What are the causes of Hypertension (HTN) in the general adult population?

What Causes Hypertension

Hypertension results from two broad categories: primary (essential) hypertension in approximately 90% of cases, which develops from complex interactions between genetic predisposition, lifestyle factors, and environmental influences, and secondary hypertension in approximately 10% of cases, which has specific identifiable causes requiring targeted evaluation and treatment. 1, 2, 3

Primary (Essential) Hypertension

Primary hypertension develops through multifactorial mechanisms without a single identifiable cause, though specific risk factors have been clearly established. 2, 3

Major Modifiable Risk Factors

• Obesity is the single most important modifiable cause, responsible for 40% of all hypertension cases and up to 78% in men and 65% in women. 2, 3 The relationship between body mass index and blood pressure is continuous and almost linear with no threshold. 2, 3

• Dietary sodium excess accounts for much of the age-related increase in blood pressure and is independently associated with increased risk of stroke and cardiovascular disease beyond its blood pressure effects. 2, 3

• Insufficient intake of potassium, calcium, magnesium, protein, fiber, and fish fats are associated with high blood pressure. 2, 3

• Excessive alcohol intake (≥3 standard drinks per day) shows a strong, direct relationship with blood pressure elevation. 3

• Physical inactivity, poor diet, and excess alcohol consumption, alone or in combination, are the underlying cause of a large proportion of hypertension. 2, 3

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

Genetic Factors

• Genetic variants collectively account for only about 3.5% of blood pressure variability, indicating that while hypertension is a complex polygenic disorder, environmental and lifestyle factors play the dominant role. 2, 3

Secondary Hypertension

Secondary hypertension accounts for approximately 10% of cases overall, but increases to 10-35% in resistant hypertension populations. 3 Screening is recommended when specific clinical indications are present. 1

Renal Causes

• Chronic kidney disease and renal parenchymal disease are the most common secondary causes, including chronic glomerulonephritis, polycystic kidney disease, and hypertensive nephrosclerosis. 1, 2, 3

• Renal artery stenosis should be suspected with onset of hypertension before age 30 or after age 55, abdominal bruit, accelerated hypertension, and recurrent flash pulmonary edema. 3

Endocrine Causes

• Primary aldosteronism presents with unprovoked hypokalemia, muscle cramps, and weakness. 1, 2, 3 Screening is recommended in adults with resistant hypertension, spontaneous or substantial diuretic-induced hypokalemia, incidentally discovered adrenal mass, or family history of early-onset hypertension. 1

• Pheochromocytoma causes blood pressure lability, episodic pallor, dizziness, headache, palpitations, and perspiration. 1, 2, 3

• Cushing's syndrome presents with central obesity, facial rounding, easy bruisability, truncal obesity, glucose intolerance, and purple striae. 1, 2, 3

• Hyperthyroidism causes weight loss, palpitations, and heat intolerance. 1, 2, 3

Obstructive Sleep Apnea

• Obstructive sleep apnea presents with snoring and hypersomnolence and should be considered in patients with resistant hypertension. 1, 2, 3

Drug-Induced Hypertension

• Nonsteroidal anti-inflammatory drugs (NSAIDs), cocaine, amphetamines, corticosteroids, and calcineurin inhibitors can cause drug-induced hypertension. 1, 2, 3

• A careful history should include prescription medications, over-the-counter substances, illicit drugs, and herbal products. 1

Vascular Causes

• Aortic coarctation is characterized by decreased pressure in lower extremities or delayed/absent femoral arterial pulses. 3 Patients with coarctation of the aorta may have systemic hypertension despite abolition of a coarctation gradient, with higher prevalence of hypertension with later repair. 1

Clinical Approach to Identifying the Cause

Features Suggesting Primary Hypertension

• Gradual blood pressure increase with slow rate of rise 1, 3
• Lifestyle factors favoring higher blood pressure (weight gain, high-sodium diet, decreased physical activity, excessive alcohol consumption) 1
• Strong family history of hypertension 1, 3

Features Suggesting Secondary Hypertension

• Absence of family history of hypertension 1
• Sudden onset or rapid progression of hypertension 3
• Resistant hypertension despite appropriate therapy 1, 3
• Specific symptoms pointing to underlying causes (as detailed above) 1
• Age of onset before 30 or after 55 years 3

Screening Recommendations

Screening for secondary hypertension is recommended when clinical indications and physical examination findings suggest a specific disorder or in adults with resistant hypertension. 1 Standard diagnostic workup should include assessment of target organ damage and exclusion of identifiable causes, with urinalysis, blood glucose levels, hematocrit, lipid panel, basic metabolic panel, and calcium levels. 1

Common pitfall: Poor compliance or adherence to drug treatment or lifestyle changes is the most common cause of resistant hypertension, and should be evaluated before extensive workup for secondary causes. 3