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JACC Vol. 29, No. 7
June 1997:1407–13
REVIEW ARTICLES
Systolic Blood Pressure Revisited
HAROLD SMULYAN, MD, FACC, MICHEL E. SAFAR, MD*
Syracuse, New York and Paris, France
The clinical importance of systolic blood pressure (SBP) needs
no emphasis. Its determinants are well known, but recent studies
of one of these determinants, arterial distensibility, have led to
results that now have clinical relevance. This review summarizes
the role of arterial stiffness in ventricular-vascular coupling in the
normal circulation and that disordered by aging and hypertension. The discussion defines the unfamiliar terms of compliance,
distensibility and modulus and indicates how they are measured.
Such measurements have increased our understanding of the
parts played by the inhomogeneity of the arterial tree and
reflected pressure waves in governing SBP. Elevated SBP is a
recognized risk factor for cardiovascular complications among
older patients, but when this elevation is due to a stiffened arterial
tree, diastolic blood pressure (DBP) is necessarily reduced.
Early epidemiologic studies in hypertension required a DBP
In 1971, the Framingham study (1) emphasized the importance
of the systolic blood pressure (SBP) level as a determinant of
cardiovascular risk in hypertensive persons .45 years old. The
Framingham data (2) have also shown a progressive increase in
the prevalence of systolic hypertension with increasing age
(Fig. 1). Because the number of elderly persons in the population has increased in the 25 years since that first report, the
incidence of systolic hypertension has risen accordingly. More
patients with the disease means more people at cardiovascular
risk and more patients under treatment to prevent complications. Hand in hand with a clinical interest in systolic hypertension have been inquiries into its nature and fundamental
studies into the determinants of SBP itself. One of these
determinants, the distensibility of the arterial tree, has been
investigated for many years, but only recently have these
studies reached a level of clinical applicability. An awareness of
these results should improve understanding of SBP in hypertension and aging and point the way for targeted therapeutic
decisions. This review attempts to look anew at SBP, its
determinants, its role in hypertension and aging and its treatment when elevated.
From the Cardiology Division, Department of Medicine, State University of
New York, Health Science Center, Syracuse, New York; and *Department of
Internal Medicine and INSERM (U337), Broussais Hospital, Paris, France.
Manuscript received November 26, 1996; revised manuscript received February 24, 1997, accepted February 28, 1997.
Address for correspondence: Dr. Harold Smulyan, Department of Medicine,
State University of New York, Health Science Center, 750 East Adams Street,
Syracuse, New York 13210. E-mail: [email protected].
©1997 by the American College of Cardiology
Published by Elsevier Science Inc.
>
290
mm Hg for hospital admission. They therefore excluded
persons with high SBP, low DBP and very wide pulse pressure
(PP). More recent inclusion of such patients has shown that
elevation of SBP and PP is a strong predictor of cardiovascular
risk. These considerations point to a possible redefinition of
hypertension to include patients with lower DBP and to the
inaccuracy but indispensability of the brachial artery pressure as
a surrogate for aortic pressure—the pressure the heart sees.
Finally, we review the known effects of available antihypertensive
drugs on the arterial wall and indicate possible future directions
of research stemming from wider understanding of the role of
arterial distensibility in hypertension.
(J Am Coll Cardiol 1997;29:1407–13)
©1997 by the American College of Cardiology
Determinants of SBP and Pulsatility
SBP and its role in hypertension were reviewed in 1973 in a
prescient letter to the editor by Koch-Weser (3). Since that
time, our view of the determinants of SBP has not changed—
stroke volume, rate of systolic ejection and the distensibility of
the arterial tree. However, there has been considerable
progress in understanding the nature of reduced arterial
distensibility and its effect on the circulation. Briefly, a stiffened arterial tree, given the same stroke volume and ejection
rate, will produce a higher SBP, a lower diastolic blood
pressure (DBP) and a wider pulse pressure (PP), but the mean
blood pressure (MBP) will be unchanged (Fig. 2) (4,5).
