Hypertension¶
Chapter 288 | Part 1: Disorders of the Cardiovascular System · Part 6 – Cardiovascular Disorders · Chapter 288
Key Clinical Points¶
- Hypertension is defined as an average of three SBP or DBP readings at or above the 95th percentile, or an SBP ≥130 and DBP ≥80 mmHg in adults ≥18 years.
- White coat hypertension (high office, normal out-of-office) has a CVD risk profile similar to normotensive individuals; masked hypertension (normal office, high out-of-office) has a risk profile similar to sustained hypertension.
- Secondary hypertension should be suspected in cases of new-onset, abrupt worsening, disproportionate target organ damage, or unprovoked hypokalemia/proteinuria/LVH.
- Obstructive sleep apnea (OSA) is the most common cause of secondary hypertension.
- Nonpharmacologic interventions include the DASH diet (-5 mmHg SBP), weight loss (-1 mmHg per kg), and sodium reduction (25% reduction → -5 mmHg SBP).
- Potassium supplementation (+2000 mg/d) is contraindicated in hyperkalemia or advanced kidney disease.
- Risk of CVD is significantly higher when hypertension is accompanied by other risk factors (over 30-fold difference in 10-year predicted risk).
- Resistant hypertension requires a systematic search for secondary causes and potential escalation to MRA or vasodilators (hydralazine/minoxidil).
- Pharmacologic management is tiered based on the severity of elevation above target goals.
- Accurate measurement requires specific positioning, such as feet flat on the floor.
DEFINITION & OVERVIEW¶
• Definition: ◦ Average of three SBP or DBP readings at or above the 95th percentile. ◦ Or an SBP ≥130 and DBP ≥80 mmHg in adults ≥18 years. • Measurement Standards: ◦ Use average of two or more readings at two or more visits to estimate usual level. ◦ If SBP and DBP are in different categories, the higher classification is chosen. • Clinical Impact: ◦ Hypertension is a leading risk factor for cardiovascular disease (CVD), including stroke, coronary heart disease (CHD), heart failure (HF), peripheral arterial disease (PAD), chronic kidney disease (CKD)/end-stage kidney disease (ESKD), dementia, and all-cause mortality. • Physiology: ◦ Blood pressure is controlled by cardiac output and peripheral resistance. ◦ Peripheral resistance is determined by vascular structure and vascular function (regulated by RAAS and sympathetic nervous system). ◦ Endothelial dysfunction may play a role in the initiation or progression of hypertension.
EPIDEMIOLOGY¶
• General Trends: ◦ Prevalence increases with age; SBP rises until the 8th decade, DBP until the 5th. ◦ Isolated systolic hypertension is common in older adults due to widened pulse pressure. • U.S. Statistics: ◦ >103 million adults have hypertension. ◦ Prevalence: 20–30% (ages 20–44) → 80–85% (age ≥75). ◦ Racial Disparity: Non-Hispanic black adults have a higher prevalence (59%) and earlier onset/more complications than other groups. • Risk Assessment: ◦ Risk of CVD is significantly higher in older adults due to co-existing risk factors. ◦ There is a >30-fold difference in 10-year predicted risk of CVD for those with multiple risk factors compared to isolated hypertension.
ETIOLOGY & PATHOPHYSIOLOGY¶
• Primary Hypertension: ◦ Most common form; no obvious underlying anatomic cause. ◦ Evidence suggests a heritable component, but genetic studies show only modest polygenic associations. • Secondary Hypertension: ◦ Minority of patients with an overt underlying anatomic or biochemical cause. ◦ Indicators for investigation: 1. Treatment-resistant hypertension 2. Abrupt worsening of hypertension 3. Disproportionate target organ damage for level of BP 4. Laboratory/diagnostic findings (unprovoked hypokalemia, proteinuria, or left ventricular hypertrophy).
CLINICAL FEATURES¶
• Symptoms: ◦ Often asymptomatic; symptoms usually relate to end-organ damage or secondary causes. • Secondary Cause Indicators: ◦ Obstructive sleep apnea (OSA): snoring, poor quality sleep, breathing pauses, and daytime sleepiness. • White Coat Hypertension: ◦ High office BP, normal out-of-office → CVD risk profile similar to normotensive individuals; may be treated with nonpharmacologic interventions. • Masked Hypertension: ◦ Normal office BP, high out-of-office → CVD risk profile similar to sustained hypertension; requires pharmacologic therapy. • Target Organ Damage: ◦ Left ventricular hypertrophy (LVH), proteinuria, and retinopathy.
