Cardiovascular

Essential hypertension: outpatient stepwise pharmacotherapy

Clinical Overview and When to Suspect Essential Hypertension

— Stage 1: 130–139/80–89

— Stage 2: ≥140/90

— Elevated BP: 120–129/<80 (lifestyle only)

— Asymptomatic adult with repeatedly elevated readings on screening

— Family history of early HTN/CV disease, African ancestry, obesity, sedentary lifestyle, high-sodium diet, heavy alcohol intake (>2 drinks/day men, >1 women), OSA risk factors

— Incidental finding during pre-op, employment, or pregnancy screening

— Adults ≥40 or high-risk: annually

— Adults 18–39 with normal BP and no risk factors: every 3–5 years

— Home BP monitoring (HBPM): 2 readings AM and PM × 7 days, discard day 1

— Ambulatory BP monitoring (ABPM): gold standard, distinguishes white-coat and masked HTN

Board pearl: A single elevated office reading is never sufficient to diagnose HTN — Step 3 stems reward you for ordering ABPM or HBPM before initiating drugs in a Stage 1 patient. Treating white-coat HTN drives unnecessary syncope falls in elderly patients and is a classic distractor wrong-answer.

Step 3 management: In the ambulatory setting, document average BP across multiple visits and out-of-office readings, then stage the patient — this drives whether you start with lifestyle alone vs lifestyle plus pharmacotherapy.

Definition (2017 ACC/AHA): Office BP ≥130/80 mmHg on ≥2 separate readings, properly measured, in the absence of an identifiable secondary cause

Essential (primary) HTN accounts for ~90–95% of adult hypertension; multifactorial (genetic, salt sensitivity, RAAS activation, sympathetic tone, obesity, age-related arterial stiffening)

When to suspect in clinic:

Screening cadence (USPSTF Grade A):

Diagnostic confirmation requires out-of-office measurement before committing to lifelong therapy:

Suspect secondary HTN if: onset <30 or >55, resistant HTN, abrupt worsening, hypokalemia, abdominal bruit, episodic spells, or features of Cushing/pheo/OSA — these patients need workup before stepwise titration

Presentation Patterns and Key History

— Early morning occipital headache (suggests sustained elevation)

— Epistaxis, blurred vision, dizziness — nonspecific but classic

— Exertional dyspnea or reduced exercise tolerance (early LV diastolic dysfunction)

— Chest pain, claudication (atherosclerotic complications)

— Nocturia (early renal involvement or OSA)

— Duration of elevated readings, prior antihypertensives and reasons for discontinuation

— Dietary sodium (processed foods, restaurant meals, canned goods) and DASH adherence

— Alcohol quantification, tobacco, stimulant use (cocaine, methamphetamine, ADHD meds)

— OTC/supplement review: NSAIDs, decongestants (pseudoephedrine), oral contraceptives, licorice, herbal stimulants, glucocorticoids, VEGF inhibitors, calcineurin inhibitors

— Sleep history: snoring, witnessed apneas, Epworth score — OSA is the most common reversible secondary cause

— Family history of HTN, stroke, MI <55 (men) / <65 (women)

— ASCVD risk factors: diabetes, dyslipidemia, smoking, CKD

— Episodic headache/palpitations/diaphoresis triad → pheochromocytoma

— Muscle weakness, polyuria, refractory hypokalemia → primary aldosteronism

— Weight gain, striae, easy bruising → Cushing

— Daytime somnolence, AM headache, BMI >30 → OSA

Key distinction: Resistant HTN = BP above goal despite 3 drugs at maximally tolerated doses including a diuretic, OR controlled on ≥4 drugs. This triggers secondary workup, not just a 4th med.

Board pearl: Always ask about NSAID use before escalating therapy — discontinuing chronic ibuprofen often drops SBP 5–10 mmHg and avoids a needless 4th agent.

