# Lecture 16: Hypertension
## Unit 1.7: Cardiovascular System
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## Learning Objectives
By the end of this lecture, students will be able to:
1. Define and classify hypertension according to current guidelines
2. Describe the epidemiology and risk factors for hypertension
3. Explain the pathophysiology of primary and secondary hypertension
4. Describe the end-organ damage caused by hypertension
5. Outline the approach to evaluation of hypertensive patients
6. Describe pharmacologic and non-pharmacologic management of hypertension
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## Lecture Content
### Definition and Classification of Hypertension
Blood pressure classification has evolved as evidence has accumulated regarding cardiovascular risk at various pressure thresholds. The 2017 American College of Cardiology/American Heart Association guidelines established current definitions based on outcomes data showing increased cardiovascular events at lower pressures than previously recognized.
Normal blood pressure is defined as systolic pressure below 120 millimeters of mercury and diastolic pressure below 80 millimeters of mercury. Elevated blood pressure encompasses systolic readings of 120 to 129 with diastolic below 80, representing a prehypertensive state carrying increased risk. Stage 1 hypertension is defined as systolic pressure of 130 to 139 or diastolic of 80 to 89 millimeters of mercury. Stage 2 hypertension requires systolic pressure of 140 or above or diastolic of 90 or above. The previous classification system (JNC 7/8) used higher thresholds, with hypertension defined at 140/90 and above, and the term "prehypertension" covering 120-139/80-89.
Hypertensive crisis describes severe blood pressure elevation exceeding 180/120 millimeters of mercury. The critical distinction within this category determines management approach. Hypertensive urgency indicates severely elevated pressure without evidence of acute end-organ damage, typically allowing gradual reduction over hours to days with oral medications. Hypertensive emergency indicates severely elevated pressure with acute end-organ damage to the brain, heart, kidney, or eyes, requiring immediate hospitalization and parenteral therapy with careful pressure reduction.
Panel A: 2017 ACC/AHA blood pressure classification on a vertical scale: Normal below 120/80 in green, Elevated 120-129 systolic with diastolic below 80 in yellow, Stage 1 Hypertension 130-139/80-89 in orange, Stage 2 Hypertension 140 or above or 90 or above in red. Panel B: Previous JNC 7/8 classification for comparison showing Normal, Prehypertension, Stage 1, and Stage 2 at higher thresholds. Panel C: Hypertensive crisis above 180/120 with branching decision point: no end-organ damage equals urgency requiring oral medications, with end-organ damage equals emergency requiring IV therapy and ICU monitoring. Panel D: Cardiovascular risk curves showing increasing events with higher blood pressures across the classification spectrum.
### Epidemiology and Risk Factors
Hypertension represents one of the most prevalent chronic conditions worldwide, affecting approximately forty-five percent of American adults under current definitions and over 1.4 billion people globally. This prevalence increases dramatically with age, affecting more than seventy percent of those over sixty-five years. Despite widespread awareness, the "rule of halves" historically described hypertension management: only half of those with hypertension knew their diagnosis, half of those aware were treated, and half of those treated achieved control. While these proportions have improved, significant gaps persist: approximately eighty percent are now aware, seventy-five percent receive treatment, but only fifty percent achieve adequate control.
Non-modifiable risk factors establish baseline susceptibility. Age represents the strongest risk factor, with systolic pressure rising throughout adulthood due to progressive arterial stiffening. Race and ethnicity significantly influence risk, with African Americans experiencing higher prevalence, earlier onset, and more severe complications including hypertensive nephropathy and stroke. Family history reflects both genetic predisposition and shared environmental factors, with thirty to fifty percent of blood pressure variability attributable to genetic factors. Male sex carries higher risk until age sixty-five, after which women's risk approximates or exceeds men's following menopause.
