What is the recommended approach to manage hypertension, including lifestyle modifications, target blood pressure, and first‑line pharmacologic therapy?

Management of Hypertension

For most adults with hypertension, initiate lifestyle modifications at blood pressure >120/80 mmHg and start pharmacologic therapy with an ACE inhibitor or ARB (or thiazide-like diuretic or calcium channel blocker) when blood pressure reaches ≥140/90 mmHg, targeting <140/90 mmHg for general populations and <130/80 mmHg for patients with diabetes, chronic kidney disease, or high cardiovascular risk. 1, 2

Blood Pressure Targets

Target blood pressure should be <140/90 mmHg for most adults. 1, 2 However, more intensive targets apply to specific populations:

• Patients with diabetes, chronic kidney disease, established cardiovascular disease, or 10-year ASCVD risk ≥20% should target <130/80 mmHg. 1, 2, 3
• Younger adults (<65 years) may pursue <130/80 mmHg if achievable without excessive treatment burden. 1, 2
• Adults ≥65 years should target systolic <130 mmHg. 3
• Pregnant patients with chronic hypertension require a target of 110-129/65-79 mmHg, with ACE inhibitors and ARBs absolutely contraindicated. 1, 2

The 2020 International Society of Hypertension guidelines emphasize that optimal blood pressure control reduces cardiovascular events by approximately 20-30% for every 10 mmHg systolic reduction. 1, 3

Lifestyle Modifications (First-Line for All Patients)

Initiate lifestyle interventions for all patients with blood pressure >120/80 mmHg, regardless of whether pharmacologic therapy is started. 1, 2 These modifications enhance medication efficacy and may obviate the need for drugs in mild hypertension. 1, 4

Specific Interventions with Expected Blood Pressure Reductions:

• Weight reduction to BMI 18.5-25 kg/m²: reduces BP by 5-20 mmHg per 10 kg lost 1, 2, 4
• DASH-style dietary pattern (8-10 servings fruits/vegetables daily, 2-3 servings low-fat dairy): reduces BP by 8-14 mmHg 1, 2, 4
• Sodium restriction to <2,300 mg/day: reduces BP by 2-8 mmHg 1, 2, 4
• Increased dietary potassium through food sources 1, 2
• Alcohol moderation (≤2 drinks/day for men, ≤1 drink/day for women): reduces BP by 2-4 mmHg 1, 2, 4
• Regular aerobic physical activity (30-60 minutes, >5 days/week): reduces BP by 4-9 mmHg 1, 2, 4
• Smoking cessation with pharmacologic support (nicotine replacement, bupropion, or varenicline) 1, 2

The combination of two or more lifestyle modifications produces additive blood pressure-lowering effects. 4, 5

Pharmacologic Therapy Initiation

Stage 1 Hypertension (140-159/90-99 mmHg)

Begin single-drug therapy together with lifestyle modifications. 2

First-line agents include: 1, 2, 3

• ACE inhibitor (e.g., enalapril)
• Angiotensin receptor blocker (ARB; e.g., losartan, candesartan)
• Thiazide-like diuretic (chlorthalidone or indapamide preferred over hydrochlorothiazide)
• Dihydropyridine calcium channel blocker (e.g., amlodipine)

Stage 2 Hypertension (≥160/100 mmHg)

Start with two antihypertensive agents simultaneously, preferably as a single-pill combination. 1, 2, 3

Preferred combinations: 1, 2

• ACE inhibitor or ARB + thiazide-like diuretic, OR
• ACE inhibitor or ARB + calcium channel blocker

Special Populations Requiring ACE Inhibitor or ARB First-Line

Patients with the following conditions must receive an ACE inhibitor or ARB at maximum tolerated dose: 1, 2, 6

• Albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g creatinine) 1, 2
• Established coronary artery disease 1, 2
• Diabetic nephropathy with elevated serum creatinine and proteinuria (UACR ≥300 mg/g) 1, 6
• Left ventricular hypertrophy (note: this benefit does not apply to Black patients) 6

If one class is not tolerated, substitute with the other class. 1, 2

Titration Strategy and Combination Therapy

Most patients require multiple drugs to achieve blood pressure goals. 1, 2, 3

Recommended Sequential Algorithm:

1. Start with ACE inhibitor or ARB 1, 2
2. Add thiazide-like diuretic as second agent 1, 2
3. Add dihydropyridine calcium channel blocker as third agent 1, 2
4. For resistant hypertension, add mineralocorticoid receptor antagonist (e.g., spironolactone) as fourth agent 2, 7

Titrate each medication to the highest tolerated dose before introducing the next agent. 2 This approach maximizes efficacy while minimizing polypharmacy.

Contraindicated Combinations

Never combine: 1, 2

• ACE inhibitor + ARB (increases risk of hyperkalemia, syncope, and acute kidney injury)
• ACE inhibitor or ARB + direct renin inhibitor

Resistant Hypertension

Resistant hypertension is defined as blood pressure ≥140/90 mmHg despite lifestyle measures, a diuretic, and two additional antihypertensive drugs at adequate doses. 1, 2, 7

Before Diagnosing Resistant Hypertension, Exclude:

• Medication nonadherence 1, 7
• White-coat hypertension (confirm with ambulatory BP monitoring) 1, 7
• Inadequate dosing or inappropriate drug combinations 7
• Interfering substances (NSAIDs, decongestants, excessive alcohol, liquorice, herbal supplements) 1, 7
• Secondary causes of hypertension 7

For true resistant hypertension, add a mineralocorticoid receptor antagonist (spironolactone), which is effective even without documented aldosterone excess. 2, 7 If blood pressure remains uncontrolled on four agents, refer to a specialist with expertise in hypertension management. 2

Monitoring Requirements

Measure blood pressure at every routine visit using validated devices and proper technique. 1, 2 Confirm elevated readings on a separate day before initiating or intensifying therapy. 1, 2

For patients on ACE inhibitors, ARBs, or diuretics, monitor serum creatinine/eGFR and serum potassium at least annually. 1, 2

Re-evaluate blood pressure 2-4 weeks after initiating or adjusting therapy. 2

Consider ambulatory blood pressure monitoring when: 1

• Clinic blood pressure shows unusual variability
• Hypertension is resistant to three or more drugs
• Symptoms suggest hypotension
• White-coat hypertension is suspected

Common Pitfalls to Avoid

Clinical inertia—delaying initiation or titration of therapy when blood pressure remains above target—is the most common cause of inadequate control. 2, 3 Despite proven benefits, only 44% of US adults with hypertension achieve control to <140/90 mmHg. 3

Other critical errors include: 2

• Persisting with monotherapy when combination therapy is needed
• Adding new agents before maximizing the dose of current medications
• Relying solely on pharmacotherapy without reinforcing lifestyle measures
• Using inappropriate drug combinations (ACE inhibitor + ARB)
• Failing to screen for interfering substances and secondary causes in resistant hypertension 1, 7

Seasonal blood pressure variation (average decline of 5/3 mmHg in summer) should prompt consideration of dose adjustment, particularly if symptoms of overtreatment appear. 1