For many years, clinical descriptions of the circulation had
simply considered the relations among the cardiac output
(CO), MBP and systemic vascular resistance (SVR). MBP,
calculated as one third PP plus DBP, represents the blood
pressure in the absence of pulsations. The ratio of MBP to CO
is the SVR that quantifies the opposition to steady blood flow
that the heart must overcome, whereas the product of CO and
MBP is an estimate of cardiac work. These variables of
resistance to blood flow and cardiac work are useful because
they assume that blood flow is steady and they avoid the
complexities of pulsatility. Steady flow and pressure afford
conceptual simplicity and are even attainable for short periods
(i.e., cardiopulmonary bypass), but the heart is an intermittent
pump providing pulsatile blood flow and pressure. Therefore,
some knowledge of the factors that influence these pulsations
is necessary to appreciate the role played by SBP and PP.
In the normal circulation, 85% to 90% of the cardiac effort
0735-1097/97/$17.00
PII S0735-1097(97)00081-8
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SMULYAN AND SAFAR
SYSTOLIC BLOOD PRESSURE REVISITED
Abbreviations and Acronyms
ACE 5 angiotensin-converting enzyme
CO 5 cardiac output
DBP 5 diastolic blood pressure
ISH 5 isolated systolic hypertension
MBP 5 mean blood pressure
MI 5 myocardial infarction
PP 5 pulse pressure
PWV 5 pulse wave velocity
SBP 5 systolic blood pressure
SVR 5 systemic vascular resistance
is spent in driving the blood steadily through the SVR. The
remaining 10% to 15% is “wasted” in making flow pulsatile.
Some of the cardiac energy spent in distending the arterial tree
in systole is returned to the circulation in diastole, because of
the elastic nature of the proximal aorta (Windkessel effect),
and some is dissipated as heat. Although the normal pulsatile
energy losses are small, they can be much higher in patients
with arteriosclerosis. In experimental animals with an artificially stiffened aorta (5.6), the pulsatile energy losses with a
slow heart rate can be 50% of the total (6) and can increase left
ventricular oxygen consumption by 30% (7).
The problem of arterial stiffening is complicated by the
heterogeneity of the arterial tree. The proximal aorta is
compliant and well suited to accepting the left ventricular
stroke volume with a relatively low SBP. The carotid arteries
are only slightly less compliant. However, as the aorta proceeds
distally, it becomes stiffer with more smooth muscle in the
walls. This process continues to more distal vessels so that the
femoral, brachial and radial arteries are very stiff. Such an
arrangement permits the proximal aorta to accept the stroke
volume at a lower peak SBP (smoothing function) and returns
some of the stored energy in diastole. The peripheral arteries
increase the SBP because of reflected waves (see later) and
dampen the flow pulse in preparation for steady flow through
the peripheral resistance. The system is admirably designed
(ventricular-vascular coupling) to receive pulsatile flow and
Figure 1. Prevalence of isolated systolic hypertension by age and
gender in the 24-year follow-up of the Framingham study. Reproduced, with permission, from Kannel et al. (2).
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deliver steady flow. More detailed accounts of these relations
are available (8).
Measurements of Arterial Stiffness
Compliance of a localized arterial segment is simply the
increase in its volume, diameter (D) or cross-sectional area (A)
(assuming no change in length of the arterial segment) for a
given increase in pressure (dP), that is, dD/dP, where dD is
increase in diameter and dP is the pulse pressure. Compliance
does not account for the rest or diastolic dimension before
distension begins. By comparison, distensibility includes the value
for the rest diameter or cross-sectional area and thus represents
change in these variables as a percent. Thus,
Distensibility 5 dD/DzdP or dA/AzdP.
Some investigators utilize the Peterson modulus of elasticity, which is the reciprocal of distensibility. As can be seen from
these relations, a more compliant artery will have a larger
increment in diameter or cross-sectional area for a given
increase in pressure than will a less compliant one. By comparison, a more distensible artery will do the same, but from a
common baseline dimension, that is, undergo a greater percent
change in diameter or cross-sectional area for a given PP.
These dimensional measurements have now been accurately made in peripheral arteries such as the carotid, brachial
and radial arteries with the use of high frequency ultrasound
(9 –12). Special ultrasound applications have also provided
measurements of wall thickness (13,14) that permit calculation
of wall stress and characterization of the arterial wall as a
material as well as its behavior as a viscoelastic tube (15).
Similar studies of the thoracic aorta have been done, but are
more difficult owing to its relative inaccessibility (16). Recently, dimensional changes of the thoracic aorta have been
Figure 2. Aortic blood pressure curve in younger and older subjects.
