Just press the “Order now” button and let the system intuitively guide you through the process.
As the world’s best bespoke custom essay writing solutions company, we offer below services
Alterations in Blood Pressure Benjamin J. Miller
K E Y Q U E S T I O N S • How do changes in cardiac output and systemic vascular
resistance affect blood pressure? • How is blood pressure regulated on a short- and long-term basis? • What are the risk factors for the development of primary
hypertension? • How is secondary hypertension defined, and what are the
• How is hypertension detected, classified, and managed? • What are the end-organ consequences of inadequately controlled
hypertension? • What are the differences between hypertensive emergency and
hypertensive urgency, and how are they managed? • What are the risk factors for orthostatic hypotension, and how is
the condition managed?
C H A P T E R O U T L I N E Arterial Blood Pressure, 337
Determinants of Systemic Blood Pressure, 337
Measurement of Blood Pressure, 338
Components of Blood Pressure Measurement, 338 Direct Measurement of Blood Pressure, 339 Indirect Measurement of Blood Pressure, 339
Mechanisms of Blood Pressure Regulation, 341 Short-Term Regulation of Systemic Blood Pressure, 341
Long-Term Regulation of Systemic Blood Pressure, 341
Normal Fluctuations in Systemic Blood Pressure, 343
Hypertension, 343 Definition and Classification, 343
Primary Hypertension, 344
Subtypes, 344 Risk Factors, 344 Outcomes, 345 Treatment Interventions, 346
Secondary Hypertension, 348
Hypertensive Emergencies and Urgency, 349
Low Blood Pressure, 350
Meeting the needs of the body’s tissues for oxygen and nutrients requires both adequate blood flow at the tissue level and sufficient perfusion pressure systemically to force that blood forward. The systemic arterial blood pressure provides the momentum, and the tissues depend on its preservation to ensure their metabolic needs are met. This maintenance requires a complex regulatory system. The body’s organs can be damaged if the perfusion pressure is insufficient or if it is excessive.
ARTERIAL BLOOD PRESSURE As described in Chapter 15, oxygenated blood is propelled from the left side of the heart into the arterial circulatory system, and following a pressure gradient, travels to the capillary beds of the body’s tissues (Fig. 16.1). There, oxygen and nutrients are exchanged for metabolic wastes, and the blood then returns to the right side of the heart via the venous circulatory system, where it passes through the lungs to repeat the process. It is the pressure difference between the left and right sides of the heart that produces the gradient allowing this systemic movement of blood. The arterial blood pressure is produced by the force of the
left ventricular contraction overcoming the resistance of the aorta to open the aortic valve, and is the pressure maintained in the arterial system throughout the cardiac cycle.
Determinants of Systemic Blood Pressure The systemic arterial blood pressure is the physiologic result of the cardiac output and the resistance to the ejection of blood from the heart. Cardiac output (CO) is the product of two variables: stroke volume (SV) and heart rate (HR) (CO = SV × HR). SV is the specific volume of blood leaving the heart with each contraction, which itself is deter- mined by the volume of blood in the heart before systole (end-diastolic volume) and the contractility of the myocardium. The end-diastolic volume is determined by the amount of blood returned to the heart between contractions, and is typically called the heart’s preload. Stroke volume multiplied by the number of contractions of the heart per minute (heart rate) determines the amount of blood leaving the heart—the cardiac output, measured in liters per minute. The resistance to ejection into the arterial circulation is known as the systemic vascular resistance (SVR) and is determined by the radius of arteries and the
• Review Questions and Answers • Glossary (with audio pronunciations for selected terms) • Animations
• Case Studies • Key Points Review
338 UNIT IV Oxygen Transport, Blood Coagulation, Blood Flow, and Blood Pressure
termed the pulse pressure. Therefore the pulse pressure for a systolic pressure of 110 mm Hg and a diastolic pressure of 70 mm Hg would be 40 mm Hg.
Systolic and diastolic values are normed by age. Standards for the identification of normal blood pressure and levels of abnormal elevation have been established. The most precise standards for children are those based on height, age, and gender (Table 16.1). Standards for blood pressure have likewise been determined for the adult (Table 16.2).
Mean arterial pressure (MAP) is the calculated average pressure within the circulatory system throughout the cardiac cycle. Because more time is spent in diastole than in systole, MAP is not the arithmetic average of diastolic and systolic pressure, but rather reflects the relative time spent in each portion of the cardiac cycle. The calculation may be performed by computer during direct arterial blood pressure measure- ment, as described later, but is most conveniently determined by a
degree of vessel compliance. SVR is synonymous with cardiac afterload, and can be altered by constricting or relaxing (dilating) arterial smooth muscle. It can be calculated by using a derivation of Poiseuille’s law (see Chapter 15). This physical law states that in a tube with laminar flow, resistance is primarily determined by three factors: the radius of the tube, the length of the tube, and the viscosity of the fluid. Applied to SVR, because the viscosity of the blood and the total length of the arterial system are normally relatively constant, the radius of the arterioles becomes the major determinant of resistance. Therefore the formula for blood pressure is BP = CO × SVR. Alteration in any one of these variables will result in a change in blood pressure. This basic concept is important to normal physiologic function, disorders of blood pressure, and the therapeutic interventions undertaken to treat them. The pul- monary vascular bed contributes minimally to total systemic resistance and is seen as a separate resistance system, called pulmonary vascular resistance. It has its own pathology discussed in Chapter 21.
Measurement of Blood Pressure Components of Blood Pressure Measurement Arterial blood pressure is measured from its highest point during cardiac systole to its lowest during diastole. These are referred to as systolic pressure and diastolic pressure, respectively, and are measured in mil- limeters of mercury (mm Hg). During ventricular contraction, the pressure in the aorta rises to an average peak value of approximately 110 mm Hg in the adult (see Fig. 16.1). Whatever this peak pressure may be, it is referred to as the systolic blood pressure. The smooth muscle of the aorta passively recoils from this point, ejecting blood forward into the peripheral arteries at that given pressure. Stroke volume is the primary factor affecting systolic pressure; an increase or decrease in SV produces a corresponding change in systolic blood pressure. During ventricular diastole, the pressure in the arterial system falls to an average minimum value of 70 mm Hg in the adult. The value of this minimum pressure is called the diastolic blood pressure. SVR is the major determinant of diastolic blood pressure; an increase or decrease in diastolic pressure is the result of a corresponding increase or decrease in arterial resistance (SVR). The difference between systolic and diastolic blood pressure is
s s u
0 Systemic Pulmonary
A o rt
L a rg
rt e ri
C a p ill
V e n u le
L a rg
V e n a e c
P u lm
o n a ry
C a p ill
V e n u le
P u lm
o n a ry
v e in
FIG 16.1 Normal pressures throughout the vascular system in the supine position. (From Hall JE: Guyton and Hall textbook of medical physiology, ed 13, Philadelphia, 2016, Saunders.)
TABLE 16.1 Blood Pressure Classification in Children and Adolescents SBP and DBP <90th percentile* Normal for children and
adolescents Average SBP and/or DBP ≥90th percentile
but <95th percentile† or SBP ≥120 and/ or DBP ≥80 mm Hg
Prehypertension in children or adolescents
SBP/DBP ≥95th percentile and <99th percentile plus 5 mm Hg
Stage I hypertension
SBP/DBP ≥99th percentile plus 5 mm Hg Stage II hypertension
Selected data from Xi B, Zong XN, Kelishadi R, et al: Establishing international blood pressure references among nonoverweight children and adolescents aged 6 to 17 years. Circulation, 133(4):398- 408, 2016. DBP, Diastolic blood pressure; SBP, systolic blood pressure. *For age, height, and gender. †For age, height, and gender measured on at least three separate occasions.
CHAPTER 16 Alterations in Blood Pressure 339
Direct Measurement of Blood Pressure Direct measurement of blood pressure is one aspect of hemodynamic monitoring and requires an intraarterial catheter and specialized equip- ment to transduce the arterial fluid pulsations into electrical signals. The catheter most often is placed in the radial artery. These signals are then displayed on a computer screen as waveforms, and the systolic, diastolic, and MAPs are digitally represented. This is the most accurate method of measuring blood pressure available, but is typically only performed in controlled settings, such as surgical or critical care units, and carries its own risk of measurement error. A detailed discussion of hemodynamic monitoring is beyond the scope of this text.
Indirect Measurement of Blood Pressure Blood pressure is most commonly measured by indirect means at the brachial artery, using a sphygmomanometer and a stethoscope for auscultation or an automated oscillometric system such as Dinamap or the Welch Allyn Spot Vital Signs. Wrist or finger monitors are not recommended because of the inaccuracy of the values obtained compared with brachial measurements. Specific, evidence-based standards are available for the correct use of these noninvasive automated systems for adults and children, including scheduled calibration, and they are inherently less accurate if the blood pressure is significantly increased or decreased, or if there are cardiac dysrhythmias. Because the values in blood pressure references are based on the auscultatory method, and it is the easiest method and least stressful to patients, it is the preferred measurement technique. Although the brachial artery is typically used for convenience, certain assessment procedures require recording the blood pressure at other arterial sites (e.g., ankle–brachial index). Several studies have reported differences between the right and left arm pressures, but no pattern of differences is evident. Other studies report that in the absence of disease, systolic pressures do not differ significantly at a clinical or statistical level between the right and left arms. In practice, it is recommended that blood pressures be initially taken in both arms and the arm with the highest value be recorded. In situations such as a shock state, when systolic and diastolic pressures cannot be auscultated, the systolic pressure alone may be obtained by palpation or by amplifica- tion of the pulse using ultrasound technology (Doppler pressure).
