systemic hypertension: mechanisms and diagnosis systemic hypertension: therapy presenter: cheng-han...
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Systemic Hypertension: Mechanisms and Diagnosis
Systemic Hypertension: Therapy
Presenter: Cheng-Han Lee
Supervisor: Wei-Chuan Tsai
Heart Disease
Braunwald
BP Measurement Techniques
Method Brief Description
In-office Two readings, 5 minutes apart, sitting in chair. Confirm elevated reading in contralateral arm.
Ambulatory BP monitoring
Indicated for evaluation of “white-coat” HTN. Absence of 10–20% BP decrease during sleep may indicate increased CVD risk.
Self-measurement Provides information on response to therapy. May help improve adherence to therapy and evaluate “white-coat” HTN.
Measurement of BP
Elevated BP soon after awakening Usual nocturnal fall in BP Exaggerated response in normotensive adul
ts rise in SBP ≧60mmHg at 5 mins of exercise
(6.3METS) or ≧70mmHg at 10 mins or rise in DBP ≧10mmHg at any time
≧3-fold HTN over 5-15 years
Ambulatory BP monitoring
Components of Cardiovascular Risk Stratificai
ton in Patients with HypertensionComponents of Cardiovascular Risk Stratificai
ton in Patients with Hypertension
Major Risk FactorsMajor Risk FactorsSmokingSmokingDyslipidemiaDyslipidemiaDiabetes mellitusDiabetes mellitusAge older than 60 yearsAge older than 60 yearsSex (men and postmenopausal women)Sex (men and postmenopausal women)Family history of cardiovascular disease:Family history of cardiovascular disease:
women under age 65 or men under age 55women under age 65 or men under age 55
Stroke and CAD Vs Diastolic BP
Cardiovascular risks of HTN
Components of Cardiovascular Risk Stratificai
ton in Patients with HypertensionComponents of Cardiovascular Risk Stratificai
ton in Patients with Hypertension
Target Organ Damage/Clinical Cardiovascular Target Organ Damage/Clinical Cardiovascular DiseaseDisease
Heart diseasesHeart diseases** Left ventricular hypertrophyLeft ventricular hypertrophy** Angina/prior myocardial infarctionAngina/prior myocardial infarction** Prior coronary revascularizationPrior coronary revascularization** Heart failureHeart failureStroke or transient ischemic attackStroke or transient ischemic attackNephropathyNephropathyPeripheral arterial diseasePeripheral arterial diseaseRetinopathyRetinopathy
HTN Vs LVH
HTN Vs CHF
Mechanisms of Primary HTNLow birth weight
Neurohumoral causes of primary HTN
Sympathetic nervous hyperactivity Renin-Angiotensin system Hyperinsulinemia/insulin resistence Endothelial cell dysfunction
Renin-Angiotensin system
Hyperinsulinemia/insulin resistence
Endothelial Dysfunction
Types of HTN
Essential (primary or idiopathic) HTN Secondary HTN (identifiable etiologies) Systolic HTN
Increased cardiac output
AR, AVF, PDA, Thyrotoxicosis, Paget
disease of bone, beriberi, hyperkinetic
Rigidity of aorta (atherosclerosis)
Secondary HTN
Secondary” HTN accounts for ~5-10% of other cases and represents potentially curable disease
Often overlooked and underscreened Controversy over screening and treatment i
n some cases
Features of Inappropriate hypertension
1. 1. Onset before age 20 or after age 50Onset before age 20 or after age 502. 2. Level of BP > 180/110 mmHgLevel of BP > 180/110 mmHg3. 3. Organ damageOrgan damage A. A. Funduscopic findings of grade 2 or higherFunduscopic findings of grade 2 or higher B. B. Serum creatinine > 1.5 mg/100mlSerum creatinine > 1.5 mg/100ml C. C. Cardiomegaly or LVHCardiomegaly or LVH4. 4. Feature indicative of secondary causesFeature indicative of secondary causes A. A. Unprovoked hypokalemiaUnprovoked hypokalemia B. B. Abdominal bruitAbdominal bruit C. C. Variable pressure with tachycardia, sweating.Variable pressure with tachycardia, sweating. D. D. Family history of renal disease Family history of renal disease 5. 5. Poor response to therapyPoor response to therapy
Causes of Secondary HTN
Common Intrinsic Renal Disea
se(GN, PCD..) Renovascular Dz Mineralocorticoid exc
ess/ aldosteronism Neurological disorder
s (sleep apnea, IICP..)
