Management of HTN: Gilbert
Ruth Olson
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Blood Pressure (BP) measurement is subject to many
sources of error/variation
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“White coat” hypertension
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Excess noise
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Poor measurement technique
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Uncalibrated equipment
“Normal” BP is 120 mm Hg systolic & 80 mm Hg diastolic
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Sexual dimorphism (female BP < male BP); men
and women have very different kidney
physiology
“Pre-hypertension” is 120-129 mmHg (SBP) and 80-89
(DBP)
Hypertension defined as > 140/90
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stage 1: 140-160/90-100
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stage 2: > 160/100
Isolated systolic hypertension
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Pulse Pressure should also be noted
Even moderate elevation of arterial pressure leads to
shortened life expectancy
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Expectancy is reduced greatly at increased MAP
50 per cent or more above normal
The lethal effects of hypertension are caused mainly in
three ways:
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Excess workload on the heart
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Blood vessel damage in the brain "stroke”
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Renal injury leading towards kidney failure
Types of HTN
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Essential hypertension (90%)
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Obesity/leptin/SNS?
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Renovascular
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Renal artery stenosis (RAS)
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Secondary hyperaldosteronism
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Chronic renal disease
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Diabetes
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Primary Hyperaldosteronism
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Sleep apnea associated hypertension
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SNS overactivity?
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Pheochromocytoma
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Adrenal medulla (catecholamine excess)
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Neurogenic (acute) [White coat hypertension?]
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SNS overactivity?
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Pregnancy induced hypertension (Preeclampsia)
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Placental ischemia
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Angiogenic factors
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Autoantibodies
Volume-loaded HTN: Progressive changes in important
circulatory system variables during the first few weeks of
volume-loading hypertension. Note especially the initial
increase in cardiac output as the basic cause of the
hypertension. Subsequently, the autoregulation
mechanism returns the cardiac output almost to normal
while simultaneously causing a secondary increase in total
peripheral resistance.
If you block the baroreceptors then BP increases straight
away with the volume expansion.
L: Inc. CO has both a direct effect to increase arterial
pressure and an indirect effect by first increasing the total
peripheral resistance via autoregulation of blood flow.
R: Athero builds up in thekidney. There are 2 phases of BP
increase: Effect of placing a constricting clamp on the renal
artery of one kidney after the other kidney has been
removed. The resulting hypertension is called "one-kidney"
Goldblatt hypertension.
Use of Ang II blockers may have negative effects on renal
function in patients with RAS
Angiotensin II is important in maintaining GFR in the
poststenotic kidney at low perfusion pressures. As
compared with other antihypertensive agents, ACE
inhibitors (and angiotensin receptor blockers ARBs) lead
to a fall in GFR and FF owing to removal of the efferent
arteriolar effects of angiotensin II. When stenosis is
sufficiently severe that pressure reduction compromises
RBF, the potential for complete occlusion is present, as
with other effective antihypertensive agents as well.
Ruth Olson
Management of HTN: Gilbert
Preeclampsia
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Preeclampsia is defined as new onset hypertension with
proteinuria during pregnancy
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Occurs in 5-10% of pregnancies in the U.S. Rate has
increased by 40% between 1990-1999 (increased age of mothers
and multiple births)
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Hypertension remits after delivery implicating the
placenta as a key component of pregnancy that leads to
preeclampsia
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Increased cytokines & endothelin-1, augmented Ang II
reactivity, oxidative stress; decreased angiogenic factors
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Endothelial cell dysfunction
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PE is the leading cause maternal and perinatal morbidity
and mortality.
**Despite the significance of this disorder the pathophysiology of
PE and in particular the HTN associated with PE remains unclear. A
large body of evidence supports the hypothesis that an ischemic
placenta is a primary underlying cause. As one might expect, HIF-1
is increased in PE placentas but surprisingly HO-1, the induceable
HO isoform has been shown to be decreased.
Furtehr, recent efforts have uncovered several interesting findings
suggesting that elevations of anti-angiogenic factors such as sFlt-1
and sEng are increased in women with PE; that many women with
PE have increased levels concentrations of anti-angiogenic factors
such as the soluble form of the VEGF-R1 (sFlt-1). The authors
reported increased sFlt-1 in the placenta and plasma along with
decreases in free VEGF and PlGF. Further, this group demonstrated
that increased circulating sFlt-1 alone results in hypertension in
pregnant rats.
In support of an important link between placental
ischemia and release of antiangiogenic factors we
recently reported
While this outlines a general pathway it does not
identify a specific mechanism by which sFlt-1 acts to
generate endothelial dysfunction.
administration of VEGF attenuates MAP and
increases GFR back to NP levels in the RUPP(Reduced
Uterine Perfusion Pressure Model) animals.
Administration of the VEGF improved vasorelaxation
to a greater extent beyond that of the NP.
ACEi or ARB are contraindicated in pregnancy
because the RAS is so important to normal fetal
kidney development. Renal Development is arrestted
with Ang/Renin blockade leads to hypertension.
Treatment of Hypertension
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What is the target BP?
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Might there be underlying conditions?
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Diabetes
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Obesity
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Preeclampsia /PIH
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End-organ damage?
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Systolic
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Diastolic
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Pulse pressure
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Lifestyle modifications
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↑Exercise, improve diet, ↓smoking, ↓drinking
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Increase physical activity and reduce weight
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Pharmacologic
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Vasodilator drugs (increase renal blood flow)
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Diuretic drugs that decrease tubular
reabsorption of salt and water
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Preeclampsia /PIH
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Must consider effects on the offspring!
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Manage hypertension to safely extend
pregnancy
Management of HTN: Gilbert
Ruth Olson
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Ideal anti-hypertensive agent
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Decreases systolic/diastolic pressure
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Does not alter cardiac output maintenance
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Does not cause orthostatic hypotension
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Minimal [deleterious] side effects
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Is not subject to the development of tolerance
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Is easy to administer to facilitate patient compliance
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Has no limiting side effects or toxicity
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Thiazide diuretics, beta blockers, renin angiotensin system inhibitors and calcium channel
antagonists are considered to be closest to ideal
Mechanisms of Hypertensive Therapies
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Vasodilators
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Act on many areas not just kidneys
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Directly relax VSMCs in renal vasculature
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Block RAS or RAAS
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Methyl-dopa
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Inhibit sympathetic nerve activity via activation of a2 receptofrs decrese TPR and CO
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Hydralazine
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Vasodilator, mechanism unclear
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Magnesium sulfate
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Prevent transition to ecclampsia
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DELIVERY
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NOT – RAS blockers/inhibitors!
Choice of Hypertensive Therapies
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Population specificity
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Elderly
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Sex/gender
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Ethnicity
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Underlying conditions
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Fixed dose combination therapy
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Treats both systolic and diastolic pressures
Ruth Olson
Management of HTN: Gilbert
Refractory Hypertension
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Pseudoresistance
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“White-coat hypertension” or
office elevations
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Pseudohypertension in older
patients
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Use of small cuff on very obese arm
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Nonadherence to therapy
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Volume overload
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Evaluate Na+ intake
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Other underlying conditions, eg.
Endocrines
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Drug-related causes
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Doses too low
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Wrong type of diuretic
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Inappropriate combinations
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Drug actions and interactions
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Sympathiomimetics, Nasal
decongestants, Appetite suppressants,
Cocaine, Caffeine, Oral contraceptives
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Adrenal steroids, Licorice (may be
found in chewing tobacco)
Concomitant conditions
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Obesity
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Sleep apnea
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Ethanol intake of >1 oz (30 mL) per day
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Anxiety, hyperventilation