DIFFERENTIAL DIAGNOSIS¶
• Primary vs. Secondary: ◦ Primary: No anatomic cause; most common. ◦ Secondary: Underlying causes including OSA, renal artery stenosis, primary aldosteronism, pheochromocytoma, Cushing syndrome, and thyroid disorders. • Medication-Induced Hypertension: ◦ Prescription: Amphetamines, antidepressants, antipsychotic agents, decongestants, oral contraceptives, NSAIDs, systemic corticosteroids. ◦ Illicit: Cocaine, marijuana, amphetamines, methylenedioxymethamphetamine. ◦ Herbal/Other: Arnica, ephedra (Ma-Huang), ginseng, guarana, licorice, St. John's wort; caffeine and some anesthetics (short-term).
INVESTIGATIONS & DIAGNOSIS¶
- Initial Evaluation: • Identify target organ damage (LVH, proteinuria), secondary causes (kidney disease, primary aldosteronism), and comorbidities (DM, hyperlipidemia).
- Laboratory Panel: ◦ CBC, Serum electrolytes (Na, K, Ca), Serum creatinine/eGFR. ◦ Lipid profile, Glycemic status (HbA1c or fasting glucose). ◦ TSH, Urinalysis, and urine albumin-to-creatinine ratio (UACR).
- Diagnostic Procedures: ◦ 12-lead ECG to assess for LVH.
- Specialized Assessment: ◦ Evaluate for secondary causes in patients with new-onset, rapid worsening, or disproportionate organ damage.
MANAGEMENT & TREATMENT¶
- Nonpharmacologic Interventions (Table 288-2): • DASH Diet: ◦ Expected change: SBP reduction of ~5 mmHg in patients with HTN; 2–3 mmHg in those without. • Weight Loss: ◦ Expected change: SBP reduction of ~1 mmHg per kg of weight loss. • Sodium Reduction: ◦ Target: <1500 to 2300 mg/day. ◦ Expected change: Reduction by ~25% → SBP reduction of ~5 mmHg. • Potassium Supplementation: ◦ Dose: +2000 mg/d (~50 mmol/d). Recommended intake is ~3500 mg/d. ◦ Contraindication: Hyperkalemia, advanced kidney disease, or medications increasing hyperkalemia risk. • Physical Activity: ◦ Recommendation: ≥150 min of aerobic exercise per week. • Alcohol Reduction: ◦ Target: ≤2 standard drinks/day (men), ≤1 (women).
- Pharmacologic Treatment (Table 288-3 & Figure 288-4): • Initial Selection (Figure 288-4): ◦ Monotherapy: For patients with SBP/DBP close to 130/80 mmHg. ◦ Combination Therapy: For patients with SBP >120 mmHg above treatment goal. ◦ Triple-drug Therapy: For patients with SBP/DBP >130/80 mmHg. • Drug Classes and Dosages: ◦ Diuretics (Thiazide/Thiazide-like): Chlorthalidone (12.5–25 mg), Hydrochlorothiazide (12.5–50 mg), Indapamide (1.25–2.5 mg). ◦ ACE Inhibitors: Enalapril (5–40 mg), Lisinopril (10–40 mg), Benazepril (10–40 mg), Ramipril (2.5–20 mg), Trandolapril (1–4 mg). ◦ ARBs: Losartan (50–100 mg), Valsartan (80–320 mg), Azilsartan (40–80 mg), Candesartan (8–32 mg), Olmesartan (20–40 mg). ◦ CCBs: Amlodipine (2.5–10 mg), Felodipine (2.5–10 mg), Nifedipine LA (30–90 mg). ◦ CCB (non-DHP): Diltiazem ER (120–360 mg), Verapamil ER (100–300 mg). ◦ Beta-blockers: Metoprolol (50–200 mg), Carvedilol (20–80 mg), Nebivolol (5–40 mg). ◦ MRAs: Spironolactone (25–100 mg), Eplerenone (50–100 mg), Finerenone (10–20 mg). ◦ Amiloride/Triamterine: Amiloride (5–10 mg), Triamterine (50–100 mg).
- Resistant Hypertension Management (Flowchart 1): • Step 1: Confirmation of Resistance ◦ If BP ≥130/80 mmHg on triple drug therapy (including a diuretic) OR ≥140/90 mmHg on quadruple therapy, and non-ordered treatments are excluded → Confirmed Resistant Hypertension. • Step 2: Exclusion of Secondary Causes ◦ Evaluate for: Lifestyle factors, OSA, Medication-induced hypertension, Anatomic causes (renal parenchymal disease, primary aldosteronism, renovascular disease, pregnancy disorders). ◦ If a secondary cause is found → Follow specific treatment path for that condition. • Step 3: Management Escalation (if no secondary cause identified) ◦ Step 1: Reaffirm adherence to lifestyle and medication. ◦ Step 2: Ensure full dosage of current medications. ◦ Step 3: Add Mineralocorticoid Receptor Antagonist (MRA). ◦ Step 4: Add vasodilator (e.g., hydralazine or potent minoxidil). • Step 4: Final Decision Point ◦ If BP remains uncontrolled after 6 months of intensive treatment → Consider antidromal secondary cause detection OR evaluation for surgical intervention.
