Essential Hypertension

Key Diagnostic Criteria

• American College of Cardiology (ACC)/American Heart Association (AHA) 2017 Guidelines:
  • Normal BP: Systolic <120 mmHg and diastolic <80 mmHg.
  • Elevated BP: Systolic 120–129 mmHg and diastolic <80 mmHg.
  • Hypertension Stage 1: Systolic 130–139 mmHg or diastolic 80–89 mmHg.
  • Hypertension Stage 2: Systolic ≥140 mmHg or diastolic ≥90 mmHg.
• European Society of Cardiology (ESC)/European Society of Hypertension (ESH):
  • Hypertension is defined as:
    • Office BP: Systolic ≥140 mmHg and/or diastolic ≥90 mmHg.
    • 24-hour Ambulatory BP: Systolic ≥130 mmHg or diastolic ≥80 mmHg.
    • Daytime BP: Systolic ≥135 mmHg or diastolic ≥85 mmHg.
    • Nighttime BP: Systolic ≥120 mmHg or diastolic ≥70 mmHg.
• World Health Organization (WHO):
  • Diagnosis of hypertension begins at a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, with pharmacologic treatment initiated after confirmation.
    
    

Specific Subtypes

• Isolated Systolic Hypertension: Systolic BP ≥130 mmHg and diastolic <80 mmHg.
• Isolated Diastolic Hypertension: Systolic BP <130 mmHg and diastolic ≥80 mmHg.
  
  

Diagnostic Approach

1. Measurement Techniques:
   • Use standardised office measurements.
   • Confirm with out-of-office monitoring methods like Ambulatory Blood Pressure Monitoring (ABPM) or Home Blood Pressure Monitoring (HBPM).
   • ABPM is preferred for identifying conditions like white-coat hypertension and masked hypertension.
2. Criteria for Hypertension Using ABPM/HBPM:
   • 24-hour Mean BP: Systolic ≥125 mmHg or diastolic ≥75 mmHg.
   • Daytime Mean BP: Systolic ≥130 mmHg or diastolic ≥80 mmHg.
   • Nighttime Mean BP: Systolic ≥110 mmHg or diastolic ≥65 mmHg.
3. Confirmatory Requirements:
   • Repeat measurements on two or more separate occasions are needed for diagnosis.
   • Utilise ABPM or HBPM to confirm persistent elevation.
     
     

Associated Guidelines for Blood Pressure Goals

• ACC/AHA: Target <130/80 mmHg for all adults with confirmed hypertension.
• ESC/ESH: Initial target <140/90 mmHg, with further reduction to <130/80 mmHg if tolerated.
• WHO: Aim for <140/90 mmHg universally, with stricter targets for patients with comorbidities like diabetes or chronic kidney disease.

Primary Hypertension

1. Disruption of Auto-Regulation
   • Reflex mechanisms that normally balance vascular resistance and cardiac output fail, leading to persistent increases in blood pressure.
2. Dietary Sodium Intake
   • High sodium intake elevates blood pressure via fluid retention and vascular changes. Sodium sensitivity varies among individuals.
3. Renal Sodium Retention
   • Impaired renal sodium excretion increases extracellular fluid volume, driving hypertension.
4. Renin-Angiotensin-Aldosterone System (RAAS) Dysregulation
   • Elevated plasma renin activity promotes sodium retention and vasoconstriction, amplifying hypertension.
5. Increased Sympathetic Nervous System Activity
   • Chronic activation elevates cardiac output and peripheral resistance, contributing to sustained hypertension.
6. Endothelial Dysfunction
   • Reduced nitric oxide bioavailability and increased oxidative stress impair vasodilation.
7. Cell Membrane Transporter Abnormalities
   • Altered ion transport mechanisms affect vascular tone and responsiveness.
8. Insulin Resistance and Hyperinsulinaemia
   • These states promote sodium retention, sympathetic activation, and vascular dysfunction.
9. Genetic Predisposition
   • Studies suggest heritability accounts for 33–57% of blood pressure variability. Genome-wide association studies have identified loci linked to hypertension.
10. Epigenetics
    • Environmental exposures, such as stress or a high-salt diet, can induce epigenetic modifications that influence blood pressure regulation.
      
      

Environmental and Lifestyle Contributors

1. Obesity
   • Increased adiposity raises blood pressure through insulin resistance, sympathetic activation, and hormonal changes.
2. Dietary Patterns
   • High-sodium, low-potassium diets exacerbate hypertension risk.
3. Physical Inactivity
   • Sedentary behavior is associated with reduced vascular compliance and increased peripheral resistance.
4. Alcohol Consumption
   • Excessive alcohol intake increases blood pressure in a dose-dependent manner.
5. Psychosocial Stress and Sleep Deprivation
   • Chronic stress and insufficient sleep disrupt autonomic regulation of blood pressure.
6. Environmental Factors
   • Exposure to air pollution and noise has been linked to higher blood pressure.
     
