R6 Hypertension

• -1 in 3 Americans
• -Increases with age: 7.3% in adults 18-39 years, 32.6% in 40 to 59 years, 66.6% in pts >60 years
• -African Americans tend to develop HTN earlier than whites
• -Second most prevalent cause of ESRD in the US - increasing BP correlates to increase risk

• *We have increased awareness and the % treated, but less than 48% of patients with HTN have controlled blood pressures
• *Only 15% of pts with diabetes and HTN have controlled BP

• -TIA, stroke
• -Retinopathy
• -Peripheral vascular disease
• -Renal failure
• -LVH, CHD, HF

*antihypertensive treatment reduces the risk of all of these complications

• Increase Systolic BP (even isolated increased SBP) is the more powerful cardiovascular risk factor
• (systolic>>diastolic BP elevations)
• Concomitant risk factors: serum cholesterol, ♂, family history of CVD, smoking, race (black)

• Measure with sphygmomanometer: BP cuff
• -If the cuff is too small --> artifactual increase in BP
• -Home monitoring: better detection and treatment (white coat HTN, masked HTN, Labile HTN)
• -Nocturnal Dip: BP dips when sleeping

• -Normal: <120/80
• -Prehypertesion: 120-139/80-89
• -Stage 1 HTN: 140-159/90-99
• Stage 2 HTN: ≥160/100

Normally, BP dips at night (sleep)

Pts with kidney disease often lack the nocturnal dip, some are even "reverse dippers"

• African American Study of Kidney disease... pts with decreased GFR
• -20% dipped at night (nl)
• -40% didn't dip (or dipped less than normal)
• -40% rose at night

MAP = (CO)*(SVR)

-↑BP must result from either ↑ CO, or ↑SVR (or both)

• Hypertension follows the kidney
• Pressure natriuresis - salt sensitivity
• Relationship between progression of renal disease and HTN
• Generations of vasoactive hormones
• Role of Renal nerves in BP regulation

• Angiotensin II has effects on:
• -Brain, pituitary gland
• -Heart
• -Kidney and Adrenal gland
• -Vasculature

Primary or Essential (unknown cause)

• Secondary
• -Renal parenchymal disaese
• -Renovascular HTN
• -Pheochromocytoma
• -Isolated Systolic HTN

• Proposed mechanism:
• -Decreased sodium/water excretion
• -Increased RAAS activity
• -Increased renal nerve activity
• -Decreased Nitric oxide activity

• Clinical findings:
• -Increased BUN/Creat
• -Proteinuria
• -Evidence of renal and/or systemic disease
• -Presence of edema
• -HTN difficult to control

• 
• -Limits transmission of blood pressure to the kidneys
• -One kidney model: RAAS system activated to try and restore volume to normal

• Proposed mechanism:
• -Decreased renal perfusion pressure secondary to stenosis
• -Increased RAAS activity
• -Decreased salt and water

• Clinical findings:
• -HTN difficult to control
• -Hypokalemia
• -Response to RAAS blockers
• -Atherosclerotic lesions: elderly patient, previous history of HTN
• -Fibromuscular dysplasia: young female, no fhx
• -Renal artery stenosis on imaging
• -Asymmetric kidney size (long-standing disease can cause damage to the contralateral kidney)

-Stenosis ≠ disease; must have significant stenosis

Prevalence varies by region (~20% of patients with resistant and/or severe hypertension)

• Proposed mechanisms:
• -Increased Na reabsorption in the distal tubule
• -Activation of the sympathetic nervous system
• -Aldosterone producing adenoma
• -Bilateral adrenal hyperplasia

• Clinical findings:
• -Hypokalemia
• -Muscle weakness
• -Poliuria
• -Nocturia
• -Response to mineralocorticoid receptor blocker
• -Increased cardiovascular risk
• **No edema
• **High aldo, suppressed renin

• high aldosterone AND high renin
• Edema

• Proposed mechanism:
• -Catecholamine secreting tumor

• Clinical findings:
• -HTN sustained or paroxysmal plus/minus tachycardia
• -orthostatic hypotension
• -Evidence of cardiovascular complication (MI, LVH, cardiomyopathy, arrhythmias, CVA)

