What are the current guideline recommendations for managing hypertension in adult patients, including target blood pressure (<130/80 mm Hg, or <140/90 mm Hg if >65 years old and frail), lifestyle modifications (DASH diet, sodium <1500 mg/day, ≥150 minutes moderate‑intensity aerobic activity/week, BMI < 25 kg/m², alcohol limits, smoking cessation), timing of pharmacologic therapy, first‑line agents (thiazide‑type diuretics, ACE inhibitors (angiotensin‑converting enzyme inhibitors), ARBs (angiotensin‑II receptor blockers), calcium‑channel blockers), special considerations for Black patients, chronic kidney disease, diabetes, heart failure, combination therapy, and treatment of resistant hypertension?

Hypertension Management Guidelines

Blood Pressure Targets

For most adults with hypertension, target an office blood pressure <130/80 mm Hg, with encouragement to further reduce systolic blood pressure to <120 mm Hg if well tolerated. 1

Age-Stratified Targets

• Adults <60 years: Target <140/90 mm Hg (minimum), ideally <130/80 mm Hg 2, 1
• Adults 60-79 years: Target <140/90 mm Hg, with optimal goal <130/80 mm Hg if tolerated 3, 4
• Adults ≥80 years (functionally independent): Target systolic 120-129 mm Hg if tolerated; minimum acceptable <140/90 mm Hg 5
• Adults ≥80 years (frail): Target 140-150 mm Hg systolic, individualized based on tolerability 5, 4
• Adults ≥85 years: Maintain the ≥140/90 mm Hg treatment threshold; continue lifelong therapy if tolerated 5

Special Populations

• Diabetes mellitus: Target <140/90 mm Hg (not the stricter <130/80 mm Hg in elderly) 5, 2
• Chronic kidney disease: Target <140/90 mm Hg, same as general population 2
• High cardiovascular risk: Target <130/80 mm Hg 6

Treatment Initiation Thresholds

Start pharmacologic therapy when blood pressure is ≥140/90 mm Hg in adults <60 years, or ≥150/90 mm Hg in adults ≥60 years without diabetes or CKD. 2

• Stage 2 hypertension (≥160/100 mm Hg): Initiate dual therapy immediately with two agents from different classes or a single-pill combination 6, 7
• Adults ≥80 years: Initiate therapy at ≥140/90 mm Hg regardless of calculated cardiovascular risk 5
• Frail elderly ≥85 years: Start with monotherapy (preferably a dihydropyridine calcium channel blocker) rather than combination therapy 5

First-Line Pharmacologic Agents

For non-Black patients, initiate treatment with an ACE inhibitor, ARB, calcium channel blocker, or thiazide-type diuretic. 2

Preferred Initial Regimens

• Non-Black patients: ACE inhibitor or ARB + calcium channel blocker OR ACE inhibitor or ARB + thiazide-like diuretic 6, 2
• Black patients: Calcium channel blocker + thiazide-type diuretic (more effective than CCB + ACE inhibitor/ARB) 6, 2
• Elderly ≥80 years: Start with dihydropyridine calcium channel blocker (amlodipine 2.5-5 mg daily) as monotherapy 5
• Stage 2 hypertension in elderly: Thiazide diuretic (chlorthalidone preferred) as first-line due to superior efficacy in preventing heart failure 7

Specific Agent Selection

Thiazide-type diuretics:

• Chlorthalidone 12.5-25 mg daily (preferred over hydrochlorothiazide for superior 24-hour BP control and cardiovascular outcomes) 6, 8
• Hydrochlorothiazide 25-50 mg daily (acceptable alternative) 6
• Indapamide 1.25-2.5 mg daily 6

Calcium channel blockers:

• Amlodipine 5-10 mg daily (start 2.5 mg in elderly) 6, 5
• Avoid non-dihydropyridines (diltiazem, verapamil) in heart failure or left ventricular dysfunction 6

ACE inhibitors:

• Lisinopril 10-40 mg daily 6
• Benazepril 20-40 mg daily 6

ARBs:

• Losartan 50-100 mg daily (maximum effective dose for hypertension is 100 mg; 150 mg evaluated only in heart failure) 6, 5
• Valsartan 160-320 mg daily 6
• Olmesartan 20-40 mg daily 6
• Candesartan (dose per titration) 6

Special Considerations for Black Patients

Initiate therapy with a calcium channel blocker or thiazide-type diuretic rather than an ACE inhibitor or ARB. 6, 2

• The combination of CCB + thiazide diuretic is more effective than CCB + ACE inhibitor/ARB in Black patients 6
• If additional agents are needed, add an ACE inhibitor or ARB as third-line therapy 6

Chronic Kidney Disease

Initiate or add an ACE inhibitor or ARB to improve kidney outcomes, regardless of race. 2

• Target blood pressure <140/90 mm Hg (same as general population) 2
• Monitor serum potassium and creatinine 2-4 weeks after initiating or uptitrating ACE inhibitor/ARB 6
• SGLT2 inhibitors are recommended for diabetic patients with CKD (eGFR >20 mL/min/1.73 m²) as they modestly lower BP and improve cardiovascular outcomes 5

Diabetes Mellitus

Target blood pressure <140/90 mm Hg; first-line agents are the same as for the general hypertensive population. 2

• ACE inhibitors or ARBs provide superior protection against diabetic nephropathy progression 5
• In elderly diabetic patients ≥85 years, target <140/90 mm Hg rather than <130/80 mm Hg 5
• Thiazide diuretics increase new-onset diabetes risk by 15-40% compared to CCBs or ACE inhibitors 5

Heart Failure

Use ACE inhibitors or ARBs as preferred agents; avoid non-dihydropyridine calcium channel blockers. 6

• Beta-blockers are indicated for heart failure with reduced ejection fraction 6
• Dihydropyridine CCBs (amlodipine) are safe in heart failure 6
• Avoid diltiazem and verapamil due to negative inotropic effects 6

Combination Therapy Algorithm

Step 1: Dual Therapy

If blood pressure remains ≥140/90 mm Hg on monotherapy, add a second agent from a different class. 6

• Preferred combinations: ACE inhibitor/ARB + CCB, ACE inhibitor/ARB + thiazide diuretic, or CCB + thiazide diuretic 6
• Use fixed-dose single-pill combinations to improve adherence 6, 5

Step 2: Triple Therapy

If blood pressure remains ≥140/90 mm Hg on dual therapy, add a third agent to create ACE inhibitor/ARB + CCB + thiazide diuretic. 6, 8

• This triple regimen targets three complementary mechanisms: renin-angiotensin blockade, vasodilation, and volume reduction 6
• Optimize doses of existing agents before adding a fourth drug 6
• Replace hydrochlorothiazide with chlorthalidone if BP remains uncontrolled 6, 8

Step 3: Resistant Hypertension (Fourth-Line)

If blood pressure remains ≥140/90 mm Hg despite optimized triple therapy, add spironolactone 25-50 mg daily as the preferred fourth-line agent. 6, 8

• Spironolactone provides additional reductions of 20-25/10-12 mm Hg systolic/diastolic 6, 8
• Monitor serum potassium and creatinine 2-4 weeks after initiation due to hyperkalemia risk, especially when combined with ACE inhibitor/ARB 6, 8
• Alternative fourth-line agents if spironolactone contraindicated: eplerenone, amiloride, doxazosin, or beta-blocker (if compelling indication) 6

Resistant Hypertension Management

Resistant hypertension is defined as BP ≥140/90 mm Hg (or ≥130/80 mm Hg in high-risk patients) despite adherence to three or more antihypertensive agents at optimal doses, including a diuretic. 6, 5

Systematic Approach

1. Verify true resistance:

   • Confirm with home BP monitoring (≥135/85 mm Hg) or 24-hour ambulatory monitoring (≥130/80 mm Hg) to exclude white-coat hypertension 6
   • Assess medication adherence (most common cause of apparent resistance) via direct questioning, pill counts, or pharmacy refill records 6, 8

2. Identify interfering substances:

   • NSAIDs, decongestants, oral contraceptives, systemic corticosteroids, stimulants, herbal supplements (ephedra, licorice, St. John's wort) 6