     

Key Mechanisms in the Pathogenesis of Hypertension

1. Blood Pressure Regulation
   • Formula: BP = CO × SVR.
   • BP changes dynamically to maintain organ perfusion. The primary regulators include:
     • Sympathetic Nervous System (SNS): Enhances cardiac output and vasoconstriction.
     • Renin-Angiotensin-Aldosterone System (RAAS): Promotes sodium retention, water reabsorption, and vascular constriction.
     • Kidneys: Regulate plasma volume and sodium excretion.
2. Structural and Functional Vascular Changes
   • Remodeling and hypertrophy of resistance arterioles increase SVR.
   • Endothelial dysfunction, characterised by reduced nitric oxide bioavailability, promotes vasoconstriction and oxidative stress.
3. Sodium Handling and Volume Expansion
   • Excessive sodium intake and renal sodium retention expand intravascular volume, increasing CO and BP.
4. Neurohormonal Dysregulation
   • Overactivation of the SNS contributes to increased vascular tone and cardiac stimulation.
   • Dysregulated RAAS amplifies sodium retention and vasoconstriction.
5. Immune System Activation
   • Emerging evidence implicates immune cells, particularly T-lymphocytes, in hypertension:
     • Lipid oxidation products act as neoantigens, activating T-cells that infiltrate vascular and renal tissues.
     • Cytokines such as interleukin-17 and tumor necrosis factor-alpha exacerbate vascular inflammation.
       
       

Natural History and Progression

1. Prehypertension (Ages 10–30 Years):
   • Elevated CO with normal SVR due to increased blood volume and adrenergic activity.
2. Early Hypertension (Ages 20–40 Years):
   • Peripheral resistance rises due to vascular remodeling and sustained SNS activity.
3. Established Hypertension (Ages 30–50 Years):
   • Vascular resistance becomes the dominant factor as cardiac output normalises or slightly decreases.
4. Complicated Hypertension (Ages 40–60 Years):
   • Chronic hypertension results in end-organ damage, including atherosclerosis, left ventricular hypertrophy, renal dysfunction, and cerebrovascular changes.
     
     

Contributing Factors and Novel Insights

1. Oxidative Stress and Endothelial Injury
   • Persistent oxidative stress damages vascular endothelium, leading to thrombotic and inflammatory cascades that perpetuate hypertension.
2. Role of the Microbiome
   • Altered gut microbiota has been implicated in immune dysregulation and increased BP, though mechanisms remain under investigation.
3. Cortisol Reactivity and Stress
   • Increased hypothalamic-pituitary-adrenal (HPA) axis activity under chronic stress elevates BP through sustained cortisol secretion.
4. Systemic Inflammation
   • Hypertension is associated with chronic low-grade inflammation, mediated by immune cells and inflammatory cytokines.
5. Genetic and Epigenetic Influences
   • Genetic predisposition contributes to susceptibility, while environmental factors (e.g., diet, stress) drive epigenetic modifications that influence RAAS, SNS, and vascular function.
     
     

End-Organ Damage

• Cardiovascular: Left ventricular hypertrophy, atherosclerosis, and heart failure.
• Renal: Nephrosclerosis and chronic kidney disease.
• Neurological: Increased risk of stroke, vascular dementia, and hypertensive encephalopathy.
• Ophthalmic: Hypertensive retinopathy.
  
  

Research 

• Studies have demonstrated the critical role of systolic BP in predicting cardiovascular complications. Systolic BP rises progressively with age, whereas diastolic BP stabilises or declines after midlife.
• Immune modulation therapies and microbiome-targeted interventions are being explored as potential treatments for resistant hypertension.
  
  

Global Prevalence

• Over 1 billion adults globally have hypertension, affecting approximately 26% of the world’s population, with projections estimating an increase to 29% (1.5 billion individuals) by 2025.
• The prevalence rises with age, affecting 60% of individuals aged 60 years or older.
• Hypertension is the leading modifiable risk factor for cardiovascular diseases, accounting for substantial disability-adjusted life years (DALYs) and mortality worldwide.
  
  

Regional Variations

1. High-Income Countries
   • Declines in prevalence have been noted due to increased awareness, better treatment, and effective blood pressure control programs.
   • Less than 25% of hypertensive individuals have adequate blood pressure control (BP <140/90 mmHg).
2. Low- and Middle-Income Countries
   • Rising rates of hypertension are driven by urbanisation, dietary changes, and reduced physical activity.
   • Hypertension management remains inadequate, with most affected individuals untreated or poorly controlled.
     
     

United States Epidemiology

• National Health and Nutrition Examination Surveys (NHANES):
  • 46.7% of adults aged ≥20 years have hypertension, equating to over 122.4 million individuals.
  • Prevalence by age groups:
    • 20–44 years: 28.5%
    • 45–64 years: 58.6%
    • ≥65 years: 76.5%
  • Control rates declined from 54.1% (2013–2014) to 48.3% (2017–2020), with a slight improvement to 51.1% by 2023.
• Sex and Ethnicity:
  • Men have a higher prevalence of hypertension than women before 65 years of age, reversing in older age groups.
  • Non-Hispanic Black populations exhibit the highest prevalence, associated with increased rates of end-stage renal disease (ESRD), stroke, and cardiovascular mortality.
    
    

United Kingdom

• In England, hypertension affects 31% of men and 26% of women, with over 25% of the adult population diagnosed with high blood pressure.
  
