Hypertension Management in Adults
Blood Pressure Classification and Diagnostic Thresholds
The ACC/AHA 2017 guideline defines hypertension as systolic ≥130 mmHg or diastolic ≥80 mmHg, while the ESC 2024 guideline retains the traditional threshold of ≥140/90 mmHg. 1
ACC/AHA classification:
ESC 2024 classification:
Diagnosis requires the average of ≥2 readings on ≥2 separate occasions, confirmed with out-of-office monitoring (home BP ≥135/85 mmHg or 24-hour ambulatory BP ≥130/80 mmHg) before starting medication. 1
Blood Pressure Treatment Targets
For most adults, target BP <130/80 mmHg; at minimum <140/90 mmHg. 1, 2
- Adults <65 years with established CVD or 10-year ASCVD risk ≥10%: <130/80 mmHg 1
- Non-institutionalized adults ≥65 years: systolic <130 mmHg if tolerated 1
- Patients with diabetes mellitus: <130/80 mmHg 1
- Patients with chronic kidney disease: <130/80 mmHg 1
- Patients with stable ischemic heart disease: <130/80 mmHg 1
- ESC 2024 optimal target for adults <65 years: 120–129/70–79 mmHg if well tolerated 1
- Critical diastolic floor: In high-risk patients, do not lower diastolic BP below 60–70 mmHg, as excessive reduction may increase adverse cardiovascular events. 1
Lifestyle Modifications (Foundation of All Therapy)
All individuals with BP ≥120/70 mmHg should adopt comprehensive lifestyle measures before or alongside drug therapy. 1
- Sodium restriction to <2 g/day: yields 5–10 mmHg systolic reduction 1, 2
- DASH dietary pattern: reduces BP by approximately 11.4/5.5 mmHg 1
- Weight loss (≈10 kg for BMI ≥25 kg/m²): lowers BP by ~6.0/4.6 mmHg 1
- Regular aerobic exercise (≥30 min most days, ≈150 min/week): reduces BP by ~4/3 mmHg 1
- Alcohol limitation: ≤2 drinks/day for men, ≤1 drink/day for women 1
- Smoking cessation: independently reduces cardiovascular events and mortality 1
Initiation of Pharmacologic Therapy
Stage 2 hypertension (≥140/90 mmHg): start lifestyle measures AND pharmacologic therapy simultaneously with a two-drug combination from different first-line classes, preferably as a single-pill formulation. 1, 3
Stage 1 hypertension (130–139/80–89 mmHg): initiate medication when the patient has:
Established atherosclerotic CVD OR 1
10-year ASCVD risk ≥10% (ACC/AHA Pooled Cohort Equations) OR 1
Diabetes mellitus OR 1
Chronic kidney disease OR 1
Hypertension-mediated organ damage 1
For elevated BP (120–139/70–89 mmHg) without the above conditions, begin with lifestyle modifications for 3 months; add medication only if BP remains ≥130/80 mmHg after this trial. 1
First-Line Pharmacologic Agents
Four drug classes are endorsed as first-line therapy: thiazide or thiazide-like diuretics, ACE inhibitors, angiotensin-receptor blockers (ARBs), and long-acting dihydropyridine calcium-channel blockers (CCBs). 1, 2
- All four classes produce comparable office BP reductions of approximately 9/5 mmHg and ambulatory reductions of about 5/3 mmHg when used as monotherapy. 1
Thiazide/Thiazide-Like Diuretics (Optimal First-Line for General Population)
Chlorthalidone 12.5–25 mg once daily is the preferred thiazide-like diuretic because of its 40–60 hour half-life, superior 24-hour BP control, and strongest cardiovascular outcome evidence from the ALLHAT trial (>50,000 participants). 1
- In ALLHAT, chlorthalidone reduced heart-failure incidence by 38% compared with amlodipine and stroke incidence by 15% compared with lisinopril. 1
- Hydrochlorothiazide 25–50 mg daily is an acceptable alternative when chlorthalidone is unavailable, though it provides inferior 24-hour coverage. 1
ACE Inhibitors and ARBs
- ACE inhibitors (e.g., lisinopril 10–40 mg, enalapril 5–40 mg): first-line in diabetes mellitus, chronic kidney disease (stage 3+ or albuminuria ≥300 mg/day), post-MI, stable ischemic heart disease, and heart failure with reduced ejection fraction 1, 2
- ARBs (e.g., losartan 50–100 mg, valsartan 80–320 mg, candesartan 8–32 mg): equivalent efficacy to ACE inhibitors with less cough and angioedema; preferred when ACE inhibitors are not tolerated 1
