP x100
AlxAortic
= Augmentation Index, the percentage
Increased Central
Pulse
ofPressure
the pulse pressure due to the AP
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Increased LV Load
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Perfusion Pressure in
Diastole
(mmHg)
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PP
Figure 3. The central pressure waveform measurements include central systolic pressure (SP),
central pulse pressure (PP), Augmentation Pressure (AP), and Augmentation Index (AIx).
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Using Pulse Wave Analysis to Guide Therapy
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Analysis of the central pulse waveform, along with corresponding central blood pressure measurements, provides
valuable information as to the choice and effectiveness of anti-hypertensive medications. Since augmentation index
is a measure of the contribution of the reflected wave for central systolic pressure, it provides an indication of the
efficacy of vasoactive drugs intended to reduce the size of the reflected wave.
In patients with elevated augmentation pressure and/or augmentation index, vasodilating drugs may have a greater
efficacy than non-vasodilating drugs. Patients with a lower augmentation pressure and/or augmentation index
indicate hypertension due to factors other than arterial stiffness (e.g., high cardiac output). A general guide to the
relative effectiveness of different anti-hypertensive medications in reducing central pressure compared to brachial
pressure is shown in Table 1.
Age/Gender
Reference Range
comparison
SphygmoCor Reference Age > 40
Figure 4: SphygmoCor XCEL Clinical Report screen
The Role of Central Blood Pressure in Clinical Management
As previously described, central blood pressure provides clinicians with better prognostic and diagnostic
information to determine the need for and type of interventions.
Hypertension
Measurement of central blood pressure can provide improved management in a variety of clinical
conditions to potentially prevent incidence or progression of target organ damage. As previously noted,
certain antihypertensive medications have a more profound effect on central blood pressure than on brachial
blood pressure. Measurement of central blood pressure may provide improved therapy guidance for borderline
hypertensive patients or those near blood pressure goal, (e.g., brachial systolic blood pressure of 130-140mmHg),
as well as improve therapy guidance in resistant hypertensive patients.
Several publications indicate that a central systolic pressure above approximately 125mmHg significantly increases
cardiovascular risk:
• In the CAFE study, a CSP of 125mmHg was associated with a 10-30% increase in CV risk compared to 121mmHg
•In
the McEniery study, 126mmHg represents the central systolic pressure equivalent to a brachial
systolic pressure of 140mmHg, the threshold for Stage 1 hypertension1
•Saladini’s
study of young to middle age subjects showed a threshold of 125mmHg for developing
hypertension requiring medications13
While the risk threshold for central systolic pressure needs to be further defined, the literature suggests that if:
• Central systolic pressure exceeds approximately 125mmHg, or
• Central pulse pressure is equal to or exceeds 50mmHg, more aggressive management of the patient’s blood pressure should be considered
Case Study 1
A 45-year-old African American man presents with a history of difficult-to-control hypertension and left ventricular hypertrophy despite use of a beta blocker, an ACE inhibitor and a diuretic. Change in therapy or
addition of a fourth drug is contemplated.
Analysis of his central pressure shows a moderately elevated central systolic pressure of 127 mmHg, and a
central pulse pressure of 51mmHg, above the threshold of 50mmHg for significantly increased CV risk. An
elevated augmentation pressure of 15mmHg (above the 95 percentile value of 7mmHg for a 45 year old
male) indicates a significantly elevated ventricular afterload. Based on this central pressure analysis, the
patient was treated to reduce the ventricular afterload and central systolic pressure including changing to
a vasoactive Beta blocker and increasing the ACE inhibitor dosage. A follow-up examination revealed a
brachial pressure of 128/76mmHg and a central pressure of 114/78mmHg, with a central pulse pressure
of 36mmHg and an augmentation pressure of 9mmHg. Central and brachial systolic and pulse pressure are
now well within normal limits as is the augmentation pressure.
Case Study 2
A 55-year-old woman presents with untreated blood pressure values of 139/77mmHg, hyperlipidemia,
mild hyperglycemia, and obstructive sleep apnea. Carotid ultrasound exam shows absence of carotid
plaque but a moderately increased composite carotid intimal-medial thickness. The patient previously
refused medications.