  

Key Risk Factors and Trends

1. Age and Sex:
   • Prevalence increases with age.
   • Females have lower rates until the fifth decade, after which their rates exceed those of males.
2. Ethnicity:
   • Hypertension is more common and severe among Black individuals, with higher rates of associated complications.
3. Lifestyle Factors:
   • Sedentary behavior, high sodium intake, and obesity contribute significantly to hypertension prevalence.
     
     

Future Trends

• The global burden of hypertension is expected to rise, particularly in developing nations, unless substantial interventions are implemented to address its primary risk factors and improve treatment accessibility.
  
  

1. Confirmation of Hypertension Diagnosis
   • Elevated BP confirmed by multiple readings on at least three separate occasions.
   • Documentation of the average BP from two or more readings during each visit.
2. Duration and Course of Hypertension
   • Onset and progression of BP readings.
   • Last known normal BP and history of previous measurements.
3. Assessment of End-Organ Damage
   • Cardiac: Left ventricular hypertrophy, heart failure, angina, or history of myocardial infarction.
   • Neurological: Stroke, transient ischemic attack, or cognitive decline.
   • Renal: Chronic kidney disease or reduced estimated glomerular filtration rate (eGFR).
   • Ophthalmic: Hypertensive retinopathy.
   • Peripheral Arterial Disease: Claudication or reduced peripheral pulses.
4. Cardiovascular Risk Factors
   • Smoking, dyslipidemia, diabetes mellitus, obesity (BMI ≥30 kg/m²), and sedentary lifestyle.
   • Microalbuminuria and elevated LDL cholesterol or low HDL cholesterol.
   • Family history of premature cardiovascular disease (men <55 years, women <65 years).
5. Potential Secondary Causes of Hypertension
   • Renal diseases (e.g., chronic kidney disease, renovascular hypertension).
   • Endocrine disorders (e.g., primary aldosteronism, pheochromocytoma, Cushing syndrome, hyperthyroidism, or hypothyroidism).
   • Obstructive sleep apnea (OSA).
   • Drug-induced hypertension (e.g., oral contraceptives, NSAIDs, corticosteroids, sympathomimetics, or illicit drugs such as cocaine).
6. Lifestyle and Dietary Factors
   • Dietary History: High sodium intake, processed foods, and low fruit and vegetable consumption.
   • Physical Activity: Aerobic exercise frequency and intensity.
   • Alcohol Consumption: Chronic intake exceeding 1 drink/day for women and 2 drinks/day for men.
   • Psychosocial Stressors: Work status, educational level, and family structure.
7. History of Medication Use
   • Current and prior antihypertensive treatments: effectiveness, side effects, and adherence.
   • Over-the-counter medications and supplements: NSAIDs, decongestants, herbal products (e.g., licorice root).
8. Symptoms Suggesting Secondary Hypertension
   • Palpitations, sweating, and labile hypertension (pheochromocytoma).
   • Flank pain (renal causes).
   • Muscle weakness (hyperaldosteronism).
   • Daytime somnolence, loud snoring, and morning headaches (OSA).
9. Symptoms of Target-Organ Damage
   • Neurological: Headaches, transient blindness, or motor/sensory deficits.
   • Cardiac: Chest pain or dyspnea.
   • Renal: Reduced urinary output or hematuria.
   • Ophthalmic: Visual disturbances, floaters, or papilledema.
     
     

Risk Factors and Strong Associations

1. Age and Sex
   • Incidence increases with age.
   • Hypertension is more common in men before age 65 and in women after 65.
2. Ethnicity
   • Highest prevalence in Black individuals, who experience earlier onset, more severe hypertension, and greater risk of complications.
3. Obesity
   • A strong association exists between abdominal obesity and hypertension due to increased circulating volume and vascular resistance.
4. Alcohol and Smoking
   • Chronic alcohol intake raises BP in a dose-dependent manner.
   • Smoking acutely raises BP and exacerbates cardiovascular risk.
5. Comorbidities
   • Diabetes mellitus and metabolic syndrome are frequently associated with hypertension and increase cardiovascular morbidity.

Blood Pressure (BP) Measurement

1. Ensure accuracy by:
   • Using a validated device and an appropriately sized cuff, particularly for larger arm circumferences (>30 cm).
   • Measuring BP in both arms and one leg on the first visit to detect conditions such as coarctation of the aorta or subclavian artery stenosis.
   • Repeating measurements at 1–2 minute intervals during the visit and averaging at least two readings.
2. Evaluate for "nondipping" BP patterns using ambulatory BP monitoring, which is associated with increased cardiovascular risk.
   
   

General Inspection

1. General Appearance: Assess for obesity, central fat distribution, or signs of metabolic syndrome.
2. Skin: Look for features of hypercortisolism (thin skin, easy bruising) or secondary hypertension causes.
3. Alertness: Note confusion or altered mental status, which may indicate hypertensive encephalopathy.
   
   

Cardiac Examination

1. Heart Sounds:
   • Fourth heart sound (S4): Suggests left ventricular hypertrophy or diastolic dysfunction.
   • Systolic ejection murmur: May indicate aortic valve disease.
   • Tambour second sound (S2): Associated with aortic root dilatation.
2. Apical Impulse:
   • Displacement and enlargement suggest left ventricular hypertrophy.
3. Peripheral Oedema and Rales:
   • Indicative of cardiac dysfunction and chronic hypertension.
     