Most patients are asymptomatic — HTN is the "silent killer"; symptoms typically reflect end-organ injury or markedly elevated pressures

Symptomatic clues that should raise concern:

Key history elements for the Step 3 outpatient encounter:

Red-flag history suggesting secondary cause:

Physical Exam Findings and Hemodynamic Assessment

— Patient seated 5 min, feet flat, back supported, arm at heart level

— No caffeine, exercise, smoking, or talking 30 min prior

— Appropriately sized cuff (bladder = 80% arm circumference); too small → falsely high

— Measure both arms initially; use the higher arm thereafter

— Take ≥2 readings 1–2 min apart, average them

— Drop ≥20 SBP or ≥10 DBP within 3 min of standing → adjust therapy, especially alpha-blockers and diuretics

— Funduscopy: AV nicking, copper/silver wiring (chronic); flame hemorrhages, cotton-wool spots, papilledema (hypertensive emergency)

— Cardiac: sustained PMI, S4 gallop (LVH/diastolic dysfunction), S3 (systolic HF), aortic regurg murmur (root dilation)

— Vascular: carotid/abdominal/femoral bruits, diminished pedal pulses, radial-femoral delay (coarctation in young pt)

— Abdominal: flank bruit → renovascular HTN; abdominal mass → polycystic kidneys

— Neurologic: focal deficits suggest prior stroke

— Skin/habitus: moon facies, buffalo hump, striae (Cushing); café-au-lait, neurofibromas (pheo association via NF1)

Step 3 management: Before labeling someone "resistant," always re-measure BP yourself with proper technique — pseudo-resistance from cuff error, white coat, and nonadherence accounts for up to 40% of apparent treatment failures.

CCS pearl: In the CCS interface, order "blood pressure, both arms" and "orthostatic vitals" early in any hypertension encounter — these advance the clock minimally and inform downstream management choices.

Proper BP technique (heavily tested):

Differences between arms >15 mmHg suggest subclavian stenosis or aortic disease

Orthostatic vitals in elderly, diabetics, on multiple agents:

End-organ exam findings:

Document: BMI, waist circumference, and screen for OSA (Mallampati, neck circumference >17" men / 16" women)

Diagnostic Workup — Initial Labs, ECG, and Baseline Studies

— BMP: sodium, potassium, creatinine, eGFR, glucose

· Hypokalemia unprovoked → screen for primary aldosteronism

· Elevated Cr/low eGFR → CKD workup, dictates drug choice

— Fasting lipid panel for ASCVD risk calculation

— HbA1c or fasting glucose — diabetes coexists in ~25% and changes BP target perception

— TSH if symptoms suggest thyroid dysfunction

— Urinalysis with albumin-to-creatinine ratio (UACR): hematuria, proteinuria, microalbuminuria all indicate target-organ damage

— CBC for baseline (anemia of CKD)

— Uric acid — baseline before thiazide; relevant to gout risk

— Look for LVH (Sokolow-Lyon: SV1 + RV5/V6 >35 mm; Cornell criteria)

— Left atrial enlargement, prior silent MI, conduction disease

— LVH on ECG is a marker of target-organ damage and shifts management urgency

— Drives whether Stage 1 HTN (130–139/80–89) gets pharmacotherapy

— Threshold ≥10% → start drug therapy at Stage 1

— Also drives statin discussion

— HBPM or ABPM before committing patient to lifelong therapy unless Stage 2 or evident target-organ damage

— ABPM threshold: 24-hr avg ≥125/75, daytime avg ≥130/80

Board pearl: A new HTN diagnosis without UACR, BMP, lipids, A1c, and ECG is incomplete on the Step 3 exam — these establish baseline target-organ status and risk-stratify for therapy initiation.

Key distinction: Stage 1 HTN with ASCVD risk <10% and no comorbidities → lifestyle for 3–6 months first; Stage 1 with risk ≥10%, DM, CKD, or established ASCVD → drug therapy immediately alongside lifestyle.

