Hypertension

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I now have comprehensive content from multiple authoritative textbooks. Here is the full overview of hypertension:

Hypertension

Definition and Epidemiology

Hypertension (HTN) is persistently elevated arterial blood pressure and is the leading risk factor for premature morbidity and mortality worldwide. It affects approximately one-third of the adult population. Despite available treatments, only about 50% of patients in the United States achieve target BP levels. The prevalence increases with age, and non-Hispanic Blacks have a higher incidence than white or Hispanic populations. - Textbook of Family Medicine 9e, p. 3206-3208

Classification

ACC/AHA 2017 (Current US Standard - Lippincott Pharmacology)

Category	Systolic (mm Hg)		Diastolic (mm Hg)
Normal	<120	and	<80
Elevated	120-129	or	<80
Stage 1 HTN	130-139	or	80-89
Stage 2 HTN	≥140	or	≥90

JNC 7 Classification (widely used internationally)

Classification	Systolic (mm Hg)		Diastolic (mm Hg)
Normal	<120	and	<80
Prehypertension	120-139	or	80-89
Stage 1 HTN	140-159	or	90-99
Stage 2 HTN	≥160	or	≥100

The ACC/AHA 2017 guideline is controversial; some international societies have declined to adopt it. It increases the overall prevalence of HTN in US adults to 46%. - Comprehensive Clinical Nephrology 7e, p. 489

Key variants:

White coat HTN: BP elevated in clinic but normal at home. Most authorities recommend lifestyle modification without drug therapy initially.
Masked HTN: Normal clinic BP but elevated on ambulatory monitoring. Prevalence ~10-15%; prognosis similar to sustained HTN.
Isolated systolic HTN: SBP >160 mm Hg with DBP <90 mm Hg - a potent stroke and CVD risk factor, especially in those over 50.

Etiology

Essential (primary) HTN: >90% of cases - no identifiable cause. Strong genetic component; family history is a major risk factor.
Secondary HTN: ~5-10% of cases. Causes include:
- Renal parenchymal disease (most common secondary cause)
- Renovascular disease
- Primary aldosteronism
- Obstructive sleep apnea
- Pheochromocytoma
- Cushing's syndrome
- Coarctation of the aorta
- Thyroid/parathyroid disease

Environmental contributors: high dietary sodium, obesity, stress, sedentary lifestyle, smoking, excessive alcohol intake. - Lippincott Illustrated Reviews: Pharmacology, p. 289

Pathophysiology

Arterial blood pressure = Cardiac Output × Peripheral Vascular Resistance. Both are controlled by:

Sympathetic nervous system and baroreflexes
Renin-angiotensin-aldosterone system (RAAS)

Most antihypertensive drugs reduce BP by decreasing cardiac output and/or peripheral resistance.

Major factors influencing arterial blood pressure

Figure: Major factors influencing blood pressure - Lippincott Illustrated Reviews: Pharmacology

Target Organ Damage

Untreated or poorly controlled HTN damages:

Heart: LVH, heart failure, coronary artery disease, MI
Brain: Stroke, transient ischemic attack, hypertensive encephalopathy
Kidneys: Hypertensive nephrosclerosis, CKD
Eyes: Hypertensive retinopathy
Vasculature: Peripheral arterial disease, aortic aneurysm/dissection

HTN carries a 2.5-fold risk (men) and 3.9-fold risk (women) for peripheral arterial disease. - Textbook of Family Medicine 9e, p. 974

Treatment Goals

Setting	Target BP
General office BP	<140/90 mm Hg (most guidelines)
Age ≥60 (JNC 8)	<150/90 mm Hg
High CV risk / ACC-AHA	<130/80 mm Hg
Home monitoring	<135/85 mm Hg
24-hour ambulatory	<130/80 mm Hg

There is ongoing debate about BP goals; the SPRINT trial demonstrated benefits of more aggressive SBP targets (<120 mm Hg), but this requires standardized measurement technique. - Textbook of Family Medicine 9e, p. 3214-3222

Lifestyle Modifications (First-line for all patients)

DASH diet (Dietary Approaches to Stop Hypertension) - rich in fruits, vegetables, low-fat dairy
Sodium restriction: <1.5-2.3 g/day
Alcohol limitation: <2 drinks/day
Regular aerobic exercise
Weight loss (if overweight/obese)
Smoking cessation
Stress reduction