Auscultated and oscillometric blood pressure measurements are burdened with the potential of measurement error, in both reliability and validity (Table 16.3). This dictates the need for careful technique, and in most cases enhances the value of trend data as opposed to individual readings. The individual patient’s heart rate, degree of arterial compliance, and dynamics of blood flow may vary over time. Inap- propriate blood pressure cuff size, arm position, and both the visual and auditory acuity of the clinician may affect the accuracy of individual readings. An additional source of error has been named the “white coat effect” for the elevation of blood pressure when taken in a clinic or office environment. First described in 1897 by Scipione Riva-Rocci, who was the first to document assessing the systolic pressure by palpating the brachial artery, these situational elevations in blood pressure are of concern because treatment may be initiated based on inaccurate data. This condition is most common in older individuals of either gender, but may occur at any age. Pickering and colleagues report that in approximately 15% to 20% of patients with stage 1 hypertension, elevated blood pressure may only be persistent under these circumstances. Significant pressure differences have been found using the automatic noninvasive technology between the supine, 45-degree elevation of the head of the bed and sitting position in the same patient, and between multiple body positions using the auscultatory method. Normal values are based on the subject being seated, with the back supported and the arm at heart level. Specific recommendations regarding all aspects of
simple formula using the values of blood pressure obtained indirectly. Several formulas are available, and they may use systolic, diastolic, or pulse pressures; the most common formula uses the systolic and diastolic pressures as follows:
( )2 3
× +diastolic pressure systolic pressure
For a person with a systolic pressure of 110 mm Hg and a diastolic pressure of 70 mm Hg, the MAP would be:
( )2 70 110 250 3 83× + = or approximately mm Hg
MAP is used clinically as part of cardiovascular assessment and in the incremental adjustment (titration) of parenterally administered vasoactive drugs.
TABLE 16.2 Blood Pressure Classification in Adults
JNC 7 Blood Pressure Classification in Adults Category SBP (mm Hg)* DBP (mm Hg)*
Normal <120 <80 Prehypertension 120–139 80–89 Stage 1 hypertension 140–159 90–99 Stage 2 hypertension ≥160 ≥100
DBP, Diastolic blood pressure; SBP, systolic blood pressure; CKD, Chronic kidney disease; DM, diabetes mellitus. From James PA, Oparil S, Carter BL, et al: 2014 evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the eighth joint national committee (JNC 8). JAMA, 311(5):507-520, 2014.
From Chobanian AV: Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Complete Report, Hypertension 42:1206–1252, 2003. DBP, Diastolic blood pressure; SBP, systolic blood pressure. *Classification determined by the higher value.
ESH-ESC Blood Pressure Classification in Adults Category SBP (mm Hg)* DBP (mm Hg)*
Optimal <120 <80 Normal 120-129 80-84 High normal 130-139 85-89 Grade 1 hypertension 140–159 90–99 Grade 2 hypertension ≥160-179 100-109 Grade 3 hypertension ≥180 ≥110 Isolated systolic hypertension ≥140 <90
From Mancia G, Fagard R, Narkiewicz K, et al: 2013 ESH/ESC practice guidelines for the management of arterial hypertension, Blood Press 23(1):3-16, 2014.
JNC 8 Blood Pressure Treatment Goals in Adults Population SBP (mm Hg)* DBP (mm Hg)*
Age <60 all health states < 140 < 90 Age > 60 with CKD or DM < 140 < 90 Age ≥ 60 without CKD or
DM < 150 < 90
340 UNIT IV Oxygen Transport, Blood Coagulation, Blood Flow, and Blood Pressure
lower than those obtained by direct, intraarterial blood pressure measure- ment. Older patients often have a period during measurement when the Korotkoff sounds disappear, returning 20 to 40 mm Hg later. This auscultatory gap may be attributed to intraarterial pressure fluctuations associated with hypertension (Fig. 16.2) and can often be eliminated by elevating the arm above the level of the head for 30 seconds before cuff inflation. This approach is postulated to enhance the audibility of Korotkoff sounds by increasing arterial flow following the increase in venous return.
Increasingly, self-monitoring of blood pressure is being performed at home. Potential sources of error as well as optimal schemes of measuring and recording have been identified. It has been found that the values documented in this setting are more accurate, if correctly obtained, because of the elimination of the white coat effect.
indirect measurement are provided by the American Heart Association, and sources of error within pediatric populations also have been documented.
The recommended approach for obtaining an auscultated blood pressure is a two-step approach, beginning with inflating the cuff to the point at which the pressure obliterates the palpated radial pulse (systolic pressure). The pressure is completely released, and after 15 to 30 seconds the cuff is reinflated to 30 mm Hg above that point and then gradually deflated while the clinician listens through the stethoscope with the diaphragm placed over the brachial artery and monitors the position of the mercury in the sphygmomanometer. The return of blood flow through the artery is signaled by the sounds produced by the turbulent flow through the partially occluded artery and named after the Russian physician who first described them in 1905 (Korotkoff sounds). This sound is recorded as the systolic pressure. As the pressure continues to be released, sounds change in intensity until the point at which the Korotkoff sounds disappear, which is noted as the diastolic pressure (Table 16.4). Nurse researchers in Britain found statistically significantly lower diastolic values using this approach compared with a one-step approach. In this approach, the systolic pressure was estimated by palpating the brachial artery during cuff inflation, and inflation continued 30 mm Hg beyond that point before proceeding with deflation. It was postulated that the first inflation and occlusion produced a reactive vasodilation that could be responsible for this difference. Regardless, the auscultation of Korotkoff sounds results in systolic values that are
TABLE 16.3 Intrinsic and Extrinsic Factors That Influence Indirect Blood Pressure Accuracy
Factor Effect on Blood Pressure Measurement
Intrinsic Factors Heart rate Elevated or decreased Arterial compliance Elevated or decreased Alterations in flow dynamics Elevated or decreased Respiratory rate Normal increase on inspiration
Extrinsic Factors Cuff Too small Too large
Falsely elevated Falsely decreased
Supine position ≈5 mm Hg lower DBP Seated, back not supported ≈6 mm Hg increased DBP Crossed legs Increased SBP 2–8 mm Hg Seated, arm position Above heart Below heart
Falsely decreased Falsely elevated
Inadequately supported Falsely elevated Excessive stethoscope pressure Diastolic pressure falsely decreased <1 min between measurements Falsely elevated Deflation rate >3 mm Hg/sec Falsely decreased SBP and
increased DBP Exercise, eating, smoking, intake of
caffeine ≤30 minutes before measurement
Talking during measurement Falsely elevated “White coat effect”/anxiety Falsely elevated Decrease in recorder auditory or
visual acuity Falsely elevated or decreased
Recorder bias Falsely elevated or decreased
TABLE 16.4 Korotkoff Sounds
I Initiation of clear tapping sounds—systolic blood pressure II Murmuring or swishing sounds III Increase in intensity and crispness of sounds IV Muffling of sounds V Disappearance of sounds—diastolic blood pressure
X X X X X X X
X X X X
Pressure (mm Hg)
200 180 160 140 120 100 80 60 40 20 0
FIG 16.2 Auscultatory gap. Palpating the blood pressure (BP) before auscultation allows assessment of the true systolic BP. Palpated BP equals 200/P. The same result can often be obtained by elevating the arm overhead for 30 seconds before inflating the cuff. Auscultated BP when the cuff is inflated to only 180 mm Hg results in a falsely low value of 140/80 mm Hg.
KEY POINTS • Systemic arterial blood pressure varies with the cardiac cycle. The highest
pressure (systolic) corresponds to ejection of blood from the left ventricle into the aorta. The lowest point in pressure (diastolic) occurs at the end of diastole, just before the next ventricular contraction.
• Blood pressure is the product of the cardiac output (CO) (HR × SV) and systemic vascular resistance (SVR). Changes in any of these variables will change blood pressure. The arterioles create most of the resistance in the vascular system; changes in the diameter of these vessels profoundly affect SVR and therefore blood pressure.
• The difference between the systolic and diastolic pressures is called the pulse pressure. The average pressure within the systemic arterial system is the mean arterial pressure (MAP), mathematically derived from the two pressure values.
• Blood pressure can be directly measured by placement of a catheter within an artery and utilization of specific computer software. More routinely it is
CHAPTER 16 Alterations in Blood Pressure 341
the lower centers of the brain monitor the body’s internal and external environments. The vasomotor center is directly activated by such stimuli as fever or external stressors to evoke increased activity and elevate systemic arterial blood pressure.
The autonomic nervous system maintains a basal level of arteriolar smooth muscle tone through the SNS and provides heart rate control through a balance of SNS and parasympathetic nervous system (PSNS) activity. Stimulation of the SNS results in the increased release of the neurotransmitters epinephrine and norepinephrine. At the smooth muscle of the arterial system, these neurotransmitters bind to α1 receptors to initiate vasoconstriction and an increase in SVR. Stimulation of the PSNS has almost no effect on most systemic vessels, other than venodilation in localized areas such as the face, producing a blush. Receptors within the brain (α2) provide negative feedback regulation, decreasing the central release of epinephrine and norepinephrine in response to stimulation. In the heart, the binding of these neurotransmitters to β1 receptors results in an increase in the rate of firing at the sinoatrial node, increasing the heart rate in response to increased demands. The PSNS is responsible for maintaining a slower heart rate during periods of rest.
Indirectly, the vasomotor center is stimulated by a decreased rate of discharge by baroreceptors. Pressure-sensitive receptors (baroreceptors) are found in the vessel walls of nearly all large arteries in the thorax and neck, but are particularly plentiful in the sinuses of the carotid arteries and in the arch of the aorta. Signals from the aorta travel through cranial nerve X, and those from the carotids are transmitted through cranial nerve IX; both terminate in the vasomotor center of the medulla. These specialized receptors are sensitive to changes in MAP. They transmit impulses continuously, altering their rate of discharge in response to changes in MAP. Their response to these changes is very brisk, especially when pressure changes occur rapidly, which makes them the perfect mechanism to respond to variations in body position and minimize the gravity-induced decreases in pressure in the upper body. A decrease in sensed pressure induces a decrease in action potential formation by the baroreceptors. This causes the vasomotor center to increase SNS outflow to the heart and arterial bed and to decrease PSNS stimulation to the heart. The net result is an increase in both heart rate and SVR, producing an increase in blood pressure. An increase in sensed pressure results in an increased rate of firing by the baroreceptors and a negative feedback response, lowering systemic arterial pressure. The responsiveness of the baroreceptor reflex declines with age; age-related stiffening of the arterial walls has been implicated along with contributions from pathologic conditions such as hypertension and diabetes mellitus, which are more common in the older population. The results of animal studies indicate that the overall effect of the baroreceptor reflex is a reduction of the minute-to-minute fluctuations in arterial blood pressure by 33% of what it would be without this mechanism. There is abundant evidence that within 1 to 2 days of exposure to chronic elevations of blood pressure, baroreceptors reset to the new level and the rate of discharge begins to decrease and then slowly returns to the norm despite an elevated baseline pressure. This finding suggests that the baroreceptor reflex may contribute to long-term blood pressure regulation through the SNS stimulation of the kidneys discussed in the next section.
