Hypertension

HYPERTENSION
(ICD -10 CODE -I10, I15….)

EPIDEMIOLOGY :
Hypertension is one of the leading causes of the global burden of disease. Approximately 7.6
million deaths (13–15% of the total) and 92 million disability-adjusted life years worldwide were
attributable to high blood pressure in 2001…(harrison’s-19th)
IN INDIA(Japi.org)-
The prevalence of hypertension in the last six decades has increased from 2% to 25% among
urban residents and from 2% to 15% among the rural residents in India. According to Directorate
General of Health Services, Ministry of Health and Family Welfare, Government of India, the
overall prevalence of hypertension in India by 2020 will be 159.46/1000 population.
Hypertension awareness, treatment and control status is low, with only half of the urban and a
quarter of the rural hypertensive individuals being aware of its presence. It has been seen that
only one in five persons is on treatment and less than 5% are controlled. Rural location is an
important determinant of poor hypertension awareness, treatment and control. It has been said
that in India the rule- of-halves is not valid and only a quarter to a third of subjects are aware of
hypertension.
CVD is the largest cause of mortality in all regions of the country.

In the United States, average systolic blood pressure is higher for men than for
women during early adulthood, although among older individuals the age-
related rate of rise is steeper for women. Consequently, among individuals age
60 and older, systolic blood pressures of women are higher than those of men.
Among adults, diastolic blood pressure also increases progressively with age
until ∼55 years, after which it tends to decrease. The consequence is a widening
of pulse pressure (the difference between systolic and diastolic blood pressure)
beyond age 60…(harrison’s 19th)
Family studies controlling for a common environment indicate that blood pressure
heritabilities are in the range 15–35%. In twin studies, heritability estimates of
blood pressure are ∼60% for males and 30–40% for females. High blood pressure
before age 55 occurs 3.8 times more frequently among persons with a positive
family history of hypertension..(harrison’s)

BP is a quantitative trait that is highly variable1 ; in
population studies, BP has a normal distribution that is
slightly skewed to the right. There is a strong positive and
continuous correlation between BP and the risk of CVD
(stroke, myocardial infarction, heart failure), renal disease,
and mortality, even in the normotensive range. This
correlation is more robust with systolic than with diastolic
BP.2 There is no specific level of BP where cardiovascular
and renal complications start to occur; thus the definition
of hypertension is arbitrary but needed for practical
reasons in patient assessment and treatment.(from
cicullation 2000)

DEFINITION & CLASSIFICATION :( from medscape)
Hypertension is defined as a systolic blood pressure (SBP) of 140 mm Hg or more, or a
diastolic blood pressure (DBP) of 90 mm Hg or more, or taking antihypertensive
medication.
Based on recommendations of the Seventh Report of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), the
classification of BP for adults aged 18 years or older has been as follows [2] :
* Normal: Systolic lower than 120 mm Hg, diastolic lower than 80 mm Hg
* Prehypertension: Systolic 120-139 mm Hg, diastolic 80-89 mm Hg
* Stage 1: Systolic 140-159 mm Hg, diastolic 90-99 mm Hg
* Stage 2: Systolic 160 mm Hg or greater, diastolic 100 mm Hg or greater
Hypertension may be primary, which may develop as a result of environmental or genetic
causes, or secondary, which has multiple etiologies, including renal, vascular, and
endocrine causes. Primary or essential hypertension accounts for 90-95% of adult cases,
and secondary hypertension accounts for 2-10% of cases.

ESSENTIAL HYPERTENSION:(circulation,ahajournals)
Essential, primary, or idiopathic hypertension is defined as high BP in which secondary
causes such as renovascular disease, renal failure, pheochromocytoma, aldosteronism,
or other causes of secondary hypertension or mendelian forms (monogenic) are not
present. Essential hypertension accounts for 95% of all cases of hypertension. Essential
hypertension is a heterogeneous disorder, with different patients having different causal
factors that lead to high BP. Essential hypertension needs to be separated into various
syndromes because the causes of high BP in most patients presently classified as having
essential hypertension can be recognized.
Known Etiological Factors in Essential Hypertension
Although it has frequently been indicated that the causes of essential hypertension are
not known, this is only partially true because we have little information on genetic
variations or genes that are overexpressed or underexpressed as well as the
intermediary phenotypes that they regulate to cause high BP.4 A number of factors
increase BP, including (1) obesity, (2) insulin resistance, (3) high alcohol intake, (4) high
salt intake (in salt-sensitive patients), (5) aging and perhaps (6) sedentary lifestyle, (7)
stress, (8) low potassium intake, and (9) low calcium intake.5 6 Furthermore, many of
these factors are additive, such as obesity and alcohol intake.