PROGNOSIS & COMPLICATIONS¶
• Cardiovascular Risk: ◦ Hypertension is a leading risk factor for stroke, CHD, HF, PAD, CKD/ESKD, and dementia. • Risk Quantification: ◦ Over 30-fold difference in 10-year predicted risk for patients with multiple risk factors vs. isolated hypertension.
SPECIAL CONSIDERATIONS¶
• White Coat & Masked Hypertension: ◦ White coat: Lower risk profile; may be managed with nonpharmacologic interventions. ◦ Masked: Higher risk profile; requires pharmacologic therapy. • Secondary Hypertension: ◦ High suspicion in patients with new-onset, rapid worsening, or disproportionate organ damage.
KEY PEARLS & CLINICAL TRAPS¶
• Measurement Accuracy: Ensure feet are flat on the floor to avoid overestimation. • Potassium Warning: Never supplement potassium in patients with advanced kidney disease or hyperkalemia. • Sodium Impact: A 25% reduction in sodium intake can lower SBP by ~5 mmHg. • Resistant Hypertension: If not controlled after 6 months of intensive treatment (including MRA/vasodilators), investigate for antidromal causes or surgery.
Reference Tables¶
TABLE 288-1 American College of Cardiology/American Heart Association Blood Pressure Classification System in Adults BP…¶
Harrison's 22e, p.2134
| BP CATEGORY | SYSTOLIC BP, mmHg |
DIASTOLIC BP, mmHg |
|
|---|---|---|---|
| Normal BP | <120 | and | <80 |
| 120–129 | and | ||
| Stage 1 hypertension | 130–139 | or | 80–89 |
| ≥140 | or |
TABLE 288-2 Summary Information for the Six Best Proven Nonpharmacologic Interventions That Lower Blood Pressure…¶
Harrison's 22e, p.2137
| CHARACTERISTIC | BP ASSOCIATION | INTERVENTION | REGIMEN | EXPECTED CHANGE IN BP |
|---|---|---|---|---|
| Diet | BPs are lower in those who consume heart-healthy diets. |
Consumption of a heart- healthy diet, especially the Dietary Approaches to Stop Hypertension (DASH) diet. |
DASH diet meal plans are readily available. |
With good adherence to the DASH diet plan, an average SBP reduction of about 5 mmHg can be expected in patients with and 2–3 mmHg in those without hypertension. |
| Increased body weight is directly associated with SBP/ DBP. Almost 75% of U.S. adults are overweight (BMI 25–<30 kg/ m2; 31%) or obese (BMI ≥30 kg/ m2; 42%). |
In most patients, weight loss should be achieved by behavioral counseling. In a minority, drug therapy should be considered. Bariatric surgery should be confined to adults with a BMI ≥40 kg/m2 or ≥35 kg/m2 and hypertension or another obesity- related comorbidity. |
Behavioral interventions are aimed at a combination of calorie reduction and increased physical activity. |
||
| Sodium intake | Dietary sodium is directly associated with SBP, and excessive intake may be important in age-related increases in BP. |
Behavioral counseling, use of salt substitutes, public health messaging, and policy to reduce the amount of sodium added during food processing and commercial preparation. |
The sodium-BP dose response is almost linear, so any reduction in sodium intake is beneficial. Optimal target recommendations vary from <1500 to 2300 mg sodium intake per day. |
In high-quality behavior change trials, average sodium intake is reduced by ~25% and SBP by ~5 mmHg and 2–3 mmHg for adults with and without hypertension, respectively. Use of salt substitutes has resulted in prevention of stroke (14%), CVD (13%), and all- cause mortality (12%) in addition to BP lowering. |
| Potassium intake is inversely associated with BP and a lower risk of CVD, especially stroke. |
Dietary or pill supplementation, but the former is preferred. An additional intake of 2000 mg/d (~50 mmol/d). |
The recommended intake of potassium in adults is ~3500 mg/d. A dose-response meta-analysis suggests supplementing usual intake by ~1200 mg/d may be optimal. Potassium supplementation is contraindicated in patients with hyperkalemia or advanced kidney disease or who are taking medicines that increase the risk of hyperkalemia. |
||