Receptors in the carotid and aortic arterials respond to chemical signals of hypoxia (H+ and CO2 level elevations) that occur when arterial pressure declines. These chemoreceptors stimulate the medullary vasomotor center to increase SNS activity. However, this mechanism responds significantly only when systolic pressures decrease below 80 mm Hg, so blood pressure can be prevented from falling even lower.
Long-Term Regulation of Systemic Blood Pressure The regulation of arterial blood pressure on a long-term basis, week after week and month after month, is accomplished through the interplay
MECHANISMS OF BLOOD PRESSURE REGULATION
Arterial blood pressure is physiologically controlled on both a short-term and a long-term basis. Regulation of blood pressure is achieved through changes in factors that affect the primary determinants of blood pressure: heart rate, stroke volume, and SVR (Fig. 16.3). These variables are affected by a complex interplay between neural, humoral, and renal factors to maintain stability in the face of ever-changing internal and external environmental demands. An understanding of these mechanisms is essential to exploring pathophysiologic alterations. Blood pressure normally fluctuates over the course of 24 hours due to physiologic changes associated with circadian rhythm.
Short-Term Regulation of Systemic Blood Pressure Changes in blood pressure must occur quickly to accommodate behavioral changes (e.g., position changes, exercise), emotional changes (e.g., fear, anxiety), and physiologic changes (e.g., fever, volume depletion). Changes in physical activity require the most frequent alterations, and rapid adjustments are initiated in seconds so that the arterial blood pressure may be increased to twice the normal value within 5 to 10 seconds. This short-term regulation is mediated by the sympathetic branch of the autonomic nervous system (the sympathetic nervous system [SNS]). Activation of the SNS influences both heart rate and SVR. The force of contraction is primarily a factor of the circulating volume (preload) and affects long-term regulation of arterial blood pressure.
Modifications in systemic blood pressure are made by activation of the SNS directly or indirectly through stimulation of the baroreceptor reflex. (Autoregulatory changes in pressure at a local level, at the tissues of body organs, are discussed in more detail in Chapter 15.) These SNS activities related to the distribution and pressure of blood are directed through the vasomotor center in the medulla of the brainstem while
Cardiac Output Systemic Vascular Resistance
Heart rate Stroke volume Arterial radius
Vagal nerve stimulation (PSNS)
Myocardial contractility �1 stimulation (SNS)
�1 stimulation (SNS)
FIG 16.3 Systemic arterial blood pressure is controlled through influences on each of its variables: heart rate, stroke volume, and SVR. Some of these provide short-term adjustments, whereas others affect the long-term management of blood pressure. PSNS, Parasympathetic nervous system; RAAS, renin–angiotensin–aldosterone system; SNS, sympathetic nervous system.
measured by auscultation. Systolic pressure is recorded as the onset of the Korotkoff sounds, and their disappearance is recorded as the diastolic pressure.
• Erroneous blood pressure values may be obtained because of a missed auscultatory gap, hydrostatic pressure changes associated with arm position, inappropriate cuff size, observer error, and other factors.
342 UNIT IV Oxygen Transport, Blood Coagulation, Blood Flow, and Blood Pressure
bloodstream. Once ADH arrives in the renal vasculature, it binds to receptors in the collecting ducts, resulting in the enhanced reabsorption of water in order to decrease osmolality (Chapter 26).
The physiologic mechanisms of the RAAS are tightly controlled and interdependent (Fig. 16.5). Prorenin, the inactive form of renin, is synthesized and stored by specialized smooth muscle cells located in the afferent arterioles of the kidney situated immediately proximal to the glomeruli. Known as the juxtaglomerular cells, these cells are stimu- lated by a decrease in arterial pressure to enzymatically cleave the precur- sor and release the activated renin enzyme into the vascular bed of the kidney. Most of the renin travels into the general circulation, where it acts on a circulating plasma protein called angiotensinogen, resulting in the release of angiotensin I, a peptide possessing minimal vasoconstric- tive capacity. Angiotensin I continues to be created by renin for about 30 to 60 minutes, until renin is removed from the body. While the blood carrying angiotensin I circulates through the pulmonary vessels, an enzyme produced by the vascular endothelium (angiotensin-converting enzyme [ACE]) comes in contact with angiotensin I, and two amino acids are fragmented from angiotensin I to produce angiotensin II. Inactivated in minutes by angiotensinases, continued production of angiotensin II maintains the profound effects it initiates. Angiotensin II is an extremely potent vasoconstrictor, primarily of the arterial bed, but also slightly affecting the venous system. The SVR is therefore increased, raising blood pressure. The vasoconstrictive response to angiotensin II requires about 20 minutes to reach maximal capacity, but is capable of elevating arterial pressure to 50% of normal after severe hemorrhage. The enhanced venous return attributable to the elevated SVR improves cardiac function by increasing myocardial fiber stretch, producing increased contractility and therefore stroke volume. Angiotensin II also is an intermediary for an additional means of raising blood pressure—increasing circulating volume to significantly increase venous return to the heart and therefore stroke volume. Angiotensin
Increased extracellular fluid volume
Increased blood volume
Increased mean circulatory filling pressure
Increased venous return of blood to the heart
Increased cardiac output
Increased total peripheral resistance
Increased arterial pressure
FIG 16.4 Mechanism by which an increase in extracellular fluid volume results in an increase in systemic arterial pressure. (From Hall JE: Guyton and Hall textbook of medical physiology, ed 13, Philadelphia, 2016, Saunders.)
INCREASE IN BLOOD PRESSURE
Vasoconstriction Aldosterone release
Sodium and water retention
Increased blood volume
FIG 16.5 The renin–angiotensin–aldosterone system (RAAS) and its systemic effects.
of neural, hormonal, and renal interaction and is intimately connected with the body’s fluid volume homeostasis. The balance of the intake of water and sodium with their excretion by the kidney remains the central feature of long-term blood pressure maintenance. Historically, the role of the renin–angiotensin–aldosterone system (RAAS) has been seen as the primary contributor to this process, and although it continues to be a major determinant, mechanisms involving the baroreceptor reflex and the vasomotor center in the brainstem as well as localized renal systems are receiving increased attention in research.
An increase in extracellular fluid (ECF) volume, because of increased intake or decreased excretion, results in an increase in cardiac output; when combined with the volume-induced increase in SVR, this results in an elevation in the arterial blood pressure (Fig. 16.4). Body tissues initiate their local autoregulation mechanisms, constricting arterioles to protect against high-flow damage, which further contributes to the overall arterial resistance in the body. Unless fluid intake or renal func- tions are abnormal, this increase in SVR will not result in a prolonged elevation in arterial pressure. The kidneys will respond quickly, increasing excretion of sodium and water and normalizing pressure within a matter of hours. This physiologic regulatory response may be disrupted if the renal vasculature is constricted, as occurs in hypertension.
Because sodium is not as rapidly eliminated by the kidney as water, elevations in sodium intake are more likely to elevate arterial pressure. Excess sodium also adds to the body’s fluid volume by several mecha- nisms. Sodium increases the osmolality of the ECF and activates the central thirst center, causing an increase in water intake. The increased serum osmolality will be sensed by the hypothalamus and posterior pituitary, causing the release of antidiuretic hormone (ADH) into the
CHAPTER 16 Alterations in Blood Pressure 343
death, myocardial infarction, and stroke are associated with circadian elevations in BP.
II in the general circulation reaches the cortex of the adrenal glands, stimulating the release of the hormone aldosterone. Aldosterone circulates to the kidneys, where it binds to receptors in the renal tubules, causing the kidneys to reabsorb more sodium. Water follows the sodium back into the bloodstream. The result is an increase in blood volume and further elevation in blood pressure. Excessive amounts of angiotensin in the bloodstream have been found to effectively reset this mechanism of blood pressure control to a higher-than-normal level, potentially contributing to hypertension.
Some of the renin released by the juxtaglomerular cells exerts local effects within the kidney to elevate blood pressure. Renin receptors in the mesangium of the glomerulus and below the endothelial cells of the renal arteries are activated to enhance the conversion of angioten- sinogen to angiotensin I. Angiotensinogen has been isolated in tubular and mesangial cells, and ACE is found both in vascular endothelium and in the epithelium of the tubular cells.
Other influences on long-term arterial blood pressure control include the activity of the SNS, levels of natriuretic peptides, and regulation of intrarenal mechanisms such as renal medullary endothelin production. Renin release is increased when neurotransmitters released by the sympathetic nervous system bind to β1 receptors in the kidney. Additional local SNS effects include decreased glomerular filtration rate (GFR) as a result of renal arteriolar constriction and increased tubular reabsorption of sodium and water caused by increased quantities of angiotensin II and aldosterone. These effects contribute to the increased systemic blood pressure associated with severe prolonged stress. Increased SNS activity has been documented to be present in hypertension, and its role is confirmed because antihypertensive drugs that affect autonomic control of heart rate and SVR are so clearly effective in treatment. A number of natriuretic hormones play a role in arterial pressure through their effects on ECF volume regulation; most important of these is atrial natriuretic peptide (ANP). Increased volume in the atria of the heart triggers stretch receptors and stimulates the release of ANP into the bloodstream by cardiac muscle fibers. ANP causes the kidneys to increase water and sodium excretion by increasing GFR and decreasing sodium reabsorption so both sodium and water remain in the filtrate. This diuretic effect reduces circulating volume and therefore blood pressure. Endothelin-1 (ET-1) is a peptide produced in the renal medulla. ET-1 binds to receptors within the kidney, initiating an autocrine-induced vasodilatory response affecting renal perfusion, water and electrolyte movement, and release of renin. This makes ET-1 an important par- ticipant in normal systemic blood pressure control, and levels have been found to be abnormal in hypertension. Most likely, long-term blood pressure control is a reflection of the unified contributions of all the factors discussed here, and more are yet to be identified.