Modifiable risk factors offer targets for prevention and treatment. Excess sodium intake, typically exceeding 3.4 grams daily in Western diets compared to recommended levels below 2.4 grams, drives volume expansion and pressure elevation. Obesity operates through multiple mechanisms including increased sympathetic activity, renal sodium retention, and activation of the renin-angiotensin-aldosterone system. Physical inactivity contributes independently of weight status. Excessive alcohol consumption (more than two drinks daily for men, one for women) raises blood pressure, while moderate consumption may have neutral or mildly beneficial effects. Chronic stress and poor sleep quality, particularly obstructive sleep apnea, contribute through sustained sympathetic activation. Certain medications including NSAIDs, decongestants, oral contraceptives, and stimulants can elevate blood pressure.
Panel A: Global and US prevalence data showing 1.4 billion affected worldwide and 45% adult prevalence in the US, with age-stratified bar graphs showing increasing prevalence from 30% at ages 40-50 to over 70% at ages 65 and above. Panel B: Treatment cascade funnel showing 100% with hypertension narrowing to 80% aware, 75% of aware on treatment, and only 50% of treated achieving control. Panel C: Non-modifiable risk factors including age with arterial stiffening, race with higher prevalence in African Americans, and family history with 30-50% heritability. Panel D: Modifiable risk factors including excess sodium causing volume expansion, obesity activating RAAS, physical inactivity, alcohol excess above recommended limits, and obstructive sleep apnea with sympathetic activation.
### Pathophysiology of Primary Hypertension
Primary hypertension, also termed essential hypertension, accounts for ninety to ninety-five percent of hypertensive patients. No single identifiable cause exists; rather, multiple interacting systems contribute to sustained pressure elevation. Understanding these mechanisms explains both the natural history of hypertension and the rationale for various therapeutic approaches.
Blood pressure equals cardiac output multiplied by total peripheral resistance. In early hypertension, elevated cardiac output from increased heart rate and contractility may predominate, often driven by heightened sympathetic nervous system activity. As hypertension becomes established, cardiac output normalizes while total peripheral resistance increases due to structural and functional vascular changes.
The renin-angiotensin-aldosterone system plays a central role in many patients. Although plasma renin activity may appear normal, it is inappropriately elevated relative to the degree of sodium retention. Angiotensin II exerts multiple pro-hypertensive effects: direct vasoconstriction, aldosterone release promoting sodium retention, sympathetic facilitation, and stimulation of vascular smooth muscle growth. These effects explain the efficacy of ACE inhibitors and angiotensin receptor blockers.
The sympathetic nervous system contributes through direct cardiac stimulation increasing heart rate and contractility, peripheral vasoconstriction via alpha-adrenergic stimulation, and renin release via renal beta-adrenergic stimulation. Elevated sympathetic activity is well-documented in hypertensive patients and may be both cause and consequence of elevated pressure.
The kidneys occupy a unique position because any sustained hypertension requires impaired renal sodium excretion. Normal pressure natriuresis increases sodium excretion when arterial pressure rises, maintaining long-term pressure stability. In hypertension, this relationship is shifted rightward: higher pressure is required to excrete the same sodium load. This resetting can occur through intrinsic renal abnormalities, RAAS activation, or sympathetic stimulation. The observation that kidney transplantation can transfer hypertension susceptibility with the donor organ underscores the kidney's central role.
Endothelial dysfunction develops early in hypertension and perpetuates the condition. Reduced nitric oxide bioavailability impairs endothelium-dependent vasodilation, and increased endothelin production promotes vasoconstriction. These changes contribute to increased vascular tone and resistance.
Vascular remodeling represents the structural adaptation to chronically elevated pressure. Smooth muscle hypertrophy and increased wall thickness narrow the vascular lumen, raising resistance and perpetuating hypertension even if the initiating stimulus resolves. This remodeling explains why blood pressure reduction with treatment often takes weeks to achieve full effect.
Panel A: Central equation BP equals cardiac output times total peripheral resistance, with cardiac output contributors including sympathetic nervous system beta-1 stimulation increasing heart rate, contractility, and renin release. Panel B: Total peripheral resistance contributors including RAAS pathway from renin to angiotensin II causing vasoconstriction, aldosterone release, and vascular growth, and endothelial dysfunction with reduced NO and increased endothelin. Panel C: Vascular remodeling showing cross-sections comparing normal vessel to hypertrophied vessel with increased wall-to-lumen ratio that perpetuates elevated resistance. Panel D: Pressure-natriuresis curve comparing normal curve with rightward-shifted hypertensive curve where higher pressure is required for the same sodium excretion.