Baseline labs at diagnosis (every newly diagnosed HTN patient):

12-lead ECG on every new HTN patient:

10-year ASCVD risk calculation (Pooled Cohort Equation):

Out-of-office BP confirmation:

Diagnostic Workup — Secondary HTN and Advanced Studies

— Age <30 with no family history

— Resistant HTN (≥3 drugs including diuretic)

— Abrupt onset or sudden worsening in previously controlled patient

— Hypertensive urgency/emergency without explanation

— Disproportionate target-organ damage

— Suggestive clinical features

— Primary aldosteronism (most common secondary cause, ~5–10% of HTN):

· Plasma aldosterone/renin ratio (ARR) as screen

· Ratio >20 with aldosterone >15 ng/dL → confirmatory salt loading

· Hold spironolactone 4–6 wk, ACEi/ARB/diuretics if possible before testing

— Renovascular disease:

· Suspect with flash pulmonary edema, AKI after ACEi, asymmetric kidney size

· Duplex ultrasound, CTA, or MRA renal arteries

· Young woman → fibromuscular dysplasia ("string of beads")

· Older smoker → atherosclerotic

— Pheochromocytoma: plasma free metanephrines (most sensitive) or 24-hr urine metanephrines; CT/MRI adrenal if positive

— Cushing syndrome: late-night salivary cortisol, 24-hr urinary free cortisol, or low-dose dex suppression

— OSA: polysomnography or home sleep apnea test

— Coarctation: echo or CT aorta in young patients with radial-femoral delay

— CKD/renal parenchymal: renal US, repeat UACR, nephrology referral

— Suspected HF, LVH on ECG, murmur, or to guide therapy in borderline cases

Step 3 management: Before sending an ARR, stop spironolactone/eplerenone for 4–6 weeks — they will falsely normalize the ratio and you'll miss the diagnosis. ACEi/ARB/thiazides can also confound but are less critical.

Board pearl: In the test patient with resistant HTN + OSA risk factors, the highest-yield next step is a sleep study, not a 4th antihypertensive — CPAP can drop SBP 5–10 mmHg.

Trigger secondary workup when:

Targeted secondary workup:

Echocardiogram (not routine) indicated for:

Risk Stratification and Treatment Threshold Logic

— Elevated (120–129/<80): lifestyle only, reassess 3–6 mo

— Stage 1 (130–139/80–89):

· ASCVD risk <10% and no DM/CKD/ASCVD → lifestyle for 3–6 mo, then reassess

· ASCVD risk ≥10%, OR established ASCVD, OR DM, OR CKD → lifestyle + 1 drug

— Stage 2 (≥140/90): lifestyle + 2 drugs from different classes (especially if BP >20/10 above goal)

— Older adults (≥65, ambulatory, community-dwelling): <130 SBP if tolerated (SPRINT-influenced)

— Diabetes: <130/80 (ADA aligns)

— CKD: <130/80

— Post-stroke: <130/80

— Frail elderly with limited life expectancy: individualize, often <140/90 acceptable

— Weight loss: ~1 mmHg per kg lost

— DASH diet: 8–11 mmHg

— Sodium <1500 mg/day (or ≥1000 mg reduction): 5–6 mmHg

— Aerobic exercise 90–150 min/wk: 5–8 mmHg

— Alcohol reduction to ≤2 (men) / ≤1 (women) drinks/day: 4 mmHg

— Smoking cessation: doesn't lower chronic BP much but markedly reduces CV events

Key distinction: Step 2 still uses JNC8 logic on some questions, but Step 3 firmly anchors to 2017 ACC/AHA ≥130/80 thresholds with ASCVD-risk-driven initiation.

Board pearl: Initial dual therapy is preferred when SBP is >20 mmHg or DBP >10 mmHg above goal — monotherapy in Stage 2 HTN is a classic wrong answer because it nearly always fails to reach target.

2017 ACC/AHA stepwise decision:

BP targets (most patients): <130/80

Lifestyle interventions and expected SBP reduction:

Compelling indications drive drug choice more than stage alone — match comorbidity to mechanism (covered next chunk)

Pharmacotherapy — First-Line Drug Regimen

— Thiazide-type diuretic — chlorthalidone (preferred, longer t½, more potent) or indapamide; HCTZ acceptable

— ACE inhibitor — lisinopril, ramipril, enalapril

— ARB — losartan, valsartan, telmisartan

— Dihydropyridine CCB — amlodipine, nifedipine ER

— Black adults without HF or CKD: initiate with thiazide or CCB (better BP response, lower stroke risk than ACEi monotherapy per ALLHAT)