In this review, variations in BP that are genetically determined will be called
“inherited BP,” although we do not know which genes cause BP to vary; we know
from family studies that inherited BP can range from low normal BP to severe
hypertension.
Factors that increase BP, such as obesity and high alcohol and salt intake, will be
called “hyperten-sinogenic factors.” Some of these factors have inherited,
behavioral, and environmental components. Inherited BP could be considered core
BP, whereas hypertensinogenic factors cause BP to increase above the range of
inherited BPs, thus creating 4 main possibilities: (1) patients who have inherited BP
in the optimal category (<120/<80 mm Hg); if 1 or more hypertensinogenic factors
are added, BP would probably increase but remain in the normal range (<135/<85
mm Hg) (Figure 1⇓, first 2 columns); (2) patients who have inherited BP in the
normal category (≤130/≤85 mm Hg); if 1 or more hypertensinogenic factors are
added, BP will probably increase to the high normal range (130 to 139/85 to 89
mm Hg) or to stage 1 of the hypertensive category (140 to 159/90 to 99 mm Hg)
(Figure 1⇓, second 2 columns); (3) patients who have inherited BP in the high
normal category (130 to 139/85 to 89 mm Hg); if 1 or more hypertensinogenic
factors are added, BP will increase to the hypertensive range (≥140/≥90 mm Hg)
(Figure 1⇓, third 2 columns); and (4) patients who have inherited BP in the
hypertensive range; addition of 1 or more hypertensinogenic factors will make
hypertension more severe, changing it from stage 1 to stage 2 or 3 (Figure 1⇓,
fourth to sixth 2 columns)….(from circulation,ahajournals)

4 MAIN POSSIBILITIES ARE:
Pts (INHERITED BP) ON ADDING
HYPERTENSIGONEGIC
FACTOR
BP WOULD PROBABLY
INCREASES TO
1. OPTIMAL RANGE
( < 120/<80)
1 OR MORE <135/<85
( NORMAL RANGE)
2. NORMAL CATEGORY
(<130/<85)
1 OR MORE 130-139/85-89
OR
STAGE 1
3. HIGH NORMAL
(130-139/85-89)
1 OR MORE ≥140/≥90
4. HYPERTENSIVE RANGE
(STAGE 1)
1 OR MORE MORE SEVERE
( STAGE 2 OR 3)

Figure 1.Additive effect of hypertensinogenic factors (hatched
areas) such as obesity and alcohol intake on hereditary systolic
(white areas) and diastolic BP (black areas). Abscissa indicates
the stage of inherited BP according to JNC VI without adding
the effect of the hypertensinogenic factors. Patients with
normal or high normal inherited BP become hypertensive stage
1 when BP is increased by a hypertensinogenic factor. In
patients with inherited hypertension in stages 1 to 3, their
hypertension becomes more severe when hypertensinogenic
factors are adde

Theoretically, in a population unaffected by hypertensinogenic
factors, BP will have a normal distribution; it will be skewed to the
right and will have a narrow base or less variance (Figure 2⇓,
continuous line). When 1 hypertensinogenic factor is added to this
population, such as increased body mass, one would expect the
normal distribution curve to be further skewed to the right;
consequently the base will be wider (more variance) and the curve
will be flatter (Figure 2⇓, broken line). If a second hypertensinogenic
factor such as alcohol intake is added to increased body mass, the
curve will be skewed more to the right and the variance will increase
further, with more subjects classified as hypertensive (Figure 2⇓,
dotted line)….(circulation,ahajournals)

Figure 2.Interaction among genetic and environmental factors in
the development of hypertension. Left side of figure shows how
environmental factors and multiple genes responsible for high BP
interact and affect intermediary phenotypes. The result of these
intermediary phenotypes is blood pressure with a normal
distribution skewed to the right. Continuous line indicates the
theoretical BP of the population that is not affected by
hypertensinogenic factors; shaded area indicates systolic BP in
the hypertensive range. Broken and dotted lines indicate
populations in which 1 (obesity) or 2 hypertensinogenic factors
(obesity plus high alcohol intake) have been added. Notice that in
these 2 populations the distribution curves are shifted to the
right (high BP) and the number of hypertensive individuals is
significantly increased when hypertensinogenic factors are
added.