### Secondary Hypertension
Secondary hypertension refers to elevated blood pressure resulting from an identifiable underlying cause. Though representing only five to ten percent of hypertensive patients in general populations, the prevalence increases substantially among those with resistant hypertension or atypical features. Identification is important because specific treatment may cure or significantly improve blood pressure control.
Clinical clues suggesting secondary hypertension include onset before age thirty or after fifty-five, sudden onset or acute worsening in previously controlled patients, resistant hypertension (uncontrolled despite three appropriately dosed agents including a diuretic), severe or accelerated hypertension causing end-organ damage, and specific symptoms or laboratory findings pointing to particular causes.
Primary aldosteronism has emerged as more common than previously recognized, affecting five to fifteen percent of hypertensive patients and an even higher proportion of those with resistant hypertension. Autonomous aldosterone production causes sodium retention, volume expansion, and potassium wasting, producing hypertension that is classically associated with hypokalemia, though normokalemia is common. Screening involves the aldosterone-to-renin ratio, with confirmatory testing and adrenal imaging if positive. Treatment involves mineralocorticoid receptor antagonists for bilateral disease or surgery for unilateral adenoma.
Renal artery stenosis produces hypertension through renal ischemia activating the RAAS. Atherosclerotic disease predominates in older patients with cardiovascular risk factors, while fibromuscular dysplasia typically affects younger women. Clinical clues include an abdominal bruit, flash pulmonary edema, and worsening renal function with ACE inhibitors or ARBs. Diagnosis involves duplex ultrasonography, CT angiography, or MR angiography. Treatment includes aggressive medical therapy for most patients; revascularization is reserved for refractory cases.
Chronic kidney disease commonly produces hypertension through impaired sodium excretion and volume expansion. Conversely, hypertension accelerates CKD progression, creating a bidirectional relationship. Blood pressure control with RAAS blockade (when tolerated) slows renal decline.
Obstructive sleep apnea is present in a high proportion of hypertensive patients, particularly those with resistant hypertension. Repeated apneic episodes cause sympathetic surges and blood pressure spikes, with sustained daytime hypertension developing over time. Screening involves symptom assessment and overnight oximetry or polysomnography. Treatment with continuous positive airway pressure (CPAP) modestly reduces blood pressure.
Less common causes include pheochromocytoma (catecholamine-producing tumor causing paroxysmal or sustained hypertension with sympathetic symptoms), Cushing syndrome (cortisol excess causing hypertension with characteristic physical features), thyroid disease (both hyperthyroidism and hypothyroidism), and coarctation of the aorta (typically detected in younger patients with upper-to-lower extremity blood pressure gradient).
Panel A: Human body outline showing secondary hypertension causes at anatomical locations: Cushing syndrome at the brain with truncal obesity and moon facies, thyroid disease at the neck, and coarctation of the aorta in the chest with arm-leg BP gradient. Panel B: Adrenal causes including primary aldosteronism with aldosterone-to-renin ratio screening and pheochromocytoma with catecholamine release causing paroxysmal headache, sweating, and palpitations. Panel C: Renal causes including renal artery stenosis with atherosclerotic plaque and bruit, chronic kidney disease with small scarred kidneys, and obstructive sleep apnea with airway obstruction and sympathetic activation. Panel D: Clinical clues for suspecting secondary hypertension: age below 30 or above 55, resistant hypertension, sudden onset or worsening, severe or accelerated hypertension, hypokalemia, and elevated creatinine.
### End-Organ Damage
Hypertension exerts its devastating effects through progressive damage to target organs, driven by the mechanical stress of elevated pressure, accelerated atherosclerosis, and microvascular injury. Understanding these complications motivates aggressive treatment and guides monitoring.
