What causes hypertension?

What Causes Hypertension

Hypertension results from two broad categories: primary (essential) hypertension, which accounts for approximately 90% of cases and arises from complex interactions between genetic predisposition, environmental factors, and behavioral influences, and secondary hypertension, which accounts for 10% of cases and has identifiable underlying causes. 1

Primary (Essential) Hypertension

Primary hypertension develops through multifactorial mechanisms without a single identifiable cause. The pathophysiology involves:

Genetic Factors

• Multiple genes influence blood pressure, though genetic variants collectively account for only about 3.5% of blood pressure variability. 1
• Hypertension is a complex polygenic disorder where no single gene polymorphism causes the condition in most people, but rather numerous common genetic variants each have small effects. 2

Modifiable Lifestyle and Environmental Factors

Obesity represents the single most important modifiable cause:

• Obesity may be responsible for 40% of all hypertension cases and up to 78% in men and 65% in women. 1
• The relationship between body mass index and blood pressure is continuous and almost linear with no threshold. 1

Dietary sodium excess:

• Sodium intake is positively associated with blood pressure and accounts for much of the age-related increase in blood pressure. 1
• Excessive sodium consumption is independently associated with increased risk of stroke and cardiovascular disease beyond its blood pressure effects. 1

Nutritional deficiencies:

• Insufficient intake of potassium, calcium, magnesium, protein, fiber, and fish fats are associated with high blood pressure. 1

Physical inactivity and alcohol:

• Poor diet, physical inactivity, and excess alcohol consumption, alone or in combination, are the underlying cause of a large proportion of hypertension. 1
• Excessive alcohol intake (≥3 standard drinks per day) shows a strong, direct relationship with blood pressure elevation. 3

Chronic stress and occupational factors:

• Chronic social conflict and occupational stress (job strain with high demands and low control) are associated with higher ambulatory blood pressures, particularly in men. 4

Pathophysiological Mechanisms

• Overactivation of the renin-angiotensin-aldosterone system (RAAS) contributes to development and maintenance of hypertension. 3
• Endothelial dysfunction impairs normal vascular regulation. 3
• Dysregulation of renal sodium handling and pressure natriuresis plays a fundamental role. 3
• Increased peripheral vascular resistance, vascular remodeling, and fibrosis with inflammation perpetuate elevated blood pressure. 3

Secondary Hypertension

Secondary hypertension accounts for approximately 10% of cases overall, but increases to 10-35% in resistant hypertension populations and up to 20-40% in patients presenting with malignant hypertension. 1, 3

Renal Causes

Chronic kidney disease and renal parenchymal disease:

• The most common parenchymal kidney diseases associated with hypertension are chronic glomerulonephritis, polycystic kidney disease, and hypertensive nephrosclerosis. 5
• These can generally be distinguished by clinical setting and additional testing, such as renal ultrasound for polycystic kidney disease. 5

Renal artery stenosis: Suspect renovascular hypertension when:

• Onset of hypertension before age 30 (especially without family history) or onset of significant hypertension after age 55. 5
• Abdominal bruit present, especially with diastolic component. 5
• Accelerated hypertension or previously controlled hypertension now resistant. 5
• Recurrent flash pulmonary edema. 5
• Renal failure of uncertain etiology without proteinuria or abnormal urine sediment. 5
• Acute renal failure precipitated by ACE inhibitor or ARB therapy. 5

Endocrine Causes

Primary aldosteronism:

• Presents with unprovoked hypokalemia, muscle cramps, and weakness. 5, 1

Pheochromocytoma:

• Suspect in patients with labile hypertension or paroxysms of hypertension accompanied by headache, palpitations, pallor, and perspiration. 5
• Causes blood pressure lability, episodic pallor, and dizziness. 1

Cushing's syndrome:

• Truncal obesity, glucose intolerance, purple striae, central obesity, facial rounding, and easy bruisability. 5, 1

Hyperthyroidism:

• Weight loss, palpitations, and heat intolerance. 1

Obstructive Sleep Apnea

• Presents with snoring and hypersomnolence. 1
• Requires continuous positive airway pressure therapy to improve blood pressure control. 1
• Causes long-term effects through nighttime hypoxia, chemoreceptor stimulation, and sleep deprivation. 5

Drug-Induced Hypertension

Over-the-counter medications, prescribed drugs, and recreational substances can cause hypertension:

• Nonsteroidal anti-inflammatory drugs (NSAIDs). 1
• Cocaine and amphetamines. 1
• Corticosteroids. 1
• Calcineurin inhibitors. 1

Vascular Causes

Aortic coarctation:

• Decreased pressure in lower extremities or delayed/absent femoral arterial pulses. 5

Clinical Approach to Identifying the Cause

Features Suggesting Primary Hypertension

• Gradual blood pressure increase with slow rate of rise. 1
• Lifestyle factors favoring higher blood pressure (obesity, high sodium intake, physical inactivity, excessive alcohol). 1
• Strong family history of hypertension. 1

Features Suggesting Secondary Hypertension

Additional diagnostic procedures are indicated when: 5

• Age, history, physical examination, severity of hypertension, or initial laboratory findings suggest secondary causes. 5
• Blood pressure control is not achieved despite appropriate therapy. 5
• Blood pressure begins to increase after being well controlled. 5
• Onset of hypertension is sudden. 5
• Absence of family history of hypertension. 1
• Sudden onset or rapid progression of hypertension. 1
• Specific symptoms pointing to underlying causes (as detailed above). 1

Common Pitfalls in Resistant Hypertension

When hypertension fails to respond to three drugs including a diuretic, consider: 5

• Poor compliance or adherence to drug treatment or lifestyle changes (most common cause). 5
• Obstructive sleep apnea. 5
• Volume overload from progressing renal insufficiency, excessive salt intake, hyperaldosteronism, or insufficient diuretic therapy. 5
• Spurious hypertension such as isolated office (white coat) hypertension. 5
• Failure to use large cuffs on large arms (overestimates blood pressure). 5
• Pseudohypertension in elderly patients (extreme arterial stiffness makes compression difficult). 5