— Add ACEi/ARB if needed; this is not a contraindication

— HFrEF: ACEi/ARB/ARNI + beta-blocker + MRA + SGLT2i (not first-line BP agents but cover the BP)

— Post-MI/CAD: beta-blocker + ACEi/ARB

— CKD with albuminuria (UACR ≥30): ACEi or ARB (renoprotective)

— Diabetes with albuminuria: ACEi/ARB; add SGLT2i

— Recurrent stroke prevention: thiazide + ACEi

— Atrial fibrillation rate control: non-DHP CCB (diltiazem/verapamil) or beta-blocker

— BPH: alpha-blocker as add-on (not monotherapy)

— Migraine: beta-blocker, candesartan

— Osteoporosis: thiazide (calcium retention)

— ACEi/ARB + thiazide (offsets RAAS activation)

— ACEi/ARB + DHP CCB (ACCOMPLISH: better outcomes than ACEi/thiazide in high-risk patients)

— Never combine ACEi + ARB — increased AKI, hyperkalemia, syncope, no mortality benefit

Step 3 management: Stage 2 HTN → start two drugs concurrently (e.g., lisinopril + amlodipine, or losartan + chlorthalidone) as single-pill combinations to improve adherence — single-pill combos are explicitly endorsed by guidelines.

Board pearl: Chlorthalidone > HCTZ for cardiovascular outcomes at equivalent BP-lowering doses — favor chlorthalidone unless cost/availability dictates otherwise.

Four first-line classes (interchangeable for most patients without compelling indications):

Race/ethnicity considerations:

Compelling indications drive choice:

Combinations that work synergistically:

Starting dose principle: initiate at low-moderate dose, titrate every 2–4 weeks; add a second agent rather than maxing one when partial response

Expanded Pharmacology — Step-Up, Resistant HTN, and Side-Effect Management

— Step 1: A (ACEi/ARB) or C (CCB) or D (thiazide) monotherapy

— Step 2: A + C, or A + D, or C + D

— Step 3: A + C + D (triple therapy)

— Step 4 (resistant): Add spironolactone 12.5–25 mg (PATHWAY-2 trial: superior to bisoprolol or doxazosin)

— Step 5: Add beta-blocker, alpha-blocker (doxazosin), central agent (clonidine), or hydralazine; refer to HTN specialist

— ACEi: cough (~10%, bradykinin-mediated, switch to ARB), angioedema (0.3%, higher in Black patients, contraindication to future use), hyperkalemia, AKI (especially with bilateral RAS), teratogenic

· Check BMP 1–2 wk after start; 30% Cr rise is acceptable if stable

— ARB: same as ACEi without cough; angioedema rare

— Thiazide: hypokalemia, hyponatremia (esp. elderly women), hyperuricemia/gout, hyperglycemia, hypercalcemia, photosensitivity, erectile dysfunction

· Avoid if eGFR <30 (use loop instead)

— DHP CCB: peripheral edema (dose-dependent, not fluid overload — don't treat with diuretic; reduce dose or add ACEi), flushing, gingival hyperplasia, reflex tachycardia

— Non-DHP CCB: bradycardia, AV block, constipation (verapamil), worsens HFrEF — contraindicated in EF <40%

— Beta-blocker: bradycardia, fatigue, bronchospasm, mask hypoglycemia, sexual dysfunction; not first-line unless compelling indication

— Spironolactone: hyperkalemia, gynecomastia (switch to eplerenone), monitor K and Cr at 1 and 4 wk

— Hydralazine: drug-induced lupus, reflex tachycardia (pair with beta-blocker)

— Clonidine: sedation, dry mouth, rebound HTN if abruptly stopped — taper over 1 wk

Board pearl: New peripheral edema on amlodipine in a euvolemic patient → reduce dose or add ACEi/ARB (which dilates venules and relieves edema); adding furosemide is the wrong answer.

CCS pearl: When restarting an ACEi after AKI resolution, recheck BMP at 1 and 2 weeks — the CCS clock rewards proactive monitoring orders.