Uncommon Pheochromocytoma Glucocorticoid exces
s/ Cushing’s dz Coarctation of Aorta Hyper/hypothyroidis
m
Oral contraceptive and postmenopausal estrogen
The most common cause of 2nd HTN in young women----oral contraceptive
5% within 5 years develop HTN Easy develop if women> 35ys, obese or
drink large alcohol Most adverse effects develop with more
than 50ug of estrogen When discontinued, BP falls to normal within
3-6 months in about 50% patients
Renal parenchymal disease
The most common cause of 2nd HTN-2-5%
Renovascular HTN Incidence: < 1% Type: Atherosclerosis: 65%, pr
oximal 2cm, progression in 50% Fibromuscular dysplasia
(medial): 35%, midportion or distal segme
nt, branch; progression in 33% Others--Other
Aortic/renal dissection Takayasu’s arteritis Thrombotic/cholesterol embo
li CVD Post transplantation stenosis Post radiation
Renovascular HTN - Pathophysiology
Decrease in renal perfusion pressure activates RAAS, renin release converts angiotensinogen Ang I; ACE converts Ang I Ang II
Ang II causes vasoconstriction (among other effects) which causes HTN and enhances adrenal release of aldosterone; leads to sodium and fluid retention
Renovascular HTN - Clinical History
Sudden onset uncontrolled HTN in previously well controlled pt
Accelerated/malignant HTN Intermittent pulm edema
PE/Lab Epigastric bruit, particulary systolic/diastoli
c Azotemia induced by ACEI Unilateral small kidney
Clinical index of suspicion Low (should not be tested) borderline, mild, or moderate HTN, in the absence of clinical clues
Moderate (noninvasive tests ) 1. severe HTN (DBP>120mmHg)
2. HTN refractory to standard treatment
3. Abrupt sustained, moderate to severe HTN at age<20 or >50
4. HTN with a suggestive abdominal bruit
5. Moderate HTN (DBP>105) in a smoker, occlusive vascular
disease
6. Normalization of BP by ACE i , particular in smoker or recent
HTN
Clinical index of suspicion
High (may consider direct angiography) 1.Severe HTN (DBP>120 with renal insufficiency or refractory
medical therapy) especially in smoker or occlusive artery dz.
2. Accelerated or malignant HTN (grade 3 or 4 retinopathy)
3. HTN with recent elevated creatinine (ACEi induce or normalize)
4. Moderate to severe HTN with incidentally detected asymmetry
of renal size.
RAS screening/diagnosticsSens Spec Limitation/Etc
Duplex U/S90-
95%60-
90%
Operator dependent
Captopril Renography
73-100%
73-95%
Meds, accuracy reduced in pt with renal insufficiency, lacks anatomical info; good predictor of BP response
MRA88-
95%95%
False positive artifact resp, peristalsis, tortuous vessels; cost
AngiographyGold std
Gold std
Invasive, nephrotoxicity, little value in predicting BP response
Adrenal causes of HTN
Primary Aldosteronism Cushing Syndrome Congenital adrenal hyperplasia Pheochromocytoma
Primary Aldosteronism Etiology
Adrenal adenoma Other: bilat adrenal hyperplasia (1/3), glucocorticoid s
uppressible hyperaldo, Licorice, Liddle syndrome, adrenal carcinoma
Clinical: May be asymptomatic; headache, muscle cramps, polyu
ria Retinopathy, edema uncommon Hypokalemia (K normal in 40%), metabolic alkalosis,
high-nl Na
Primary Aldosteronism
Familial glucocorticoid-suppressible aldosteronism
1. unequal crossing over of CYP11B1 (11beta-hydroxylase gene)
and CYP11B2 (aldosterone synthase gene) during meiosis,
producing a fusion product that couples the ACTH-sensitive
promoter of CYP11B1 to the CYP11B2 gene
2. ACTH-dependent aldosterone production and production of 17-
hydroxylated analogs of 18-hydroxycortisol under ACTH regulation
from ectopic enzyme expression in the zona fasciculata.