These measures are initiated for all patients and continued alongside pharmacotherapy when drugs are started. - Textbook of Family Medicine 9e, p. 3432

Antihypertensive Drug Classes

First-line agents (for uncomplicated HTN)

Thiazide/thiazide-like diuretics (hydrochlorothiazide, chlorthalidone)
ACE inhibitors (lisinopril, enalapril, ramipril)
Angiotensin receptor blockers / ARBs (losartan, valsartan)
Calcium channel blockers / CCBs (amlodipine, nifedipine)

When to start combination therapy

If BP is >20/10 mm Hg above target, start two drugs from the outset. About 75% of patients ultimately require two or more medications. The strongest evidence favors:

ACE inhibitor + CCB (e.g., benazepril + amlodipine) - based on the ACCOMPLISH trial, which showed a 20% reduction in CV events vs. ACE inhibitor + thiazide.
ACE inhibitor + thiazide diuretic is an acceptable alternative.

Combinations to AVOID

ACE inhibitor + ARB
ARB + direct renin inhibitor (aliskiren)
Two or more RAAS-blocking agents together (almost always contraindicated)
β-blocker or α-blocker as monotherapy (inferior evidence vs. other first-line agents)

Compelling Indications by Comorbidity

Drug classes indicated for hypertension by concomitant disease

Figure: Preferred antihypertensive drug classes by concomitant disease - Lippincott Illustrated Reviews: Pharmacology

Comorbidity	Preferred Agents
Heart failure with reduced EF	ACE inhibitor/ARB + β-blocker + diuretic ± aldosterone antagonist
Previous MI	β-blockers, ACE inhibitors/ARBs, aldosterone antagonists
Stable ischemic heart disease	β-blockers, ACE inhibitors/ARBs, CCBs
CKD or proteinuria	ACE inhibitor or ARB (reduces proteinuria)
Diabetes	Diuretics, ACE inhibitors, ARBs, CCBs
Recurrent stroke prevention	Diuretics, ACE inhibitors, ARBs

Lippincott Illustrated Reviews: Pharmacology, p. 295; Textbook of Family Medicine 9e, p. 3422

Resistant Hypertension

Defined as BP above goal despite three drugs including a diuretic. Affects ~10% of the hypertensive population. Approaches include:

Empirical addition of spironolactone (aldosterone blockade, 2.5-50 mg/day) - very effective
Check for secondary causes (primary aldosteronism is underdiagnosed)
Ensure medication adherence
Optimize lifestyle interventions
Rule out white coat effect, pseudohypertension, or inadequate dosing
Textbook of Family Medicine 9e, p. 3237

Hypertensive Urgency vs. Emergency

Urgency: Severely elevated BP (usually ≥180/120) without acute target organ damage. Gradual reduction over 24-48 hours with oral agents.
Emergency: Severely elevated BP with acute target organ damage (hypertensive encephalopathy, aortic dissection, acute MI, acute pulmonary edema, eclampsia). Requires IV agents and ICU monitoring - goal is controlled reduction by ~25% in first hour.

Special Populations

Pregnancy: Methyldopa, labetalol, nifedipine are safe. ACE inhibitors and ARBs are contraindicated (teratogenic). Gestational HTN and preeclampsia require obstetric co-management.
CKD: Target SBP <120 mm Hg recommended by KDIGO (based on weak evidence); ACE inhibitor or ARB preferred.
Elderly (>80 years): Careful monitoring warranted; excessive DBP lowering (<65 mm Hg) and orthostatic hypotension are concerns.
Black patients: Tend to respond better to thiazides and CCBs; less responsive to ACE inhibitors/ARBs as monotherapy.

Follow-up Schedule (JNC 7)

Initial BP	Follow-up
<130/85	Recheck in 1 year
130-139/85-89	Recheck in 1 year + lifestyle counseling
140-159/90-99	Confirm within 2 months
160-179/100-109	Evaluate within 1 month
≥180/≥110	Evaluate immediately or within 1 week

Comprehensive Clinical Nephrology 7e, p. 490

Sources:

Textbook of Family Medicine 9e (Pfenninger & Fowler; Family Medicine chapters on HTN)
Lippincott Illustrated Reviews: Pharmacology (Chapter 8: Antihypertensive Drugs)
Comprehensive Clinical Nephrology, 7th Edition (Chapter 34: Hypertension)
Brenner and Rector's The Kidney, 2-Volume Set (Hypertension chapters)

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