Discovering which genetic variations place BP on the left or right side of the distribution curve is
of both theoretical and practical importance because it could help the physician to better treat
or cure hypertension.7 Recognition of the hypertensinogenic factors may allow
nonpharmacological prevention, treatment, or cure of hypertension. Hypertensinogenic factors
such as obesity, insulin resistance, or high alcohol intake also have an important genetic
component. Furthermore, there are interactions between genetic and environmental factors
(Figure 2⇑) that influence intermediary phenotypes such as sympathetic nerve activity, the
renin-angiotensin-aldosterone and renal kallikrein-kinin systems, and endothelial factors, which
in turn influence other intermediary phenotypes such as sodium excretion, vascular reactivity,
and cardiac contractility. These and many other intermediary phenotypes determine total
vascular resistance and cardiac output and, consequently, BP. Recognition of the
hypertensinogenic factor(s) and establishing that the patient’s hypertension is the result of
obesity (either alone or combined with other factors such as insulin resistance or high alcohol
intake) or old age instead of essential hypertension may help the physician as well as the patient
and his or her family to modify or eliminate these hypertensinogenic and CVD risk factors when
possible, which may cure the hypertension or at least facilitate control of BP. When the
hypertensinogenic factor cannot be reduced or eliminated, as with systolic hypertension
induced by aging (arteriosclerosis), recognition of the underlying cause of high BP will
emphasize the need for (1) further studies to determine whether the patient has arteriosclerosis
and/or atherosclerosis, the magnitude of the disease, and whether there are occlusive lesions;
(2) treatment of the atherosclerosis with lifestyle and dietary changes and lipid-lowering agents
if necessary; and (3) pharmacological treatment of systolic hypertension to decrease passive
stiffness (arteriosclerosis) of the major central elastic arteries and decrease morbidity and
mortality rates.

Thus recognition of factors that induce hypertension is not only
of theoretical but also of practical importance. In conclusion, as
stated by Beilin,8 “it is no longer appropriate to define essential
hypertension as a rise in blood pressure without cause,” since a
number of causes can be clearly identified in most cases of so-
called “essential hypertension.”
Hence changes in lifestyle, including dietary changes that reduce
body weight, fat, and alcohol intake and increase potassium and
calcium intake,9 as well as exercise,10 11reduce or normalize BP in
many patients.(circulation,ahajournal)

TABLE Systolic Hypertension with Wide Pulse Pressure
1. Decreased vascular compliance (arteriosclerosis)
2. Increased cardiac output
a. Aortic regurgitation
b. Thyrotoxicosis
c. Hyperkinetic heart syndrome
d. Fever
e. Arteriovenous fistula
f. Patent ductus arteriosus

CLINICAL APPROACH TO HYPERTENSION

HISTORY
Following the documentation of hypertension, which is confirmed after an elevated blood
pressure (BP) on at least 3 separate occasions (based on the average of 2 or more readings
taken at each of ≥2 follow-up visits after initial screening), a detailed history should extract
the following information:
Extent of end-organ damage (eg, heart, brain, kidneys, eyes)
Assessment of patients’ cardiovascular risk status
Exclusion of secondary causes of hypertension
Patients may have undiagnosed hypertension for years without having had their BP checked.
Therefore, a careful history of end-organ damage should be obtained.
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation,
and Treatment of High Blood Pressure (JNC 7) identifies the following as targets of end-
organ damage [2] :
Heart: left ventricular hypertrophy, angina/previous myocardial infarction, previous
coronary revascularization, and heart failure
Brain: stroke or transient ischemic attack, dementia
Chronic kidney disease
Peripheral arterial disease
Retinopathy

The historical and physical findings that suggest the possibility of
secondary hypertension are:(from medscape)
a history of known renal disease, abdominal masses, anemia, and
urochrome pigmentation.
A history of sweating, labile hypertension, and palpitations
suggests the diagnosis of pheochromocytoma.
A history of cold or heat tolerance, sweating, lack of energy, and
bradycardia or tachycardia may indicate hypothyroidism or
hyperthyroidism.
A history of obstructive sleep apnea may be noted.
A history of weakness suggests hyperaldosteronism.
Kidney stones raise the possibility of hyperparathyroidism.

Characteristically, a “hypertensive headache” occurs in the morning and is localized to the
occipital region. Other nonspecific symptoms that may be related to elevated blood pressure
include dizziness, palpitations, easy fatigability, and impotence. When symptoms are present,
they are generally related to hypertensive cardiovascular disease or to manifestations of
secondary hypertension.
•TABLE 298-5 Patient’s Relevant History
•Duration of hypertension
•Previous therapies: responses and side effects
•Family history of hypertension and cardiovascular disease
•Dietary and psychosocial history
•Other risk factors: weight change, dyslipidemia, smoking, diabetes, physical inactivity
•Evidence of secondary hypertension: history of renal disease; change in
appearance; muscle weakness; spells of sweating, palpitations, tremor; erratic
sleep, snoring, daytime somnolence; symptoms of hypo-or hyperthyroidism;
use of agents that may increase blood pressure
•Evidence of target organ damage: history of TIA, stroke, transient blindness;
•angina, myocardial infarction, congestive heart failure; sexual function
•Other comorbidities
(harrison’s..19th)