Cardiovascular complications represent the leading cause of morbidity and mortality. Left ventricular hypertrophy develops as the heart adapts to increased afterload, initially preserving function but eventually leading to diastolic dysfunction and ultimately systolic failure. The hypertrophied ventricle is prone to arrhythmias, increasing sudden cardiac death risk. Hypertension accelerates coronary atherosclerosis while simultaneously increasing myocardial oxygen demand, promoting ischemic heart disease. The aorta suffers accelerated atherosclerosis, with risk of aneurysm formation (particularly thoracic) and dissection.
Cerebrovascular disease includes both ischemic and hemorrhagic stroke, with hypertension being the most important modifiable risk factor for both. Large vessel atherosclerosis promotes thrombotic stroke, while small vessel disease causes lacunar infarcts. Chronic small vessel ischemia contributes to vascular dementia and cognitive decline. Hypertensive encephalopathy represents an acute crisis with severely elevated pressure causing cerebral edema, headache, confusion, and visual changes.
Renal complications develop through damage to the renal microvasculature. Hypertensive nephrosclerosis involves arteriolosclerosis of afferent arterioles, causing glomerular ischemia and sclerosis. Progressive nephron loss leads to chronic kidney disease, which itself worsens hypertension. Microalbuminuria serves as an early marker of hypertensive renal damage and systemic endothelial dysfunction.
Hypertensive retinopathy provides a window into systemic microvascular damage through fundoscopic examination. The Keith-Wagener-Barker classification grades severity: Grade I shows arteriolar narrowing with increased light reflex. Grade II adds arteriovenous nicking where arterioles compress underlying venules. Grade III demonstrates hemorrhages (flame-shaped or dot-blot) and exudates (hard or soft). Grade IV adds papilledema, indicating severe hypertension with raised intracranial pressure. Grades III and IV constitute "malignant" or "accelerated" hypertension requiring urgent treatment.
Panel A: Heart showing concentric left ventricular hypertrophy with thickened walls, diastolic dysfunction on pressure-volume loop, coronary atherosclerosis, and ECG with LVH voltage criteria. Panel B: Brain showing large vessel stroke in middle cerebral artery territory, lacunar infarcts in basal ganglia, and white matter hyperintensities from chronic small vessel disease. Panel C: Kidney showing nephrosclerosis with thickened afferent arterioles, sclerosed glomeruli, and tubular atrophy, with a small cortically-scarred kidney compared to normal size. Panel D: Eye showing four grades of hypertensive retinopathy: Grade I with arteriolar narrowing, Grade II with AV nicking, Grade III with hemorrhages and exudates, and Grade IV with papilledema.
### Evaluation of Hypertensive Patients
The goals of hypertension evaluation extend beyond simply documenting elevated blood pressure to confirming the diagnosis through proper measurement technique, assessing for target organ damage, screening for secondary causes when indicated, evaluating overall cardiovascular risk, and identifying barriers to treatment adherence.
Accurate blood pressure measurement is fundamental yet frequently performed incorrectly. The patient should be seated comfortably with back supported, feet flat on the floor, and arm supported at heart level for at least five minutes before measurement. An appropriately sized cuff (bladder encircling at least eighty percent of arm circumference) must be used, as too-small cuffs falsely elevate readings. The average of at least two readings taken on at least two separate occasions establishes the diagnosis. Ambulatory blood pressure monitoring (ABPM) provides twenty-four-hour pressure profiles and is superior for diagnosing white coat hypertension (elevated office but normal ambulatory pressures) and masked hypertension (normal office but elevated ambulatory pressures). Home blood pressure monitoring (HBPM) with validated devices offers practical advantages for ongoing management.
History should assess duration of hypertension, previous treatments and responses, symptoms suggesting target organ damage (headache, visual changes, dyspnea, chest pain), symptoms suggesting secondary causes, medications that might raise blood pressure (NSAIDs, decongestants, steroids, estrogen), and lifestyle factors including diet, physical activity, alcohol, and tobacco use. Family history of hypertension, premature cardiovascular disease, and renal disease informs both etiology and risk assessment.