Primary Aldosteronism
Hypokalemia, metabolic alkalosis and urinary K excretion > 30mmol/day
Screening test: serum Aldo/renin> 30
Primary Aldosteronism
Solitary adenoma surgery Bilateral adrenal hyperplasia spironolacto
ne
Cushing Syndrome
24h urine free cortisol> 90-100ug
Diagnosis Screening test: 1. 24h urine free cortisol level 2. Overnight dexamethasone 1mg suppression ( normal cortisol at 8am: <2ug/100mg) specificity: 87% 3. 0.5mg q6h for 2 days dexa. specificity: 100% Confirm test: 1. high dose 2mg q6h for 2 days dexa. cortisol was suppressed to <40% control pituitary origin 2. Plasma ACTH and cortisol at 4pm or later A. plasma cortisol >15 mg/dl and the corticotropin concentration is less than 5 pg/dl, cortisol secretion is corticotropin-independent B. plasma corticotropin > 15 pg /ml, the cortisol secretion is corticotropin-dependent
Features Suggestive of Pheochromocytoma
Hypertension: Persistent or Paroxysmal Markedly variable blood pressures (± orthostatic hypotension)
Sudden paroxysms (± subsequent hypertension) in relation to Stress: anesthesia, angiography
Pharmacological provocation: histamine, nicotine, caffeine, beta blockers, glucocorticoids, tricyclic antidepressants
Manipulation of tumors: abdominal palpation, urination Rare patients persistently normotensive Unusual settings Childhood, pregnancy, familial Multiple endocrine adenomas: medullary carcinoma of the thyroid
(MEN-2), mucosal neuromas (MEN-2B) Neurocutaneous lesions: neurofibromatosis
Associated SymptomsSudden spells with headache, sweating, palpitations, nervousness, nausea, and vomitingPain in chest or abdomen-associated SignsSweating, tachycardia, arrhythmia, pallor, weight loss
Pheochromocytoma
85% arise in adrenal medulla 10% are bilateral 10% are malignant Epinephrine from adrenal medulla Norepinephrine from extraadrenal tumors May be provoked by triggers such as tyramine-con
taining foods (beer,cheese,wine), pain, trauma, drugs (clonidine, TCA, opiates)
Pheochromocytoma - Screen Best detected during or immediately
after episodesSensitivity Specificity
Plasma free metanephrine >.66nmol/L
99% 89%
24hr urine metanephrine
(>3.7nmol/d)
77% (95%) 93% (96%)
24 urine VMA 64% 95%
Lenders, et al. JAMA 2002 Mar 20;287(11):1427-34
Pheochromocytoma - treatment Surgical removal of tumor
Anesthesia- avoid benzo, barbiturates or demerol which can trigger catechol release
Complications include ligation of renal artery, post op hypoglycemia, hemorrhage and volume loss
Mortality 2%, 5 yr survival 95% with <10% recurrence
Caution with Beta blocker – can cause unopposed alpha stimulation/pheo crisis
BP control with alpha blockers (phentolamine, phenoxybenzamine, and prazosin)
Coarctation of Aorta
Just beyond the origin of left subclavian a. or distal to the insertion of the ligmentum arteriosum
Coarctation of Aorta
Congenital defect, male>female Clinical
Differential systolic BP arms vs legs (=DBP) May have differential BP in arms if defect is prox to L su
bclavian art Diminished/absent femoral a. pulse Often asymptomatic Assoc with Turners, bicuspid AV
If uncorrected 67% will develop LV failure by age 40 and 75% will die by age 50
Surgical Rx, long term survival better if corrected early
Hypertension during pregnancy
Chronic HTN before GA 20 weeks Gestational HTN after GA 20 weeks more frequent in primigravid or in subsequent pregnancy with a d
