How does prolonged hypertension cause left ventricular hypertrophy (LVH)?

Pathophysiology of Left Ventricular Hypertrophy in Prolonged Hypertension

Prolonged hypertension causes left ventricular hypertrophy primarily through increased systolic wall stress, which triggers concentric remodeling with parallel addition of sarcomeres, widening of cardiac myocytes, and increased myocyte cross-sectional area, ultimately leading to increased wall thickness and left ventricular mass. 1

Mechanical and Hemodynamic Mechanisms

• Pressure overload response: Hypertension creates an increased left ventricular output impedance and intramyocardial wall tension, raising myocardial oxygen demand 1
• Concentric remodeling pattern: Initially, pressure elevation leads to increased wall thickness and relative wall thickness (RWT), known as concentric remodeling 1
• Progression to hypertrophy: With sustained pressure overload, systolic wall stress triggers concentric hypertrophy through:
  • Addition of sarcomeres in parallel (widening cardiac myocytes)
  • Increased myocyte cross-sectional area
  • Increased LV wall thickening 1

Cellular and Molecular Adaptations

• Myocyte changes: Cardiac myocytes respond to pressure overload by adding sarcomeres in parallel rather than in series, increasing cell width rather than length 2
• Extracellular matrix changes: The remodeling process involves alterations in:
  • Balance of collagen types I and III
  • Increased collagen fraction
  • Altered myocardial tone 1
• Renin-angiotensin system activation: Chronic hypoxemia, hypercarbia, and acidosis can stimulate the renin-angiotensin system, elevating afterload and contributing to hypertrophy 1

Vascular and Arterial Changes

• Arterial stiffness: Prolonged hypertension leads to:
  • Thinning, fragmentation, and fracture of elastin fibers
  • Increased collagen deposition in arteries
  • Decreased arterial compliance 1
• Wave reflection: Increased arterial stiffness enhances pressure wave reflection, leading to central systolic pressure augmentation, which increases LV pressure load and cardiac work 1
• Negative intrathoracic pressure: More negative intrathoracic pressure during inspiration increases left ventricular afterload, further contributing to hypertrophy 1

Oxidative Stress and Inflammation

• Oxidative damage: Excessive generation of reactive oxygen species damages endothelial and muscular cells, contributing to vascular remodeling 1
• Inflammatory processes: Oxidative stress stimulates release of chemotactic cytokines and adhesion molecules, promoting a low-grade, self-perpetuating vascular inflammatory process 1
• Myocardial scarring: Chronic pressure overload can produce scarring of the myocardium, further contributing to the pathological remodeling 1

Clinical Implications and Progression

• Functional consequences: LVH leads to:
  • Diastolic dysfunction
  • Coronary perfusion abnormalities
  • Increased sensitivity to ischemic injury 2
• Disease progression: Without intervention, LVH can progress from compensated hypertrophy to heart failure, often with increased LV volumes and decreased ejection fraction 2
• Mortality risk: LVH represents an independent risk factor for cardiovascular morbidity and mortality 3

Therapeutic Considerations

• Regression potential: Controlling arterial pressure, sodium restriction, and weight loss independently facilitate regression of LVH 3
• Medication selection: Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and calcium channel antagonists most rapidly facilitate regression of LVH 3, 4
• Blood pressure targets: Current guidelines indicate a blood pressure target in most patients with hypertensive LVH of 120-130/80 mmHg 4

Understanding this pathophysiology is crucial for early detection and management of LVH in hypertensive patients, as regression of LVH reduces cardiovascular morbidity and mortality, improves diastolic function, enhances coronary flow reserve, and decreases cardiovascular risk.