| Physical activity | Observational studies identify a strong inverse association between physical activity and BP, hypertension, and CVD. |
Aerobic, dynamic resistance, and isometric resistance exercises. |
Most trials have evaluated aerobic exercise interventions, and this type of exercise is commonly prescribed. Most guidelines recommend ≥150 min of aerobic exercise per week. However, any increase in physical activity and any type of exercise are likely to be be beneficial. |
In adults with hypertension, aerobic exercise is likely to reduce SBP by ~5 mmHg and, when combined with dynamic resistance exercise, by ~7 mmHg. The extent of BP lowering depends on the starting level of BP and success of the intervention. |
| Alcohol intake is associated with BP and hypertension in a direct and roughly linear fashion, with no threshold for the association. |
Most commonly, substitution of lower alcoholic or nonalcoholic beverages, but behavioral counseling and abstinence, without access to alcohol, have been used in some trials. |
Most interventions have targeted a reduction in alcohol consumption, often to ≤2 and ≤1 standard drinks per day in men and women, respectively. However, any reduction in alcohol consumption is helpful. |
TABLE 288-4 Summary Information for the Major Antihypertensive Drug Classes Used to Manage High Blood Pressure CLASS…¶
Harrison's 22e, p.2144
| CLASS | EXAMPLES | DOSE RANGE, mg |
DOSE FREQUENCY/D |
METHOD OF ACTION | SBP REDUCTION VERSUS PLACEBO, mmHg (APPROXIMATE) |
MOST COMMON ADVERSE EFFECTS |
FREQUENCY OF ADVERSE EVENTS |
COMMENTS |
|---|---|---|---|---|---|---|---|---|
| First-Step Drugs | ||||||||
| Diuretics (thiazide and thiazide-like). |
Chlorthalidone Hydrochlorothiazide Indapamide |
12.5–25 12.5–50 1.25–2.5 |
1 1 1 |
Block sodium reabsorption in distal convoluted tubule |
12 | Hyponatremia Hypokalemia Hypercalcemia Hyperuricemia Hyperglycemia Dyslipidemia |
Similar to placebo |
Chlorthalidone preferred due to long half-life and use in most U.S. trials |
| Enalapril Lisinopril Benazepril Ramipril Trandolapril |
5–40 10–40 10–40 2.5–20 1–4 |
1 or 2 1 1 or 2 1 1 |
Inhibit ACE activity and Ang II production |
12.0 | Cough Hyperkalemia in CKD AKF in severe bilateral RAS Hypotension Angioedema |
Similar to placebo |
||
| ARB | Losartan Valsartan Azilsartan Candesartan Olmesartan |
50–100 80–320 40–80 8–32 20–40 |
1 or 2 1 1 1 1 |
Block Ang II binding to Ang receptors |
12 | Hyperkalemia in CKD Reduced GFR AKF in severe bilateral RAS Hypotension |
Similar to placebo |
Do not use in combination with ACE inhibitor; contraindicated in pregnancy |
| Amlodipine Felodipine Nifedipine LA |
2.5–10 2.5–10 30–90 |
1 1 1 |
Blocks calcium from entering cells, primarily inhibiting vasoconstriction |
10 | Peripheral edema (dose-dependent) Gingival hyperplasia |
Similar to placebo |
||
| CCB (non-DHP) |
Diltiazem ER Verapamil ER |
120–360 100–300 |
1 1 (evening administration recommended) |
Blocks calcium from entering cells, reducing heart rate and vasoconstriction |
9.0 | Bradycardia Nausea Constipation. |
Similar to placebo |
Do not use in combination with β-blockers Do not use in HFrEF or in high- grade AV or SA block |
| Other Drugs | ||||||||
| Metoprolol Carvedilol Nebivolol |
50–200 20–80 5–40 |
1 1 1 |
Block β-adrenergic receptors |
10 | Asthma Bradycardia Fatigue Exercise intolerance Impaired concentration |
Similar to placebo |
||
| MRA | Spironolactone Eplerenone Finerenone |
25–100 50–100 10–20 |
1 2 1 |
Block distal tubule mineralocorticoid receptor activity |
9 | Hyperkalemia, especially in CKD and with potassium- sparing agents Spironolactone may cause tender breasts, gynecomastia, and erectile dysfunction in men |
9–20% | Especially useful in resistant hypertension and low-renin states |
| Amiloride Triamterene |
5–10 50–100 |
1 or 2 1 or 2 |
Block distal tubule sodium reabsorption |
NA | Hyperkalemia, especially in CKD or with other agents that favor potassium retention |
Similar to placebo |