     

Vascular Examination

1. Coarctation of the Aorta:
   • Look for radio-radial or radio-femoral pulse delay and a >20 mmHg BP difference between the arms or between upper and lower limbs.
2. Bruits:
   • Carotid or abdominal bruits may indicate renovascular hypertension or fibromuscular dysplasia (FMD).
     
     

Abdominal Examination

1. Palpation:
   • Detect renal masses, as in polycystic kidney disease.
2. Auscultation:
   • Renal artery bruits with systolic and diastolic components suggest renovascular disease.
     
     

Funduscopic Examination

1. Hypertensive Retinopathy:
   • Retinal changes include:
     • Hemorrhages, cotton-wool spots, and hard exudates.
     • Arteriolar narrowing, arteriovenous nicking, or copper/silver wiring.
     • Papilledema in severe or malignant hypertension.
   • Retinopathy is associated with higher risks of stroke and cardiovascular events.
     
     

Endocrine Assessment

1. Thyroid Gland:
   • Palpate for enlargement or nodules, suggestive of hypothyroidism or hyperthyroidism.
2. Adrenal Function:
   • Symptoms like muscle weakness and hyperpigmentation may indicate hyperaldosteronism or Cushing syndrome.
     
     

Neurological Examination

1. Look for:
   • Visual disturbances (e.g., transient blindness or papilledema).
   • Focal neurological deficits, which may indicate stroke or transient ischemic attack.
     
     

Signs Suggesting Secondary Hypertension

• Renovascular Hypertension: Abdominal bruit, especially with both systolic and diastolic components.
• Endocrine Disorders: Features such as hyperglycemia, truncal obesity, or abnormal skin findings.
• Obstructive Sleep Apnea (OSA): Daytime somnolence, loud snoring, and morning headaches.

• Measure BP in both arms.
• If inter-arm difference >15 mmHg, repeat measurements and use the higher reading arm for subsequent assessments.
  
  

• If BP is ≥140/90 mmHg:
  • Take a second reading; if substantially different, take a third.
  • Record the lower of the last two measurements as the clinic BP.
    
    

• For clinic BP between 140/90 mmHg and 180/120 mmHg, confirm with:
  • Ambulatory BP Monitoring (ABPM): Average at least 14 readings taken during usual waking hours.
  • Home BP Monitoring (HBPM): Record twice daily for at least 4 days (preferably 7); average the readings excluding the first day.
    
    

• Hypertension is confirmed with:
  • Clinic BP ≥140/90 mmHg and
  • ABPM daytime average or HBPM average ≥135/85 mmHg.
    
    

• Assess for target organ damage and evaluate cardiovascular risk using appropriate tools.
  
  

Initial Investigations

1. Urinary Albumin-to-Creatinine Ratio (UACR)
   • Detects microalbuminuria, an early marker of chronic kidney disease (CKD) and end-organ damage.
   • Recommended for all newly diagnosed hypertensive patients.
   • For moderate-to-severe CKD, repeat UACR, serum creatinine, and estimated glomerular filtration rate (eGFR) annually.
2. Urinalysis
   • Screens for secondary hypertension and underlying renal disease.
   • Findings:
     • Proteinuria or haematuria suggests renal involvement.
3. Electrocardiogram (ECG)
   • Detects:
     • Left ventricular hypertrophy.
     • Past myocardial infarction or arrhythmias.
   • A normal ECG does not exclude coronary artery disease.
4. Fasting Metabolic Panel with eGFR
   • Evaluates:
     • Renal function (e.g., GFR and creatinine).
     • Electrolyte imbalances (e.g., hypokalemia in hyperaldosteronism).
     • Hyperglycemia, hypercalcemia, or hyperuricemia.
5. Lipid Panel
   • Hypertension frequently coexists with dyslipidemia.
   • May reveal:
     • Elevated LDL cholesterol.
     • Low HDL cholesterol.
     • Elevated triglycerides.
6. Thyroid-Stimulating Hormone (TSH)
   • Indicated if thyroid dysfunction is suspected.
   • Abnormal results suggest hypo- or hyperthyroidism.
7. Haemoglobin and Hematocrit
   • Findings:
     • Anaemia: Suggests chronic kidney disease.
     • Polycythemia: Associated with pheochromocytoma.
       
       

Additional Investigations 

1. Plasma Renin Activity and Aldosterone Levels
   • Indicated for:
     • Unprovoked hypokalemia.
     • Resistant hypertension or adrenal incidentaloma.
   • Findings:
     • Low renin and elevated aldosterone suggest primary hyperaldosteronism.
2. Renal Imaging (Ultrasound, MRA, CT Angiography)
   • Indicated in:
     • Young patients (<40 years) with severe hypertension.
     • Renal artery bruit.
   • Detects:
     • Renal artery stenosis or fibromuscular dysplasia.
3. 24-Hour Urine Catecholamines and Plasma Fractionated Metanephrines
   • Indicated with signs of catecholamine excess (e.g., episodic hypertension, palpitations).
   • Elevated levels suggest pheochromocytoma.
4. Sleep Study
   • Considered in:
     • Resistant hypertension.
     • Symptoms of obstructive sleep apnea (OSA) such as loud snoring, daytime fatigue, or morning headaches.
5. 24-Hour Urine Free Cortisol
   • Indicated for suspected Cushing’s syndrome.
   • Elevated levels confirm hypercortisolism.
6. Echocardiography
   • Assesses left ventricular function and hypertrophy.
   • Provides prognostic insights in hypertensive patients.
     
