Hypertension

Definition and Classification

• Brenner and Rector's The Kidney, Table 46.1

Epidemiology and Risk

• Affects approximately 46% of adults in the United States (using the 130/80 mm Hg threshold).
• It is the leading modifiable risk factor for cardiovascular disease, stroke, and chronic kidney disease.
• Hypertension in PAD carries a 2.5-fold (men) and 3.9-fold (women) age-adjusted risk increase.
• Among adults over 50, systolic BP is a stronger predictor of CVD and renal disease than diastolic BP.
• "Isolated systolic hypertension" (SBP > 160 mm Hg with DBP < 90 mm Hg) is a potent stroke and CVD risk factor, especially in the elderly.
• Textbook of Family Medicine 9e; Goldman-Cecil Medicine

Pathophysiology

• Activation of the renin-angiotensin-aldosterone system (RAAS)
• Sympathetic nervous system overactivity
• Endothelial dysfunction and impaired nitric oxide production
• Sodium and volume retention (especially relevant in renal disease)
• Genetic factors - advances in blood pressure genomics continue to reveal polygenic contributions
• Secondary causes (5-10% of cases): primary aldosteronism, renovascular disease, obstructive sleep apnea, pheochromocytoma, Cushing syndrome, thyroid disorders, coarctation of the aorta

Lifestyle Modifications (Non-pharmacologic Treatment)

• National Kidney Foundation Primer on Kidney Diseases, 8e, Table 64.9

Pharmacologic Treatment

BP Targets

• Most adults: < 130/80 mm Hg (ACC/AHA 2017)
• CKD patients: < 130/80 mm Hg (treat with antihypertensive if BP > 130/80)
• Diabetes: < 130/80 mm Hg
• Elderly (≥ 65): < 130 mm Hg systolic; start at low doses; watch for orthostatic hypotension

• Goldman-Cecil Medicine

First-line Drug Classes

1. Thiazide/thiazide-like diuretics - Chlorthalidone is preferred over hydrochlorothiazide (more potent, longer acting, strongest RCT evidence - ALLHAT trial)
2. ACE inhibitors (ACEIs) - e.g., lisinopril, enalapril
3. Angiotensin receptor blockers (ARBs) - e.g., losartan, irbesartan
4. Calcium channel blockers (CCBs) - e.g., amlodipine

Beta-blockers are NOT recommended as initial therapy for uncomplicated hypertension - they are inferior in stroke prevention and less effective at reducing cardiovascular events than the above agents. They remain useful in specific indications (heart failure, post-MI, angina).

Avoid: Combining two RAAS inhibitors (e.g., ACEI + ARB) - offers minimal additional BP lowering and markedly increases risk of renal impairment and hyperkalemia.

• Textbook of Family Medicine 9e; Goldman-Cecil Medicine

Compelling Indications (Disease-Specific Drug Selection)

• Textbook of Family Medicine 9e, Table 27-10

Hypertensive Crisis

• Hypertensive urgency: Very high BP but no acute end-organ damage. Treat with oral antihypertensives; can be managed outpatient.
• Hypertensive emergency: Very high BP with active end-organ damage (hypertensive encephalopathy, acute LV failure, acute kidney failure, retinal hemorrhage, aortic dissection, eclampsia). Requires IV antihypertensives in an emergency/ICU setting with a controlled, gradual BP reduction.

• Nicardipine IV - most commonly used dihydropyridine CCB; no dose adjustment needed in elderly (avoid in severe aortic stenosis)
• Labetalol IV - effective but contraindicated in obstructive airway disease, bradycardia, or heart block
• Sodium nitroprusside - potent vasodilator; monitor carefully to avoid overshoot hypotension

• Harrison's Principles of Internal Medicine 22E (2025)

Special Populations

Elderly

• Isolated systolic hypertension predominates in patients ≥ 65 years.
• RCTs confirm treatment benefit even after age 80 and in frail elderly.
• Higher risk of orthostatic and postprandial hypotension - start with low doses.
• Home BP or ambulatory BP monitoring (ABPM) is especially important to avoid overtreatment.

Pregnancy (Preeclampsia)

• Defined as BP ≥ 140/90 mm Hg after 20 weeks + proteinuria (≥ 300 mg/24h or P:Cr ≥ 0.3) OR end-organ features (thrombocytopenia, renal insufficiency, elevated transaminases, pulmonary edema, cerebral/visual symptoms).
• Safe antihypertensives: labetalol, nifedipine (oral), methyldopa.
• ACEIs and ARBs are contraindicated in pregnancy.

CKD / Diabetic Nephropathy

• ACEIs and ARBs are preferred - reduce proteinuria and slow progression (Lewis 1993; Brenner RENAAL trial).
• Target BP: < 130/80 mm Hg.
• Chlorthalidone preferred over HCTZ for diuretic if needed; loop diuretics if Stage 4-5 CKD.

Resistant Hypertension

• Defined as BP above goal on 3 or more antihypertensives (including a diuretic) at maximum tolerated doses.
• Evaluate for secondary causes, medication non-adherence, and interfering drugs (NSAIDs, decongestants, OCPs, stimulants).
• CPAP therapy for obstructive sleep apnea can meaningfully lower BP in resistant hypertension (HIPARCO trial).

Ten Tips for Achieving Goal BP (Summary)

1. If BP is ≥ 20/10 mm Hg above goal, start with combination therapy (ACEI/ARB + CCB is first choice based on ACCOMPLISH).
2. Allow 2-4 weeks before titrating up - but avoid "therapeutic inertia."
3. ~75% of patients will need 2+ drugs.
4. Always initiate lifestyle measures: DASH diet, sodium < 1.5-2.3 g/day, limit alcohol, aerobic exercise, weight loss.
5. Ensure accurate BP measurement technique (avoid white coat effect, pseudo-resistance).
6. Minimize BP-raising medications: NSAIDs, OTC decongestants, OCPs.
7. Include an appropriate diuretic in multi-drug regimens - chlorthalidone is preferred.
8. Use home BP or ABPM when white coat or masked hypertension is suspected.
9. Target organ damage (LVH, microalbuminuria, retinal changes) guides treatment intensity.
10. Treat other cardiovascular risk factors (lipids, glucose, smoking) simultaneously.

• Textbook of Family Medicine 9e