3. Screen for secondary hypertension:

   • Primary aldosteronism, renal artery stenosis, obstructive sleep apnea, pheochromocytoma 6, 8

4. Optimize diuretic therapy:

   • Replace hydrochlorothiazide with chlorthalidone 12.5-25 mg daily for superior 24-hour BP control 6, 8
   • Increase chlorthalidone dose to 50 mg if needed (though doses >25 mg significantly increase hypokalemia risk in elderly) 5

5. Add spironolactone 25-50 mg daily as preferred fourth-line agent 6, 8

Lifestyle Modifications

Comprehensive lifestyle interventions can lower systolic/diastolic BP by 10-20 mm Hg and should be implemented alongside pharmacotherapy. 6

Dietary Sodium Restriction

• Limit sodium intake to <2 g/day (approximately 5 g salt), yielding a 5-10 mm Hg systolic reduction. 6, 8
• Greater benefit observed in elderly patients 6

DASH Diet

• Adopt the Dietary Approaches to Stop Hypertension (DASH) pattern (high in fruits, vegetables, whole grains, low-fat dairy; low in saturated fat), reducing BP by approximately 11.4/5.5 mm Hg. 6

Weight Management

• Target BMI 20-25 kg/m²; losing approximately 10 kg reduces BP by 6.0/4.6 mm Hg (systolic/diastolic). 6

Physical Activity

• Engage in ≥150 minutes/week of moderate-intensity aerobic exercise (≥30 minutes most days), lowering BP by approximately 4/3 mm Hg. 6

Alcohol Limitation

• Limit alcohol to ≤2 drinks/day for men and ≤1 drink/day for women (≤100 g/week total). 6
• Excessive intake significantly interferes with BP control 6

Smoking Cessation

• Mandatory for all patients, as smoking independently drives cardiovascular disease and mortality. 5

Monitoring and Follow-Up

Re-measure blood pressure 2-4 weeks after initiating or adjusting therapy, with the goal of achieving target BP within 3 months. 6, 5

• Check serum potassium and creatinine 2-4 weeks after starting thiazide diuretics, ACE inhibitors, ARBs, or spironolactone 6
• In elderly patients, measure BP after 5 minutes seated/lying, then at 1 and/or 3 minutes after standing to detect orthostatic hypotension 5
• Once BP control is achieved, schedule at least annual reviews 5

Critical Pitfalls to Avoid

Do not combine an ACE inhibitor with an ARB (dual RAS blockade), as this increases hyperkalemia and acute kidney injury risk without additional cardiovascular benefit. 6, 2

Do not add a beta-blocker as second or third agent unless compelling indications exist (angina, post-MI, heart failure with reduced ejection fraction, atrial fibrillation requiring rate control), as beta-blockers are less effective than CCBs or diuretics for stroke prevention. 6, 7

Do not delay treatment intensification in stage 2 hypertension (≥160/100 mm Hg); prompt action within 2-4 weeks is required to reduce cardiovascular risk. 6

Do not withhold antihypertensive treatment solely based on age; continue therapy beyond 85 years if tolerated. 5

Do not rely on monotherapy dose escalation as the primary strategy; combination therapy with agents from different classes is more effective. 6

Do not use thiazide diuretics in elderly patients ≥75 years with urinary incontinence, as they exacerbate nocturia, poor sleep, and urinary frequency. 6

Do not use chlorthalidone doses >12.5 mg in elderly patients without careful monitoring, as doses ≥25 mg significantly increase hypokalemia risk (3-fold higher), which eliminates cardiovascular protection and increases sudden death risk. 5

Do not assume treatment failure without first confirming medication adherence and excluding secondary causes or interfering substances. 6

Do not use alpha-blockers or central alpha-agonists as initial therapy in older adults due to higher likelihood of adverse effects, including falls. 7

Do not add a fourth medication class before maximizing doses of existing triple therapy. 6

Do not abruptly discontinue antihypertensive medications without physician guidance, as this can cause rapid rebound hypertension. 5