     

Advanced Imaging

• Digital Subtraction Angiography (DSA):
  • Gold standard for renal artery evaluation, though invasive and associated with risks such as contrast nephropathy.
• Carotid Doppler Ultrasound and Brain Imaging:
  • Performed if cerebrovascular disease or carotid artery stenosis is suspected.
    
    

Cardiovascular Risk and Target-Organ Damage Assessment

1. Ankle-Brachial Index (ABI)
   • Indicates peripheral arterial disease if <0.9.
2. Fundoscopy
   • Detects hypertensive retinopathy:
     • Arteriovenous nicking, hemorrhages, papilledema, or cotton-wool spots.
3. Pulse Wave Velocity
   • Predicts hypertension progression in younger adults (age 30–45).
     
     

Secondary Hypertension

Drug-Induced Hypertension

• Signs/Symptoms: History of drug use, including:
  • Nonsteroidal anti-inflammatory drugs (NSAIDs), oral contraceptives, sympathomimetics, herbal remedies (e.g., liquorice, black cohosh), or certain immunosuppressants (e.g., cyclosporine, tacrolimus).
  • Symptoms of acute intoxication, withdrawal, or cravings in cases of substance use (e.g., cocaine).
• Investigations:
  • Drug toxicology screen.
  • Hypokalemia with excessive liquorice ingestion.
    
    

Renal Causes

1. Chronic Kidney Disease (CKD):
   • Signs/Symptoms: Pruritus, edema, or altered urine output.
   • Investigations:
     • Elevated serum creatinine and albuminuria.
     • Renal ultrasound may show sclerotic or polycystic kidneys.
2. Renal Artery Stenosis:
   • Signs/Symptoms: Difficult-to-control hypertension in younger patients or older individuals with atherosclerosis. Renal bruits may be present.
   • Investigations:
     • Renal duplex ultrasound, magnetic resonance angiography (MRA), or CT angiography confirms diagnosis.
       
       

Endocrine Causes

1. Hyperaldosteronism:
   • Signs/Symptoms: Hypokalemia, mild hypernatremia, and metabolic alkalosis.
   • Investigations:
     • High plasma aldosterone and low renin levels.
     • Failure of aldosterone suppression with salt loading.
2. Cushing’s Syndrome:
   • Signs/Symptoms: Weight gain, abdominal striae, moon face, dorsocervical fat pad.
   • Investigations:
     • Abnormal dexamethasone suppression test.
     • Elevated 24-hour urine free cortisol or late-night salivary cortisol.
3. Pheochromocytoma:
   • Signs/Symptoms: Episodic hypertension, flushing, headaches, and palpitations.
   • Investigations:
     • Elevated urinary or plasma metanephrines and catecholamines.
4. Thyroid Dysfunction:
   • Hypothyroidism: Dry skin, cold intolerance, weight gain, and bradycardia.
     • Elevated thyroid-stimulating hormone (TSH) and low free T4.
   • Hyperthyroidism: Heat intolerance, weight loss, tachycardia, and tremors.
     • Suppressed TSH and elevated free T4/T3.
5. Hyperparathyroidism:
   • Signs/Symptoms: Hypercalcemia, renal colic, or abdominal pain.
   • Investigations:
     • Elevated parathyroid hormone (PTH) and serum calcium.
6. Acromegaly:
   • Signs/Symptoms: Acral enlargement (hands, feet, jaw).
   • Investigations:
     • Elevated insulin-like growth factor-1 (IGF-1).
     • Lack of growth hormone suppression with glucose loading.
       
       

Cardiovascular Causes

1. Coarctation of the Aorta:
   • Signs/Symptoms: Differential BP between upper and lower limbs, absent femoral pulses.
   • Investigations:
     • Echocardiography, CT angiography, or MRI.
2. Collagen Vascular Disease:
   • Signs/Symptoms: Sclerodactyly, vasculitis, or systemic lupus erythematosus manifestations.
   • Investigations:
     • Positive autoimmune markers (e.g., anti-DNA, anti-Smith antibodies).
       
       

Obstructive Sleep Apnea (OSA)

• Signs/Symptoms: Daytime somnolence, snoring, and choking during sleep.
• Investigations:
  • Polysomnography shows nocturnal oxygen desaturation.
    
    

Gestational Hypertension

• Signs/Symptoms: Hypertension detected after 20 weeks of gestation.
• Investigations:
  • Urinary albumin excretion to evaluate for pre-eclampsia.
    
    

Rare Causes

1. Congenital Adrenal Hyperplasia:
   • Associated with hypokalemia, hypertension, and low renin levels.
2. Drug-Induced Secondary Causes:
   • Includes erythropoietin, chemotherapy agents (e.g., bevacizumab), and tyrosine kinase inhibitors.
     
