What is the comprehensive overview of hypertension, including clinical features, pathophysiology, relevant diagnostics, and management plan for a patient with hypertension, considering their medical history, demographics, and comorbidities?

Comprehensive Overview of Hypertension

Definition and Classification

Hypertension is defined as persistent systolic blood pressure (SBP) ≥130 mmHg or diastolic blood pressure (DBP) ≥80 mmHg, affecting approximately 116 million adults in the US and over 1 billion worldwide. 1, 2

• Stage 1 hypertension: SBP 130-139 mmHg or DBP 80-89 mmHg 1
• Stage 2 hypertension: SBP ≥140 mmHg or DBP ≥90 mmHg 1
• Elevated BP: SBP 120-129 mmHg and DBP <80 mmHg 1

Pathophysiology

The pathophysiology involves complex interplay of multiple systems 3:

• Vascular mechanisms: Increased peripheral vascular resistance due to arterial remodeling, endothelial dysfunction, and increased sympathetic nervous system activity 3
• Renal mechanisms: Sodium retention, activation of the renin-angiotensin-aldosterone system (RAAS), and impaired pressure natriuresis 3
• Cardiac mechanisms: Increased cardiac output initially, followed by structural changes including left ventricular hypertrophy 3
• Genetic predisposition: Complex polygenic inheritance patterns interact with environmental factors 3
• Environmental factors: High sodium intake, obesity, physical inactivity, excessive alcohol consumption, and chronic stress 3

Clinical Features and Evaluation

History Taking

Obtain a comprehensive history focusing on duration of hypertension, previous BP levels, current medications (including NSAIDs, decongestants, oral contraceptives, corticosteroids), and cardiovascular risk factors. 4

Primary hypertension features 1, 4:

• Gradual increase in BP with slow rate of rise 1
• Family history of hypertension 1
• Lifestyle factors: weight gain, high-sodium diet, decreased physical activity, excessive alcohol consumption 1

Secondary hypertension red flags 1, 5:

• Age of onset <30 years or sudden onset at any age 5
• Severe hypertension (>180/120 mmHg) or resistant hypertension (BP >140/90 mmHg despite ≥3 drugs including a diuretic) 5
• BP lability with episodic symptoms (pheochromocytoma) 1
• Muscle weakness, cramps (hypokalemia from primary aldosteronism) 1
• Snoring, daytime sleepiness (obstructive sleep apnea) 1
• Sudden deterioration of previously controlled hypertension 5

Physical Examination

Accurate BP measurement is critical—use automated oscillometric devices with proper technique, including appropriate cuff size and patient positioning. 1

Key examination findings 4, 5:

• Radio-femoral delay (coarctation of aorta) 5
• Abdominal bruits (renovascular disease) 1
• Enlarged kidneys on palpation (polycystic kidney disease) 5
• Cushingoid features: central obesity, facial rounding, striae 1
• Fundoscopy: retinal changes, hemorrhages, papilledema 5

Diagnostic Workup

Initial Laboratory Tests (All Patients)

Every patient with newly diagnosed hypertension requires basic laboratory screening to assess cardiovascular risk and detect secondary causes. 1, 4

• Serum electrolytes (sodium, potassium) 1, 5
• Serum creatinine and estimated glomerular filtration rate (eGFR) 1, 5
• Fasting blood glucose or HbA1c 1
• Lipid profile (total cholesterol, LDL, HDL, triglycerides) 1
• Urinalysis and urinary albumin-to-creatinine ratio 1, 5
• 12-lead ECG (assess for left ventricular hypertrophy, ischemia) 1, 5
• Thyroid-stimulating hormone (TSH) 5

Screening for Secondary Hypertension

The 2024 ESC guidelines now recommend measuring renin and aldosterone in ALL adults with confirmed hypertension (Class IIa recommendation), representing a major paradigm shift. 5

Additional targeted testing based on clinical suspicion 5:

• Primary aldosteronism (8-20% of resistant hypertension): Plasma aldosterone-to-renin ratio (ARR >20 with elevated aldosterone and suppressed renin), followed by confirmatory testing (saline infusion test) and CT adrenal imaging 5
• Renovascular disease: Renal ultrasound with Doppler, followed by CT or MR renal angiography 5
• Pheochromocytoma: 24-hour urinary metanephrines or plasma metanephrines, followed by abdominal/adrenal imaging 5
• Obstructive sleep apnea: Home sleep apnea testing or polysomnography 5

Cardiovascular Risk Assessment

Calculate 10-year atherosclerotic cardiovascular disease (ASCVD) risk to guide treatment intensity—higher risk patients benefit from more aggressive BP targets. 1

• Use validated risk calculators (e.g., ACC/AHA Pooled Cohort Equations) 1
• Assess for target organ damage: left ventricular hypertrophy (echocardiography), retinopathy, chronic kidney disease, peripheral arterial disease 1

Management Plan

Lifestyle Modifications (First-Line for All Patients)

Lifestyle modifications are mandatory for all patients with elevated BP or hypertension and should be continued even when pharmacological therapy is initiated. 1, 2

Evidence-based interventions with Class I, Level A recommendations 1:

1. Weight loss: Achieve and maintain healthy body mass index (BMI 18.5-24.9 kg/m²) 1

   • Expected BP reduction: 5-20 mmHg per 10 kg weight loss 2

2. DASH diet: High in fruits, vegetables, whole grains, low-fat dairy; low in saturated fat and sodium 1

   • Expected BP reduction: 8-14 mmHg 2

3. Sodium restriction: Reduce intake to <2,300 mg/day (ideally <1,500 mg/day for optimal BP reduction) 1

   • Expected BP reduction: 2-8 mmHg 2

4. Potassium supplementation: Increase dietary potassium to 3,500-5,000 mg/day through fruits, vegetables, low-fat dairy (unless contraindicated by CKD or potassium-sparing medications) 1