The areas under the two curves are identical. Because cardiac periods
are the same, the mean arterial pressure is identical. Consequently,
peak systolic blood pressure is higher and end-diastolic blood pressure
is lower in older subjects for the same mean arterial pressure. a 5 peak
systolic blood pressure; b 5 end-diastolic blood pressure; a 2 b 5
pulse pressure; c 5 mean arterial pressure; d 5 cardiac period; e 5
inflexion point produced by onset of reflected wave, in the diastolic
(younger subjects) or the systolic (older subjects) portion of the blood
pressure curve. Reproduced, with permission, from Nichols and
O’Rourke (4).
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measured from images obtained by using the transesophageal
ultrasound probe (17), but direct measurements have also been
made (18).
The compliance of the entire arterial tree can also be
evaluated on the basis of a single Windkessel model, analogous
to an electrical resistance capacitance system, which assumes a
single capacitance discharging into a single resistance (4,5).
This method requires a direct recording of the arterial pulse
and a measurement of CO for the calculation of SVR.
Assuming that the diastolic portion of the arterial pulse trace
decays in monoexponential fashion, the time constant of the
decay (reciprocal of the slope) is determined by the capacitance of the system and the resistance to run off. Therefore,
C 5 t/R, where C is the capacitance (representative of the
compliance), t is the time constant, and R is the systemic
vascular resistance (19). This method is of limited use because
the circulation is neither a single capacitance nor a single
resistance; more important, the method ignores wave reflections (see later) that distort the diastolic decay of the pressure
pulse and make it nonexponential. More complex mathematic
models of the arterial tree have been described to account for
the assumptions involved in the single-chamber model with a
monoexponential diastolic decay (20,21).
The stiffness of arterial segments can be assessed indirectly
by measuring pulse wave velocity (PWV). The stiffer the tube,
the faster a pressure wave will travel through it. If one can
invasively or noninvasively sense the arrival of a pulse in two
positions in the arterial tree, and measure the distance between them, the velocity of wave travel can be determined and
the distensibility of that length of artery calculated. PWV
measurements have been made in a variety of arterial positions
and lengths: femoral to dorsal pedal, brachial to radial, and
carotid to femoral. The last estimates overall aortic distensibility by subtracting the distance from the suprasternal notch to
the carotid artery from the distance from the suprasternal
notch to the femoral artery. Several techniques are available to
sense pulse arrival, and computerized automatic detection has
been described (22). Technically, arrival times are not difficult
to detect, but arterial distances measured over the body surface
may be inaccurate.
Considerations of PWV offer interesting insights into the
normal and disordered functioning of the arterial tree. Because of the increasing stiffness of the arterial tree, from
proximal to distal, a traveling pulse picks up speed as it moves
along. When it reaches the peripheral resistance, some of the
pulsatile energy is returned as a reflected wave that travels
retrograde—fast at first, then slower. In young normal persons
the rate of travel of these waves is such that the reflected wave
reaches the central aorta in diastole, amplifying the early or
mid-DBP. In peripheral arteries closer to the reflecting sites,
the reflected wave amplifies the primary wave, which accounts
for the higher SBP in the brachial and femoral arteries than in
the aorta. With aging or hypertension, or both, there is little
change in the functional stiffness of the muscular peripheral
arteries (9,23), but the elastic proximal aorta becomes less
compliant and more like peripheral arteries in stiffness (4,5,9).
SMULYAN AND SAFAR
SYSTOLIC BLOOD PRESSURE REVISITED
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Figure 3. Pressure wave recorded along the arterial tree from the
proximal ascending aorta to the femoral artery in three adult subjects
aged 24, 54 and 68 years, respectively. In the youngest subject, the
amplification of the pressure wave increases ;60% during transmission. In the oldest there is very little amplification of the pressure wave
during transmission. There is no change in mean arterial pressure but
a progressive increase in SBP and decrease in DBP. Reproduced, with
permission, from Nichols WW, Avolio AP, Kelly RP, O’Rourke MF.
Effects of age and of hypertension on wave travel and reflections. In:
O’Rourke MF, Safar ME, Dzau JV, editors. Arterial Vasodilation:
Mechanisms and Therapy. London: Edward Arnold 1993:32.