     

Goals of Treatment

• Reduce mortality and morbidity related to cardiovascular and renal complications.
• Target Blood Pressure (BP):
  • ACC/AHA: <130/80 mmHg for all adults with confirmed hypertension and cardiovascular risk ≥10%.
  • ESC/ESH: <140/90 mmHg initially, with gradual reduction to <130/80 mmHg if well tolerated.
  • WHO: <140/90 mmHg for general patients; <130/80 mmHg for high-risk groups.
    
    

Lifestyle Modifications

• Sodium reduction (<1.5 g/day), potassium supplementation (3.5–5.0 g/day), and adherence to the DASH diet.
• Weight loss to maintain BMI ~25 kg/m² and waist circumference <102 cm (men) or <88 cm (women).
• At least 150 minutes/week of moderate aerobic activity.
• Limit alcohol intake (<20–30 g/day for men, <10–20 g/day for women).
• Smoking cessation and managing dyslipidemia.
  
  

Pharmacologic Treatment

1. Stage 1 Hypertension:
   • Initiate with lifestyle changes; add monotherapy if cardiovascular risk ≥10%.
   • Options: thiazide diuretics, ACE inhibitors, angiotensin-II receptor blockers (ARBs), or calcium channel blockers (CCBs).
2. Stage 2 Hypertension:
   • Start with a combination of two drugs (e.g., ACE inhibitor + CCB).
3. Resistant Hypertension:
   • Add spironolactone or consider α-blockers, β-blockers, or hydralazine if uncontrolled with 3 drugs.
     
     

Management of Hypertension: Comprehensive Approach

• The primary goal is to reduce cardiovascular and renal morbidity and mortality.
• Evidence-Based Targets:
  • SPRINT Trial: Lowering systolic BP to 120 mmHg reduced cardiovascular events in high-risk adults without diabetes.
  • HOPE-3 Trial: BP lowering benefits were significant only in patients with baseline systolic BP >143.5 mmHg.
    
    

1. Diet:
   • Sodium intake ≤1.5 g/day.
   • Potassium-rich diet unless contraindicated.
   • DASH diet: 8–10 servings of fruits and vegetables daily.
2. Physical Activity:
   • 30 minutes of moderate aerobic exercise on most days.
3. Weight Management:
   • Aim for BMI ~25 kg/m²; reduce abdominal obesity.
4. Alcohol Intake:
   • Men: ≤2 drinks/day; Women: ≤1 drink/day.
5. Smoking Cessation:
   • Improves vascular health but not directly linked to BP reduction.
6. Other:
   • Discourage excess caffeine and recommend structured interventions for adherence.
     
     

• First-line Options:
  1. Angiotensin-Converting Enzyme (ACE) Inhibitors:
     • Examples: Lisinopril, Ramipril, Enalapril.
     • Mechanism: Inhibits the conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion.
     • Indications:
       • Preferred in younger patients (<55 years) without Black ancestry.
       • Particularly effective in patients with diabetes, chronic kidney disease (CKD), or heart failure.
     • Side Effects: Dry cough (due to bradykinin accumulation), angioedema, hyperkalemia.
     • Contraindications: Pregnancy, history of angioedema, bilateral renal artery stenosis.
  2. Angiotensin-II Receptor Blockers (ARBs):
     • Examples: Losartan, Valsartan, Candesartan.
     • Mechanism: Block angiotensin II from binding to its receptor, reducing vasoconstriction and aldosterone effects.
     • Indications:
       • First-line for patients intolerant to ACE inhibitors.
       • Preferred in Black patients due to lower risk of adverse effects.
     • Side Effects: Hyperkalemia, dizziness, rare angioedema.
     • Contraindications: Same as ACE inhibitors.
  3. Calcium Channel Blockers (CCBs):
     • Examples: Amlodipine, Felodipine, Nifedipine (dihydropyridines).
     • Mechanism: Inhibits calcium entry into vascular smooth muscle, promoting vasodilation.
     • Indications:
       • Effective across all age groups and ethnicities.
       • Particularly useful in Black and elderly patients.
     • Side Effects: Peripheral edema, headache, flushing.
     • Non-dihydropyridine CCBs (e.g., Diltiazem, Verapamil) may be used in atrial fibrillation or angina but are less effective for BP reduction.
  4. Thiazide or Thiazide-like Diuretics:
     • Examples: Hydrochlorothiazide, Chlorthalidone, Indapamide.
     • Mechanism: Inhibits sodium reabsorption in the distal tubule, reducing plasma volume.
     • Indications:
       • Effective as monotherapy or in combination.
       • Preferred in Black patients and those with isolated systolic hypertension.
     • Side Effects: Hypokalemia, hyponatremia, hyperuricemia, hyperglycemia.
     • Contraindications: Gout, severe renal impairment.
       
       

• If BP remains uncontrolled with monotherapy, a second antihypertensive agent from a different class should be added.
• Preferred Combination:
  • ACE Inhibitor (or ARB) + CCB:
    • Synergistic effect: ACE inhibitors/ARBs counteract fluid retention caused by CCBs.
    • Example: Ramipril + Amlodipine.
  • Alternatively:
    • ACE Inhibitor (or ARB) + Thiazide Diuretic:
      • Effective in patients with edema or heart failure.
      • Example: Lisinopril + Chlorthalidone.
    • CCB + Thiazide Diuretic:
      • Useful in patients intolerant to renin-angiotensin system blockers.
      • Example: Amlodipine + Hydrochlorothiazide.
        