Physical examination should measure blood pressure in both arms (difference greater than twenty millimeters of mercury suggests coarctation or subclavian stenosis), assess body habitus including BMI and fat distribution, examine the fundoscopic findings for retinopathy, evaluate thyroid for nodules or enlargement, auscultate for cardiac murmurs or gallops, palpate for displaced point of maximal impulse suggesting cardiomegaly, auscultate the abdomen for renal artery bruits, and examine peripheral pulses and edema.
Laboratory evaluation includes baseline metabolic panel (assessing renal function and potassium), fasting glucose or hemoglobin A1c (diabetes screening), lipid panel (cardiovascular risk assessment), urinalysis (proteinuria detection), and twelve-lead electrocardiogram (LVH and ischemia assessment). Additional testing based on clinical suspicion might include thyroid function tests, aldosterone-to-renin ratio, overnight dexamethasone suppression test, catecholamine measurements, or renal artery imaging.
Panel A: Proper blood pressure measurement technique showing patient seated with back supported, feet flat, arm at heart level, properly sized cuff with bladder length 80% of arm circumference, 5-minute rest period, and comparison of common measurement errors. Panel B: Diagnostic 2x2 grid for white coat and masked hypertension with office BP and ambulatory BP axes labeling sustained hypertension, white coat hypertension, masked hypertension, and normotension. Panel C: Baseline evaluation workup including BMP, glucose or HbA1c, lipids, and urinalysis with corresponding purposes, and ECG showing LVH criteria using Sokolow-Lyon voltage. Panel D: Flowchart for when to pursue secondary hypertension workup based on clinical clues including age, resistant hypertension, and laboratory abnormalities.
### Non-Pharmacologic Management
Lifestyle modifications form the foundation of hypertension treatment, appropriate as initial therapy for elevated blood pressure and Stage 1 hypertension without compelling indications, and as adjuncts to pharmacotherapy in all patients. The blood pressure reductions achievable through lifestyle changes rival those of single antihypertensive medications.
Weight loss produces approximately five to twenty millimeters of mercury systolic blood pressure reduction per ten kilograms lost. The mechanisms involve reduced sympathetic activity, decreased RAAS activation, and improved insulin sensitivity. Even modest weight reduction benefits blood pressure, and the effect is amplified when combined with dietary modifications and exercise.
The Dietary Approaches to Stop Hypertension (DASH) diet reduces systolic blood pressure by eight to fourteen millimeters of mercury. This eating pattern emphasizes fruits, vegetables, and whole grains while including low-fat dairy products and reducing saturated fat and cholesterol. The diet is rich in potassium, calcium, magnesium, and fiber while being lower in sodium than typical Western diets. The blood pressure reduction occurs within two weeks of adoption and is additive to other lifestyle interventions.
Sodium restriction reduces systolic blood pressure by two to eight millimeters of mercury. The optimal goal is below 1.5 grams daily, with reasonable benefit from restricting to below 2.4 grams. Given average intakes exceeding 3.4 grams, reduction requires conscious effort to avoid processed foods, restaurant meals, and added salt. Salt sensitivity varies among individuals, with African Americans, older adults, and those with diabetes or CKD showing greater responses.
Physical activity produces four to nine millimeters of mercury systolic blood pressure reduction. Recommended exercise includes aerobic activity for ninety to one hundred fifty minutes weekly at moderate intensity. The acute post-exercise hypotensive effect lasts several hours, while chronic training produces sustained vascular adaptations. Exercise benefits blood pressure independently of weight loss.
Alcohol moderation reduces blood pressure by two to four millimeters of mercury in those with excessive consumption. Men should limit intake to no more than two drinks daily and women to no more than one drink daily.
Panel A: Weight loss intervention showing 5-20 mmHg reduction per 10 kg lost with target BMI below 25, and DASH diet showing 8-14 mmHg reduction emphasizing fruits, vegetables, whole grains, and low-fat dairy. Panel B: Sodium restriction showing 2-8 mmHg reduction with optimal target below 1.5 g daily and avoidance of processed foods, restaurant meals, and added salt. Panel C: Physical activity showing 4-9 mmHg reduction with prescription of 90-150 minutes per week of moderate aerobic exercise, and alcohol moderation showing 2-4 mmHg reduction with limits of 2 drinks daily for men and 1 for women. Panel D: Summary showing combined potential blood pressure reduction of 20-40 mmHg or more with comprehensive lifestyle changes implemented together.