- Never combine an ACE inhibitor with an ARB (or add a direct renin inhibitor): dual RAS blockade increases hyperkalemia and acute kidney injury without added cardiovascular benefit. 1
Calcium-Channel Blockers
- Long-acting dihydropyridine CCBs (e.g., amlodipine 5–10 mg, extended-release nifedipine 30–90 mg): provide 24-hour BP control with proven cardiovascular benefit comparable to thiazides for all outcomes except heart failure 1
- Non-dihydropyridine CCBs (diltiazem, verapamil) should not be used in patients with left ventricular dysfunction or heart failure due to negative inotropic effects. 1
Population-Specific First-Line Drug Choices
Black Patients Without Heart Failure or CKD
Initiate therapy with a thiazide diuretic (chlorthalidone preferred) or a CCB; ACE inhibitors and ARBs are 30–36% less effective for stroke prevention in this population because of lower renin activity. 1
- ARBs may cause less cough and angioedema than ACE inhibitors but do not provide additional cardiovascular advantage. 1
Patients with Diabetes Mellitus
Prefer an ACE inhibitor or ARB as initial therapy to protect renal function, especially when albuminuria ≥300 mg/day is present. 1
- Target BP <130/80 mmHg 1
- Monitor serum creatinine, eGFR, and potassium within 1–2 weeks of initiation, after each dose increase, and annually thereafter. 1
- An increase in serum creatinine up to 50% above baseline or to 3 mg/dL (whichever is greater) is acceptable. 1
Patients with Chronic Kidney Disease (Stage 3+ or Albuminuria)
An ACE inhibitor or ARB is first-line to slow eGFR decline and reduce proteinuria. 1
- Target BP <130/80 mmHg 1
- Thiazide diuretics remain effective even when eGFR <30 mL/min/1.73 m² and should not be avoided solely because of reduced kidney function. 1
Post-Myocardial Infarction or Stable Ischemic Heart Disease
Combine a β-blocker with an ACE inhibitor or ARB as foundational therapy; if angina persists and BP remains uncontrolled, add a dihydropyridine CCB. 1
- Target BP <130/80 mmHg 1
- β-blockers should be continued for ≥3 years post-MI, with longer duration reasonable for ongoing hypertension control. 1
Heart Failure with Reduced Ejection Fraction
Use a three-drug regimen: ACE inhibitor or ARB + β-blocker + diuretic. 1
Older Adults (≥65 Years)
Non-institutionalized, ambulatory adults ≥65 years with systolic ≥130 mmHg should be treated to a systolic target <130 mmHg if tolerated. 1
- Caution is advised when initiating combination therapy in older adults at risk for orthostatic hypotension. 1
- For adults ≥85 years or those with high comorbidity burden or limited life expectancy, individualized clinical judgment and team-based risk-benefit assessment are reasonable. 1
- Continue BP-lowering therapy lifelong if well tolerated; asymptomatic orthostatic hypotension alone should not prompt drug withdrawal. 1
Pregnancy
Women who become pregnant while hypertensive should be switched to methyldopa, extended-release nifedipine, or labetalol. 1
- ACE inhibitors, ARBs, and direct renin inhibitors are absolutely contraindicated in pregnancy because of fetal toxicity. 1
Combination Therapy Strategy
Stage 1 hypertension (130–139/80–89 mmHg): initiate single-agent therapy and titrate upward as needed. 1
Stage 2 hypertension (≥140/90 mmHg or >20/10 mmHg above goal): begin treatment with a two-drug combination, preferably as a single-pill formulation. 1, 3
- Combination therapy using two submaximal doses from different classes yields larger BP reductions with fewer adverse effects than maximal dosing of a single agent. 1
- Single-pill combinations improve medication adherence and persistence. 1
Recommended Two-Drug Regimens
Preferred combinations:
Escalation to Triple Therapy
If BP remains ≥140/90 mmHg despite dual therapy at optimal doses, add a third agent from the remaining class to create the standard triple regimen: ACE inhibitor or ARB + CCB + thiazide diuretic. 1, 3
- Optimize the doses of the first two drugs before adding the third agent. 3
- Use single-pill combinations whenever possible to improve adherence. 3