        

• If BP remains uncontrolled on dual therapy, a combination of three drugs is recommended:
  • ACE Inhibitor (or ARB).
  • CCB.
  • Thiazide or Thiazide-like Diuretic.
• Clinical Considerations:
  • Ensure all drugs are titrated to optimal doses before escalating to triple therapy.
  • Use fixed-dose combination pills where possible to improve adherence.
  • Monitor for adverse effects such as electrolyte imbalances, particularly hypokalemia with diuretics.
    
    

1. Add-on Therapy:
   • Spironolactone (Preferred):
     • Mechanism: Aldosterone antagonist, reduces sodium retention.
     • Indications: Effective in resistant hypertension, particularly in primary aldosteronism.
     • Dose: Typically 25–50 mg daily.
     • Side Effects: Hyperkalemia, gynecomastia (less with eplerenone).
     • Contraindications: Severe renal impairment, hyperkalemia.
   • Eplerenone:
     • Alternative to spironolactone with fewer endocrine side effects.
2. Alternative Agents:
   • α-Blockers:
     • Examples: Doxazosin, Prazosin.
     • Mechanism: Reduce vascular resistance via alpha-1 receptor blockade.
     • Indications: Considered for patients with concurrent benign prostatic hyperplasia (BPH).
     • Side Effects: Orthostatic hypotension, dizziness.
   • β-Blockers:
     • Examples: Bisoprolol, Carvedilol.
     • Indications: Effective in patients with heart failure, atrial fibrillation, or post-myocardial infarction.
     • Side Effects: Bradycardia, fatigue, worsening asthma.
   • Hydralazine:
     • Mechanism: Direct arterial vasodilation.
     • Indications: Reserved for refractory cases due to side effects.
     • Side Effects: Reflex tachycardia, lupus-like syndrome.
3. Other Considerations:
   • Minoxidil: Potent vasodilator used in rare cases of severe, refractory hypertension. Requires co-prescription of a diuretic and β-blocker.
   • Evaluate for secondary causes of hypertension if resistant hypertension persists despite optimal therapy.
     
     

• Regularly monitor BP, renal function, and electrolytes during therapy.
• Use home BP monitoring (HBPM) or ambulatory BP monitoring (ABPM) to confirm control and assess white-coat or masked hypertension.
• Tailor therapy based on individual response, tolerability, and comorbidities.
  
  

1. Chronic Kidney Disease (CKD):
   • ACE inhibitors or ARBs reduce proteinuria and slow progression.
2. Heart Failure:
   • Reduced ejection fraction: ACE inhibitors, β-blockers, aldosterone antagonists.
   • Preserved ejection fraction: Diuretics for volume control.
3. Diabetes Mellitus:
   • ACE inhibitors or ARBs preferred to protect against nephropathy.
   • Avoid intensive systolic BP targets <120 mmHg.
4. Atrial Fibrillation:
   • β-blockers or non-dihydropyridine CCBs (e.g., diltiazem).
     
     

• Target BP:
  • <140/90 mmHg in most adults.
  • <130/80 mmHg for high-risk patients (e.g., diabetes, CKD).
• Annual review of BP control, adherence, and cardiovascular risk.
  
  

1. Association Between BP Levels and Outcomes:
   • Cardiovascular Risk:
     • Every 20 mmHg rise in systolic BP (SBP) or 10 mmHg rise in diastolic BP (DBP) doubles the risk of ischemic heart disease and stroke mortality.
     • Systolic BP has a more pronounced effect on cardiovascular outcomes compared to diastolic BP, but both independently increase risks.
   • Atherosclerosis and End-Organ Damage:
     • Untreated mild-to-moderate hypertension increases the risk of atherosclerotic disease by 30% and organ damage by 50% within 8–10 years of onset.
   • Resistant Hypertension:
     • Associated with poor outcomes, especially in patients with chronic kidney disease (CKD) or ischemic heart disease.
     • Effective BP control reduces risks for stroke, coronary heart disease, and heart failure.
       
       
2. Impact of BP Control:
   • Clinical trials have demonstrated significant benefits of antihypertensive therapy:
     • Stroke: 35–40% reduction in incidence.
     • Myocardial Infarction: 20–25% reduction in occurrence.
     • Heart Failure: >50% reduction in incidence.
   • Achieving a sustained 12 mmHg reduction in systolic BP over 10 years prevents:
     • 1 death per 11 patients with stage 1 hypertension and cardiovascular risk factors.
     • 1 death per 9 patients with cardiovascular disease or end-organ damage.
       
       
3. Prognostic Impact of Specific Conditions:
   • Hypertensive Retinopathy:
     • Associated with an increased long-term stroke risk, even with controlled BP.
     • Moderate-to-severe retinopathy increases stroke risk 2.37-fold.
   • Diabetes Mellitus:
     • Hypertensive patients with diabetes experience a 57% higher risk of cardiovascular events and a 72% higher all-cause mortality risk.
     • Ambulatory BP monitoring indicates that nocturnal BP reduction ("asleep BP") is the strongest predictor of event-free survival.
   • Chronic Kidney Disease (CKD):
     • Hypertension-induced nephrosclerosis is a leading cause of end-stage renal disease (ESRD).
     • Black patients face a higher ESRD risk, even with well-controlled BP.
       
