What is hypertension, its assessment, pharmacology, and pathophysiology?

Hypertension: Assessment, Pharmacology, and Pathophysiology

Hypertension is defined as persistent systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg, affecting approximately 116 million adults in the US and over 1 billion adults worldwide, significantly increasing risk of cardiovascular disease events, stroke, heart failure, and kidney disease. 1, 2

Definition and Diagnosis

• Blood Pressure Classification:

  • Normal: <120/80 mmHg
  • Elevated: 120-129/<80 mmHg
  • Hypertension: ≥130/80 mmHg 1

• Diagnostic Approach:

  • Blood pressure should be measured at every routine clinical visit or at least every 6 months 1
  • Confirm elevated readings using multiple measurements, including on separate days 1
  • Consider 24-hour ambulatory blood pressure monitoring or home BP monitoring to exclude white-coat hypertension 3
  • Normal values for 24-hour ABPM: 24-hour average <126/76 mmHg; awake average <132/79 mmHg; sleep average <114/66 mmHg 3

Pathophysiology

Hypertension involves complex interactions between genetic, environmental, and multiple organic systems 3:

1. Endothelial Dysfunction:

   • Impaired production of vasodilators (nitric oxide, prostacyclin)
   • Overexpression of vasoconstrictors (thromboxane A2, endothelin-1)
   • Results in elevated vascular tone 3

2. Vascular Remodeling:

   • Affects all layers of vascular wall
   • Involves proliferative and obstructive changes
   • Increased production of extracellular matrix
   • Leads to increased peripheral vascular resistance 3

3. Neurohormonal Activation:

   • Renin-angiotensin-aldosterone system dysregulation
   • Sympathetic nervous system overactivity
   • Contributes to sodium retention and vasoconstriction 3

4. Genetic Factors:

   • Polygenic complex disorder with multiple genetic influences
   • More than 25 rare mutations and 120 single nucleotide polymorphisms identified
   • Collective effect of identified loci represents only ~3.5% of blood pressure variability 3

Risk Factors

• Excessive dietary sodium intake
• Poor dietary potassium, calcium, and magnesium
• Overweight and obesity
• Physical inactivity
• Excessive alcohol consumption
• Psychosocial stress
• Diabetes mellitus
• Chronic kidney disease 1, 3

Target Organ Damage

Untreated hypertension leads to damage in multiple systems:

1. Cardiovascular:

   • Left ventricular hypertrophy
   • Coronary artery disease
   • Heart failure
   • Peripheral arterial disease 3, 4

2. Renal:

   • Chronic kidney disease
   • Decreased glomerular filtration rate
   • Proteinuria 1, 3

3. Neurological:

   • Stroke
   • Cognitive decline
   • Dementia 3, 4

4. Ocular:

   • Hypertensive retinopathy 3

5. Vascular:

   • Macro and microangiopathy
   • Accelerated atherosclerosis 3, 5

Assessment

1. Medical History:

   • Duration and severity of hypertension
   • Prior treatments and responses
   • Current medications (including OTC and herbal)
   • Symptoms of secondary causes
   • Family history
   • Cardiovascular risk factors 1

2. Physical Examination:

   • Accurate BP measurement (proper cuff size, patient position)
   • BMI calculation
   • Signs of target organ damage
   • Signs of secondary hypertension 1

3. Laboratory Testing:

   • Basic metabolic panel (electrolytes, renal function)
   • Lipid profile
   • Urinalysis
   • Electrocardiogram 1

4. Secondary Hypertension Screening (when suspected):

   • Obstructive sleep apnea (snoring, witnessed apnea, daytime sleepiness)
   • Primary aldosteronism (elevated aldosterone/renin ratio)
   • Chronic kidney disease (creatinine clearance <30 ml/min)
   • Renal artery stenosis (young female, atherosclerotic disease, worsening renal function)
   • Pheochromocytoma (episodic hypertension, palpitations, diaphoresis)
   • Cushing's syndrome (moon facies, central obesity, abdominal striae) 1

Pharmacological Management

First-line medications include:

1. Thiazide or Thiazide-like Diuretics:

   • Hydrochlorothiazide, chlorthalidone
   • Mechanism: Inhibit sodium-chloride cotransporter in distal tubule

2. ACE Inhibitors:

   • Lisinopril, enalapril
   • Mechanism: Inhibit conversion of angiotensin I to angiotensin II
   • Indicated for hypertension to lower blood pressure and reduce risk of fatal and non-fatal cardiovascular events 6

3. Angiotensin Receptor Blockers (ARBs):

   • Candesartan, losartan
   • Mechanism: Block angiotensin II type 1 receptor

4. Calcium Channel Blockers:

   • Amlodipine, nicardipine
   • Mechanism: Block L-type calcium channels in vascular smooth muscle
   • Indicated for hypertension treatment to reduce risk of fatal and nonfatal cardiovascular events 7

Treatment Goals:

• Target BP <130/80 mmHg for most patients 1
• Goals should be individualized based on cardiovascular risk, medication side effects, and patient preferences 1
• In pregnant individuals with diabetes and chronic hypertension, a threshold of 140/90 mmHg for treatment initiation is recommended 1

Hypertensive Crisis Management

Hypertensive crisis (BP >180/120 mmHg) requires immediate attention:

• Hypertensive Emergency (with end-organ damage):

  • Requires ICU admission
  • IV antihypertensive medications (labetalol, nicardipine, clevidipine)
  • Avoid rapid excessive BP reduction 8

• Hypertensive Urgency (without significant end-organ damage):

  • May be treated with oral medications
  • Close follow-up 8

Special Populations

1. Chronic Kidney Disease:

   • RAS modulators (ACEi or ARB) preferred
   • Target BP <130/80 mmHg
   • Multiple medications typically required 1

2. Diabetes:

   • Target BP <130/80 mmHg
   • ACEi or ARB preferred as part of regimen
   • Average of 2.8-4.2 medications needed for control 1

3. Resistant Hypertension:

   • Defined as BP >140/90 mmHg despite optimal doses of ≥3 medications including a diuretic
   • Screen for secondary causes
   • Consider specialist referral 1

Non-Pharmacological Interventions

• Weight loss in overweight/obese patients
• DASH diet (rich in fruits, vegetables, low-fat dairy)
• Sodium restriction (<2.3g/day)
• Regular physical activity (150 min/week moderate-intensity)
• Alcohol limitation (≤2 drinks/day for men, ≤1 drink/day for women)
• Smoking cessation 2

Effective hypertension management requires comprehensive assessment, appropriate medication selection, and consistent monitoring to prevent target organ damage and reduce cardiovascular morbidity and mortality.