### Pharmacologic Treatment
Four drug classes are recommended as first-line agents for hypertension based on evidence of cardiovascular outcome reduction: ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, and thiazide diuretics. Selection among these classes depends on patient characteristics, comorbidities, and potential side effects.
ACE inhibitors such as lisinopril, enalapril, and ramipril reduce blood pressure by blocking angiotensin II formation, thereby decreasing vasoconstriction and aldosterone-mediated sodium retention. These agents also preserve bradykinin, contributing to vasodilation but also causing dry cough in five to twenty percent of patients. Additional important adverse effects include angioedema (rare but potentially life-threatening), hyperkalemia, and acute kidney injury in patients with bilateral renal artery stenosis. ACE inhibitors are contraindicated in pregnancy due to teratogenicity. They are particularly valuable in patients with heart failure, diabetes with proteinuria, chronic kidney disease with proteinuria, and post-myocardial infarction.
Angiotensin receptor blockers such as losartan, valsartan, and candesartan directly block the AT1 receptor, providing similar benefits to ACE inhibitors without accumulating bradykinin. This eliminates the cough seen with ACE inhibitors, making ARBs an appropriate alternative in patients who develop this side effect. Other considerations, including hyperkalemia risk and pregnancy contraindication, are shared with ACE inhibitors.
Calcium channel blockers include the dihydropyridine subclass (amlodipine, nifedipine) and non-dihydropyridines (diltiazem, verapamil). Dihydropyridines act predominantly on vascular smooth muscle, causing arteriolar vasodilation that reduces peripheral resistance. They are particularly effective in salt-sensitive and elderly populations. Common adverse effects include peripheral edema (a vasodilatory effect, not fluid retention), flushing, and headache. Non-dihydropyridines have significant cardiac effects (reduced heart rate and contractility) limiting their use in heart failure but making them useful for rate control in atrial fibrillation.
Thiazide diuretics such as hydrochlorothiazide and chlorthalidone reduce blood pressure initially through volume depletion and subsequently through decreased vascular resistance. They are particularly effective as monotherapy in African American patients and the elderly. Chlorthalidone has longer duration of action and stronger outcome evidence than hydrochlorothiazide. Adverse effects include hypokalemia, hyponatremia, hyperuricemia, and hyperglycemia.
Most patients require two or more medications to achieve blood pressure goals. When blood pressure exceeds goal by twenty/ten millimeters of mercury or more, initiating two-drug combination therapy is reasonable. Single-pill combinations improve adherence compared to taking multiple separate tablets.
Panel A: Schematic of the RAAS and vascular system with four first-line drug classes mapped to sites of action: ACE inhibitors blocking angiotensin conversion, ARBs blocking the AT1 receptor, thiazide diuretics at the distal tubule, and calcium channel blockers at vascular smooth muscle. Panel B: Comparison table of four first-line classes listing examples, key benefits, major adverse effects, and compelling indications for each: ACE-I for heart failure, diabetic proteinuria, and post-MI; ARB for ACE-I cough; CCB for elderly and isolated systolic hypertension; thiazide for elderly and African Americans. Panel C: Stepped therapy approach showing monotherapy for BP 10-20/5-10 above goal versus initial combination therapy for BP more than 20/10 above goal. Panel D: Common effective drug combinations showing RAAS inhibitor plus CCB or diuretic with caution against combining ACE-I plus ARB due to increased adverse events without benefit.
### Treatment Goals and Special Populations
Blood pressure targets have been refined by recent evidence, most notably the SPRINT trial demonstrating cardiovascular benefit from intensive treatment to a systolic target below 120 millimeters of mercury in high-risk patients. Current guidelines generally recommend a target below 130/80 millimeters of mercury for most patients, including those with established cardiovascular disease, diabetes, chronic kidney disease, and elevated cardiovascular risk.
