Hypertension

Question 1

Define the different types of HT

Answer 1

• Normal: <120 systolic AND <80 diasolic
• Pre-HT: 120-139 or 80-89
• Type I HT: 140-159 or 90-99
• Type 2 HT: ≥160 or or ≥100

Question 2

List the epidemiologic parameters that are associated with the increased prevalence of hypertension within populations.

Answer 2

• Age
o Systolic BP increases with age
o Diastolic BP increases until about 55-60 years, then decreases as vascular stiffness increases/elasticity decreases
o Until age 55, more men have HT than women; after age 64, more women have HT than men
• Category of HT
o Pre-HT still at increased risk for future CV diseases & chronic kidney disease
• Race and Ethnicity
o More prevalent and more severe: African-Americans
o Puerto Ricans in US: high HT-related mortality rate
• Recent increase is among Mexican Americans
• Tobacco use
• Genetic factors(30-60% attributable)
• Low SES
• Obesity (especially central obesity) and increased amounts of leptin
• High sodium diet: increases fluid volume and CO
• Sedentary lifestyle
• Psychosocial stressors
• Intrauterine growth retardation
• Family history of HT (usually a combination of genetic, environmental, and behavioral influences)
**• Excessive Alcohol consumption **

Question 3

Describe common pathologic changes that hypertension induces or aggravates in target organs and its relationship with cardiovascular disease risk.

Answer 3

• Higher the systolic or diastolic BP, the greater the chance for MI or stroke
o Correlation is continuous, consistent, and independent of other cardiovascular risk factors
o HT decreases life expectancy
• Result from increased workload of hear, arterial damage from increased BP, and accelerated atherosclerosis
• Damage to major organs:
o Left ventricular hypertrophy
o Heart failure
o Chronic kidney disease
o Renal failure
o Aortic dissection
o Retinal abnormalities

Question 4

Describe the equation for BP

Answer 4

• BP = CO x SVR

Question 5

Equation for CO

Answer 5

• CO = HR x SV

Question 6

Equation for MAP

Answer 6

• MAP = DBP + 1/3 (SBP – DBP) or MAP = DBP + 1/3 (pulse pressure)

o Because ventricle spends more time in diastole than systole

Question 7

Equation for SVR

Answer 7

• SVR = (MAP – CVP)/CO

o CVP: Central venous pressure (pressure in thoracic vena cava and right atrium)

o Main sources of SVR: blood vessel diameter, blood viscosity, total vessel length, vessel elasticity, blood volume

Question 8

Describe the roles of the renin-angiotensin-aldosterone system in the pathogenesis of hypertension

Answer 8

o Renin released:
• Low Na+ sensed in Macula Densa
• Decreased renal perfusion
• Sympathetic stimulation
o Converts angiotensinogen → angiotensin I
o ACE in lungs
• Converts angiotensin I → Angiotensin II
• Degrades bradykinin (a vasodilator)
• Vasoconstriction
• Elevated BP
• Decreased levels of NO (from less bradykinin stimulation)
o Angiotensin II
• Release of aldosterone → increase Na+ reabsorption from distal nephron → increased blood volume
• Binds G-protein coupled receptors → vasoconstriction and increased BP
• CNS: increases thirst
• Vascular smooth muscle: proliferation
o Aldosterone
• Na+ and H20 retention
• K+, Mg+ loss
• Increased collagen synthesis (cardiac and vascular)
• Increased sensitivity to catecholamines

Question 9

Describe the roles of the sympathetic nervous system in the pathogenesis of hypertension

Answer 9

o Regulate constriction of blood vessels
o Help control HR, blood flow, and BP
• Renin release, vascular remodeling (thickening), renal Na+ retention
o SNS activity increases with age, weight, SVR
o Arterial baroreceptors
• Stretch-sensitive sensory nerve endings in carotid sinuses and aortic arch
• Detect BP changes
• Can decrease BP

Question 10

Describe the roles of obesity in the pathogenesis of hypertension.

Answer 10

o Central adiposity associated with HT
o Hemodynamic, metabolic, and endocrine mechanisms contribute to HT
o Increased Leptin (hormone from white adipose) correlates with increased BP

Question 11

Describe the roles of sodium in the pathogenesis of hypertension.