The central pressure analysis shows an elevated central systolic pressure of 130mmHg (>95th percentile)
and elevated central pulse pressure of 53mmHg (>50mmHg threshold for increased CV risk), but with a
moderately elevated augmentation pressure of 14mmHg, indicating only a moderately elevated ventricular
afterload. Based on this central pressure analysis, antihypertensive medication is not recommended, however, the patient is recommended for a sleep study and subsequently placed on CPAP therapy. Niacin and
omega-3 fatty acid are prescribed for lipid therapy due to the patient’s aversion to statin therapy). Follow-up
examination revealed a brachial pressure of 113/71mmHg and a central pressure of 104/71mmHg, with a
central pulse pressure of 33mmHg and an augmentation pressure of 8mmHg. Central and brachial pressure
are now within normal limits as is the augmentation pressure (<30th percentile).
Conclusion
While sound clinical judgment cannot be replaced in the management of patients, the scientific literature
and case studies suggest a general approach for using central pressure:
•Patients with a central pulse pressure > 50mmHg or central systolic > 125mmHg are at higher risk
for cardiovascular disease and may benefit from more aggressive management
•In patients with elevated augmentation pressure and/or augmentation index, vasodilating drugs
(e.g., ACEIs, ARBs, CCBs, vasoactive beta blockers) may have a greater efficacy than non-vasodilating
drugs (e.g., beta blockers, thiazide diuretics)
• Patients with a lower augmentation pressure and/or augmentation index indicate hypertension due to factors other than arterial stiffness
Central blood pressure measurement can aid in reducing central systolic blood pressure and central pulse
pressure, thereby preventing or improving target organ damage and cardiovascular events. It also provides
valuable information not available from standard brachial cuff measurements as to the efficacy of
antihypertensive medications.
References
1
McEniery et al., Central pressure: variability and impact on cardiovascular risk factors, Hypertension, 2008; 51:1475-82.
2
K122129 US FDA clearance for SphygmoCor XCEL, Nov, 2012.
3
illiams et al., Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results
W
of the Conduit Artery Function Evaluation (CAFE) study. Circulation 2006; 113(9): 1213–1225.
4
ampus et al., Differential Effects of Nebivolol and Metoprolol on CentralAortic Pressure and Left Ventricular Wall Thickness, HypertenK
sion.2011;57:1122-1128
5
elly et al., Nitroglycerin has more favourable effects on left ventricular afterload than apparent from measurement of pressure in a
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peripheral artery, European Heart Journal, 1990; 11(2):138-44.
6
anisty and Hughes, Meta-analysis of comparative effects of different classes of antihypertensive agents on central and brachial systolic
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blood pressure and augmentation index, British Journal of Clinical Pharmacology, 2012; 75(1): 79-92.
7
McEniery, CM, Antihypertensive drugs and central blood pressure, Current Hypertension Reports, 2009; 11:253–259
8
roterogou et al., The effect of antihypertensive drugs on central blood pressure beyond peripheral blood pressure.
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Part I: (patho)-physiology, rationale and perspective on pulse pressure amplification, Current Pharmaceutical Design, 2009; 15:267-71.
9
oman et al., High central pulse pressure is independently associates with adverse cardiovascular outcome, Journal of the American
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College of Cardiology, 2009, 54:1730-4.
10
elson et al., Noninvasive Measurement of Central Vascular Pressures With Arterial Tonometry: Clinical Revival of the Pulse Pressure
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Waveform, Mayo Clinic Proceedings, 2010;85(5):460-472.
11
ooysen et al., Aortic, but not brachial blood pressure category enhances the ability to identify target organ changes in normotensives,
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Journal of Hypertension, AOP February 22, 2013.
12
aess et al., Aortic stiffness, blood pressure progression, and incident hypertension, Journal of the American Medical Association, 2012;
K
308(9): 375-81.
13
aladini et al., Isolated systolic hypertension of young to middle-age individuals implies relatively low risk of needing treatment when
S
central blood pressure is low, Journal of Hypertension, 2011, 29:1311-9
Noninvasive Central Blood Pressure Assessment
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