   • Expected BP reduction: 4-5 mmHg in hypertensive patients 1

5. Physical activity: Engage in aerobic exercise 90-150 minutes/week or dynamic resistance training 90-150 minutes/week 1

   • Expected BP reduction: 4-9 mmHg 2

6. Alcohol limitation: Men ≤2 standard drinks/day (maximum 14/week), women ≤1 standard drink/day (maximum 9/week) 1

   • Expected BP reduction: 2-4 mmHg 2

For patients with elevated BP (120-129/<80 mmHg) or Stage 1 hypertension (130-139/80-89 mmHg) without high cardiovascular risk, implement lifestyle modifications for 3-6 months before considering pharmacotherapy. 1, 6

Pharmacological Therapy

Indications for Drug Therapy

Initiate antihypertensive medication based on BP level and cardiovascular risk 1:

• Immediate drug therapy: SBP ≥140 mmHg or DBP ≥90 mmHg regardless of cardiovascular risk 1
• Drug therapy for Stage 1 hypertension (SBP 130-139 or DBP 80-89 mmHg): If 10-year ASCVD risk ≥10%, or presence of diabetes, chronic kidney disease, or established cardiovascular disease 1

Blood Pressure Targets

For most adults <65 years: Target BP <130/80 mmHg 1

For adults ≥65 years: Target SBP <130 mmHg (if tolerated), DBP <80 mmHg 1

For patients with diabetes, chronic kidney disease, or established cardiovascular disease: Target BP <130/80 mmHg 1

First-Line Antihypertensive Medications

First-line drug therapy consists of four classes, which should be selected based on comorbidities and titrated to achieve target BP 2, 3:

1. Thiazide or thiazide-like diuretics (e.g., chlorthalidone, hydrochlorothiazide) 2

   • Preferred for initial monotherapy in most patients 2
   • Use loop diuretics if eGFR <30 mL/min/1.73m² 1

2. Angiotensin-converting enzyme (ACE) inhibitors (e.g., lisinopril, enalapril) 7, 2

   • Preferred in patients with diabetes, chronic kidney disease, heart failure, or post-myocardial infarction 7
   • Starting dose lisinopril: 10 mg once daily, titrate to 40 mg once daily 7

3. Angiotensin II receptor blockers (ARBs) (e.g., losartan, candesartan) 8, 2

   • Alternative to ACE inhibitors, especially if ACE inhibitor-induced cough 8
   • Starting dose losartan: 50 mg once daily, titrate to 100 mg once daily 8
   • Do NOT combine ACE inhibitors with ARBs 5

4. Calcium channel blockers (CCBs) (e.g., amlodipine) 2

   • Preferred in elderly patients and those with isolated systolic hypertension 2

Treatment Algorithm

For most patients, initiate therapy with a single first-line agent and titrate to maximum dose before adding a second agent. 2

If BP remains uncontrolled on monotherapy, add a second agent from a different class 2:

• Preferred combinations: ACE inhibitor or ARB + CCB, ACE inhibitor or ARB + thiazide diuretic, CCB + thiazide diuretic 2

If BP remains uncontrolled on two-drug therapy, add a third agent 2:

• Preferred triple therapy: ACE inhibitor or ARB + CCB + thiazide diuretic 2

Resistant hypertension (BP >140/90 mmHg on ≥3 drugs including a diuretic) 1, 5:

• Ensure medication adherence and exclude white coat effect 5
• Screen for secondary causes (especially primary aldosteronism) 5
• Add spironolactone 25-50 mg daily as fourth-line agent (if serum potassium <4.5 mmol/L and eGFR >45 mL/min/1.73m²) 1, 5
• Consider referral to hypertension specialist 5

Special Populations

Hypertension with left ventricular hypertrophy: Start losartan 50 mg daily, add hydrochlorothiazide 12.5 mg daily, titrate losartan to 100 mg daily, then increase hydrochlorothiazide to 25 mg daily based on BP response 8

Diabetic nephropathy: Start with ACE inhibitor or ARB, titrate to maximum dose (e.g., losartan 100 mg daily), target BP <130/80 mmHg 8

Chronic kidney disease: Use ACE inhibitor or ARB as first-line, monitor serum creatinine and potassium closely, target BP <130/80 mmHg 1

Heart failure with reduced ejection fraction: Use ACE inhibitor or ARB, beta-blocker, and mineralocorticoid receptor antagonist 1

Hepatic impairment: Start losartan at 25 mg once daily in mild-to-moderate hepatic impairment 8

Follow-Up and Monitoring

Reassess BP within 1 month of initiating or adjusting therapy until target BP is achieved 1

Once BP is controlled, follow-up every 3-6 months 1

Monitor for adverse effects: electrolyte abnormalities (especially with diuretics and RAAS inhibitors), renal function changes, medication adherence 1

Encourage home BP monitoring to detect white coat hypertension and masked hypertension 1

Common Pitfalls and Caveats

Inaccurate BP measurement is the most common error—always use proper technique with validated devices 1

White coat hypertension affects 15-30% of patients—confirm diagnosis with ambulatory or home BP monitoring before initiating treatment 1

Medication non-adherence is the leading cause of apparent resistant hypertension—assess adherence before escalating therapy 5

Secondary hypertension is underdiagnosed—maintain high index of suspicion in young patients, those with sudden onset/worsening, and resistant hypertension 5

Beta-blockers should NOT be started on the day of surgery in beta-blocker-naïve patients 1

Abrupt discontinuation of beta-blockers or clonidine perioperatively is potentially harmful 1