MEASUREMENT OF BLOOD PRESSURE
Individual should be seated quietly in a chair (not the exam table) with feet on the floor
for 5 min in a private, quiet setting with a comfortable room temperature.
At least two measurements should be made. The center of the cuff should be at heart
level, and the width of the bladder cuff should equal at least 40% of the arm
circumference; the length of the cuff bladder should encircle at least 80% of the arm
circumference.
It is important to pay attention to cuff placement, stethoscope placement, and the rate of
deflation of the cuff (2 mmHg/s). Systolic blood pressure is the first of at least two regular
“tapping” Korotkoff sounds, and diastolic blood pressure is the point at which the last
regular Korotkoff sound is heard. Currently available ambulatory monitors are fully
automated, use the oscillometric technique, and typically are programmed to take
readings every 15–30 min. Twenty-four-hour ambulatory blood pressure monitoring more
reliably predicts cardiovascular disease risk than do office measurements. However,
ambulatory monitoring is not used routinely in clinical practice and generally
is reserved for patients in whom white coat hypertension is suspected. The Seventh Report
of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of
High Blood Pressure (JNC 7) has also recommended ambulatory monitoring
for treatment resistance, symptomatic hypotension, autonomic failure, and episodic
hypertension.

LABORATORY TESTING
Table 298-6 lists recommended laboratory tests in the initial evaluation of hypertensive
patients. Repeat measurements of renal function, serum electrolytes, fasting glucose, and
lipids may be obtained after the introduction of a new antihypertensive agent and then
annually or more frequently if clinically indicated. More extensive laboratory testing is
appropriate for patients with apparent drug resistant hypertension or when the clinical
evaluation suggests a secondary form of hypertension.
TABLE 298-6 Basic Laboraory Tests for Initial Evaluation
System Test
Renal Microscopic urinalysis, albumin excretion, serum BUN
and/or creatinine
Endocrine Serum sodium, potassium, calcium, ?TSH
Metabolic Fasting blood glucose, total cholesterol, HDL and LDL
(often computed) cholesterol, triglycerides
Others Hematocrit, electrocardiogram

The JNC 8 Hypertension Guidelines
Published Online: January 21, 2014
Michael R. Page, PharmD, RPh
Compared with previous hypertension treatment guidelines, the Joint National
Committee (JNC 8) guidelines advise higher blood pressure goals and less use
of several types of antihypertensive medications.
Patients will be asking about the new JNC 8 hypertension guidelines, which
were published in the Journal of the American Medical Association on
December 18, 2013.1
The new guidelines emphasize control of systolic blood pressure (SBP) and
diastolic blood pressure (DBP) with age- and comorbidity-specific treatment
cutoffs. The new guidelines also introduce new recommendations designed to
promote safer use of angiotensin converting enzyme (ACE) inhibitors and
angiotensin receptor blockers (ARBs).

Important changes from the JNC 7 guidelines2 include the following:
• In patients 60 years or older who do not have diabetes or chronic kidney disease, the goal
blood pressure level is now <150/90 mm Hg.
• In patients 18 to 59 years of age without major comorbidities, and in patients 60 years or older
who have diabetes, chronic kidney disease (CKD), or both conditions, the new goal blood
pressure level is <140/90 mm Hg.
• First-line and later-line treatments should now be limited to 4 classes of medications: thiazide-
type diuretics, calcium channel blockers (CCBs), ACE inhibitors, and ARBs.
• Second- and third-line alternatives included higher doses or combinations of ACE inhibitors,
ARBs, thiazide-type diuretics, and CCBs. Several medications are now designated as later-line
alternatives, including the following: beta-blockers, alphablockers, alpha1/beta-blockers (eg,
carvedilo), vasodilating beta-blockers (eg, nebivolol), central alpha2/-adrenergic agonists (eg,
clonidine), direct vasodilators (eg, hydralazine), loop diruretics (eg, furosemide), aldosterone
antagoinsts (eg, spironolactone), and peripherally acting adrenergic antagonists (eg, reserpine).
• When initiating therapy, patients of African descent without CKD should use CCBs and
thiazides instead of ACE inhibitors.

• Use of ACE inhibitors and ARBs is recommended in all patients with CKD regardless of ethnic
background, either as first-line therapy or in addition to first-line therapy.
• ACE inhibitors and ARBs should not be used in the same patient simultaneously.
• CCBs and thiazide-type diuretics should be used instead of ACE inhibitors and ARBs in patients
over the age of 75 years with impaired kidney function due to the risk of hyperkalemia,
increased creatinine, and further renal impairment.
The change to a more lenient systolic blood pressure goal may be confusing to many patients
who are accustomed to the lower goals of JNC 7, including the <140/90 mm Hg goal for most
patients and <130/80 mm Hg goal for patients with hypertension and major comorbidities.
The guidelines were informed by results of 5 key trials: the Hypertension Detection and Follow-
up Program (HDFP), the Hypertension-Stroke Cooperative, the Medical Research Council (MRC)
trial, the Australian National Blood Pressure (ANBP) trial, and the Veterans’ Administration (VA)
Cooperative. In these trials, patients between the ages of 30 and 69 years received medication
to lower DBP to a level <90 mm Hg. Results showed a reduction in cerebrovascular events, heart
failure, and overall mortality in patients treated to the DBP target level.
The data were so compelling that some members of the JNC 8 panel wanted to keep DBP <90
mm Hg as the only goal among younger patients, citing insufficient evidence for benefits of an
SBP goal lower than 140 mm Hg in patients under the age of 60 years. However, more
conservative panelists pushed to keep the target SBP goal as well as the DBP goal.