• Strong genetic component; twin studies
• Multifactorial disease
• 

• Lifestyle assessment:
• -BMI
• -Sodium intake
• -Potassium intake
• -Alcohol intake
• -Smoking habits
• -Exercise habits

• Exclude secondary causes:
• -Age of onset
• -Spontaneous hypokalemia
• -Labile hypertension
• -Resistant hypertension
• -Vascular bruits (RVH)
• -Familial

• Target organ injury:
• -24 hour urine protein
• -Serum Creatinine
• -EKG or ECHO (LVH)
• -Peripheral pulsations
• -History of stroke
• -History of myocardial infarction
• -Heart failure
• -Retinopathy

• 1. History and PE
•  - Consequences of HTN: target organ damage
•  - Cause of HTN (2° hypertension)

• 2. Laboratory evaluation
•  - Hemogram
•  - Chemistry panel (BUN, creatinine, electrolytes)
•  - EKG
•  - Chest Xray
•  - Urinalysis

• Lifestyle modification:
• -Avoid excessive Na intake (<100mEq/d) (good luck!)
• -Weight loss (BMI 18-25)
• -Reduce sodium intake 
• -Physical activity
• -Adopt DASH eating plan
• -Limit alcohol consumption
• -Dietary potassium supplementation

• NSAIDs (nonselective and COX-2 selective) - increase BP through retention of sodium and water
• Sympathomimetic agents (wt loss pills, cocaine)
• Amphetamines
• Exogenous glucocorticoids and mineralocorticoids
• Antidepressants
• Alcohol
• Oral contraceptive pills
• Immunosuppressants
• Erythropoietin
• Natural licorice
• Herbal agents ephedra or ma huang

• Elevated blood pressure on 3 anti-hypertensive meds
• OR
• Normal blood pressure on 4anti-hypertensive meds

• 
• Central sympatholytics (clonidine, methyldopa)
• β-blockers (many)
• α-blockers (prazosin, doxazosin)
• Angiotensin-receptor blockers (many)
• Converting-enzyme inhibitors (many)
• Thiazide diuretics (many)
• Calcium channel blockers (many)
• Direct vasodilators (hydralazine, minoxidil)
• Renin inhibitors (aliskiren)

• 
• -Renin converts Angiotensinogen to Ang I
• -ACE converts Ang I to Ang II
• -Ang II acts on AT1 and AT2 (receptors)

• Effects of AT1:
• -Vasoconstriction
• -Inotropism
• -Glomerular filtration
• -Renal blood flow
• -Vascular hypertrophy
• -LVH
• -Fibrosis
• -Oxidative stress
• -Inflammation

• Effects of AT2:
• -Vasorelaxation
• -Cellular growth inhibition

• *Ang II causes increase Aldosterone
• +inflammation
• +Sodium reuptake
• +K and Mg excretion
• +CNS enhancement
• +Myocardial fibrosis

• Vascular AT₁ receptor
• -Constantly expressed
• -Mediate vasoconstriction
• -Mediate angiotensin II arterial wall growth effects

• Vascular AT₂ receptors
• -Expressed only after injury (sustained hypertension might provoke expression)
• -Mediate vasodilation
• -Mediate antiproliferative actions
• -Activate other factors (nitric oxide, tissue kinins)

• Potential double action of selective AT₁ blockers
• -Directly block vasoconstrictor and growth actions of Ang II at AT1 receptors
• -Increase circulating AngII
• -Unblocked AT₂ receptors (if expressed), stimulated by increased Ang II activity, mediate vasodilation and growth inhibition
• -Net effect: AT₁ blockade plus AT₂ stimulation

• Damage:
• -Atherosclerosis
• -Vasoconstriction
• -Vascular inflammation
• -Endothelial dysfunction
• -LVH
• -Fibrosis (cardiac)
• -Remodeling (cardiac)
• -Apoptosis
• -↑ Glomerular capillary pressure