Normal Fluctuations in Systemic Blood Pressure Many homeostatic mechanisms of the body undergo daily variations in their function governed by an area of the brain called the suprachi- asmatic nuclei—the body’s internal clock. Brain wave activity, cell regeneration, cortisol release, body temperature, heart rate, and blood pressure are only a few of the numerous circadian rhythms. In the case of blood pressure, it is known that it rises before awakening (morning surge), is highest in the middle of the morning, then begins to fall, and reaches its lowest level at night (nocturnal dip). In their review of the available research, Peixoto and White found these basic fluctuations to be primarily determined by internal neural and hormonal regulation, as well as by external environmental factors such as sodium intake and physical activity. Additional factors known to affect the normal rhythmic changes in blood pressure include lifestyle influences such as alcohol consumption and cigarette smoking, as well as cognitive activity and emotional state. Development of diabetic nephropathy, sudden cardiac
KEY POINTS • Blood pressure is regulated on a short-term basis through the interaction
of the carotid and aortic baroreceptors, the vasomotor center in the brainstem, and the activation of the sympathetic nervous system (SNS) and inhibition of the parasympathetic nervous system (PSNS) influences on the heart and smooth muscle in the arterioles. Short-term regulation primarily involves heart rate and systemic vascular resistance (SVR).
• Regulation of blood pressure on a long-term basis is complex, involving the influence of the nervous system, release of hormones, and responses of the kidneys to pressure changes. The vasomotor center and activation of α1 receptors in the smooth muscle of the arterioles and the β1 receptors of the heart continue to be involved when pressure changes are sensed by the baroreceptors.
• Secretion of antidiuretic hormone (ADH) in response to osmolality and of aldosterone from the activation of the renin–angiotensin–aldosterone system (RAAS) affects fluid balance, whereas angiotensin II produces an increase in SVR. Natriuretic peptides and intrarenal mechanisms contribute to the process of long-term blood pressure management. Long-term regulation involves all of the blood pressure variables: heart rate, stroke volume, and SVR.
• Normal fluctuations of blood pressure occur in a cyclic pattern attributable to changes in the body’s internal and external environments.
HYPERTENSION The current and projected global prevalence of hypertension is stunning. Hypertension is the most common primary diagnosis in the United States. About 32% or 80 million adults in the United States have high blood pressure. The prevalence of high blood pressure remains higher among non-Hispanic black adults (44.9% & 46.1%; men and women, respectively) compared with non-Hispanic white (32.9% & 30.1%; men and women respectively) and Mexican American adults (29.6% & 29.9%; men and women, respectively). Global estimates suggest more than 40% of adults 25 years of age or older are diagnosed with hypertension, affecting more than 1 billion people. Changes in the standard of living of those in developing countries mirror the trends in economically developed ones: increasing obesity, diabetes, and sedentary lifestyles. Increased consumption of alcohol, cigarette smoking, and diets deficient in fruits and vegetables contribute to the problem of escalating hyperten- sion worldwide. Hypertension will affect nearly half of the adult popula- tion in the majority of the world. India and Asia have the lowest current and projected prevalence, whereas the former socialist republics, sub- Saharan Africa, the Caribbean, and Latin America have the highest rates. Given the risks to health with blood pressure elevations the future impact of hypertension is profound. Hypertension increases morbidity and mortality associated with heart disease, kidney disease, peripheral vascular disease, and stroke. It is responsible for a worldwide annual death rate of 7.6 million, and it is the most common risk factor for cardiovascular disease worldwide. An understanding of the types and causes of hypertension and the interventions associated with its treatment is essential to having an impact on the current and future effects of this disease.
Definition and Classification The standard for the definition and classification of hypertension in adults continues to be drawn from the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), published in 2003. For those individuals age 18 years and older, normal blood pressure is defined as <120 mm Hg
344 UNIT IV Oxygen Transport, Blood Coagulation, Blood Flow, and Blood Pressure
subtype of hypertension in those older than age 55. The level of the systolic pressure, MAP, and the difference between systolic and diastolic pressures (pulse pressure), among other factors, are used to guide pharmacologic interventions. Given this normal age-related development of hypertension, most early and subsequent data related to the increased risk of mortality and morbidity are based on this population, and systolic pressure elevation clearly affects risk more than diastolic, as noted in the earliest and most famous cardiovascular research in the Framingham Study.
Age is not a risk factor for hypertension in childhood or adolescence. Hypertension does occur in these age groups, however, and the distribu- tion of subtypes and the proposed bases and prognosis are worth noting. Determination of hypertension is based on the normal expectations for the child’s age, gender, and height (see Table 16.1). Although IDH is more common among younger adults, ISH can occur. ISH in ado- lescents and young adults (<45 years of age) has been attributed to the increased elasticity of their arteries in the face of rapid growth; this produces an increase in brachial systolic pressure, although aortic pressure is unchanged. Others have found an increase in stroke volume with or without aortic stiffening to be the basis of ISH in this age group. IDH often seems to develop in prehypertensive young adults, and the prognosis remains open to debate. One study found that IDH does not appear to predict the development of ISH but is a strong predictor of the later development of SDH. The report of a review of the literature indicated that below the age of 50, diastolic pressure was a greater predictor of coronary artery disease (CAD), whereas CAD risk in those age 60 and older was greater with elevated systolic pressure. In children, hypertension is a risk both for adult hypertension and for subsequent development of adult cardiovascular disease.
Another significant nonmodifiable risk factor is ethnicity, which combines race with genetics. Adult African Americans have the highest risk, but there is controversy about this finding for the pediatric popula- tion. A concrete reason for this finding in adults continues to elude researchers, although increased salt sensitivity seems most likely. The number of individual genes and their signaling pathways and organi- zational arrangements that affect the control of blood pressure are vast and beyond the scope of this text. Despite the identification of the genetic role in hypertension, specifying the mechanisms themselves is a challenge. Genetics may be responsible for low renin levels and salt
systolic and <80 mm Hg diastolic; stage 1 hypertension begins at a systolic pressure of 140 mm Hg or a diastolic pressure of 90 mm Hg (see Table 16.2). The range of pressures between normal blood pressure and stage 1 hypertension has been identified as prehypertension as part of efforts to initiate interventions early enough to prevent or at least slow the progression of the disease process. In 2014 the Eighth Joint National Committee released treatment goals based on age, but did not change the JNC 7 criteria for defining hypertension (see Table 16.2). These values differ from those established by the World Health Organiza- tion, International Society of Hypertension, and European Society of Hypertension/European Society of Cardiology in that those used in the United States are more conservative, identifying both normal and elevated levels at lower values. Standards for children and adolescents also have been established (see Table 16.1). Differing etiologies and risk factors have led to the differentiation of two major types of hypertension: primary and secondary.
Primary Hypertension Primary hypertension, also called essential hypertension, does not have a clearly identifiable known etiology and is therefore an idiopathic disorder. This differentiates primary from secondary hypertension, in which blood pressure elevation occurs secondarily to another, identifiable cause. Primary hypertension is by far the most common form of the disease, representing somewhere between 90% and 95% of the known cases. Early diagnosis and intervention for adults with hypertension has been a major focus of health care for many decades; the more recent escalating incidence in children has generated alarm. Primary hyperten- sion is increasing in prevalence among children and adolescents and is associated with positive family history of hypertension, obesity, and lifestyle factors. The prevalence of hypertension in children and ado- lescents is approximately 3.5%. Primary hypertension is rare before children reach the age of 10 years. Most of the hypertension diagnosed in preadolescents has a secondary etiology; by adolescence, 85% to 95% of the cases are primary hypertension.
Subtypes Primary hypertension in adults less than 60 years of age has one of several presentations: isolated systolic hypertension (ISH) in which the systolic blood pressure is ≥140 mm Hg and the diastolic pressure remains <90 mm Hg; isolated diastolic hypertension (IDH) in which the diastolic pressure is ≥90 mm Hg with a systolic pressure of <140 mm Hg; and the combination of systolic and diastolic hypertension (SDH) occurring when both systolic and diastolic pressures exceed prehypertension values. The differing subtypes are more prevalent in specific populations, and researchers increasingly focus on subtypes in long-term outcome predic- tions and interventions. The evidence suggests that systolic blood pressure is the major risk for subsequent cardiovascular disease.
Risk Factors In Western populations, there is a 90% lifetime risk for the development of hypertension. Many of the risk factors for hypertension have been known for decades and because so many are modifiable by lifestyle changes, targeted interventions are urged to address them. Other factors remain nonmodifiable, yet predictive of the development of hypertension. Ample data indicate that primary hypertension arises as a consequence of the interplay of several genes and environmental factors. Hypertension risk factors are listed in Table 16.5.
Increasing age is a nonmodifiable risk and an independent risk factor for hypertension beginning at midadulthood. Normal aging produces a rising systolic pressure over the course of a lifetime, whereas diastolic pressure increases for approximately 50 years, levels off during the sixth decade, and remains stable or declines thereafter. ISH is the dominant
TABLE 16.5 Risk Factors for the Development of Primary Hypertension
Nonmodifiable Risk Factors Modifiable Risk Factors
Increasing age Family history
Obesity Sedentary lifestyle Metabolic syndrome Dietary factors • Increased fat intake • Increased sodium intake • Inadequate potassium intake • Inadequate calcium intake Tobacco use Laboratory data • Elevated blood glucose • Elevated total cholesterol • Elevated triglycerides • Decreased high-density lipids (HDL) • Elevated low-density lipids (LDL)
CHAPTER 16 Alterations in Blood Pressure 345
of hypertension from the maternally provided intrauterine environment through the childhood and adolescent period. Maternal smoking, pregnancy-induced hypertension, and maternal dietary habits have been shown to influence the later development of hypertension. Low birth weight, followed later by rapid growth in both height and weight, seems to be more common in the history findings of patients with hypertension. Lower socioeconomic level of the mother and inadequate dietary calcium intake during pregnancy appear to increase the risk for later development of hypertension, whereas breast feeding seems to act as a protective factor against hypertension.