Answer 11

o Excess sodium intake stimulates endogenous digitalis (proliferation of arterial smooth muscle cells)
• Increases peripheral vascular resistance and CO
• Inhibits renal tubular Na+/K+ ATPase → less Na+ reabsorption
o Increases fluid volume and CO
o More common among elderly, Afro-Caribbeans, people with familial genetic influence, Type II diabetics, obesity, patients using NSAIDs

Question 12

Explain the benefit of lowering blood pressure (BP) on cardiovascular outcomes

Answer 12

• Reduces cardiovascular and renal morbidity and mortality
• 35-40 % reduction in stroke incidence
• 20-25% reduction in MI
• >50% reduction in heart failure

Question 13

Describe the types and benefits of lifestyle modification for hypertension prevention and management

Answer 13

• Reduce other CVS risk factors
• Enhance efficacy of antihypertensive medications
• Modifications:
o Weight reduction–as little as 10 lbs has effect (5-20 mmHg/10 kg wt loss)
o Adopt DASH diet (8-14 mmHg)
• Diet low in saturated fats, cholesterol
• Emphasis on fruits, vegetables, low fat dairy products
• Reduce red meat, sugar, sweets, and sugar-containing beverages
o Dietary Na+ reduction (2-8 mmHg)
o Physical activity (4-9 mmHg)
o Moderate alcohol consumption (2-4 mmHg)
o Smoking cessation (3.5 mmHg after one week of cessation)

Question 14

Describe accurate blood pressure measurement technique

Answer 14

• Critical to guide therapy and decrease CV disease
• For accuracy:
o Patient be seated for 5 minutes before
o Back supported, legs uncrossed, feet flat on floor, arms resting
o Measured arm supported at level of heart
o Measure arm with highest BP
o Caffeine, exercise, and smoking avoided at least 30 minutes before
o Cuff placed over bare arm
o Bladder of cuff circle 80% arm circumference, cover about 2/3 length of arm, lower edge about 1 inch above antecubital fossa
o Inflate to 20 mmHg above palpable radial pulse
o Pressure released at 2 mmHg/second
o At least 2 readings should be taken; more if vary by over 5 mmHg
o No talking during measurement
• “pseudohypertension” if cuff too small → falsely high readings
• Home BP monitoring
o Digital, automatic monitor, upper arm NOT wrist cuff
o HT if home BP >135/85
• 24 Hour Ambulatory BP monitoring
o Readings every 20-30 minutes
o HT if >130/80 in 24 hr period
o Evaluates for white coat HT, nocturnal HT, masked HT

Question 15

Explain the initial assessment of a patient with a new diagnosis of hypertension.

Answer 15

• If significant difference (>15 mmHg) between arms, check for subclavian stenosis
o Lower BP on affected side
o Lower palpable radial pulse on affected side
• Initial evaluation
o Identify possible secondary causes of HT
o Identify other CVD risk factors
o Assess for target organ damage
• Physical Exam
o Check BP in both arms
o Obtain orthostatic BP
• Orthostatic HT:
• ≥20 mmHg fall in systolic P
• ≥10 mmHg fall in diastolic P
• Symptoms of cerebral hypoperfusion
o Cardiac: palpation and auscultation
o Vascular: pulses, carotid, abdominal, and femoral bruits
o Abdomen: masses and aortic pulsation
o Lower extremities: edema
o Palpate thyroid
o Examine optic fundi
• Labs:
o Urinalysis
o Blood glucose
o Hematocrit
o Serum potassium, calcium, creatinine, GFR
o 12-lead ECF
o TSH
o Fasting lipid panel: HDL-c, LDL-c, triglycerides

Question 16

Describe the goal of antihypertensive medications

Answer 16

• Generally requires 2 or more antihypertensive medications from different classes
• Better to combine 2 low dose drugs with different mechanisms than high dose of one
• Goal: <140/90 mmHg; <130/80 mmHg if DM or chronic kidney disease
• Black box warning: Angiotensin II needed for normal kidney development, so do not use ACE-inhitiors, angiotensin receptor blockers, or rennin inhibitors in women who are pregnant or planning on becoming pregnant.