       

Long-Term Outcomes

1. Morbidity and Mortality:
   • Meta-analyses show increasing SBP and DBP correlate with rising cardiovascular and cerebrovascular mortality.
   • For prehypertension (120–139/80–89 mmHg), patients face a 66% increased stroke risk, with those in the high range (130–139/85–89 mmHg) having a 95% increased risk.
2. Hypertensive Emergencies:
   • Mortality risk depends on the severity of end-organ dysfunction at presentation.
   • With BP control and medication adherence, 10-year survival after hypertensive crises approaches 70%.
3. All-Cause Mortality Trends:
   • While mortality among hypertensive adults has decreased over time, it remains significantly higher than in normotensive individuals.
     
     

Prognostic Impact of BP Variability

• BP variability is an independent risk factor for adverse cardiovascular outcomes.
• Studies, such as the ACCORD trial, suggest limited benefits of aggressive BP control in diabetes for reducing cardiovascular events, though stroke incidence decreases modestly.
  
  

Uncontrolled and Masked Hypertension

1. White-Coat Hypertension:
   • Associated with increased cardiovascular events and all-cause mortality when untreated.
   • No proven benefit of treating white-coat hypertension based on current evidence.
2. Masked Hypertension:
   • Linked to higher prevalence of target organ damage and cardiovascular events compared to normotensive individuals.
   • Preliminary data suggest potential benefits of treatment, but more research is needed.

Major Complications

1. Coronary Heart Disease (CHD) and Myocardial Infarction (MI):
   • Mechanism: Chronic hypertension accelerates atherosclerosis, increasing myocardial oxygen demand and reducing coronary perfusion.
   • Risk: For every 20/10 mmHg increase in BP, the lifetime risk of mortality from ischemic heart disease doubles.
   • Management: Aggressive BP control, lipid management, and antiplatelet therapy.
2. Left Ventricular Hypertrophy (LVH):
   • Prevalence: Seen in >30% of hypertensive patients.
   • Impact: Strongly linked to cardiovascular morbidity and mortality.
   • Treatment: ACE inhibitors, ARBs, and aldosterone antagonists reduce LVH and improve outcomes.
3. Congestive Heart Failure (CHF):
   • Prevalence: Hypertensive patients are three times more likely to develop CHF.
   • Mechanism: Hypertension contributes to systolic and diastolic dysfunction.
   • Management: ACE inhibitors, ARBs, β-blockers, aldosterone antagonists, and SGLT2 inhibitors reduce mortality; diuretics alleviate fluid overload.
4. Aortic Aneurysm and Dissection:
   • Prevalence: Over 70% of aortic dissection cases have a history of hypertension.
   • Impact: High mortality, especially with proximal (type A) dissections.
   • Prevention: BP control is critical to reduce aortic wall stress.
5. Peripheral Artery Disease (PAD):
   • Impact: Hypertension increases the risk of myocardial infarction, stroke, and heart failure in PAD patients.
   • Management: Antihypertensive therapy reduces systemic cardiovascular risks.
     
     

Cerebrovascular System

1. Stroke:
   • Types: Ischemic stroke and intracerebral hemorrhage.
   • Risk: Stroke risk increases linearly with BP levels; for every 20/10 mmHg increase above 115/75 mmHg, mortality doubles.
   • Management: BP control reduces the risk of primary and recurrent strokes.
2. Hypertensive Encephalopathy:
   • Mechanism: Acute BP elevation leads to cerebral edema and neurological dysfunction.
   • Management: Requires rapid BP reduction in controlled settings.
     
     

Renal System

1. Chronic Kidney Disease (CKD):
   • Impact: Hypertension is a leading cause of CKD and end-stage renal disease (ESRD).
   • Disparities: Black patients have a higher risk of ESRD despite BP control.
   • Management: ACE inhibitors and ARBs slow CKD progression by reducing proteinuria.
2. Hypertensive Nephrosclerosis:
   • Prevalence: Common among long-standing hypertensive patients.
   • Outcome: May progress to ESRD without intervention.
     
     

Ocular System

1. Hypertensive Retinopathy:
   • Findings: Includes arteriolar narrowing, haemorrhages, cotton-wool spots, and papilledema.
   • Impact: Associated with increased stroke risk and cardiovascular events.
   • Screening: Fundoscopic exams are recommended for hypertensive patients.
2. Retinal Vascular Occlusion:
   • Risk: Hypertension predisposes patients to retinal vein and artery occlusions.
     
     

Other Complications

1. Hypertensive Emergencies:
   • Definition: Severe BP elevation (>180/120 mmHg) with acute end-organ damage.
   • Management: Requires immediate BP reduction in a monitored setting.
2. Orthostatic Hypotension:
   • Prevalence: Affects ~10% of hypertensive adults, particularly elderly patients.
   • Management: Optimize antihypertensive therapy and monitor for postural symptoms.
     
     

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