• -↑ Proteinuria
• -↑ Aldosterone release
• -Glomerular sclerosis

• *Stroke
• *Hypertension
• *Heart failure
• *Myocardial infarction
• *Renal failure

• "Prils" and "sartans"
• Both excellent first line therapies for HTN
• Poor side effect profile in combination and little to no benefit

• Available compounds:
• -Phenylalkylamines: Verapamil ("V" for ventricles)
• -Benzothiazepines: Diltiazem
• -Dihydropyridines: nifedipine, amlodipine, felodipine, isradipine

• Mode of action:
• -Decrease cellular calcium entry through L-type channel
• -Negative inotropic effect
• -Reduction in total peripheral resistance
• -Natriuresis
• -Interference with Ang II, α₁- and α₂-mediated vasoconstriction

• Indications:
• -HTN
• -Salt-sensitive HTN
• -Diastolic dysfunction
• -Variant angina
• -Cerebral vascular disease
• -Cyclosporine hypertension

• Contraindications:
• -Heart block and HF
• -MI

• Side effects:
• -Tachycardia
• -Edema
• -Flushing
• -Headache

• Antihypertensive effects:
• 1. Reduction in heart rate and CO
• 2. CNS effect
• 3. Inhibition of renin release
• 4. Reduction in venous return and plasma volume
• 5. Reduction in SVR
• 6. Reduction in vasomotor tone
• 7. Improvement in vascular compliance
• 8. Resetting of baroreceptor levels
• 9. Effects on prejunctional β-receptors: reduction in NE release
• 10. Attenuation of pressor response to catecholamines with exercise and stress

*Not often used in younger patients (bradycardia)

• -Methyldopa (Aldomet)
•  -- Aldoclor = methyldopa + chlorothiazide
•  -- Aldoril (Methyldopa + HCTZ)

• -Clonidine (Catapres)
•  -- Clorpres = Clonidine + chlorthalidone

*Never used as first line defense; third choice...

• Hydralazine
• -mainly used in pregnancy
• -part of triple therapy with diuretic and adrenergic inhibitors

• Minoxidil
• -only for severe refractory hypertension
• -also used in Rogaine

• Monotherapy: completely satisfactory in ~60%
• Combination: needed in ~40% of patients
• Must choose/add a second drug with different action

• TZ → decrease serum potassium
• Beta blockers
• -Combination therapy improved BP better than individual therapy alone
• -Combination didn't drop serum potassium as much as Diuretics alone (less risk for hypokalemia)

• ACE-In
• -Combination blocks the adverse metabolic effects of TZ

Different mechanism of action → Additive effect

SBP and DBP drop significantly with combination (captopril + Nifedipine)

• Sodium nitroprusside: IV, can titrate minute to minute
• Glyceril trinitrate
• Nicardipine
• Verapamil
• Fenoldopam
• Hydralazine
• Enalaprilat
• labetalol
• esmolol
• phentolamine

• Severe hypertension:
• >180/110mmHg
• Sx: often asymptomatic, HA, anxiety

• Hypertensive urgency:
• >180/110mmHg
• Sx: severe HA, SOB, Edema
• Management: lower BP, observe for 3-6hrs

• Hypertensive Emergency = Malignant HTN:
• >220/140mmHg
• Sx: prolonged chest pain, motor impairment/neurologic deficit, altered mental status, uncontrolled bleeding, pulmonary edema, MI, CVA, Encephalopathy...

• Common in elderly
• ↓ arterial "compliance" (↓ SV/PP) → ↑PP → ↑ SBP
• 

• -African Americans are over-represented in the ESRD population
• -HTN is especially common (prevalence ~50%)
• -Blacks are more hypersensitive to salt than whites

-TZ are as effective in blacks and whites

-Beta blocker efficacy white > black

-Combination (TZ+BB) works additively in all patients

-CCB have equal effects as initial (mono) therapy of htn for blacks and whites

-Incidence of ESRD is lower with ACE-In

New(er) treatment for treatment-resistant hypertension