What are the recommended treatment guidelines for a general adult population with primary hypertension, considering lifestyle modifications and pharmacological interventions?

Hypertension Management Guidelines

Blood Pressure Targets

For most adults under 65 years, target blood pressure should be <130/80 mmHg, while adults 65 and older should achieve systolic blood pressure <130 mmHg if well tolerated. 1 The most recent 2024 European Society of Cardiology guidelines recommend an even more aggressive target of 120-129 mmHg systolic for most adults with hypertension, provided treatment is well tolerated. 1, 2

• If the 120-129 mmHg target cannot be achieved due to poor tolerance, apply the "as low as reasonably achievable" (ALARA) principle rather than abandoning treatment intensification. 1
• For pregnant women with chronic or gestational hypertension, lower blood pressure below 140/90 mmHg but avoid diastolic pressures below 80 mmHg. 2
• The minimum acceptable target remains <140/90 mmHg for all patients, though this is suboptimal for most. 1

Lifestyle Modifications (First-Line Therapy)

All patients with hypertension or elevated blood pressure should receive intensive lifestyle counseling before or alongside pharmacological treatment. 1, 2

Dietary Interventions

• Adopt a DASH diet or Mediterranean dietary pattern with 8-10 servings of fruits/vegetables daily and 2-3 servings of low-fat dairy products. 1, 3
• Restrict sodium intake to <2,300 mg/day (ideally <2,000 mg/day), which provides 5-10 mmHg systolic reduction. 3, 4
• Supplement potassium intake through diet to enhance blood pressure lowering effects. 1, 4
• Eliminate sugar-sweetened beverages and restrict free sugar to maximum 10% of energy intake. 3

Weight and Physical Activity

• Achieve and maintain ideal body weight through caloric restriction; a 10 kg weight loss produces approximately 6.0 mmHg systolic and 4.6 mmHg diastolic reduction. 3, 4
• Engage in regular aerobic exercise (minimum 30 minutes most days), which reduces blood pressure by approximately 4 mmHg systolic and 3 mmHg diastolic. 1, 4

Substance Use

• Limit alcohol to ≤2 drinks/day for men and ≤1 drink/day for women (maximum 14/week for men, 9/week for women). 1, 3
• Complete tobacco cessation with referral to smoking cessation programs, as tobacco use strongly and independently causes cardiovascular disease. 1

Expected Benefits

• These lifestyle modifications are partially additive and can provide blood pressure reductions of 10-20 mmHg when combined, while also enhancing the efficacy of pharmacological therapy. 1, 4
• For adults with elevated blood pressure (120-139/70-89 mmHg) and low/medium cardiovascular risk (<10% over 10 years), implement lifestyle modifications for 3 months before considering pharmacological treatment. 1, 2

Pharmacological Treatment Initiation

For adults with confirmed blood pressure ≥140/90 mmHg, initiate both lifestyle modifications and pharmacological treatment promptly, regardless of cardiovascular risk. 1, 2

• For adults with elevated blood pressure (130-139/80-89 mmHg) and high cardiovascular risk (≥10% over 10 years or established cardiovascular disease), initiate pharmacological treatment after 3 months of lifestyle intervention if blood pressure remains ≥130/80 mmHg. 1
• Confirm hypertension diagnosis with out-of-office blood pressure measurements (home monitoring ≥135/85 mmHg or 24-hour ambulatory monitoring ≥130/80 mmHg) before initiating treatment. 2

Initial Pharmacological Strategy

Initiate combination therapy with two drugs as first-line treatment for most patients with confirmed hypertension (≥140/90 mmHg), preferably as a single-pill combination. 1, 2, 3

Preferred Initial Combinations

• Combine a renin-angiotensin system (RAS) blocker (ACE inhibitor or ARB) with either a dihydropyridine calcium channel blocker OR a thiazide/thiazide-like diuretic. 1, 2, 3
• Single-pill combinations are strongly preferred over separate pills, as they significantly improve medication adherence and persistence. 1, 2

Exceptions to Combination Therapy

• Consider monotherapy for patients aged ≥85 years, those with symptomatic orthostatic hypotension, moderate-to-severe frailty, or elevated blood pressure (120-139/70-89 mmHg) with a concomitant indication for treatment. 1