Question 17

ACE inhibitors: mechanism, indications, side effects

Answer 17

a. Lowers BP by decreasing peripheral arterial resistance and blood volume
b. Bind to angiotensin converting enzyme (ACE) active site so can’t cleave Ang I and bradykinin
i. Increases Angiotensin I levels
ii. Decreases Angiotensin II levels → Na+ excretion
iii. Increases renin
c. Note: Ang II stimulates adrenals, so ACE inhibitors decrease aldosterone levels
d. Bradykinin is protected from degradation
e. Indications:
i. Benefits treatment of chronic kidney disease associated with DM
ii. Decrease rate of progression of kidney disease/ preserve renal function
f. Side effects
i. Dry cough:
1. Increases bradykinin in lungs sensitizes bronchial epithelium to irritants
2. Can occur any time after start drug
3. Dose-dependent, often requires cessation of therapy
4. Change to angiotensin receptor blocker
ii. Worsened renal function
1. Increased creatinine,
2. Greater in chronic kidney disease, renal artery stenosis, CHF, diabetes mellitus
3. Safe for creatinine to rise by up to 30%
iii. Sulfhydryl-related effects
1. Neutropenia, rash
iv. Cholestatic jaundice
v. Hyperkalemia from increases serum K+
vi. Angioedema
1. Potentiation of bradykinin
2. Usually seen in 1st month
3. Get hives that may not itch, swelling of tongue and laryngeal mucosa
4. >90% can safely take an Angiotensin Receptor blocker
5. Greater risk among African-Americans

Question 18

Angiotensin Receptor blockers

Answer 18

a. Block pathways independent of the RAS system
b. Block only AT1 receptor (so no vasoconstriction, sympathetic activation, cell growth, Na+ and fluid retention)
c. Clinically as effective as ACE-Inhibitors
d. No effect on bradykinin
e. Lower incidence of kinin-mediated side-effects (cough, angioedema)
f. Other similar side effects as ACE-Inhibitors

Question 19

Direct Renin Inhibitor

Answer 19

a. Ex. Aliksiren
b. Blocks rate limiting step of RAAS cascade
c. Side effect: dose-dependent diarrhea
d. Contraindicated:
i. Concomitant use with ARBs or ACEIs in patients with diabetes
1. Risck of renal impairment, hypotension, hyperkalemia
ii. Avoid use with ARBs or ACEIs in patients with GFR <60mL/min

Question 20

Ca+ channel blockers

Answer 20

a. Bind to receptors on the α1-subunit of L-type Ca2+ channel → decrease Ca2+ entry for contraction
b. Vaodilates arteriolar smooth muscle
c. Decreases peripheral vascular resistance
d. Types:
i. Dihydropyridine: decrease Ca2+ influx in vascular smooth muscle
ii. Non-dihydropyridine: decrease Ca2+ influx in vascular smooth muscle and mycardium
* *e. Side effects:**
i. Gingival hyperplasia
ii. Inhibit CYP3A4 isoenzyme → increased levels of common drugs
iii. Dihydropyridines: edema, headache, flushing, dizziness, palpitations, reflex tachycardia, edema
iv. Non-dihydropyridines: constipation, bradycardia, AV block
v. AVOID: short acting nifedipine, dose-related increased risk of MI and mortality with ischemic heart disease

Question 21

Diuretics

Answer 21

a. Increase urinary excretion of Na+ and H2O in kidneys
b. Venodilation, decreases intravascular volume → decreases BP
c. Subclasses:
i. Thiazides
1. Ex. Hydrochlorothiazide, chlorthalidone
2. Decrease extracellular fluid volume, dilate peripheral arterioles
3. Inhibit Na+/Cl- reabsorption pump → increases urinary excretion
4. Increase excretion of K+ and Mg2+
5. Early treatment: reduce blood volume, cardiac preload, CO
6. Chronic treatment: CO returns to baseline, SVR decreases
ii. Loop (furosemide)
1. Act in thick ascending loop of Henle: venodilators, natriureteic effects
2. Prostaglandin sensitive: drugs that interfere with prostaglandin synthesis (NSAIDs) decrease action
3. Cause vasodilation, Na+ excretion → decreases preload, EC fluid volume, BP
4. Used in decompensated heart failure (pulmonary edema) or reduced GFR
iii. K+-sparing diuretics
d. Side effects:
1. Volume depletion
2. Hypotension, orthostasis
3. Electrolyte changes:
a. Hypokalemia, hypomagnesemia, Hyponatremia (thiazole), hypercalcemia (thiazaole)
b. Hyperkalemia (K+ sparing)
4. Ototoxicity, hypocalcemia (loop)
5. Metabolic side effects: hyperglycemia, hypercholesterolemia, hyperuricemia
6. Erectile dysfunction
7. Sulfa-allergy

Question 22

Aldosterone Antagonists

Answer 22

a. Aldosterone interacts with mineralcorticoid receptors → increase Na+ reabsorption, increased K+ excretion → increased BP
b. Beneficial in resistant HT and when combined with other diuretics
c. Increased risk of hyperkalemia with ACE-I or ARBs
d. Ex. Spironolactone (non-selective) effective when given with thiazide diuretics (also treats HF)
i. Men: erectile dysfunction, gynecomastia
ii. Women: menstrual abnormalities
e. Ex. Eplerenone (selective)