Elderly patients require particular attention to avoid both undertreatment and overtreatment. While hypertension treatment benefits persist into advanced age, the risk of adverse effects increases. The approach of "start low, go slow" involves initiating at lower doses with gradual titration. Standing blood pressure should be assessed to detect orthostatic hypotension, which may be exacerbated by treatment. Despite these precautions, systolic targets below 130 millimeters of mercury are generally appropriate for ambulatory elderly patients if tolerated.
African American patients experience higher hypertension prevalence, earlier onset, and more severe complications. They are generally more salt-sensitive and have lower circulating renin levels on average. Calcium channel blockers and thiazide diuretics are more effective as monotherapy in this population compared to ACE inhibitors or ARBs, though RAAS inhibitors remain valuable in combination therapy and when compelling indications exist.
Chronic kidney disease patients benefit from blood pressure control to slow progression and reduce cardiovascular events. ACE inhibitors or ARBs are preferred, particularly with proteinuria, as they reduce intraglomerular pressure and slow nephropathy progression. Monitoring of creatinine and potassium is essential, and loop diuretics may be needed when GFR falls below thirty. Targets remain below 130/80 millimeters of mercury.
Pregnancy presents unique considerations because many antihypertensives are contraindicated. ACE inhibitors and ARBs are teratogenic and absolutely contraindicated. Methyldopa has the longest safety track record. Labetalol is commonly used. Nifedipine is another option. Treatment is typically initiated when blood pressure reaches 160/110 millimeters of mercury to prevent maternal stroke, with lower thresholds used in preeclampsia.
Resistant hypertension, defined as blood pressure remaining above goal despite three appropriately dosed medications including a diuretic, requires systematic evaluation. First, pseudo-resistance must be excluded by confirming adherence, assessing measurement technique, and considering white coat effect. Secondary causes should be investigated, particularly primary aldosteronism and obstructive sleep apnea. Adding spironolactone as a fourth agent is often effective, reflecting the high prevalence of aldosterone excess in resistant hypertension.
Panel A: Elderly patient management with start low go slow approach, orthostatic BP measurement, target below 130 if tolerated, and avoidance of overtreatment; and African American population showing higher prevalence and salt-sensitivity with preferred CCB and thiazide initial agents. Panel B: CKD management showing ACE-I or ARB preference for proteinuria with mechanism of efferent arteriole dilation reducing glomerular pressure, potassium and creatinine monitoring, and loop diuretics when GFR falls below 30. Panel C: Pregnancy management showing ACE-I and ARB contraindicated due to teratogenicity, safe options including methyldopa, labetalol, and nifedipine, with treatment threshold of 160/110 to prevent maternal stroke. Panel D: Resistant hypertension evaluation flowchart: confirm adherence, optimize doses, check measurement technique, exclude white coat effect, screen for secondary causes, and add spironolactone as fourth agent.
### Hypertensive Emergencies
Hypertensive emergency is defined by severely elevated blood pressure (typically exceeding 180/120 millimeters of mercury) with evidence of acute end-organ damage. This distinction from hypertensive urgency (severe elevation without acute damage) is crucial because it determines the urgency and method of blood pressure reduction. Hypertensive emergency requires immediate hospitalization, typically in an intensive care setting with continuous arterial pressure monitoring and parenteral antihypertensive therapy.
Target organ manifestations define hypertensive emergency. Neurological emergencies include hypertensive encephalopathy (altered mental status, headache, visual disturbances due to cerebral edema), ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Cardiovascular emergencies include acute heart failure with pulmonary edema, acute coronary syndrome, and aortic dissection. Renal emergencies manifest as acute kidney injury with hematuria and proteinuria. Ophthalmologic emergencies present as acute severe retinopathy with papilledema. Obstetric emergencies include eclampsia and HELLP syndrome.
