Hypertension:

Definition:
- Persistently elevated arterial blood pressure

Isolated Systolic Hypertension:

- DBP < 80 mm Hg
- SBP ≥ 130 mm Hg

Hypertensive Crisis:
- BP > 180/120 mm Hg
- Categorized as:
Hypertensive Emergency:
- Extreme BP elevation with acute or progressing end-organ damage

Hypertensive Urgency:
- Extreme BP elevation without acute or progressing end-organ injury

Pathophysiology of Hypertension:
Etiology:
- Primary or essential hypertension: Unknown cause.
- Secondary hypertension: Results from a specific cause.

Causes of Secondary Hypertension:

- Chronic kidney disease (CKD).
- Renovascular disease.

Medications Associated with Increased BP:

- Corticosteroids.
- Estrogens.
- NSAIDs.
- Cyclosporine.
- Erythropoietin.
- Venlafaxine.

Complications:
- Cerebrovascular events.
- Cardiovascular (CV) events.
- Renal failure.
Clinical Presentation of Hypertension:
Primary Hypertension:
- Initially asymptomatic.

Secondary Hypertension:
- May present with symptoms of the underlying disorder

Diagnosis of Hypertension:
Blood Pressure (BP) Measurement:
- Elevated BP may be the only sign of primary hypertension on physical examination.
- Diagnosis based on the average of two or more readings taken at each of two or more clinical encounters.

End-Organ Damage:
- Signs occur primarily in:
- Eyes
- Brain
- Heart
- Kidneys
- Peripheral vasculature

Treatment of Hypertension:
Goals of Treatment:
- Reduce morbidity and mortality from CV events.
- 2017 ACC/AHA guideline recommends a goal BP of <130/80 mm Hg for most patients.

Special Considerations:
- For institutionalized older patients and those with a high disease burden or limited life expectancy:
- Consider a relaxed SBP goal of <150 mm Hg (or <140 mm Hg if tolerated).
Nonpharmacologic Therapy:
Lifestyle Modifications:
- Implement in all patients with elevated BP or stage 1 or 2 hypertension.

Strategies Include:
A. Weight Loss:
- Recommended for overweight or obese individuals.

B. Dietary Approaches to Stop Hypertension (DASH) Eating Plan:

- Emphasizes fruits, vegetables, whole grains, and lean proteins.

C. Reduced Salt Intake:

- Aim for ideally 1.5 g/day sodium (3.8 g/day sodium chloride).

D. Physical Activity:
- Engage in 90–150 min/week of aerobic or dynamic resistance training.

E. Moderation of Alcohol Intake:

- Limit alcohol consumption to reduce blood pressure.

F. Smoking Cessation:
- While it doesn't directly control BP, it reduces cardiovascular disease risk.

Pharmacologic Therapy General Approach:

Initial Drug Selection:
- Depends on the degree of BP elevation and presence of compelling indications.

Stage 1 Hypertension:
- Use a single first-line drug as initial therapy.

Stage 2 Hypertension:
- Start combination drug therapy (preferably with two first-line drugs) as initial regimen.

First-Line Options:
- ACE inhibitors
- ARBs
- CCBs
- Thiazide diuretics

β-Blockers:
- Reserved for compelling indications or in combination with first-line agents for patients without.

Other Antihypertensive Drug Classes:

- α1-Blockers
- Direct renin inhibitors
- Central α2-agonists
- Direct arterial vasodilators
Notes:
Stable Ischemic Heart Disease (SIHD):
- First-line therapy: β-Blockers (without ISA).

Acute Coronary Syndromes:

- First-line therapy: β-blocker and ACE inhibitor (or ARB).

Hypertension Management in Diabetes:

- Any first-line agent can be used in absence of albuminuria.

ACE Inhibitors and ARBs in Chronic Kidney Disease:

- Reduce intraglomerular pressure, slowing disease progression.

Hypertension Management in Patients with History of Stroke:

- Start drug therapy when BP >140/90 mm Hg (goal <130/80 mm Hg).
Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors):
Mechanism of Action:
- Block conversion of angiotensin I to angiotensin II.
- Inhibit aldosterone secretion.

Dosage and Administration:

- Start with low doses and titrate slowly due to risk of acute hypotension.