ifferent father, increased age, black, multiple gestations, concomitant renal and heart disease
Preeclampsia gestational HTN, edema, proteinuria, thrombocytopenia or thrombocytopenia
Eclampsia convulsions and preeclampsia
Hypertension during pregnancy
Most authorities recommend anti-HTN therapy if DBP>100mmHg
ACEi and ARB are contraindicated Methyldopa and hydralazine are first choice
HTN Crisis
HTN emergency need reduction of BP within 1 hour
HTN urgency reduction of BP more slowly Persistent DBP>130mmHg vascular injury Most HTN crisis appear in preexisting
primary HTN
CIRCUMSTANCES REQUIRING RAPID TREATMENT OF HYPERTENSION
Accelerated-malignant hypertension with papilledema( or exudate, hemorrhage) Cerebrovascular Hypertensive encephalopathy Atherothrombotic brain infarction with severe hypertension Intracerebral hemorrhage Subarachnoid hemorrhageCardiac Acute aortic dissection Acute left ventricular failure Acute or impending myocardial infarction After coronary bypass surgeryRenal Acute glomerulonephritis Renal crises from collagen-vascular diseases Severe hypertension after kidney transplantationExcessive circulating cathecholamines Pheochromocytoma crisis Food or drug interactions with monoamine oxidase inhibitors Sympathomimetic drug use (cocaine) Rebound hypertension after sudden cessation of antihypertensive drugsEclampsiaSurgical Severe hypertension in patients requiring immediate surgery Postoperative hypertension Postoperative bleeding from vascular suture linesSevere body burnsSevere epistaxis
CLINICAL CHARACTERISTICS OF HYPERTENSIVE CRISIS
Blood pressure: Usually >140 mm Hg diastolic Funduscopic findings: Hemorrhage, exudate, papilledema
Neurological status: Headache, confusion, somnolence, stupor, visual loss, focal deficits, seizures, coma
Cardiac findings: Prominent apical impulse, cardiac enlargement, congestive failure
Renal: Oliguria, azotemia
Gastrointestinal: Nausea, vomiting
CONDITIONS TO BE DIFFERENTIATED FROM A HYPERTENSIVE CRISIS
Acute left ventricular failure
Uremia from any cause, particularly with volume overload
Cerebrovascular accident
Subarachnoid hemorrhage
Brain tumor
Head injury
Epilepsy (postictal)
Collagen diseases, particularly lupus, with cerebral vasculitis
Encephalitis
Overdose and withdrawal from narcotics, amphetamines, etc.
Hypercalcemia
Acute anxiety with hyperventilation syndrome
Chap 29 Systemic HTN-Therapy
Benefits of Lowering BP
Average Percent Reduction
Stroke incidence 35–40%
Myocardial infarction 20–25%
Heart failure 50%
Goals of Therapy
Reduce CVD and renal morbidity and mortality.
Treat to BP <140/90 mmHg or BP <130/80 mmHg in patients with diabetes or chronic kidney disease.
Achieve SBP goal especially in persons >50 years of age.
Therapy
MODIFICATION RECOMMENDATIONAPPROXIMATE SBP
REDUCTION (RANGE)
Weight reduction body weight (body mass index 18.5–24.9
kg/m2 ).
5–20 mmHg/10 kg weight loss]
Adopt DASH eating plan diet rich in fruits, vegetables, and low
fat.
8–14 mmHg]
Dietary sodium reduction
Reduce Na to no more than 100 mmol per
day (2.4 g sodium or 6 g sodium chloride).
2–8 mmHg]
Physical activity regular aerobic activity such as brisk walking (at least 30 min per
day)
4–9 mmHg]
Moderation of alcohol consumption 2 drinks/D (30 mL ethanol) in most men and to no more than 1 drink per day in w
omen
2–4 mmHg
.