- This triple combination achieves BP control in >80% of patients. 1
Agents Not Recommended as First-Line in Uncomplicated Hypertension
β-blockers should not be used as first-line therapy in uncomplicated hypertension, especially in patients >60 years, because they are approximately 36% less effective than CCBs and 30% less effective than thiazides for stroke prevention. 1
- Reserve β-blockers for compelling indications: angina, post-MI, heart failure with reduced ejection fraction, or atrial fibrillation requiring rate control. 1
Alpha-blockers are not first-line because they are less effective for cardiovascular disease prevention than thiazide diuretics. 1
Monitoring and Follow-Up
After initiating or adjusting antihypertensive therapy, review patients monthly until the BP target is achieved, then every 3–5 months for maintenance. 1, 2
- Dose adjustments should be spaced at least 4 weeks apart to allow full BP response. 1
- Aim to achieve target BP within 3 months of initiating or modifying therapy. 1, 3
Baseline Laboratory Evaluation
- Serum creatinine, estimated glomerular filtration rate (eGFR), potassium, fasting glucose or HbA1c, and lipid panel 1
When ACE Inhibitors, ARBs, or Diuretics Are Prescribed
- Repeat creatinine, eGFR, and potassium within 1–2 weeks of initiation, after each dose increase, and annually thereafter. 1
- An increase in serum creatinine up to 50% above baseline or to 3 mg/dL (whichever is greater) is acceptable. 1
Out-of-Office Blood Pressure Monitoring
Out-of-office BP monitoring (home or ambulatory) is essential to assess treatment response, detect white-coat effect, and identify masked uncontrolled hypertension. 1
Resistant Hypertension
Defined as BP ≥130/80 mmHg despite ≥3 antihypertensive agents at optimal doses (including a diuretic), or BP <130/80 mmHg requiring ≥4 agents. 1
Systematic Approach
- Confirm true resistance by excluding white-coat effect with out-of-office monitoring and assessing adherence (non-adherence is the most common cause of apparent resistance). 1, 3
- Identify contributing lifestyle factors: obesity, excess alcohol (>2 drinks/day for men), high sodium intake (>2 g/day), NSAIDs, decongestants, oral contraceptives, systemic corticosteroids, herbal supplements (ephedra, licorice). 1
- Screen for secondary causes: primary aldosteronism, chronic kidney disease, renal artery stenosis, pheochromocytoma, obstructive sleep apnea, Cushing syndrome, coarctation of the aorta. 1
- Optimize diuretic therapy: replace hydrochlorothiazide with chlorthalidone 12.5–25 mg daily for superior 24-hour BP control; use loop diuretics in CKD (eGFR <30 mL/min/1.73 m²). 1
- Add a mineralocorticoid-receptor antagonist (spironolactone 25–50 mg daily) as the preferred fourth-line agent; this provides additional BP reductions of 20–25/10–12 mmHg when added to triple therapy. 1
- Refer to a hypertension specialist if uncontrolled after 6 months or if BP remains ≥160/100 mmHg despite four-drug therapy at optimal doses. 1
Common Pitfalls to Avoid
- Delaying combination therapy in stage 2 hypertension (≥140/90 mmHg) increases cardiovascular risk; start two drugs immediately. 1
- Using β-blockers as first-line agents in patients >60 years without a compelling indication leads to inferior stroke prevention. 1
- Excessive diastolic lowering below 60 mmHg in high-risk patients may increase adverse cardiovascular events. 1
- Initiating therapy with α-blockers or central α-agonists is associated with higher adverse-effect rates, especially in the elderly. 1
- Combining an ACE inhibitor with an ARB (or adding a direct renin inhibitor) should be avoided due to lack of benefit and higher adverse-event risk. 1
- Continuing ACE inhibitors or ARBs during pregnancy is contraindicated because of fetal toxicity. 1
- Failing to employ out-of-office BP monitoring can miss white-coat or masked hypertension, compromising management. 1
- Assuming treatment failure without first confirming adherence and excluding secondary causes or interfering substances. 1