In younger patients without major comorbidities, elevated DBP is a more important
cardiovascular risk factor than is elevated SBP. The JNC 8 panelists are not the first
guideline authors to recognize this relationship. The JNC 7 guideline authors also
acknowledged that DBP control was more important than SBP control for reducing
cardiovascular risk in patients <60 years of age. However, in patients 60 years and
older SBP control remains the most important factor.
Other recent evidence suggests that the SBP goal <140 mm Hg recommended by the
JNC 7 guidelines for most patients may have been unnecessarily low. The JNC 8
guideline authors cite 2 trials that found no improvement in cardiovascular
outcomes with an SBP target <140 mm Hg compared with a target SBP level <160
mm Hg or <150 mm Hg. Despite this finding, the new guidelines do not disallow
treatment to a target SBP <140 mm Hg, but recommend caution to ensure that low
SBP levels do not affect quality of life or lead to adverse events.
The shift to a DBP-based goal may mean younger patients will be prescribed fewer
medications if diagnosed with hypertension; this may improve adherence and
minimize adverse events associated with low SBP, such as sexual dysfunction.

Patients With Kidney Disease
Although 1 post hoc analysis showed a possible advantage in kidney outcomes with the lower
target of 130/80 mm Hg recommended by JNC 7, 2 other primary analyses did not support
this finding. Additionally, another 3 trials did not show an advantage with the <130/80 mm Hg
goal over the <140/90 mm Hg goal level for patients with chronic kidney disease.
As a result, the new guidelines recommend that patients with chronic kidney disease receive
medication sufficient to achieve the higher <140/90 mm Hg goal level. However, in an
exception to this goal level, the guidelines suggest that patients with chronic kidney disease
or albuminuria 70 years or older should receive treatment based on comorbidities, frailty, and
other patient-specific factors.
Evidence was insufficient to support a goal blood pressure of <140/90 mm Hg in patients over
the age of 70 years with CKD or albuminuria.
Patients With Diabetes
Adults with diabetes and hypertension have reduced mortality as well as improved
cardiovascular and cerebrovascular outcomes with treatment to a goal SBP <150 mm Hg, but
no randomized controlled trials support a goal <140/90 mm Hg. Despite this, the panel opted
for a conservative recommendation in patients with diabetes and hypertension, opting for a
goal level of <140/90 mm Hg in adult patients with diabetes and hypertension rather than the
evidencebased goal of <150/90 mm Hg.

Follow-up
The JNC 8 guideline authors simplified a complicated recommendation
for followup in patients with hypertension. The JNC 7 panel
recommended that after an initial high blood pressure reading,
followup with a confirmatory blood pressure reading should occur
within 7 days to 2 months, depending on how high the initial reading
was and whether or not the patient had kidney disease or end-organ
damage as a result of hypertension. Under JNC 8, in all cases, goal
blood pressure targets should be reached within a month of starting
treatment either by increasing the dose of an initial drug or by using a
combination of medications.

Treatments
Like the JNC 7 panel, the JNC 8 panel recommended thiazide-type diuretics as initial therapy
for most patients. Although ACE inhibitors, ARBs, and calcium channel blockers (CCBs) are
acceptable alternatives, thiazide-type diuretics still have the best evidence of efficacy.
The JNC 8 panel does not recommend first-line therapy with beta-blockers and alpha-blockers
due to 1 trial that showed a higher rate of cardiovascular events with use of beta-blockers
compared with use of an ARB, and another trial in which alpha-blockers resulted in inferior
cardiovascular outcomes compared with use of a diuretic. In addition, a lack of evidence
comparing the 4 first-line therapies with carvedilol, nebivolol, clonidine, hydralazine,
reserpine, furosemide, spironolactone, and other similar medications precludes use of any
medications other than ACE inhibitors, ARBs, CCBs, and thiazide-type diuretics in the vast
majority of patients.
Before receiving alpha-blockers, betablockers, or any of several miscellaneous agents, under
the JNC 8 guidelines, patients would receive a dosage adjustment and combinations of the 4
first-line therapies. Triple therapy with an ACE inhibitor/ARB, CCB, and thiazide-type diuretic
would precede use of alpha-blockers, beta-blockers, or any of several other agents.
These new guidelines all but eliminate use of beta-blockers (including nebivolol), alpha-
blockers, loop diuretics, alpha 1/beta-blockers, central alpha2/adrenergic agonists, direct
vasodilators, aldosterone antagonists, and peripherally acting adrenergic antagonists in
patients with newly diagnosed hypertension. Caution is warranted in patients who are already
stable on these therapies.