Outcomes End-organ damage. The great concern for the prevention, early
identification, and treatment of hypertension is because of the harm it may cause in body tissues and organs and the resulting significant morbidity and mortality (Fig. 16.6). This end-organ damage is a function of both the stage of hypertension and its duration. Unfortunately, early hypertension causes no overt clinical manifestations, and individu- als may have considerable end-organ damage before the diagnosis is made. This has earned hypertension the moniker of the “silent killer” and explains the rationale for screening programs to encourage early diagnosis. Hypertension is an important independent risk factor for the development of renal failure, stroke, and CAD. CAD and hypertension heighten the risk of angina, myocardial infarction, and heart failure. As the systolic and diastolic pressures rise from normal levels, mortal- ity from ischemic heart disease and stroke also increases linearly and progressively.
Cardiovascular disease is the most commonly recognized outcome of hypertension. For those older than age 50 years, systolic hypertension presents a far greater risk for the development of cardiovascular disease than does an elevated diastolic blood pressure. Risk for the occurrence
sensitivity, heightened responses to angiotensin II, altered amounts or responses to local tissue factors such as endothelin and nitric oxide, and any number of mechanisms accounting for primary hypertension that have been proposed. At the same time, none of the currently identified genetic disorders have been demonstrated to be accountable for a noteworthy proportion of hypertension in the general population, either as individual genes or as several genes working in concert. A family history of hypertension is a risk factor in both adults and children, although these mechanisms are unclear.
Modifiable risk factors are often called lifestyle factors in acknowledg- ment of the role of individual choice in both their development and their control. Both weight gain and obesity are significant risk factors for all subtypes of primary hypertension at all ages. Obesity has reached epidemic proportions and represents between 65% and 75% of the overall risk for the development of hypertension. Diet and activity levels contribute to the development and continuation of obesity in all age groups. Diets high in fat and sodium and low in potassium and in fruits have been found to increase the risk of developing hypertension. Obesity not only increases the risk of hypertension, but also is a risk factor for hyperlipidemia, salt sensitivity, and insulin resistance. Known as metabolic syndrome and characterized by elevated circulating insulin and lipid levels, hypertension, and obesity, this condition was previously only identified as a risk factor for hypertension in adults but is now becoming more common in children. It has been estimated that the prevalence of metabolic syndrome is 7% in adolescents at risk for becoming overweight, 29% in overweight adolescents, and 50% in severely obese adolescents. Elevated blood glucose levels, diabetes mellitus, and elevated total cholesterol level, as well as smoking and excessive alcohol intake, are all implicated as risk factors for hypertension.
Recently the apparent increased incidence of childhood and adolescent hypertension has spawned research into predictors of the development
Hypertension and Atherosclerosis
Heart and Arteries Kidneys
Increased myocardial work
Increased pressure and
Aneurysm Autoregulation failure
Stable angina Acute coronary syndrome: Unstable
angina and myocardial infarction
End-stage renal failure
Heart failure Hemorrhage Ischemia
Increased pressure and
decreased flow Retinal detachment
FIG 16.6 Effects of chronic hypertension and atherosclerosis on target end organs.
346 UNIT IV Oxygen Transport, Blood Coagulation, Blood Flow, and Blood Pressure
not attained for many patients with hypertension. The problem appears to be even greater in Europe, where only 5% to 12% achieve control compared with 27% in the United States. Cumulative data from clinical drug trials indicate the risk of stroke can be reduced 35% to 40% by decreasing blood pressure, myocardial infarction 20% to 25%, and heart failure by more than 50%. Approaches to treatment are affected by several factors, including the patient’s age, stage of hypertension, identified risk factors, concomitant disorders, ethnicity, and medication history. Interventions fall into two categories: lifestyle alterations and pharma- cologic interventions. Whatever the chosen therapy, it is important to get to the goal or target blood pressure for the individual. For those under 60 years of age, the goal is a systolic BP under 140 mm Hg and a diastolic BP under 90 mm Hg. One of the major changes of JNC 8 was to alter the target systolic BP to less than 150 mm Hg (instead of 140 mm Hg) for those 60 years old and older. The target diastolic BP was not changed and remains at under 90 mm Hg. JNC 8 also eliminated the various target BPs that were suggested in JNC 7 for those with conditions such as diabetes and heart disease. The overall approach to treatment is detailed in Fig. 16.7. Although an in-depth discussion of treatments is beyond the scope of this book, they are summarized in the following text.
Lifestyle alterations assume special importance because addressing modifiable risk factors has a documented effect in preventing hyperten- sion from developing, as well as treating it in adults and children. Primary prevention of hypertension could have a profound influence on the morbidity and mortality associated with end-organ damage throughout the world and includes lifestyle changes and effective screening procedures to facilitate early diagnosis. These lifestyle changes are listed in Table 16.6. Weight loss is clearly an important intervention, with substantial evidence that it reduces cardiovascular mortality. The efficacy of exercise in blood pressure control is also well substantiated by research. Brisk
of cardiovascular disease doubles with each incremental increase of 20/10 mm Hg in BP.
Hypertension itself is directly harmful to the arterial system, but it also acts in concert with the other risk factors associated with the development and acceleration of atherosclerosis. Atherosclerosis is the underlying pathophysiologic basis of coronary artery disease (see Chapter 18). Evidence of atherosclerosis has been found in adolescents and very young children. The increased tension that high blood pressure generates on the walls of arteries precipitates an increase in the accumulation of collagen as well as reduction, fragmentation, and breakage of elastin fibers. An ongoing low level of inflammation occurs in arteries exposed to hypertension, and combined with the dyslipidemia commonly seen, the development of atherosclerotic plaques is escalated. CAD predisposes to stable angina and the acute coronary syndrome of unstable angina and myocardial infarction (see Chapter 18).
Hypertension reflects an elevation in SVR; rising afterload increases myocardial oxygen demand and overall cardiac workload. In an effort to compensate for this increased effort, the left ventricle hypertrophies. The development of left ventricular hypertrophy also has been noted in children and adolescents. The CAD typically found in association with hypertension limits the supply of oxygen to the heart, and this combination of increased demand and decreased supply predisposes the heart to ischemia. Ischemia may result in stable or unstable angina or myocardial infarction. Myocardial infarction and left ventricular hypertrophy increase the risk for the development of heart failure. Patients may seek health care intervention because of these conditions so that the presence of hypertension is discovered only secondarily.
The atherosclerotic process described previously with coronary artery disease (Chapter 18) is likely to be the basis for the damage to the microcirculation of the kidneys that develops with chronic hypertension. Within a proscribed MAP, healthy kidneys are able to autoregulate blood flow delivered to the glomerulus, but with prolonged or severe hypertension this regulatory ability is lost and glomerular damage ensues. Damage to the glomerulus allows large molecules not normally filtered out of the bloodstream to appear in the urine. The presence of micro- albuminuria (proteinuria) is reflective of increased glomerular perme- ability and an early indicator of hypertensive renal injury. At this point, the patient is usually asymptomatic, but if interventions for blood pressure control are not initiated, renal impairment progresses, culminat- ing in end-stage renal disease, which requires long-term renal dialysis or transplantation.
Identifiable damage to the kidneys is often preceded by changes in the microcirculation of the retina of the eye. Atherosclerosis also contributes to the retinal injury produced by hypertension. The result may be retinal detachment or hemorrhage, which can cause blindness.
Hypertension and the accelerated development of atherosclerosis affect arteries of all sizes throughout the body. Decreased flow or rupture of weakened blood vessels within the brain results in strokes. Ischemic strokes are associated with atherosclerosis, whereas hypertension is the major risk factor for hemorrhagic strokes. This type of stroke results in high morbidity and mortality. Hypertension is also the primary risk factor for the development and rupture of aortic aneurysms. The peripheral arteries of the lower extremities are common targets of atherosclerosis, and the resulting peripheral vascular arterial disease is the source of significant impairment of independence and mobility and potential amputation in the elderly.
Treatment Interventions Effective treatment of hypertension results in decreased morbidity and mortality associated with cardiovascular, cerebrovascular, and renal disease. However, the goal of normal systolic and diastolic pressures is
TABLE 16.6 Lifestyle Modifications to Prevent and Treat Primary Hypertension in Adults*
Modification Recommendation Range of Sbp Reduction†
Weight reduction Attain and maintain BMI of 18.5–24.9 kg/m2
5–20 mm Hg/10 kg
DASH diet High in fruits and vegetables and low-fat dairy products with decreased total and saturated fat
8–14 mm Hg
Decreased sodium intake
No more than 100 mmol/day (2.4 gm sodium or 6 gm sodium chloride)
2–8 mm Hg
Exercise plan Regular aerobic activity for at least 30 min/day most days of week
4–9 mm Hg
Moderate intake of alcohol
≤2 drinks/day for men ≤1 drink/day for women
2–4 mm Hg
Modified from Ozemek C, Phillips SA, Popovic D, et al: Nonpharmacologic management of hypertension: A multidisciplinary approach. Curr Opin Cardiol, March 17, 2017. [Epub ahead of print.] BMI, Body mass index; DASH, Dietary Approaches to Stop Hypertension. *Smoking cessation increases the overall reduction in cardiovascular risk. †Results vary based on individual response, amount, and time of modification accomplished.
CHAPTER 16 Alterations in Blood Pressure 347
Adult aged ≥18 years with hypertension
Implement lifestyle Interventions (continue throughout management).
Set blood pressure goal and initiate blood pressure lowering-medication based on age, diabetes, and chronic kidney disease (CKD).
