What are the pillars of etiology of hypertension in a general adult population?

Etiology of Hypertension in Adults

The etiology of hypertension involves three fundamental pillars: genetic predisposition (accounting for only ~3.5% of blood pressure variability), environmental/lifestyle factors (responsible for the majority of cases), and secondary causes (representing ~10% of cases). 1

Primary (Essential) Hypertension: The Dominant Pathway

Primary hypertension accounts for approximately 90% of all cases and results from complex interactions between multiple factors rather than a single identifiable cause. 2

Genetic Component

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

Environmental and Lifestyle Factors: The Major Contributors

Obesity represents the single most important modifiable factor, potentially responsible for 40% of all hypertension cases and up to 78% in men and 65% in women. 2 The relationship between body mass index and blood pressure is continuous and almost linear with no threshold, and the association is even stronger for waist-to-hip ratio and central fat distribution. 1

Dietary factors play critical roles: 1, 2

• Excess sodium intake is positively associated with blood pressure and accounts for much of the age-related increase; it is independently associated with increased stroke and cardiovascular disease risk beyond blood pressure effects
• Insufficient potassium, calcium, magnesium, protein (especially from vegetables), fiber, and fish fats are all associated with elevated blood pressure
• The DASH (Dietary Approaches to Stop Hypertension) eating plan—rich in fruits, vegetables, and low-fat dairy with reduced saturated fat—can lower systolic blood pressure by 8-14 mm Hg 1

Physical inactivity and excess alcohol consumption, alone or in combination with poor diet, are underlying causes of a large proportion of hypertension cases. 1, 2 Alcohol intake should be limited to no more than 2 drinks daily in men and 1 drink daily in women. 1

Pathophysiological Mechanisms

The complex interplay involves: 1

• Overactivation of the renin-angiotensin-aldosterone system
• Activation of the sympathetic nervous system
• Inhibition of the cardiac natriuretic peptide system
• Endothelial dysfunction

These mechanisms are shared across multiple cardiovascular risk factors, explaining why hypertension rarely occurs in isolation. 1

Secondary Hypertension: The Identifiable 10%

Secondary hypertension accounts for approximately 10% of cases and has specific identifiable causes. 2

Renal Causes

• Chronic kidney disease and renal parenchymal disease are the most common secondary causes 2
• Renal artery stenosis should be suspected with renal failure of uncertain etiology (especially without proteinuria), acute renal failure precipitated by ACE inhibitors/ARBs, or resistant hypertension 1

Endocrine Causes 2

• Primary aldosteronism: presents with hypokalemia, muscle cramps, and weakness
• Pheochromocytoma: causes blood pressure lability, episodic pallor, and dizziness
• Cushing's syndrome: presents with central obesity, facial rounding, and easy bruisability
• Hyperthyroidism: causes weight loss, palpitations, and heat intolerance

Other Secondary Causes

• Obstructive sleep apnea: presents with snoring and hypersomnolence; requires CPAP therapy to improve blood pressure control 2
• Drug-induced hypertension: NSAIDs, cocaine, amphetamines, corticosteroids, and calcineurin inhibitors all elevate blood pressure 2

Clinical Approach to Distinguishing Primary from Secondary

Features suggesting primary hypertension: 2

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

Features suggesting secondary hypertension: 2

• Absence of family history
• Sudden onset or rapid progression
• Specific symptoms pointing to underlying causes (as listed above)
• Age <30 years at onset
• Resistant hypertension despite multiple medications

Common Pitfalls

The most critical error is attributing all hypertension to "essential" causes without screening for secondary causes in patients with atypical presentations. 2 Young patients (<30 years), those with sudden onset, and those with resistant hypertension warrant investigation for secondary causes even when they have obesity or family history. 2

Another pitfall is underestimating the cumulative impact of multiple lifestyle factors—addressing only one factor (e.g., sodium reduction alone) without comprehensive lifestyle modification limits blood pressure reduction potential. 1