Does hypertension cause atherosclerosis (hardening of the arteries)?

Does Hypertension Cause Hardening of the Arteries?

Yes, hypertension directly causes arterial hardening through both mechanical stress and biochemical mechanisms, leading to diffuse arteriosclerosis and accelerating atherosclerotic plaque formation. 1

Mechanisms of Hypertension-Induced Arterial Hardening

Physical and Mechanical Damage

Elevated blood pressure causes direct structural damage to arterial walls through increased vascular wall tension. 1 This mechanical stress leads to:

• Thinning, fragmentation, and fracture of elastin fibers in the arterial wall, particularly pronounced in individuals with sustained systolic hypertension 1
• Increased collagen deposition replacing damaged elastin, resulting in decreased arterial compliance and increased stiffness 1
• Arterial wall thickening with changes in wall composition that increase effective stiffness 1

The process is particularly accelerated in persons with elevated or high-normal blood pressure starting at an early age, where chronic increased vascular wall tension progressively damages the arterial structure. 1

Oxidative Stress Pathways

Hypertension induces oxidative stress on the arterial wall, which is a critical feature in both hypertension and atherogenesis. 1 The mechanisms include:

• Activation of NAD(P)H oxidases by mechanical forces (elevated blood pressure), generating superoxide anions that damage endothelial and vascular smooth muscle cells 1
• Formation of peroxynitrite through reaction of superoxide with nitric oxide, creating a toxic metabolite that oxidizes lipids and makes them more atherogenic 1
• Endothelial dysfunction developing over time as a consequence of both aging and hypertension, contributing functionally to increased arterial rigidity 1

Humoral and Inflammatory Mechanisms

Hypertension activates the renin-angiotensin-aldosterone system (RAAS), which promotes both arterial stiffening and atherosclerosis through multiple pathways. 1 Specifically:

• Angiotensin II promotes vascular smooth muscle cell hypertrophy directly via AT1 receptor activation and indirectly by stimulating growth factors (platelet-derived growth factor, basic fibroblast growth factor, transforming growth factor-β) 1
• Upregulation of inflammatory mediators including monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1, promoting leukocyte adhesion to vessel walls 1
• Enhanced oxidative stress through angiotensin II-mediated activation of NAD(P)H oxidase 1

Types of Arterial Hardening Caused by Hypertension

Diffuse Arteriosclerosis

Hypertension causes diffuse arteriosclerosis throughout the arterial tree, distinct from but overlapping with focal atherosclerotic plaques. 1 This involves:

• Fibromuscular thickening of the intima and media with luminal narrowing of small arteries and arterioles 2
• Increased arterial stiffness measurable through pulse-wave velocity, associated with increased systolic blood pressure and pulse pressure 3
• Remodeling of medium and small coronary arteries that may share common pathophysiological mechanisms with atherosclerotic lesions 1

Accelerated Atherosclerosis

Hypertension aggravates and accelerates atherosclerosis, particularly in coronary and cerebral vessels, beyond causing diffuse arterial stiffening. 2, 4 The physical stress of hypertension:

• Increases susceptibility of arteries to atherosclerosis through synergistic effects with other atherogenic stimuli like hyperlipidemia 4
• Promotes formation of patchy atherosclerotic lesions in epicardial coronary arteries 1
• Facilitates lipid accumulation and inflammatory cell recruitment into the arterial wall through endothelial injury 1

Cerebrovascular Changes

Chronic hypertension causes narrowing and sclerosis of small penetrating arteries in subcortical brain regions. 1, 5 This results in:

• Hypoperfusion and loss of autoregulation in cerebral circulation 1, 5
• Subcortical white matter demyelination and microinfarction visible on MRI as white matter lesions 1, 5
• Cognitive decline and increased dementia risk, with effective antihypertensive therapy reducing (but not reversing) white matter changes 1, 5

Clinical Implications and Outcomes

Cardiovascular Consequences

The arterial hardening caused by hypertension leads to multiple downstream cardiovascular complications. 1, 3 These include:

• Increased left ventricular afterload from elevated aortic impedance, raising cardiac work and myocardial oxygen demand 1
• Left ventricular hypertrophy developing in response to increased pressure load, predisposing to heart failure 1, 3
• Compromised coronary perfusion due to decreased diastolic blood pressure when pulse pressure widens 1
• Increased risk of myocardial infarction and stroke through both occlusive disease and vessel rupture 2

Measurement and Detection

Arterial stiffness from hypertension can be detected noninvasively before clinical complications develop. 1, 3 Methods include:

• Pulse-wave velocity (PWV) as the emerging gold standard, which increases with arterial stiffness and predicts cardiovascular events 1, 3
• Arterial distensibility measured by ultrasound, which decreases in hypertension and correlates with cardiovascular risk 1
• Augmentation index from pulse contour analysis, elevated in conditions predisposing to cardiovascular disease 1

Important Clinical Caveats

The relationship between hypertension and atherosclerosis is complex and indirect. 6 While hypertension clearly causes arterial hardening:

• Lowering blood pressure prevents arteriolar complications (heart failure, renal failure, lacunar strokes, brain hemorrhage) more reliably than it prevents atherosclerotic complications 6
• Different antihypertensive drugs have varying effects on lipoprotein profiles and arterial flow disturbances that may influence atherosclerosis prevention beyond blood pressure reduction alone 1, 6
• ACE inhibitors and ARBs may have vasoprotective effects beyond blood pressure lowering by blocking NAD(P)H oxidase activation and limiting oxidative reactions 1

Once established, structural arterial changes may not be fully reversible. 1 Existing white matter changes from chronic hypertension do not appear reversible with treatment, though progression can be slowed. 1, 5 This emphasizes the importance of early blood pressure control before irreversible arterial damage occurs.