General population (no diabetes or CKD) Diabetes or CKD present
Age ≥60 years Age <60 years All ages Diabetes present No CKD
All ages CKD present with or without diabetes
Blood pressure goal SBP < 150 mm Hg DBP < 90 mm Hg
Blood pressure goal SBP < 140 mm Hg DBP < 90 mm Hg
Blood pressure goal SBP < 140 mm Hg DBP < 90 mm Hg
Blood pressure goal SBP < 140 mm Hg DBP < 90 mm Hg
Initiate thiazide-type diuretic or ACEI or ARB or CCB, alone or in combination.a
Initiate thiazide-type diuretic or CCB, alone or in combination.
Initiate ACEI or ARB, alone or in combination with other drug class.a
Select a drug treatment titration strategy A. Maximize first medication before adding second or B. Add second medication before reaching maximum close of first medication or C. Start with 2 medication classes separately or as fixed-dose combination.
At goal blood pressure? Yes
Reinforce medication and lifestyle adherence. For strategies A and B, add and titrate thiazide-type diuretic or ACEI or ARB or CCB (use medication class not previously selected and avoid combined use of ACEI and ARB). For strategy C, titrate doses of initial medications to maximum.
Reinforce medication and lifestyle adherence. Add and titrate thiazide-type diuretic or ACEI or ARB or CCB (use medication class not previously selected and avoid combined use of ACEI and ARB).
Reinforce medication and lifestyle adherence. Add additional medication class (eg. β-blocker, aldosterone antagonist, or others) and/or refer to physician with expertise in hypertension management.
Continue current treatment and monitoring.b
SBP indicates systolic blood pressure; DBP, diastolic blood pressure; ACEI, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; and CCB, calcium channel blocker.
a ACEIs and ARBs should not be used in combination. b If blood pressure fails to be maintained at goal, reenter the algorithm where appropriate based on the current individual therapeutic plan.
At goal blood pressure? No
At goal blood pressure? No
At goal blood pressure? No
FIG 16.7 Treatment recommendations for primary hypertension. (From James PA, Oparil S, Carter BL, et al: 2014 Evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the eighth joint national committee (JNC 8). JAMA, 311(5):507-520, 2014.) ACEI, Angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, β-blocker; BP, blood pressure; CCB, calcium channel blocker; DBP, diastolic blood pressure; SBP, systolic blood pressure.
348 UNIT IV Oxygen Transport, Blood Coagulation, Blood Flow, and Blood Pressure
ruled out, but from the age of 18 years, primary hypertension is far more common. Interventions for secondary hypertension are directed at removing the cause, if possible. Drug therapy may be indicated, using the same agents previously discussed in the treatment of primary hypertension. As with primary hypertension, both the severity of the elevation and its duration must be considered because they heighten the risks for end-organ damage. The most common etiologies of second- ary hypertension are discussed next.
Renal disease may be the result of a disease process either involving the parenchyma of the kidney or involving its vascular system. Hyperten- sion is a risk factor for the development of renal failure, but it can also develop secondary to renal pathologies. In adults with renal disease, hypertension is common and develops early, primarily as a result of heightened SNS activity. In children one of the most common causes of hypertension is renal disorders; however, by the age of 12 to 18, the major cause becomes idiopathic primary hypertension. As renal disease progresses, the kidneys’ ability to excrete sodium effectively is lost and the RAAS, as well as the SNS, are inappropriately activated. Renal artery stenosis should be considered in the diagnostic evaluation of new-onset hypertension in patients younger than 30 or older than 55 years, and an abdominal bruit is often found on auscultation.
Another common cause of hypertension in children younger than age 6, along with renal disease, is coarctation of the aorta. Without treatment, median life expectancy is only 31 years, with death from
exercise of at least 30 minutes most days of the week plus the acceptance of the Dietary Approaches to Stop Hypertension (DASH) diet address a number of hypertensive risk factors. Because they have been found to augment drug efficacy, these lifestyle adjustments also are included for those who require medication interventions for primary hypertension; however, it is unlikely that lifestyle interventions alone will be sufficient for those with stage 1 hypertension.
Drug therapy for hypertension addresses one or more of the variables responsible for blood pressure: heart rate, SVR, and stroke volume, which is primarily a function of the volume of blood returned to the heart during diastole. This is reflected in how the classifications of oral medications used in the treatment of hypertension are listed in Box 16.1. Combination drugs, taking advantage of the effects of more than one classification without increasing the total number of medications a patient is taking, are becoming increasingly popular. Because there is considerable variation in individual response to antihypertensive drug therapy, long-term monitoring is essential, and alterations in treatment may be necessary.
Secondary Hypertension When hypertension is found to have a specific identifiable cause, it is termed secondary hypertension. The cause may be a specific pathology or condition that results in hypertension, or the development of high blood pressure may be the result of the ingestion of certain drugs, foods, or chemicals. Conditions associated with secondary hypertension are listed in Box 16.2. Some common substances that increase blood pressure are shown in Box 16.3.
In infants and preschool children, hypertension is usually of a second- ary etiology, and primary hypertension is rare. In a study of 220 hypertensive children, 85% of the cases were found to be of a secondary etiology. The four variables independently associated with primary hypertension were absence of signs and symptoms, normal serum creatinine level, family history of hypertension, and elevated body weight. In the diagnostic assessment of adults, secondary etiologies should be
Reduce Stroke Volume Thiazide diuretics Loop diuretics Potassium-sparing diuretics Aldosterone receptor blockers Angiotensin (ACE) inhibitors Angiotensin II receptor blockers Venodilators
Reduce Systemic Vascular Resistance Combination α1- and β-blockers Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers Calcium channel blockers α1-Blockers Central α2 agonists Direct-acting vasodilators (arterial)
Decrease Heart Rate β-Blockers Combination α1- and β-blockers
BOX 16.1 Drug Classifications Used to Treat Hypertension and the Variables They Affect
Renal (Parenchymal or Vascular) Renal artery stenosis Renal failure* (end-stage renal failure attributable to any etiology; acute renal
failure) Polycystic kidney disease Glomerulonephritis* Hypertensive nephrosclerosis
Cardiovascular Coarctation of the aorta*
Tumors Pheochromocytoma* Neuroblastoma* Wilms tumor* Adrenal adenocarcinoma*
Endocrine Hyperthyroidism* Cushing disease* Congenital adrenal hyperplasia* Primary hyperaldosteronism*
Neurologic Guillain-Barré syndrome* Increased intracranial pressure*
Other Systemic arteritis (e.g., Henoch–Schönlein purpura) Sleep apnea*
BOX 16.2 Common Pathologic Causes of Secondary Hypertension in Children and Adults
*Also seen in children.
CHAPTER 16 Alterations in Blood Pressure 349
Obstructive sleep apnea (OSA) is closely associated with obesity; it is found in 2% to 4% of adults, and hypertension is present in 45% to 60% of those diagnosed with OSA. Historically, there has been debate as to whether OSA itself was an etiologic factor in hypertension or whether obesity simply increased the risk of both. Researchers now take the position that the potential causality between hypertension and OSA entails both an independent role of OSA in chronic blood pressure elevation and the obesity–hypertension linkage. Certain molecular mechanisms, including increased vasomotor activity mediated by angiotensin II, endothelin, and nitric oxide, may occur in both. The severity of OSA has a direct relationship to the level of blood pressure elevation, and when untreated, mortality and morbidity resulting from cardiovascular pathologies is increased. A milder form of OSA is found in children, and evidence is increasing that it, too, is associated with discernible cardiovascular abnormalities, including hypertension, decreased arterial distensibility, and left ventricular hypertrophy.
Pheochromocytoma is a catecholamine-secreting tumor of the adrenal medulla that generates hypertension on either a short-term or a long-term basis. The condition is rare, although well recognized; it can result in angina, myocardial infarction, acute heart failure, dilated cardiomyopathy, cerebral ischemia or hemorrhagic stroke, and cardiac dysrhythmias. Treatment involves control of blood pressure pharmacologically and then surgical removal of the tumor.
Hypertension is a predictable finding in primary hyperaldosteronism. Most frequently it is caused by a hypersecreting benign adenoma of the adrenal cortex or either unilateral or bilateral idiopathic adrenal hyperplasia. Although evidence exists that aldosterone is produced by other body tissues, hormone from the adrenal gland represents by far the majority of circulating aldosterone. The ratio of aldosterone to renin may be genetically influenced, but this has not been consistently documented. For decades, hyperaldosteronism was thought to be a rare cause of hypertension; it is now known to be the most common form of secondary hypertension, responsible for at least 12% of all cases, and it is believed that this number would be higher with improved screening. Screening for hyperaldosteronism is recommended for hypertensive patients with decreased potassium levels or those found to be refractive to three or more antihypertensive agents. Diagnosis requires measurement of serum aldosterone and renin levels. Surgical removal of the involved adrenal gland results in a cure for 30% to 60% of cases and improved blood pressure levels in the remainder. Removal of one or both adrenal glands in bilateral disease rarely appears curative, so bilateral disease is treated medically with agents that block aldosterone’s binding sites in the kidney.
Hypertensive Emergencies and Urgency Acute rises in blood pressure are identified by several names, complicating discussion of the condition. Hypertensive crisis (HTN-C) was the term introduced to replace the initial term malignant hypertension, which originated as early as 1914. Eighty million Americans have been diagnosed with hypertension, and about 7% of these will experience a hypertensive crisis during their lifetime. The 1 year mortality of untreated HTN-C is 79% with a median survivial of 10 months. Most cases of HTN-C seem to be caused by secondary hypertension or poorly or uncontrolled primary hypertension. Some other notable etiologies for hypertensive crisis include autonomic dysfunction, as is seen in Guillain-Barré syndrome, and autonomic dysreflexia, which can manifest in patients with high spinal cord injuries as well as in patients discontinuing certain drugs, such as β-blockers. The contemporary use of hypertensive crisis is associated with two differentiated sub groups: hypertensive emergency and hypertensive urgency. In both cases, the diastolic blood pressure is usually >120 mm Hg. Hypertensive emergencies are situations character- ized by a sudden increase in either or both systolic and diastolic pressures
hypertension-related systemic effects. It is for this reason that palpation of peripheral pulses and measurement of blood pressure in both arms are recommended both in routine pediatric physical examinations and in physical examinations in those whom hypertension is present. Early diagnosis facilitates early surgical intervention, reducing both premature mortality and end-organ damage. Hypertension persists after surgical repair in 20% to 30% of patients, but the pathophysiologic basis of this finding has yet to be determined. Unfortunately, this means that these individuals remain at risk for the long-term effects and increased mortality associated with hypertension.