Adverse Effects:
- Hyperkalemia risk, particularly in CKD patients or those on potassium supplements.
- AKI risk, especially in patients with preexisting kidney disease or renal artery stenosis.
- Modest serum creatinine elevations usually do not require treatment changes.
- Angioedema (<1% incidence) may necessitate drug withdrawal and supportive measures.
- Persistent dry cough (up to 20% incidence) due to bradykinin inhibition.
- Contraindicated in pregnancy, along with ARBs and direct renin inhibitors.

Recommendations:
- Consider ARBs in patients with a history of ACE inhibitor-induced angioedema.

Angiotensin II Receptor Blockers (ARBs):

Mechanism of Action:
- Directly block the angiotensin II type 1 receptor.
- Mediate the effects of angiotensin II.

Comparison with ACE Inhibitors:

- Unlike ACE inhibitors, ARBs do not block bradykinin breakdown.
- Lack of cough as a side effect.

Side Effects:
- Low incidence of side effects.
- May cause renal insufficiency, hyperkalemia, and orthostatic hypotension.
Calcium Channel Blockers
Dihydropyridine (DHP) and Nondihydropyridine (Non-DHP) CCBs:
- First-line antihypertensive therapies
- Used in ischemic heart disease

Dihydropyridine CCBs:
- May cause reflex sympathetic activation
- Negative inotropic effects (except amlodipine and felodipine)
- Side effects: dizziness, flushing, headache, gingival hyperplasia, peripheral edema

Verapamil:
- Negative inotropic effect
- May precipitate HF in patients with borderline cardiac reserve
- Side effects: constipation7% of patients.

Diltiazem:
- Decreases heart rate to a lesser extent than verapamil
- Side effects: peripheral edema, hypotension

Diuretics
Thiazides:
- Preferred type of diuretic for most patients with hypertension
- Chlorthalidone (thiazide-like) preferred over hydrochlorothiazide, especially in resistant hypertension
- More potent on a milligram-per-milligram basis

Loop diuretics (Furosemide, Bumetanide, Torasemide):

- More potent for inducing diuresis
- Not ideal antihypertensives unless edema treatment is also needed
- Preferred over thiazides in severe CKD when eGFR is <30 mL/min/1.73 m2
- Pronounced hypokalemia and risk of hypocalcemia

Potassium-sparing diuretics:
- Weak antihypertensives when used alone
- Used in combination with another diuretic to counteract potassium-wasting properties
- Mineralocorticoid receptor antagonists (spironolactone and eplerenone) used in resistant hypertension and HFrEF

Acute effects:
- Lower BP by causing diuresis

Side effects:
- Thiazides: Hypokalemia, hypomagnesemia, hypercalcemia, hyperuricemia, hyperglycemia, dyslipidemia, sexual dysfunction
- Loop diuretics: Pronounced hypokalemia, hypocalcemia
- Potassium-sparing diuretics: Hyperkalemia, especially in CKD or diabetes patients, gynecomastia with spironolactone
`
β-Blockers
1. Initial Use:
- β-blockers may not reduce CV events as effectively as other drugs like ACE inhibitors, ARBs, CCBs, or thiazides when used initially.

2. Compelling Indications:
- Appropriate first-line agents for specific compelling indications or when other drugs cannot be used.

3. β1-Cardioselective Agents:
- Atenolol, betaxolol, bisoprolol, metoprolol, and nebivolol are β1-cardioselective at low doses.
- Less likely to provoke bronchospasm and vasoconstriction, safer in patients with asthma or diabetes.

4. Agents with Intrinsic Sympathomimetic Activity (ISA):

- Acebutolol, carteolol, and pindolol possess ISA or partial β-receptor agonist activity.
- May have advantages in select patients with HF or sinus bradycardia but are rarely needed.

5. Pharmacokinetics:
- Atenolol and nadolol have relatively long half-lives and are excreted renally.
- Dosage may need adjustment in patients with renal insufficiency.

6. Dosage Administration:
- Once-daily administration may still be effective for β-blockers with shorter half-lives.

7. Cardiac Side Effects:

- Bradycardia, AV conduction abnormalities, and acute HF may occur.
- Blocking β2-receptors in arteriolar smooth muscle may cause cold extremities and worsen intermittent claudication or Raynaud phenomenon.

8. Lipid and Glucose Effects:

- Increases in serum lipids and glucose are transient and of little clinical significance.

9. Discontinuation:
- Abrupt cessation should be avoided; dose should be tapered gradually over 1–2 weeks before discontinuation.