Proximal aortic stiffening not only increases the pressure of the
incident wave, but it increases wave velocity such that the
reflected wave returns to the aorta during systole rather than
diastole. This amplifies the primary wave, or may even produce
a second systolic peak (Fig. 2) (24). In the elderly, this process
minimizes the difference in SBP between the central aorta and
peripheral arteries present in younger, normotensive persons
(Fig. 3). More important, it amplifies the SBP, widens the PP,
increases cardiac work and increases the risks of stroke and
myocardial infarction (MI) (see later).
Because both the elastic central aorta and the stiff muscular
arteries of the periphery are nonlinearly elastic (viscoelastic)
structures, an increase in blood pressure will make them stiffer.
Any measurement of arterial compliance, distensibility or
modulus in a hypertensive patient will therefore show increased stiffness. Blood pressure itself must therefore be
controlled as a variable if arterial wall behavior alone is to be
assessed.
SBP in Hypertension
The usual hemodynamic pattern in the young or middleaged patient with established hypertension is increased SVR
and normal CO. But the increased blood pressure alone will
make the arterial tree stiffer. Because the relation between
distensibility and blood pressure is curvilinear, further increases in blood pressure will produce exaggerated decreases
in distensibility. Very early in the course of hypertension SBP
may be elevated because of increased arterial stiffness (25) or
a large stroke volume (26). Later, stroke volume returns to
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Figure 4. SBP and PP according to the level of DBP in different age
ranges according to the Hypertension Detection and Follow-Up
Program study (31) in never-treated subjects. 1 5 30 to 39 years; 2 5
40 to 49 years; 3 5 50 to 59 years; 4 5 60 to 69 years. Data from Polk
et al. (31).
normal and is replaced by elevated SVR (27). At this stage, the
augmented stiffness of the arteries is due largely to the
increased blood pressure alone, and cardiovascular risk relates
best to MBP or DBP (28).
Hypertension accelerates the vasculopathy of aging, and in
hypertensive patients .55 years old, the central aorta dilates
and the walls become less distensible. This leads to a disproportionate increase in SBP, from loss of the aortic cushioning
effect of systolic ejection and the addition of reflected waves
during systole. All this may occur without a significant change
in SVR or MBP but with an associated decrease in DBP.
Although the heart faces the same MBP and the same SVR
through which it must drive the blood, its external work is
increased by the need to raise the SBP disproportionately. It is
now understandable that the increase in cardiac mass, detected
echocardiographically, is strongly associated with increased
SBP, increased PP and increased aortic PWV but is largely
independent of MBP (29,30). Simultaneous lowering of DBP
in the presence of increased cardiac work also has potentially
deleterious effects on coronary perfusion, especially when
coronary artery stenoses are present (7). It is not surprising to
find that at age 55 and older, the cardiovascular complications
of hypertension relate better to SBP and PP than to DBP or
MBP (28). How frequently disproportionate systolic hypertension occurs in the overall population of hypertensive patients is
not known. In 7,833 subjects described in the Hypertension
Detection and Follow-Up Program study (31), the mean values
of SBP, DBP, MBP and PP were divided into three strata of
DBP with the lowest tertile defined as 90 to 104 mm Hg. It
appeared that the prevalence of disproportionately increased
SBP increased with age, irrespective of the severity of the
disease as judged by DBP (Fig. 4). By including only patients
whose DBP was .90 mm Hg, this study omitted patients with
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lower DBP, even those with elevated SBP. The same selection
bias was present in other trials (32,33) that included only
patients with increased DBP and therefore were unable to
assess the risks to patients with the widest PP.