First-Line Drug Classes

• ACE inhibitors, ARBs, dihydropyridine calcium channel blockers, and thiazide/thiazide-like diuretics (chlorthalidone, indapamide) have demonstrated the most effective reduction of blood pressure and cardiovascular events. 1, 4
• Chlorthalidone is preferred over hydrochlorothiazide due to its longer duration of action and superior cardiovascular outcomes data. 1, 2

Special Population Considerations

• For Black patients: Initial therapy should include a thiazide diuretic or calcium channel blocker, either in combination or with a RAS blocker. 2, 3
• For pregnant women: Transition to methyldopa, nifedipine, or labetalol; avoid ACE inhibitors, ARBs, or direct renin inhibitors. 2, 5
• For patients with albuminuria or chronic kidney disease: RAS blockers are first-line due to superior albuminuria reduction. 3

Treatment Escalation Algorithm

If blood pressure remains uncontrolled on two-drug combination therapy, escalate to three-drug combination therapy. 1, 2, 3

Three-Drug Combination

• Combine a RAS blocker + dihydropyridine calcium channel blocker + thiazide/thiazide-like diuretic, preferably as a single-pill combination. 1, 2, 3
• Achieve target blood pressure within 3 months of initiating or modifying therapy. 1, 2

Four-Drug Therapy (Resistant Hypertension)

• If blood pressure remains ≥130/80 mmHg on three medications at maximum tolerated doses, add spironolactone 25-50 mg daily as the preferred fourth-line agent. 2, 3
• Before adding a fourth agent, verify medication adherence (the most common cause of apparent treatment resistance), screen for secondary causes, and maximize diuretic therapy. 2

Critical Contraindications

• Never combine two RAS blockers (ACE inhibitor + ARB), as this increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit. 1, 5
• Avoid combining aliskiren with ARBs or ACE inhibitors, particularly in patients with diabetes or renal impairment (creatinine clearance <60 mL/min). 5

Beta-Blocker Use

Beta-blockers are NOT first-line agents for uncomplicated hypertension but should be combined with other major drug classes when compelling indications exist. 1

Compelling Indications for Beta-Blockers

• Angina pectoris 1
• Post-myocardial infarction 1
• Heart failure with reduced ejection fraction 1
• Need for heart rate control (e.g., atrial fibrillation) 1

Medication Adherence Strategies

Simplify medication regimens to once-daily dosing and use single-pill combinations whenever possible to improve adherence. 1

• Medication adherence is greatest with once-daily dosing (71-94%) and declines as dosing frequency increases. 1
• Instruct patients to take medications at the most convenient time of day to establish a habitual pattern and improve adherence. 1
• Use self-report tools in a nonthreatening fashion to identify barriers, combined with objective methods (pill counts, medication refill data) for optimal adherence assessment. 1

Monitoring and Follow-Up

Reassess blood pressure within 2-4 weeks after initiating or changing medications. 2

• After achieving target blood pressure, follow up every 3-6 months for blood pressure monitoring. 1
• Monitor serum potassium and creatinine at least annually when using ACE inhibitors, ARBs, or diuretics, and 2-4 weeks after initiating diuretic therapy. 2, 3
• For patients with resistant hypertension uncontrolled after 6 months, refer to a hypertension specialist. 2

Lifelong Treatment

Maintain blood pressure-lowering drug treatment lifelong, even beyond age 85 years, if well tolerated. 1, 2

• Use clinical judgment and a team-based approach for treatment intensity decisions in older adults with high comorbidity burden and limited life expectancy. 2
• Individualize blood pressure targets for elderly patients based on frailty, but do not withhold appropriate treatment intensification solely based on age. 1

Secondary Hypertension Screening

Perform comprehensive screening for secondary causes of hypertension in adults diagnosed before age 40 years (except obese young adults, who should start with obstructive sleep apnea evaluation). 1

• Screen for primary aldosteronism, renal artery stenosis, obstructive sleep apnea, and pheochromocytoma if blood pressure remains severely elevated despite optimal therapy. 2

Renal Denervation

Renal denervation is NOT recommended as a first-line blood pressure-lowering intervention due to lack of adequately powered outcomes trials demonstrating safety and cardiovascular benefits. 1

• Renal denervation is contraindicated in patients with moderate-to-severely impaired renal function (eGFR <40 mL/min/1.73 m²) or secondary causes of hypertension. 1