Hypertension arises in 5% to 12% of all pregnancies. Hypertension during pregnancy is of concern because of increased risk of maternal, fetal, and neonatal morbidity and mortality. Preterm labor, abruptio placentae, disseminated intravascular coagulation, hemorrhagic stroke, liver failure, and acute renal failure are all potential outcomes of hypertension during pregnancy. When hypertension is diagnosed during pregnancy, it is classified into one of four categories: chronic hypertension (preexisting), preeclampsia, chronic hypertension with superimposed preeclampsia, or gestational hypertension. Pharmacologic interventions are used cautiously, and lifestyle interventions such as limiting salt intake and avoiding the use of alcohol or tobacco may be sufficient.
Over-the-Counter Drugs, Prescription Drugs, and Illicit Drugs Sympathomimetic agents (e.g., decongestants, amphetamines) Glucocorticoids Cocaine Calcineurin inhibitors (e.g., cyclosporine, tacrolimus) Oral contraceptives, especially if high in estrogen Nonsteroidal antiinflammatory drugs Erythropoietin Antidepressants Phenylpropanolamine analogs (e.g., ma huang, “herbal ecstasy”) Nicotine (and withdrawal) Anabolic steroids Narcotic withdrawal Ergotamine St. John’s wort
Foods Foods containing tryptophan or tyramine
• Chicken liver • Pickled herring • Yeast extract • Lima beans • Aged cheeses • Beer and wine
Caffeine Sodium chloride Alcohol Licorice
Chemical Elements Lead Mercury Lithium salts Thallium and other heavy metals
BOX 16.3 Substances Known to Contribute to High Blood Pressure
350 UNIT IV Oxygen Transport, Blood Coagulation, Blood Flow, and Blood Pressure
accompanied by evidence of acute end-organ damage. These same references use the term hypertensive urgency to describe similar blood pressure elevations, but without the end-organ damage. The differentia- tion is necessary because it is the presence of end-organ damage and not the level of the blood pressure that usually determines the treatment.
Hypertensive emergencies can occur in the previously undiagnosed patient or the patient with chronic hypertension; these emergencies are twice as common in males as in females, and elderly African Americans have the highest incidence. Hypertensive emergencies can occur at any age and are estimated to be responsible for more than 25% of emergency department visits. Of all the end-organ damage with which hypertensive emergencies are associated, abnormalities of the central nervous system are the most frequent. These include ischemic stroke, encephalopathy, and subarachnoid or intracerebral hemorrhages. Acute heart failure, including acute pulmonary edema, myocardial infarction, and aortic dissection, is among the common cardiovascular complications, and retinopathy is a frequent finding. From a pathophysiologic standpoint, hypertensive emergencies are the result of multiple factors, including an abrupt release of catecholamines, mechanical stress producing endothelial damage, inappropriate activation of the RAAS, and oxidative stress. These changes overwhelm the normal autoregulatory mechanisms and result in a sudden and significant increase in systemic vascular resistance, initiating an inflammatory response. Because of the evidence of end-organ damage, recommendations are for the rapid but controlled reduction of blood pressure using primarily parenteral antihypertensive agents closely monitored in a critical care setting. The standard goal is to decrease the diastolic blood pressure to 100 to 110 mm Hg or about a 25% decrease in the MAP.
Hypertensive urgency is actually more common than hypertensive emergency. The approach to treatment of hypertensive urgency, when end-organ damage is not evident, is quite different. Once measurement error is eliminated, other sources of rapid-onset reactive hypertension should be ruled out. These may include anxiety, pain, abrupt withdrawal of alcohol or antihypertensive medications, postoperative hypertension especially after cardiac and vascular surgery, and full bladder. In some of these cases, interventions other than antihypertensive drugs are indicated. In patients with hypertensive urgency, rapidly decreasing blood pressure has been associated with a substantial mortality. Blood pressure in these patients is usually brought under control over 24 to 48 hours through the use of oral medications, although there are indications for more aggressive intervention with parenteral agents.
KEY POINTS • Primary hypertension has no identifiable etiology, but risk factors include
age; dietary factors, including excess sodium and obesity; ethnicity and family history; sedentary lifestyle; and tobacco use.
• In adults, a normal blood pressure is <120 mm Hg systolic and <80 mm Hg diastolic pressure. Stage 1 hypertension begins with a systolic pressure of 140 mm Hg or a diastolic pressure of 90 mm Hg. Between these values, the individual is said to have prehypertension, and interventions related to lifestyle changes should be initiated.
• Treatment of primary hypertension includes lifestyle modifications and drug therapy. Lifestyle changes address the modifiable risk factors. Drug therapy targets one or more of the variables of blood pressure: heart rate, stroke volume, and systemic vascular resistance (SVR).
• In secondary hypertension, the elevated blood pressure is the result of identifiable pathologic conditions or certain drugs or foods. It is less common in adults, but is the major cause of hypertension in children. The underlying cause must be treated; drug interventions may also be necessary.
• Hypertension is usually asymptomatic until there is significant damage to vulnerable organs or tissues. This process is augmented by atherosclerosis in the coronary, renal, and cerebral arteries. Ultimately, hypertension increases the risk of stroke, angina, myocardial infarction, heart failure, renal failure, and blindness caused by retinopathy.
• Extreme and rapidly developing hypertension is divided into two groups: emergency, where there is evidence of end-organ damage; and urgency, where there is not. Urgencies are treated more slowly and with oral medications; emergencies require hospitalization and more rapid-acting interventions.
LOW BLOOD PRESSURE The mechanism for short-term maintenance of blood pressure described previously is designed to respond rapidly to changes in both internal and external environments. Over the course of the day, this system of increased autonomic activity usually accommodates changes in activity, especially changes in position. Recall that when moving from a supine position to sitting or standing, gravity pulls blood away from the upper body and stimulates the baroreceptors in the carotid arteries and aortic arch; 500 to 1000 mL of a person’s circulating blood volume pools in the venous system of the lower extremities. Messages transmitted from these receptors to the vasomotor center of the brain result in SNS activation, increasing both heart rate and arterial smooth muscle tone. The effect of these SNS-mediated responses to position change is the rapid increase in blood pressure and improved perfusion to the upper body, especially the brain. When this mechanism fails to produce this response in a timely fashion, the drop in blood pressure with position change is called orthostatic hypotension (OH), and may have serious consequences.
OH (postural) is a widespread but often unrecognized disorder with potentially serious consequences. It has been reported to occur in 6% to 30% of healthy elderly persons with normal blood pressures. When perfusion is not rapidly returned to the brain, dizziness, blurred vision, fainting (syncope), and injury from falls are familiar outcomes. But OH can have even more serious consequences. It has been demonstrated to be associated with cardiovascular disease, and research results indicate it may predict stroke, cognitive impairment, and death.
The standard definition of orthostatic hypotension is a decrease in systolic blood pressure of ≥20 mm Hg or a decrease in diastolic pressure that is ≥10 mm Hg within 3 minutes of moving to an upright position. An excessive increase in heart rate, by 20 to 30 beats/minute, is also diagnostic. Some researchers have found that the response can be delayed well beyond that timeframe in the elderly, perhaps up to 10 minutes or more.
An ineffective response to position change may be associated with problems within the nervous system resulting from a number of pathologies, a vasovagal reaction, depletion in circulating volume, or cardiac dysrhythmias. It can also occur as an adverse effect of drug therapy, most frequently antihypertensive, tricyclic antidepressant, and pain medications. The elderly are at special risk of OH when they are taking these medications. They also commonly have an inadequate fluid intake, age-related decreases in autonomic nervous system function, and disorders such as Parkinson disease and diabetes with which postural hypotension is associated. OH also is more common in the presence of arterial stiffness, which may be caused by an alteration in baroreceptor sensitivity. Alcohol ingestion and exposure to heat will also cause vasodilation and may precipitate OH.
A normal response to the SNS activation by the baroreceptors depends on effective functioning of all components of the system. Damage to
CHAPTER 16 Alterations in Blood Pressure 351
Squatting, bending forward to lower the head, or crossing the legs while tightening calf, thigh, and buttocks muscles may counter the effects. Elastic compression stockings and abdominal binders have documented value, as does elevating the head of the bed. Unless contraindicated, liberal intake of both salt and fluids is encouraged. Medication history should be carefully reviewed; a thorough history and physical examina- tion, chemistry panel and blood count, and 12-lead electrocardiogram should be carried out. Elderly patients may find use of a cane with a folded tripod seat or a walker equipped with a seat helpful to reduced OH-related falls.
the vasomotor center or neurons within the central or peripheral nervous system may be responsible for a lack of sufficient response. This may be caused by disease or blunted responses associated with normal aging, prolonged bed rest, or medications. The prevalence of OH in Parkinson disease has been reported to be 37% to 58%. Direct damage to nerve fibers by elevated blood glucose levels in diabetes or an autoimmune injury as in multiple sclerosis can blunt the response, as well as impaired transmission resulting from spinal cord injury. Altered sensitivity of the baroreceptors has been well documented. The vasovagal response is a paradoxical increase in parasympathetic activity and a decrease in sympathetic activity resulting in bradycardia and vasodilation rather than an increase in heart rate and vasoconstriction. This contradictory response can be triggered by other stimuli such as stress, painful or unpleasant events, and activities such as coughing that increase intraabdominal or intrathoracic pressures. Dysrhythmias that impair cardiac output or an inadequate volume in the vascular space to respond to vasoconstriction signals will both also produce OH. Volume depletion as occurs in hemorrhage, burns, or severe diarrhea may reach a point where normal compensatory responses to position changes are inad- equate; this happens after about a 30% volume loss. The development of postural changes in vital signs is a useful clinical indicator of inadequate circulating volume.