The place of aged patients with isolated systolic hypertension (ISH) in this schema is unclear. The aging process,
accelerated by hypertension, induces aortic dilation and stiffening due to thickening of the intima and media, degeneration
of elastic lamina with fragmentation and rupture of elastic
fibers and deposition of calcium. In the more muscular peripheral arteries thicker walls also develop, but lumen diameter is
unchanged (9,34). Surprisingly, the distensibility of these arteries is little affected or may even be improved with increasing
age (23,34). Reduction in compliance of the arterial tree with
aging (in the absence of atherosclerosis) therefore takes place
primarily in the central aorta. Although suspected, there is no
definite evidence to show that aortic stiffening beyond that
expected with aging alone is entirely responsible for ISH. If it
were, the DBP should be low. Unfortunately, the DBP measured by cuff is unreliable (35) and is often falsely high because
of reduced compressibility of the brachial artery despite its
normal compliance. The elderly may also suffer from occlusive
arterial disease of the legs. SBP will be further elevated by
greater wave reflections from more proximal reflecting sites,
whereas MBP, SVR and stroke volume are unchanged (36). In
the absence of peripheral vascular disease, some of these
patients will have increased SVR, and others increased stroke
volume, which could also explain the high SBP (37). Although
a salutary response to diuretic therapy in this disease is clear
(38), the mechanism of action is not. Diuretics do not increase
the distensibility of peripheral arteries (39), but their effect on
aortic stiffness is unknown. Whatever the mechanism, the
resultant reduction in blood pressure itself accounts for the
benefit.
PP in Predicting Cardiovascular Risk
As indicated, SBP is a better predictor of cardiovascular
risk than is DBP in hypertensive patients aged $55 years. This
is probably so because of the increasing importance of aortic
stiffness with hypertension and aging, leading to disproportionate increases in SBP and the resulting effects on target organs.
As increased aortic stiffness not only increases SBP, but also
decreases DBP, PP would appear to be even better than SBP
as an index of aortic stiffness. However, there has been only
limited study of the role of PP in cardiovascular morbidity and
mortality independent of MBP or DBP.
The relations among MBP, PP and cardiovascular risk were
investigated in 18,336 men and 9,351 women, aged 40 to 69
years, living in Paris (40). With cross-sectional analysis, the
cardiovascular risks were related to the levels of MBP, SBP
and DBP, similar to those previously reported in other epidemiologic studies; that is, all three blood pressures were strong
determinants of the risks to the brain, heart and kidney.
However, in this study, PP alone was shown to be independently related to the degree of cardiac hypertrophy. Further-
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SMULYAN AND SAFAR
SYSTOLIC BLOOD PRESSURE REVISITED
more, in a 10-year survival analysis, PP was an independent
predictor of cardiac mortality in women aged $55 years.
The prognostic value of pretreatment PP was also evaluated
in New York City as a predictor of MI in a union-sponsored
hypertension control program (41) in which 2,207 patients with
blood pressure .160/.95 mm Hg were grouped by tertile of
PP. During an average follow-up interval of 5 years, 132
cardiovascular events (50 MIs, 23 strokes) were observed. MI
rates per 1,000 person-years were positively related to PP, and
wide PP was identified as a predictor of MI. This finding was
confirmed in a larger group of 5,730 participants (42) in whom
a wide pretreatment PP (.63 mm Hg) was associated with
subsequent cardiovascular complications. Wide PP with low
DBP was also used to identify a subgroup of patients at greater
risk of MI from either too large or too small a treatmentinduced decrease in DBP (J curve) (43).
Taken together, these findings indicate that the brachial PP
is a significant predictor of cardiovascular risk, especially left
ventricular hypertrophy and MI. Both epidemiologic and hemodynamic findings support the belief that increased arterial
stiffness, the major contributor of disproportionate SBP over
DBP, should be considered in future evaluations of cardiac and
other target organ complications.
The Problem of Pressure Wave Transmission:
Should Hypertension Be Redefined?
Clinically, the diagnosis of hypertension has been based on
sustained elevation of SBP, DBP, and therefore MBP, as
measured by cuff in the brachial artery. But these pressures
may not be what the heart sees. The young person with
“borderline hypertension” as measured in the brachial artery
may have a normal or low aortic DBP. Older patients with
elevated SBP in the brachial artery and aorta may have normal
DBP in the brachial artery and low DBP in the aorta. Such
patients would not have been included as “hypertensive”
subjects in earlier epidemiologic studies and therapeutic trials
because the brachial artery DBP was not elevated. Yet the left
ventricle and the cerebral circulation would have been subjected to a pulsatile risk. Are such patients with normal MBP
hypertensive? This is an important question because as many
as 30% of patients with elevated SBP fit this description.
Hypertensive or not, such patients benefit from treatment (32),
whereas young patients with SBP elevation only in the brachial
artery do not. If possible, therapy in the elderly should be
directed in part toward the reduction of aortic stiffness (see
later). The brachial artery cuff pressures offer only a small
window through which we see the arterial tree. But because it
is readily available, better use could be made of it by attending
more to elevations of SBP and PP and to normal or reduced
DBP—all indicators of reduced arterial distensibility.