Question 23

8. β-Blockers

Answer 23

a. Inhibit effects of catecholamines → decreases SNS activity
b. Decreased CO, inhibit renin secretion, inhibit norepinephrine release
c. Negative chronotropic effect: decreased HR due to decreased automaticity in sinus node
d. Reduces ventricular hypertrophy, stroke, heart failure, coronary events, and mortality
e. Some have intrinsic sympathomimetic activity: weak β-adrenergic activation (partial agonist) → decrease HR and CO less effectively but prevent effect of catecholamine stimulation on heart during stress and exercise
f. Vasodilatory properties: antagonize α-adrenergic receptors and increase NO release
g. Usually not first line agent to treat HT
h. Types β-receptors:
i. β1: heart (selective, less effect on airways)
ii. β2: myocardium, vascular, bronchial cells
iii. β3: fat cells
i. Types β-blockers:
i. Non-selective: both β1 and β2
ii. Selective: only β1
j. Lipid-soluble β-blockers: metabolized by liver, shorter ½ lives
k. Hydrophilic β-blockers: metabolized by kidney, longer ½ lives
l. Side effects:
i. Bradycardia, heart block, dizziness
ii. Bronchospasm, cold extremities (β2 effect)
iii. CNS effects: fatigue, depression, mental slowness, vivid dreams, dry mouth
iv. Skin reactions: (Steven-Johnson’s syndrome)
v. Erectile dysfunction, hyperglycemia
vi. Lipid abnormalities (TAG elevation, HDL reduction)

Indicated: not for 1st line HT treatment, but combined with other drugs in patients with other comorbidities (MI, CAD, angina, HF, and in treating cardiac arrhythmias)

Question 24

Direct Vasodilators

Answer 24

a. Hydralazine
i. Directly relaxes smooth muscle
ii. Decreases peripheral resistance
iii. Used for hypertensive emergencies and pregnancy-associated HT
iv. Usually given with diuretic and β-blocker to prevent pseudotolerance (compensatory tachycardia and volume retention)
v. Metabolism is genetically determined by N-acetyltransferase
b. Minoxidil
i. Opens K+ channels in vascular smooth muscle
ii. Similar hemodynamics as hydralazine
iii. Most useful in patients with severe HT and renal failure
iv. Given with diuretic and β-blocker to prevent pseudotolerance
v. Side effects: pericardial effusion, facial hirsutism, ECG changes

Question 25

α-Adrenergic Receptor Blockers

Answer 25

a. Selective α1-antagonists
b. Blocks site for norepinephrine
c. Decreases arteriolar resistance
d. Beneficial in patients with prostate symptoms
e. Side effects: postural hypotension, dizziness, syncope, reflex tachycardia, nasal congestion

Question 26

Central Sympatholytics (α2 agonists)

Answer 26

a. Act on brainstem –> Reduce sympathetic outflow to heart and blood vessels → vasodilation
b. Clonidine: careful because rebound HT with sudden discontinuation
c. Methyldopa: treat pregnancy-induced HT
d. Side effects: sedation, dry mouth, erectile dysfunction
e. Methyldopa→ Coomb’s positive hemolytic anemia, elevated liver function tests

Question 27

Initial Therapy options for heart failure, post-MI, diabetes, Chronic kidney disease

Answer 27

Heart failure: Diuretics, BB, ACEI, ARB, AldoANT

Post-MI: BB, ACEI, AldoANT

Diabetes: ACEI, ARB, CCB, diuretic, BB

Chronic kidney disease: ACEI or ARB

Question 28

Explain the causes and describe the definition of resistant hypertension.

Answer 28

• BP ≥140/90 mmHg while on 3 different BP medication classes (including diuretic)
• OR on medications from 4 antihypertensive classes regardless of BP
• Need to: exclude pseudo-resistance, identify and reverse contributing factors, discontinue interfering substances, screen for secondary causes
• Patient characteristics: older age, obesity, left ventricular hypertrophy, females, African-American, diabetes
• Causes: volume retention, non-adherence, excess alcohol, licorice, inappropriate medication combinations, decongestants, chronic kidney disease, inadequate medication dosing, OTC supplements, improper BP measurements, illicit drugs, oral contraceptive hormones, mediation interactions

Question 29

Identify factors affecting patient adherence.

Answer 29

• Misunderstanding of condition or need for treatment
• Absence of symptoms
• Adverse effects of meds
• Cost and simplicity of medication regimen
• Cost of follow-up visits
• Perceived lack of involvement in plan of care