Special Therapeutic Considerations
ACE inhibitors and ARBs may not be an ideal choice in patients of African descent. Results of a
subgroup analysis in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack
Trial (ALLHAT) found that ACE inhibitors led to worse cardiovascular outcomes than thiazide-type
diuretics or CCBs in patients with African ancestry. Despite the subgroup analysis of ALLHAT,
results of the African American Study of Kidney Disease and Hypertension (AASK) support use of
first-line or add-on ACEIs to improve kidney-related outcomes in patients of African descent
with hypertension, CKD, and proteinuria.
As a result, the JNC 8 panelists recommend that all patients with chronic kidney disease and
hypertension, regardless of ethnic background, should receive treatment with an ACE inhibitor
or ARB to protect kidney function, either as initial therapy or add-on therapy.
One exception to the use of ACE inhibitors or ARBs in protection of kidney function applies to
patients over the age of 75 years. The panel cited the potential for ACE inhibitors and ARBs to
increase serum creatinine and produce hyperkalemia. As a result, for patients over the age of 75
years with decreased renal function, thiazide-type diuretics or CCBs are an acceptable
alternative to ACEIs or ARBs. In addition, the panel expressly prohibits simultaneous use of an
ACE inhibitor and an ARB in the same patient. This combination has not been shown to improve
outcomes. Despite the fact that the 2 medications work at different points in the renin-
angiotensin-aldosterone system, other combinations of medications are better options, and the
simultaneous use of ACEIs and ARBs is not supported by evidence.

Lifestyle Changes
As in JNC 7, the JNC 8 guidelines also recommend lifestyle changes as an important component
of therapy. Lifestyle interventions include use of the Dietary Approaches to Stop Hypertension
(DASH) eating plant, weight loss, reduction in sodium intake to less than 2.4 grams per day, and
at least 30 minutes of aerobic activity most days of the week.
In addition, to delay development of hypertension, improve the blood pressure–lowering effect
of existing medication, and decrease cardiovascular risk, alcohol intake should be limited to 2
drinks daily in men and 1 drink daily in women. Note that 1 drink constitutes 12 ounces of beer,
5 ounces of wine, or 1.5 ounces of 80-proof liquor. Quitting smoking also reduces cardiovascular
risk.
Conclusion
The JNC 8 guidelines move away from the assumption that lower blood pressure levels will
improve outcomes regardless of the type of agent used to achieve the lower level. Instead, the
JNC 8 guidelines encourage use of agents with the best evidence of reducing cardiovascular risk.
In addition, the guidelines may lead to less use of antihypertensive medications in younger
patients, which will produce equivalent outcomes in terms of cardiovascular events with less
potential for adverse events that limit adherence..(till conclusion- jnc viii)

Malignant hypertension (harrison’s 19th) is a syndrome associated with an abrupt
increase of blood pressure in a patient with underlying hypertension
or related to the sudden onset of hypertension in a previously normotensive individual.The
absolute level of blood pressure is not as important as its rate of rise.
Pathologically, the syndrome is associated with diffuse necrotizing vasculitis, arteriolar
thrombi, and fibrin deposition in arteriolar walls. Fibrinoid necrosis has been observed in
arterioles of kidney, brain, retina, and other organs.
Clinically, the syndrome is recognized by progressive retinopathy (arteriolar spasm,
hemorrhages, exudates, and papilledema), deteriorating renal function with proteinuria,
microangiopathic hemolytic anemia, and encephalopathy.
Historic inquiry should include questions about the use of monoamine oxidase inhibitors and
recreational drugs (e.g., cocaine, amphetamines). Although blood pressure should be lowered
rapidly in patients with hypertensive encephalopathy, there are inherent risks of overly
aggressive therapy. In hypertensive individuals, the upper and lower limits of autoregulation
of cerebral blood flow are shifted to higher levels of arterial pressure, and rapid lowering of
blood pressure to below the lower limit of autoregulation may precipitate cerebral schemia or
infarction as a consequence of decreased cerebral blood flow. Renal and coronary blood flows
also may decrease with overly aggressive acute therapy.