The principles of blood pressure reduction in hypertensive emergency reflect a careful balance between reducing pressure to limit ongoing damage while avoiding precipitous drops that could cause hypoperfusion injury to organs that have adapted to higher pressures. The general approach involves reducing mean arterial pressure by no more than twenty-five percent in the first hour, then to 160/100 millimeters of mercury over the subsequent two to six hours, then gradually to normal over twenty-four to forty-eight hours.
Aortic dissection represents a critical exception requiring much more aggressive pressure reduction. The shear force driving dissection propagation depends on both pressure and the rate of pressure rise. The target is systolic below 120 millimeters of mercury and heart rate below sixty beats per minute achieved as rapidly as possible. This typically requires combined beta-blocker (to slow heart rate and rate of pressure rise) and vasodilator therapy.
Intravenous antihypertensive agents are selected based on the specific clinical scenario. Nicardipine, a dihydropyridine calcium channel blocker, is preferred in many situations due to predictable dose-response, ease of titration, and lack of significant cardiac conduction effects. Labetalol provides combined alpha and beta blockade but should be avoided in heart failure and asthma. Nitroprusside offers rapid onset and offset but carries risk of cyanide toxicity with prolonged infusion. Nitroglycerin is particularly useful for acute coronary syndrome and pulmonary edema. Hydralazine is often used in pregnancy due to its safety profile. Esmolol is useful in aortic dissection due to its short half-life and beta-selective blockade.
Panel A: Decision node at BP above 180/120 distinguishing urgency without acute end-organ damage requiring oral medication and gradual reduction, from emergency with acute end-organ damage requiring ICU admission, IV therapy, and continuous monitoring. Panel B: Target organs and emergency manifestations: brain with encephalopathy and stroke, heart with acute heart failure and aortic dissection, kidney with acute injury, and eye with papilledema. Panel C: Blood pressure reduction timeline showing gradual approach of 25% reduction in the first hour then 160/100 over 2-6 hours then normal over 24-48 hours, with aggressive approach for aortic dissection targeting SBP below 120 and HR below 60 rapidly. Panel D: IV drug reference table listing nicardipine, labetalol, nitroprusside, nitroglycerin, hydralazine, and esmolol with mechanism, primary uses, and cautions for each.
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## Summary
Hypertension is defined as blood pressure 130/80 millimeters of mercury or above under 2017 ACC/AHA guidelines, affecting approximately forty-five percent of American adults. Primary (essential) hypertension accounts for ninety to ninety-five percent of cases and results from multiple interacting factors including RAAS activation, sympathetic nervous system activity, and impaired renal sodium excretion. Secondary hypertension should be considered in resistant or atypical cases, with primary aldosteronism and obstructive sleep apnea being particularly common causes. End-organ damage affects the heart (LVH, heart failure, coronary disease), brain (stroke, dementia), kidneys (nephrosclerosis, CKD), and eyes (retinopathy). Evaluation confirms the diagnosis through proper measurement technique, assesses target organ damage, and screens for secondary causes when indicated. Lifestyle modifications including weight loss, DASH diet, sodium restriction, and exercise can reduce blood pressure substantially. First-line pharmacotherapy includes ACE inhibitors, ARBs, calcium channel blockers, and thiazide diuretics, selected based on patient characteristics and comorbidities. Treatment targets are generally below 130/80 millimeters of mercury. Hypertensive emergency requires immediate parenteral therapy with careful blood pressure reduction to avoid hypoperfusion injury.
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## Key Terms
| Term | Definition |
|------|------------|
| Primary hypertension | Elevated blood pressure without an identifiable underlying cause |
| Secondary hypertension | Elevated blood pressure resulting from an identifiable condition |
| Resistant hypertension | Blood pressure remaining above goal despite three appropriately dosed medications including a diuretic |
| Hypertensive emergency | Severely elevated blood pressure with evidence of acute end-organ damage |
| Pressure natriuresis | The relationship between arterial pressure and renal sodium excretion |
| White coat hypertension | Elevated blood pressure in clinical settings with normal ambulatory measurements |
| Masked hypertension | Normal blood pressure in clinical settings with elevated ambulatory measurements |
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