Because OH is often caused by physiologic conditions that are not amenable to modification, patients must be taught how to make changes to avoid initiating the response or to reduce its impact. In addition to changing positions slowly to reduce the initial drop in blood pressure, patients are encouraged to avoid hot environments (baths or saunas), because of their vasodilating effects, and large or carbohydrate-heavy meals, because postprandial hypotension can result from the increased blood volume drawn to the splanchnic bed. When symptoms begin, before fainting, actions can be taken to prevent the progression of OH.
KEY POINTS • Orthostatic hypotension (OH) is an extreme response to the change from
supine to upright position, where the activation of the short-term control mechanisms is slow or inadequate in its response. Heart rate and diastolic and systolic blood pressures are more affected by gravitational effects of position change than is normally expected.
• OH results in dizziness, blurred vision, confusion, and possible syncope, which may cause injuries secondary to falls. OH is associated with cardio- vascular disease and is a risk factor for stroke, cognitive impairment, and death.
• OH may be the result of a number of pathologies involving the baroreceptor response, damage to the vasomotor center or the peripheral nervous system, a vasovagal reaction, or cardiac dysrhythmias, or it may be an adverse drug effect. Most often it occurs because of insufficient circulating volume.
• Nonpharmaceutical interventions may be used if the cause cannot be ameliorated.
Adequate perfusion of body organs and tissues depends on the main- tenance of arterial blood pressure. This is accomplished through the highly orchestrated interaction of multiple systems on both a short-term and a long-term basis.
Blood pressure may be elevated secondary to other pathologic conditions or to food or drug ingestion. Secondary hypertension is treated by managing the causative factors, although medication also may be necessary. More commonly the etiology is not discernible, although risk factors are identified, and primary hypertension is
diagnosed. Primary hypertension affects millions of Americans and is a public health concern worldwide. Once identified, lifestyle modifications and pharmaceutical interventions are initiated to avoid the significant pathologic outcomes to body organs.
When the mechanism for short-term blood pressure regulation fails to adequately respond to position changes, the resulting OH can cause syncope and potential injury. If the cause cannot be identified and treated, accommodations can be used to decrease its occurrence and minimize risks.
S U M M A R Y
RESOURCES Measuring Blood Pressure and Definitions of Hypertension American Association of Critical-Care Nurses: Practice alert: noninvasive
blood pressure monitoring. AACN News 23(6):4–5, 2006. Argarwal R, et al: Role of home blood pressure monitoring in overcoming
therapeutic inertia and improving hypertension control: a systematic review and meta-analysis. Hypertension 57(1):29–38, 2011.
Cicolini G, Gagliardi G, Ballone E: Effects of Fowlers body position on blood pressure measurement. J Clin Nurs 19(23-24):3581–3583, 2010.
Eguchi K, et al: Consistency of blood pressure differences between the left and right arms. Arch Intern Med 167:388–393, 2007.
Eşer I, et al: Issues in clinical nursing: the effect of different body positions on blood pressure. J Clin Nurs 16:137–140, 2006.
Godwin M, et al: A primary care pragmatic cluster randomized trial of the use of home blood pressure monitoring on blood pressure levels in
hypertensive patients with above target blood pressure. Fam Pract 27:135–142, 2010.
Hall JE: Guyton and Hall textbook of medical physiology, ed 13, Philadelphia, 2016, Saunders.
Headley JM: Arterial pressure-based technologies: a new trend in cardiac output monitoring. Crit Care Nurs Clin North Am 18(2):179–187, 2006.
James PA, et al: 2014 Evidence-based guideline for the management of high blood pressure in Adults: Report from the panel members appointed to the eight joint national committee (JNC 8). JAMA 311(5):507–520, 2014.
Jones S, Simpson H, Ahmed H: A comparison of two methods of blood pressure measurement. Br J Nurs 15(17):948–951, 2006.
O’Rourke MF, Seward JB: Central arterial pressure and arterial pressure pulse: new views entering the second century after Korotkov. Mayo Clin Proc 81(8):1057–1068, 2006.
Parati G, Mancia G: Assessing the white-coat effect: which blood pressure measurement should be considered? J Hypertens 24:29–31, 2006.
352 UNIT IV Oxygen Transport, Blood Coagulation, Blood Flow, and Blood Pressure
Materson BJ: Variability in response to antihypertensive drugs. Am J Med 120(4A):S10–S20, 2007.
Mathew B: Obesity-hypertension: emerging concepts in pathophysiology and treatment. Am J Med Sci 334(1):23–30, 2007.
Mattace-Raso F, et al: Arterial stiffness, cardiovagal baroreflex sensitivity in older adults: the Rotterdam study. J Hypertens 25(7):1421–1426, 2007.
McCrindle BW: Assessment and management of hypertension in children and adolescents. Nat Rev Cardiol 7:155–163, 2010.
McEniery CM, et al: Increased stroke volume and aortic stiffness contribute to isolated systolic hypertension in young adults. Hypertension 46:221–226, 2005.
Mozaffarian D, Benjamin EJ, Go AS, et al: Heart Disease and Stroke Statistics—2016 Update, 2015. A Report From the American Heart Association.
Narchi H: Assessment and management of hypertension in children and adolescents: part B—investigation and management. J Med Sci 4(1):14–24, 2011.
Peixoto AJ, White WB: Circadian blood pressure: clinical implications based on the pathophysiology of its variability. Kidney Int 71(9):855–860, 2007.
Public Library of Science (June 18): Circadian rhythms dominate all life functions, Science Daily, 2007. Available at www.sciencedaily.com/ releases/2007/06/070615075550.htm.
Rosendorff C, et al: Treatment of hypertension in the prevention and management of ischemic heart disease. Circulation 115:2761–2788, 2007.
Siragy HM: Angiotensin II compartmentalization within the kidney: effects of salt diet and blood pressure alterations. Curr Opin Nephrol Hypertens 15:50–53, 2006.
Spiotta RT, Luma GB: Evaluating obesity and cardiovascular risk factors in children and adolescents. Am Fam Physician 78(9):1052–1058, 2008.
Tanemoto M: Regulatory mechanism of “K+ recycling” for Na+ reabsorption in renal tubules. Clin Exp Nephrol 11:1–6, 2007.
Vehaskari VM: Developmental origins of adult hypertension: new insights into the role of the kidney. Pediatr Nephrol 22:490–495, 2007.
Yoon EY, et al: Medical management of children with primary hypertension by pediatric subspecialists. Pediatr Nephrol 24:147–153, 2009.
Yoon S, Ostchega Y, Louis T: Recent trends in the prevalence of high blood pressure and its treatment and control, 1999-2008, NCHS Data Brief No. 48, Hyattsville, MD, 2010, National Center for Health Statistics.
Secondary Hypertension Cay S, Metin F, Korkmaz S: A common cause of secondary hypertension:
coarctation of the aorta. Heart 92:734, 2006. Chan DK, Chow AS, Kwok K: Childhood sleep-disordered breathing and its
implications for cardiac and vascular diseases. J Paediatr Child Health 41:640–646, 2005.
Chandar J, Zilleruelo G: Hypertensive crisis in children. Pediatr Nephrol 27(5):741–751, 2012.
Chow CK, Teo KK, Rangarajan S, et al: Prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries. JAMA 310(9):959–968, 2013.
De Caro E, et al: Aortic arch geometry and exercise-induced hypertension in aortic coarctation. Am J Cardiol 99:1284–1287, 2007.
Doi S, et al: Optimal use and interpretation of the aldosterone renin ratio to detect aldosterone excess in hypertension. J Hum Hypertens 20(7):482–489, 2006.
Driscoll DM, et al: Acute cardiovascular changes with obstructive events in children with sleep disorder breathing. Sleep 32(10):1265–1271, 2009.
Feldstein C: Management of hypertensive crises. Am J Ther 14:135–139, 2007. Fernandes GH, et al: Delayed diagnosis of pheochromocytoma associated
with chronic kidney disease. Indian J Nephrol 20(3):166–167, 2010. Frishman WH, et al: Pathophysiology and medical management of systemic
hypertension in pregnancy. Cardiol Rev 13(6):274–284, 2005. Hernandez-Vila E: A Review of the JNC 8 Blood Pressure Guideline. Tex
Heart Inst J 42(3):226–228, 2015. Ipek E, Oktay AA, Krim SR: Hypertensive crisis: an update on clinical
approach and management. Curr Opin Cardiol 2017. March 16, 2017. [Epub ahead of print].
Pickering TG, et al: Recommendations for blood pressure measurement in humans and experimental animals, I: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Hypertension 45:142–161, 2005.
Podoll A, et al: Inaccuracy in pediatric outpatient blood pressure measurement. Pediatrics 119(3):e538–e543, 2007. Available at: www.pediatrics.org/cgi/content/full/119/3/e538.
Schell KA: Evidence-based practice: noninvasive blood pressure measurement in children. Pediatr Nurs 32(3):263–267, 2006.
Shaw J, et al: Are stroke patients’ reports of home blood pressure readings reliable? Cross sectional study. Fam Pract 28:118–122, 2011.
Urbina E, et al: Ambulatory blood pressure monitoring in children and adolescents: recommendations for standard assessment: a scientific statement from the American Heart Association Atherosclerosis, Hypertension and Obesity Youth Committee of the Council on Cardiac Disease in the Young and the Council for High Blood Pressure Research. Hypertension 52:433–451, 2008.
U.S. Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, 2004, NIH Pub No. 04–5230. Available at www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.
Xi B, Zong XN, Kelishadi R, et al: Establishing International Blood Pressure References Among Nonoverweight Children and Adolescents Aged 6 to 17 Years. Circulation 133(4):398–408, 2016.
Mechanisms, Risks and Treatment of High Blood Pressure Adrogué H, Madias NE: Sodium and potassium in the pathogenesis of
hypertension. N Engl J Med 356(19):1966–1978, 2007. Aronow W, et al: ACCF/AHA 2011 expert consensus document on
The papers we provide serve as model papers for research candidates and are not to be submitted ‘as is’. These papers are intended to be used for reference purposes only. We only offers consultation and research support and assistance in research design, editing, and statistics.
+254 769 316 835