What are the physiological mechanisms and treatment options for managing hypertension?

Physiological Mechanisms and Treatment Options for Hypertension Management

Blood pressure management should focus on both lifestyle modifications and pharmacological interventions targeting specific physiological pathways, with a goal of <130/80 mmHg for most patients to reduce cardiovascular morbidity and mortality. 1, 2

Physiological Mechanisms of Blood Pressure Regulation

• The renin-angiotensin-aldosterone system (RAAS) plays a central role in blood pressure regulation, with angiotensin II acting as a potent vasoconstrictor and stimulating aldosterone secretion from the adrenal cortex 3
• Sympathetic nervous system activation increases heart rate, cardiac output, and peripheral vascular resistance, contributing to elevated blood pressure 4
• Sodium and fluid balance regulation by the kidneys is crucial for maintaining blood pressure, with increased sodium retention leading to increased blood volume and hypertension 1
• Vascular endothelial function affects arterial compliance and peripheral resistance, with dysfunction contributing to hypertension 5
• Seasonal variations in blood pressure occur with higher readings during colder temperatures, requiring potential medication adjustments 1

Lifestyle Modifications as First-Line Therapy

• Weight reduction should be prioritized for overweight/obese individuals, as a loss of approximately 5 kg can reduce systolic BP by 4.4 mmHg and diastolic BP by 3.6 mmHg 4, 2
• Dietary approaches should include:
  • DASH (Dietary Approaches to Stop Hypertension) diet with increased fruits, vegetables, and low-fat dairy products 1, 2
  • Sodium restriction to <2.3 g/day (equivalent to about 5 g salt) 1, 2
  • Increased potassium intake through dietary sources to achieve a favorable sodium-to-potassium ratio of 1.5-2.0 1
• Regular aerobic exercise reduces resting systolic and diastolic BP by 3.0/2.4 mmHg in the general population and by 6.9/4.9 mmHg in hypertensive individuals 1, 4
• Alcohol consumption should be limited to no more than 2 standard drinks per day for men and 1 for women 1, 2
• Smoking cessation is essential as smoking causes acute increases in blood pressure and heart rate through sympathetic nervous system stimulation 4, 2

Pharmacological Treatment Strategies

First-Line Medications

• First-line antihypertensive medications include:

  • Thiazide or thiazide-like diuretics (e.g., hydrochlorothiazide, chlorthalidone) 2, 6
  • Angiotensin-converting enzyme (ACE) inhibitors (e.g., lisinopril) 2, 7
  • Angiotensin receptor blockers (ARBs) (e.g., losartan) 2, 3
  • Calcium channel blockers (e.g., amlodipine) 2, 6

• ACE inhibitors and ARBs work by blocking the RAAS pathway, preventing the vasoconstrictor and aldosterone-secreting effects of angiotensin II 7, 3

• Thiazide diuretics act by increasing sodium and water excretion, reducing blood volume and cardiac output 6

• Calcium channel blockers cause arterial vasodilation by preventing calcium entry into vascular smooth muscle cells 6

Combination Therapy Approach

• For most patients with confirmed hypertension (BP ≥140/90 mmHg), combination therapy is recommended as initial treatment 2
• Preferred combinations include a RAAS blocker (ACE inhibitor or ARB) with either a calcium channel blocker or diuretic 2
• Fixed-dose single-pill combinations improve adherence and should be considered 2
• For resistant hypertension (BP uncontrolled on ≥3 medications), mineralocorticoid receptor antagonists like spironolactone are effective add-on agents 8, 9

Special Considerations

Target Blood Pressure Goals

• For most adults, target BP should be <130/80 mmHg 1, 2
• For patients with diabetes, systolic BP target should be <130 mmHg and diastolic BP <80 mmHg 1, 2
• For older adults (≥65 years), frail patients, or those with orthostatic hypotension, higher targets may be appropriate to avoid adverse effects 1

Management of Resistant Hypertension

• Resistant hypertension (BP uncontrolled on ≥3 medications including a diuretic) affects approximately 10% of hypertensive individuals 1
• Evaluate for pseudoresistance (poor BP measurement technique, white coat effect, medication nonadherence) 1, 9
• Screen for secondary causes of hypertension (e.g., primary aldosteronism, renal artery stenosis) 1, 9
• Consider adding a mineralocorticoid receptor antagonist (spironolactone) as a fourth-line agent 8, 9

Common Pitfalls and Monitoring

• Many patients believe not adding salt to food equals a low-sodium diet, but education about checking food labels and hidden sodium sources is essential 2
• Potassium supplementation should be avoided in patients with chronic kidney disease or those taking potassium-sparing medications 1, 2
• Regular monitoring of blood pressure (both office and home measurements) is crucial for assessing treatment efficacy 2
• Medication adherence is a major challenge, with 10-80% of hypertensive patients being non-adherent to treatment 1
• Seasonal variations in blood pressure should be considered when symptoms of over-treatment appear with temperature changes 1