The initial goal of therapy is to reduce mean arterial blood pressure by no more than 25%
within minutes to 2 h or to a blood pressure in the range of 160/100–110 mmHg. This
may be accomplished with IV nitroprusside. Parenteral labetalol and nicardipine are also
effective agents for the treatment of hypertensive encephalopathy.
In patients with malignant hypertension without encephalopathy or another catastrophic
event, it is preferable to reduce blood pressure over hours or longer rather than minutes.
This goal may effectively be achieved initially with frequent dosing of short-acting oral
agents such as captopril, clonidine, and labetalol.
Acute, transient blood pressure elevations that last days to weeks frequently occur after
thrombotic and hemorrhagic strokes. Autoregulation of cerebral blood flow is impaired
in ischemic cerebral tissue, and higher arterial pressures may be required to maintain
cerebral blood flow. Although specific blood pressure targets have not been defined for
patients with acute cerebrovascular events, aggressive reductions of blood pressure are
to be avoided.
(continue..harrisons 19th)

Currently, in the absence of other indications for acute
therapy, for patients with cerebral infarction who are not candidates
for thrombolytic therapy, one recommended guideline is to institute
antihypertensive therapy only for patients with a systolic blood
pressure >220 mmHg or a diastolic blood pressure >130 mmHg. If
thrombolytic therapy is to be used, the recommended goal blood
pressure is <185 mmHg systolic pressure and <110 mmHg diastolic
pressure.
In patients with hemorrhagic stroke, suggested guidelines
for initiating antihypertensive therapy are systolic >180 mmHg
or diastolic pressure >130 mmHg. The management of hypertension
after subarachnoid hemorrhage is controversial. Cautious
reduction of blood pressure is indicated if mean arterial pressure is
>130 mmHg.
In addition to pheochromocytoma, an adrenergic crisis due to
catecholamine excess may be related to cocaine or amphetamine
overdose, clonidine withdrawal, acute spinal cord injuries, and an
interaction of tyramine-containing compounds with monoamine
oxidase inhibitors. These patients may be treated with phentolamine
or nitroprusside. (harrison’s 19th)

TABLE 298-9 Preferred Parenteral Drugs for Selected Hypertensive
Emergencies(harrison’s 19th)
*Hypertensive encephalopathy Nitroprusside, nicardipine, labetalol
*Malignant hypertension (when IV
therapy is indicated)
Labetalol, nicardipine, nitroprusside,
enalaprilat
*Stroke Nicardipine, labetalol, nitroprusside
*Myocardial infarction/unstable
angina
Nitroglycerin, nicardipine, labetalol,
esmolol
Acute left ventricular failure Nitroglycerin, enalaprilat, loop
diuretics
Aortic dissection Nitroprusside, esmolol, labetalol
Adrenergic crisis Phentolamine, nitroprusside
Postoperative hypertension Nitroglycerin, nitroprusside, labetalol,
nicardipine
Preeclampsia/eclampsia of
pregnancy
Hydralazine, labetalol, nicardipine*

TABLE 298-10 Usual Intravenous Doses of Antihypertensive Agents
Used in Hypertensive Emergencies (harrison’s 19th)
Antihypertensive Agent Intravenous Dose
Nitroprusside Initial 0.3 (μg/kg)/min; usual 2–4 (μg/kg)/min;
maximum 10 (μg/kg)/min for 10 min.
Nicardipine Initial 5 mg/h; titrate by 2.5 mg/h at 5–15 min
intervals; max 15 mg/h.
Labetalol 2 mg/min up to 300 mg or 20 mg over 2 min,
then 40–80 mg at 10-min intervals up
to 300 mg total.
Enalaprilat Usual 0.625–1.25 mg over 5 min every 6–8 h;
maximum 5 mg/dose.
Esmolol Initial 80–500 μg/kg over 1 min, then
50–300 (μg/kg)/min.
Phentolamine 5–15 mg bolus.
Nitroglycerin Initial 5 μg/min, then titrate by 5 μg/min at
3–5-min intervals; if no response is seen at
20 μg/min, incremental increases of
10–20 μg/min may be used.
Hydralazine 10–50 mg at 30-min intervals
aConstant blood pressure monitoring is required. Start with the lowest dose.
Subsequent doses and intervals of administration should be adjusted according to
the blood pressure response and duration of action of the specific agent.

Extra edge
Lowering systolic blood pressure by 10–12 mmHg and diastolic blood
pressure by 5–6 mmHg confers relative risk reductions of 35–40% for
stroke and 12–16% for CHD within 5 years of the initiation of treatment.
Risk of heart failure is reduced by >50%.
Most available agents reduce systolic blood pressure by 7–13 mmHg and
diastolic blood pressure by 4–8 mmHg when corrected for placebo effect
Prevention and treatment of obesity are important for reducing blood
pressure and cardiovascular disease risk. In short-term trials, even modest
weight loss can lead to a reduction of blood pressure and an increase in
insulin sensitivity. Average blood pressure reductions of 6.3/3.1 mmHg
have been observed with a reduction in mean body weight of 9.2 kg.
Regular physical activity facilitates weight loss, decreases blood pressure,
and reduces the overall risk of cardiovascular disease. Blood pressure may
be lowered by 30 min of moderately intense physical activity, such as
brisk walking, 6–7 days a week, or by more intense, less frequent
workouts. There is individual variability in the sensitivity of blood pressure