(Circulation. 2004;109:3081-3088.)
Diuretics
Thiazide Loop diuretics Potassium-sparing diurectics- amiloride, tria
mterene, spironolactone When Cre< 2mg/dl, thiazide is adequate; if
Cre> 2mg/dl or Ccr<25ml/min, thiazide is not effective
Diurectics
Initial effect
Adrenergic Inhibitors
Peripheral neuronal inhibitors—reserpine, guanethidine
Central adrenergic inhibitors—methyldopa, clonidine, guanabenz
α-receptor blocker—non-selective blocker (phentolamine); α1 blocker—doxazolin, prazosin, terazosin(hytrin)
β-blocker α, and β-blocker—labetalol, carvedilol
Deplete norepinephrine
Inhibit norepinephrine release
Reduce central sympathetic outflow
α-receptor blockers
Can be safely used in renal failure Improve lipid profiles Mildly increase insulin sensitivity Excellent choice for older man with BPH However, in ALLHAT trial (>55ys, doxazosi
n), higher risk for stroke and CHF compared with chlorthalidone
β-blockers
ISA—intrinsic sympathomimetic activity measureable agonist and greater antagonist effect less decline in HR, cardiac output and renin
β-blockers Lipid solubility atenolol and nadolol are le
ast lipid soluble less CNS side effects Side effects fatigue, insomnia, nightmares,
hallucinations Non-selective agents cause greater rise in T
G and reduction in HDL Use in pregnancy fetal retardation
Vasodilators
relative action on artery or vein
Direct
Hydralazine A>>V
Minoxidil (opening K channel) A>>V hirsutism, pericardial effu.
Nitroprusside A=V
NTG A<V
CCB A>>V
ACEi, ARB A>V
α-blocker A=V
Causes of Resistant Hypertension Improper BP measurement Excess sodium intake Inadequate diuretic therapy Medication
• Inadequate doses• Drug actions and interactions (e.g., nonsteroidal anti-inflammatory
drugs (NSAIDs), illicit drugs, sympathomimetics, oral contraceptives)• Over-the-counter (OTC) drugs and herbal supplements
Excess alcohol intake Identifiable causes of HTN
Therapy for HTN crisis
If DBP persistently >140mmHg combines with acute target organ damages, immediately reduce 20-25% BP within 1 hour
Drug Dosage Onset
Nitroprusside 0.25-10ug/kg/min immediate
NTG 5-100ug/min 2-5 mins
Nicardipine 5-15mg/hr 5-10 mins
Hydralazine 10-20 IV bolus 10-20 mins
Enalapril 1.25-5mg IV bolus 15 mins
Fenoldopam 0.1-0.3ug/kg/min <5 mins
Phentolamine 5-15mg IV bolus 1-2 mins
Esmolol 500ug/kg/min for 4 mins then 150-300ug/kg/min 1-2 mins
Labetalol 20-80mg IV bolus q10mins;2mg/min
5-10 mins
Seventh Report of the Joint National Committee (JNC 7)
on Prevention, Detection, Evaluation, and Treatment of High BP
older than 50 y/o, SBP≧ 140 mmHg is a much more important cardiovascular disease (CVD) risk factor than DBP
The risk of CVD beginning at 115/75 mmHg doubles with each increment of 20/10 mmHg; individuals who are normotensive at age 55 have a 90 percent lifetime risk for developing hypertension.
JNC (7)
Individuals with SBP of 120–139 mmHg or a DBP of 80–89 mmHg prehypertensive and require health-promoting lifestyle modifications to prevent CVD
Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension
Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (ACEI, ARB, beta-blockers, CCB)
JNC (7)
Most patients with hypertension will require two or more antihypertensive medications to achieve goal blood pressure (<140/90 mmHg, or <130/80 mmHg for patients with diabetes or chronic kidney disease).
• If blood pressure is >20/10 mmHg above goal blood pressure, consideration should be given to initiating therapy with two agents, one of which usually should be a thiazide-type diuretic
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