α1-Receptor Blockers
Medications:
- Prazosin
- Terazosin
- Doxazosin

Mechanism of Action:
- Selective α1-receptor blockers
- Inhibit catecholamine uptake in smooth muscle cells of peripheral vasculature
- Result in vasodilation and lowering of blood pressure (BP)

Clinical Considerations:
- Symptomatic benefit in men with benign prostatic hyperplasia (BPH)
- Should be used to lower BP only in combination with first-line antihypertensive agents
Direct Renin Inhibitor (Aliskiren)
Mechanism of Action:
- Blocks the Renin-Angiotensin-Aldosterone System (RAAS) at its point of activation
- Reduces plasma renin activity and blood pressure (BP)

Approved Uses:
- Monotherapy
- Combination therapy

Role in Hypertension Management:

- Limited role in the management of hypertension

Central α2-Agonists
Mechanism of Action:
- Lower BP by stimulating α2-adrenergic receptors in the brain
- Reduces sympathetic outflow from the vasomotor center

Medications:
1. Clonidine
2. Guanfacine
3. Methyldopa

Clinical Use:
- Clonidine:
- Often used in resistant hypertension
- Methyldopa:
- Frequently used for pregnancy-induced hypertension

Direct Arterial Vasodilators

Hydralazine:
- Mechanism: Directly relaxes arteriolar smooth muscle
- Result: Vasodilation
- Effect: Lowers blood pressure

Minoxidil:
- Mechanism: Directly relaxes arteriolar smooth muscle
- Result: Vasodilation
- Effect: Lowers blood pressure
Older Persons
Blood Pressure Characteristics:
- Presentation:
- Isolated systolic hypertension or elevated SBP and DBP
- Correlation with CV Morbidity:
- More correlated with SBP than DBP in patients aged 50+

Antihypertensive Treatment:
- First-line Antihypertensives:
- Provide significant benefits
- Safe in older patients
- Use smaller-than-usual initial doses for therapy initiation

Children and Adolescents: Hypertension

Secondary Hypertension Workup:
- Required if elevated BP identified
- More common in children/adolescents than adults

Nonpharmacologic Treatment:
- Cornerstone of therapy for primary hypertension

Pharmacologic Treatment Options:

- ACE inhibitors
- ARBs
- β-blockers
- CCBs
- Thiazide diuretics
Pregnancy Complications: Preeclampsia and Eclampsia

Preeclampsia:
- Life-threatening complications for mother and fetus
- Definitive treatment: Delivery
- Induction of labor if eclampsia is imminent or present
- Management: Restrict activity, bed rest, close monitoring
- Avoid salt restriction or measures that contract blood volume

Treatment:
- Antihypertensives used if DBP >105 mm Hg
- Target DBP: 95–105 mm Hg
- IV hydralazine or labetalol commonly used
- Chronic Hypertension:
- First-line: Labetalol, long-acting nifedipine, or methyldopa
- Alternatives: β-blockers (except atenolol) and CCBs

Black Patients
First-line Medications:
- CCBs (Calcium Channel Blockers)
- Thiazides

Indications:
- Most effective in African Americans
- Use first-line in the absence of compelling indications
Pulmonary Disease and Peripheral Arterial Disease (PAD)
β-Blockers and Pulmonary Disease
Common Concern
- Nonselective β-blockers generally avoided in hypertensive patients with asthma and COPD.
- Fear of inducing bronchospasm.
Solution
- Cardioselective β-blockers can be used safely.

β-Blockers and PAD

Theoretical Concern
- Possible decreased peripheral blood flow due to unopposed stimulation of α1-receptors causing vasoconstriction.
Evidence
- β-Blockers do not worsen claudication symptoms.
- β-Blockers do not cause functional impairment.

Treatment Principles
- Antihypertensive treatment for patients with PAD should follow the same general principles as for patients without PAD.

Hypertensive Urgencies and Emergencies

Urgencies
- Acute administration of a short-acting oral drug:
- Options: captopril, clonidine, or labetalol

Emergencies
- Immediate BP reduction with parenteral agent required
- Aim: Limit new or progressing end-organ damage

Evaluation of Therapeutic Outcomes

BP Response Evaluation
- Assess clinic BP 4 weeks after therapy initiation or changes
- Compare clinic readings with home BP measurements

Ongoing Monitoring
- Once goal BP achieved:
- Monitor BP every 3–6 months
- Assume no acute end-organ damage symptoms

Patient Adherence Assessment

- Regularly evaluate patient adherence to the regimen