Thiazides are safe, efficacious, inexpensive, and reduce clinical events.
They provide additive blood pressure–lowering effects when combined
with beta blockers, angiotensin-converting enzyme inhibitors
(ACEIs), or angiotensin receptor blockers (ARBs). In contrast,
addition of a diuretic to a calcium channel blocker is less effective.
Loop diuretics generally
are reserved for hypertensive patients with reduced glomerular
filtration rates (reflected in serum creatinine >220 μmol/L [>2.5 mg/
dL]), CHF, or sodium retention and edema for some other reason,
such as treatment with a potent vasodilator, e.g., minoxidil.
chlorthalidone has a longer half-life (40–60 h vs. 9–15 h)
and an antihypertensive potency ~1.5–2.0 times that of
hydrochlorothiazide.
Potassium loss is also greater with chlorthalidone
Beta blockers are particularly effective
in hypertensive patients with tachycardia, and their hypotensive
potency is enhanced by coadministration with a diuretic.

In patients with CHF, beta blockers have been shown to reduce
the risks of hospitalization and mortality
Aldosterone Antagonists:
It may be a particularly effective agent in patients
with low-renin primary hypertension, resistant hypertension, and
primary aldosteronism. In patients with CHF, low-dose spironolactone
reduces mortality and hospitalizations for heart failure when
given in addition to conventional therapy with ACEIs, digoxin,
and loop diuretics.
Calcium Channel Blockers:
it is unclear
if adding a diuretic to a calcium blocker results in a further lowering
of blood pressure.

COMPARISONS OF ANTIHYPERTENSIVES
On average, standard doses of most antihypertensive agents reduce blood pressure by
8–10/4–7 mmHg; however, there may be subgroup differences in responsiveness
Younger patients may be more responsive to beta blockers and ACEIs, whereas
patients over age 50 may be more responsive to diuretics and calcium antagonists.
Patients with high-renin hypertension may be more responsive to ACEIs and ARBs than
to other classes of agents, whereas patients with low-renin hypertension are more
responsive to diuretics and calcium antagonists
ACEIs and ARBs decrease intraglomerular pressure and proteinuria and may retard the
rate of progression of renal insufficiency, not totally accounted for by their hypotensive
effects, in both diabetic and nondiabetic renal diseases.

Among African Americans with hypertensionrelatedrenal disease, ACEIs appear to be
more effective than beta blockers or dihydropyridine calcium channel blockers in
slowing, although not preventing, the decline of glomerular filtration rate.
In most patients with hypertension and heart failure due to systolic and/or diastolic
dysfunction, the use of diuretics, ACEIs or ARBs, and beta blockers is recommended to
improve survival.
Independent of blood pressure, in both hypertensive and normotensive individuals, ACEIs
attenuate the development of left ventricular hypertrophy, improve symptomatology and
risk of death from CHF, and reduce morbidity and mortality rates in post-myocardial
infarction patients
Similar benefits in cardiovascular morbidity and mortality rates in patients with CHF have
been observed with the use of ARBs.
ACEIs provide better coronary protection than do calcium channel blockers, whereas calcium
channel blockers provide more stroke protection than do either ACEIs or beta blockers.

Results of a large, double-blind, prospective clinical trial (Avoiding Cardiovascular Events
through Combination Therapy in Patients Living with Systolic Hypertension [ACCOMPLISH
Trial]) indicated that combination treatment with an ACEI (benazepril) plus a calcium
antagonist (amlodipine) was superior to treatment with the ACEI plus a diuretic
(hydrochlorothiazide) in reducing the risk of cardiovascular events and death among high-
risk patients with hypertension. However, the combination of an ACEI and a diuretic has
recently been shown to produce major reductions in morbidity and mortality in the very
elderly.
After a stroke, combination therapy with an ACEI and a diuretic, but not with an ARB, has been
reported to reduce the rate of recurrent stroke.

Both interventions inhibit sympathetic drive and decrease blood pressure by
increasing the capacity of the kidney to excrete sodium and by decreasing renin
release.
To date, the most impressive results have been observed in patients with
“resistant” hypertension and patients with obesity-related hypertension.
There is a recent resurgence of interest in two nonpharmacologic,
antihypertensive therapies that interrupt sympathetic outflow: (1) device-based
carotid baroreflex activation by electrical stimulation of the carotid sinus; and (2)
endovascular radiofrequency ablation of the renal sympathetic nerves. Whereas
renal denervation is a minimally invasive procedure, carotid baroreceptor
stimulation is a surgical procedure, usually performed under general anesthesia,
that currently involves implanting electrodes on both the right and left carotid
arteries.

Resistant hypertension is defined as blood pressure that remains above goal in spite of the
concurrent use of 3 antihypertensive agents of different classes. Ideally, one of the 3 agents
should be a diuretic and all agents should be prescribed at optimal dose amounts.
patients whose blood pressure is controlled but require 4 or more medications to
do so should be considered resistant to treatment.

Hypertension

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