1.1 Hypertension (Essential & Secondary)

Hypertension (Essential & Secondary)

PANCE High-Yield Focus: Hypertension is the most common primary care presentation and a major contributor to cardiovascular disease. On the PANCE, prioritize the 2017 ACC/AHA diagnostic criteria, the differentiation between primary and secondary hypertension, specific diagnostic workups for secondary causes (such as Conn syndrome, pheochromocytoma, and renal artery stenosis), and the selection of antihypertensive agents based on compelling clinical indications and their side effect profiles.

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Pathophysiology of Blood Pressure Regulation

Systemic arterial pressure is determined by the product of cardiac output (CO) and systemic vascular resistance (SVR). Cardiac output is a function of stroke volume and heart rate, while SVR is primarily regulated by the tone of arterioles (resistance vessels).

• Primary (Essential) Hypertension: Accounts for approximately 90-95% of adult cases. The pathophysiology is multifactorial, arising from a complex interaction of genetic predisposition, sympathetic nervous system (SNS) hyperactivity, chronic activation of the renin-angiotensin-aldosterone system (RAAS), defects in renal sodium excretion, and vascular endothelial dysfunction leading to increased SVR.
• Secondary Hypertension: Accounts for 5-10% of cases and is defined by an identifiable underlying cause. Clinicians should suspect secondary hypertension in patients with:
  1. Abrupt onset or rapid worsening of blood pressure.
  2. Age of onset <30 years (especially in non-obese, non-black patients without family history) or >65 years.
  3. Resistant hypertension (uncontrolled on >=3 antihypertensive medications, one being a diuretic).
  4. Severe target-organ damage (e.g., left ventricular hypertrophy, retinopathy, nephropathy) disproportionate to the duration of hypertension.

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Diagnostic Criteria and Thresholds

The diagnosis of hypertension must be established through accurate, standardized measurements. It requires at least two readings obtained on at least two separate clinical encounters, or a single reading >=180/120 mmHg in the presence of acute target-organ damage (hypertensive emergency). The 2017 ACC/AHA guidelines classify adult blood pressure as follows:

Note: Hypertensive crisis is divided into Hypertensive Urgency (severe BP elevation without acute target-organ damage, managed with oral medications to slowly lower BP over 24-48 hours) and Hypertensive Emergency (severe BP elevation with acute target-organ damage, requiring immediate admission and IV medications like esmolol, nicardipine, or sodium nitroprusside to lower mean arterial pressure by no more than 25% in the first hour).

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Diagnostic Workup for Secondary Hypertension

Identifying secondary hypertension requires a targeted clinical workup to rule out key structural, endocrine, and renal etiologies:

1. Renal Artery Stenosis (RAS)

RAS is the most common correctable cause of secondary hypertension. It involves narrowing of one or both renal arteries, reducing renal perfusion, which triggers massive RAAS activation.

• Pathophysiology: Caused by atherosclerosis (in older males) or fibromuscular dysplasia (in young females, exhibiting a classic "string of beads" appearance on angiography).
• Clinical Clues: Abdominal bruits, sudden worsening of renal function (creatinine rise >30%) after initiating an ACE inhibitor or ARB, or flash pulmonary edema.
• Workup: Initial screening with Renal Duplex Ultrasonography, Magnetic Resonance Angiography (MRA), or Computed Tomography Angiography (CTA). The gold standard for diagnosis and potential intervention is renal arteriography.

2. Primary Aldosteronism (Conn Syndrome)

Conn syndrome is characterized by autonomous excess production of aldosterone by the adrenal cortex, leading to sodium retention, potassium wasting, and suppressed renin.

• Clinical Clues: Resistant hypertension accompanied by spontaneous or easily provoked hypokalemia, muscle weakness, or polyuria.
• Workup: Screen by calculating the Plasma Aldosterone Concentration to Plasma Renin Activity (PAC/PRA) ratio (also called Aldosterone-to-Renin Ratio, ARR). A ratio >20-30 with a PAC >15 ng/dL is positive. Confirm with oral or IV saline suppression testing (failure to suppress aldosterone). Localize with an adrenal CT scan.

3. Pheochromocytoma

A rare, catecholamine-secreting neuroendocrine tumor arising from the chromaffin cells of the adrenal medulla (or extra-adrenal paragangliomas).

• Clinical Clues: Paroxysmal hypertension accompanied by the classic triad of episodic headaches, diaphoresis, and palpitations.
• Workup: Screen with plasma free fractionated metanephrines (high sensitivity) or 24-hour urine fractionated metanephrines and catecholamines (high specificity). Localize with abdominal CT or MRI.

4. Coarctation of the Aorta

Congenital narrowing of the descending thoracic aorta, typically distal to the left subclavian artery.

• Clinical Clues: Upper extremity hypertension with lower extremity hypotension, delayed or diminished femoral pulses (femoral-to-radial pulse lag), and a systolic murmur heard in the left interscapular region.
• Workup: Chest X-ray may show rib notching (due to collateral intercostal arterial flow) and the "figure 3 sign." Confirm with Echocardiogram, magnetic resonance imaging (MRI), or CTA.

5. Other Causes

• Cushing Syndrome: Excess cortisol. Screen with a 24-hour urinary free cortisol or low-dose dexamethasone suppression test.
• Obstructive Sleep Apnea (OSA): Screen with a polysomnography (sleep study). Highly linked to resistant nocturnal hypertension.

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Pharmacotherapy and Compelling Indications

Initial therapy for Stage 1 hypertension begins with lifestyle modifications (DASH diet, weight reduction, aerobic exercise, sodium restriction <2.4 g/day, and limiting alcohol). Pharmacotherapy is added for Stage 1 if the 10-year ASCVD risk is >=10% or if the patient has clinical cardiovascular disease, diabetes, or CKD. Stage 2 hypertension requires immediate lifestyle changes plus two antihypertensive agents from different classes.

First-line agents include Angiotensin-Converting Enzyme Inhibitors (ACEi), Angiotensin Receptor Blockers (ARBs), Calcium Channel Blockers (CCBs), and Thiazide Diuretics.

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PANCE Clinical Traps

• Bilateral Renal Artery Stenosis: Never prescribe an ACEi or ARB. Patients with bilateral RAS depend on Angiotensin II-mediated efferent arteriolar vasoconstriction to maintain intraglomerular pressure and glomerular filtration rate (GFR). Blocking this pathway causes acute, severe renal failure.
• Pheochromocytoma Surgery Preparation: Always administer an alpha-blocker first (e.g., phenoxybenzamine) for 7-14 days before initiating a beta-blocker. If a beta-blocker is started first, it blocks beta-2-mediated vasodilation while leaving alpha-1 receptors unopposed to catecholamine stimulation, precipitating a life-threatening hypertensive crisis.
• Pregnancy Antihypertensives: Avoid ACEi, ARBs, and direct renin inhibitors. Safe first-line agents in pregnancy include Labetalol, Methyldopa, and long-acting Nifedipine.
• Diuretic Calcium Regulation: Remember that thiazides save calcium (hypercalcemia), which is beneficial for osteoporosis, whereas loop diuretics lose calcium (hypocalcemia), making loop diuretics useful for treating acute hypercalcemia.