What are the causes of hypertension?

Causes of Hypertension

Hypertension results from complex interactions between genetic predisposition, environmental factors, and behavioral influences, with approximately 90% of cases being primary (essential) hypertension of unknown exact cause and 10% being secondary hypertension with identifiable causes. 1

Primary (Essential) Hypertension

Genetic Factors

• Hypertension is a complex polygenic disorder where multiple genes influence blood pressure, though genetic variants collectively account for only about 3.5% of blood pressure variability. 1
• Rare monogenic forms exist (glucocorticoid-remediable aldosteronism, Liddle's syndrome, Gordon's syndrome) but these single-gene mutations are uncommon. 1, 2
• The presence of multiple small-effect alleles associated with higher blood pressure results in more rapid blood pressure increases with age. 1

Environmental and Behavioral Risk Factors

Obesity and Overweight:

• Obesity may be responsible for 40% of hypertension cases (Nurses' Health Study) and up to 78% in men and 65% in women (Framingham Offspring Study). 1
• The relationship between body mass index and blood pressure is continuous and almost linear, with no threshold. 1
• Waist-to-hip ratio and central fat distribution show even stronger associations with blood pressure than body mass index alone. 1
• Continuous obesity from adolescence or acquiring obesity carries a relative risk of 2.7 for developing hypertension, while achieving normal weight reduces risk to levels similar to those never obese. 1

Dietary Sodium:

• 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, cardiovascular disease, and other adverse outcomes beyond its blood pressure effects. 1
• Salt sensitivity is particularly common in Black individuals, older adults, and those with higher baseline blood pressure, chronic kidney disease, diabetes, or metabolic syndrome—collectively representing more than half of all US adults. 1

Other Dietary Factors:

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

Physical Inactivity:

• Poor diet, physical inactivity, and excess alcohol consumption, alone or in combination, are the underlying cause of a large proportion of hypertension. 1

Alcohol Consumption:

• Excessive alcohol intake (≥3 drinks/day) contributes to hypertension development. 1

Pathophysiological Mechanisms

• The pathophysiology involves complex interactions between environmental factors, genes, hormonal networks, and multiple organ systems (renal, cardiovascular, central nervous), along with vascular and immune mechanisms. 1
• Dysregulation includes endothelial dysfunction, vasoreactivity, vascular remodeling, fibrosis and inflammation, and increased peripheral vascular resistance. 1

Secondary Hypertension

Secondary hypertension accounts for approximately 10% of cases (though some studies suggest substantially higher prevalence with systematic screening) and has identifiable causes. 1

Major Secondary Causes

Renal Disease:

• Chronic kidney disease and renal parenchymal disease are common secondary causes. 1
• Renovascular disease (renal artery stenosis) causes secondary aldosteronism with associated muscle cramps, weakness, and hypokalemia. 1

Endocrine Disorders:

• Primary aldosteronism presents with hypokalemia, muscle cramps, and weakness. 1
• Pheochromocytoma causes blood pressure lability, episodic pallor, and dizziness. 1
• Cushing's syndrome presents with central obesity, facial rounding, and easy bruisability. 1
• Hyperthyroidism causes weight loss, palpitations, and heat intolerance. 1
• Hyperparathyroidism and thyroid disease are less common causes. 1

Obstructive Sleep Apnea:

• Presents with snoring and hypersomnolence. 1
• Moderate (AHI 15-30) and severe (AHI >30) obstructive sleep apnea requires continuous positive airway pressure therapy, which improves blood pressure control and helps resolve resistant hypertension. 1

Drug-Induced Hypertension:

• Over-the-counter medications, prescribed drugs, and recreational substances can cause hypertension. 1
• Anticancer drugs (vascular endothelial growth factor inhibitors cause blood pressure increases in 80-90% of patients, tyrosine kinase inhibitors, proteasome inhibitors) are increasingly recognized causes. 1
• Nonsteroidal anti-inflammatory drugs, cocaine, amphetamines, corticosteroids, and calcineurin inhibitors elevate blood pressure. 1

Vascular Causes:

• Aortic coarctation should be suspected in adults ≤30 years with elevated brachial blood pressure if thigh blood pressure is lower than arm pressures. 1

Other Rare Causes:

• Excess liquorice consumption, acromegaly, and genetic syndromes (Liddle's syndrome, glucocorticoid-remediable aldosteronism). 1, 2

Clinical Approach to Identifying Causes

Historical features suggesting primary hypertension include:

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

Historical features suggesting secondary hypertension include:

• Absence of family history of hypertension. 1
• Sudden onset or rapid progression of hypertension, especially before age 30. 1, 2
• Specific symptoms pointing to underlying causes (as detailed above). 1