Therapy
Most antihypertensive drugs lower peripheral resistance
and reduce MBP and nonpulsatile ventricular work. Reduction
1411
in MBP will also passively reduce the stiffness of the arterial
tree and the cardiac work of pulsations. Currently there is
interest in whether any available drugs, through an effect on
the arterial wall, can increase arterial distensibility beyond
what would be expected from blood pressure reduction alone.
What follows is not a review of currently accepted antihypertensive therapy. Rather, it indicates those available drugs that
favorably affect arterial distensibility in addition to their other
antihypertensive actions.
The most effective drugs to reduce arterial stiffness studied
to date are the nitrates. One study (44) showed clear improvement in forearm arterial distensibility, independent of blood
pressure reduction, with short-term intravenous infusions of
nitroglycerin. In the systemic arterial circulation, nitrates selectively decrease aortic SBP through delay of wave reflections,
although as expected, brachial artery SBP is much less reduced
than aortic SBP (4). Nitrates are not now widely used for the
treatment of hypertension, although in randomized therapeutic trials they selectively decrease SBP in elderly patients with
ISH (45). They are valuable adjuncts in the treatment of many
hypertensive patients with congestive heart failure or angina
and might become a primary form of therapy in others.
Angiotensin-converting enzyme (ACE) inhibitors have
been repeatedly shown to lower blood pressure and to selectively improve arterial distensibility both in humans and in
animal experiments (46,47). These agents might be better used
early in the course of hypertension to prevent secondary
stiffening due to collagen deposition, rather than late when it
cannot be reversed (48). The smooth muscle relaxing effects of
calcium channel antagonists (49,50) also operate in the arterial
wall to selectively improve distensibility. Both ACE inhibitors
and calcium channel antagonists increase flow through peripheral arteries, suggesting that their relaxing effect on the arterial
wall is mediated in part by the endothelium, sensitive to
increases in shear stress, as previously reported from human
(47) and animal (51) experiments.
Increased sodium intake and sodium sensitivity increase
arterial stiffness whereas sodium withdrawal reduces it (52–
54). The elderly are known to be salt sensitive, and it is
tempting to attribute some of the salutary effects of diuretic
drugs in ISH to improved arterial distensibility (38). However,
no such effect could be demonstrated in forearm arteries
(39,55). Studies are needed on the elderly and other hypertensive groups to determine the effects of diuretics on aortic
distensibility.
Studies on the full range of antihypertensive agents have
shown favorable effects on the arterial wall, beyond that
expected from the decrease in blood pressure alone, from
nitrates, ACE inhibitors and calcium channel antagonists.
There is little selective effect from direct vasodilators and
nonselective beta-blocking agents; the effects of autonomic
blocking agents fall in between (9).
Patients with elevated SBP, normal or reduced DBP and
inordinately widened PP should be suspected of having reduced arterial distensibility as a feature of their disease. The
choice of appropriate drugs to improve distensibility should
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SYSTOLIC BLOOD PRESSURE REVISITED
have favorable effects on the relief of left ventricular hypertrophy and prevention of MI, areas benefited marginally by
conventional, untargeted therapy. There is no information at
present on whether or not such an approach will prolong life.
Future Directions
Wider understanding of the role of arterial distensibility in
hypertension should lead to new areas of research. Examination of the effects of genetic polymorphisms on arterial wall
behavior with aging will be important, because recent reports
(56,57) have indicated an association of angiotensin II type 1
receptor gene polymorphism with an increase in aortic stiffness, SBP elevation and DBP reduction. Constrictors or dilators of arterial wall smooth muscle elaborated by the endothelium are being investigated that can influence the stiffness of
vessel walls. Using sophisticated techniques, the study of
superficial arteries such as the carotid, brachial and radial
arteries has reached a high level, but newer, easily applicable
methods to study the inaccessible central aorta are needed.
With the use of endovascular ultrasound, compliance studies
of the coronary arteries should be possible. When available,
these techniques can be used to study the effects of drugs and
diets on hypertension and aging and to follow up patients
during the course of their disease. Future epidemiologic
studies might well focus more attention on PP as an easily
obtainable surrogate for arterial distensibility.
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