Stepwise escalation when not at goal at 1 month:

Class-specific adverse effects and monitoring:

Special Populations — Elderly and Renal/Hepatic Impairment

— SPRINT supports SBP <130 in community-dwelling patients ≥75 with reduced CV events and mortality

— Start low, go slow: half the usual starting dose, titrate every 4 weeks

— Check orthostatics at each visit; falls and syncope are the dose-limiting toxicities

— Avoid alpha-blockers as monotherapy (orthostatic hypotension, fall risk — Beers criteria)

— Avoid clonidine (sedation, cognitive impairment — Beers)

— Preferred: thiazide, CCB, ACEi/ARB

— Frail/institutionalized/limited life expectancy: individualize; <140/90 acceptable, avoid intensive lowering if it causes symptoms

— First-line: thiazide or DHP CCB

— Lower SBP but watch DBP — avoid pushing DBP <60 in CAD patients (J-curve concern)

— eGFR ≥30: thiazide effective; chlorthalidone works down to eGFR 20 per CLICK trial

— eGFR <30: loop diuretic (furosemide BID, torsemide daily) preferred for volume control

— Albuminuria (UACR ≥30): ACEi or ARB first-line regardless of BP, renoprotective

— Monitor K and Cr; accept ≤30% Cr rise after initiation

— Add finerenone (nonsteroidal MRA) in diabetic CKD with albuminuria for CV/renal benefit

— SGLT2 inhibitors add BP-lowering and renoprotection in diabetic and non-diabetic CKD

— Most antihypertensives safe; avoid methyldopa (hepatotoxicity), use caution with labetalol

— Cirrhotic ascites: spironolactone ± furosemide (100:40 ratio) — addresses both portal HTN sequelae and BP

Step 3 management: In a 78-year-old with new HTN, measure orthostatics and gait before and after each titration — falls cause more morbidity in this group than the HTN itself in the short term.

Key distinction: Acceptable Cr rise after ACEi = up to 30%; >30% rise or hyperkalemia >5.5 → stop the drug and evaluate for bilateral renal artery stenosis.

Elderly (≥65) ambulatory adults:

Isolated systolic HTN (wide pulse pressure, common in elderly):

CKD:

Hepatic impairment:

Special Populations — Pregnancy, Reproductive-Age Women, and Pediatrics

— Chronic HTN in pregnancy: BP ≥140/90 before 20 wk or pre-pregnancy

— Gestational HTN: new ≥140/90 after 20 wk without proteinuria

— Preeclampsia: ≥140/90 after 20 wk + proteinuria or end-organ dysfunction

— Treatment threshold (CHAP trial, 2022): treat chronic HTN at ≥140/90 (not 160/110 as historically); target <140/90

— Labetalol (first-line, IV or PO)

— Nifedipine ER (first-line oral)

— Methyldopa (older first-line, less potent, still acceptable)

— Hydralazine (acute severe HTN of pregnancy, IV)

— ACEi, ARB, direct renin inhibitor — renal dysgenesis, oligohydramnios, fetal death (2nd/3rd trimester); avoid all trimesters when possible

— Thiazides — relative contraindication; can impair plasma volume expansion

— Spironolactone — anti-androgenic, avoid

— Counsel on teratogenicity of ACEi/ARB; ensure reliable contraception or switch preemptively when planning pregnancy

— Combined OCPs can raise BP — consider progestin-only or non-hormonal if HTN

— Safe: labetalol, nifedipine, enalapril, captopril (ACEi acceptable postpartum), methyldopa

— Avoid: atenolol (concentrates in breast milk)

— HTN = BP ≥95th percentile for age/sex/height on 3 occasions

— Higher likelihood of secondary HTN (renal parenchymal, coarctation, renovascular)

— Workup: renal US, BMP, UA, echo, plasma renin

— First-line: ACEi, ARB, CCB, or thiazide; lifestyle paramount

Board pearl: A 28-year-old woman on lisinopril with positive pregnancy test → stop ACEi today and transition to labetalol or nifedipine; don't wait for the next visit.

Key distinction: Severe-range BP in pregnancy (≥160/110) sustained ≥15 min is an emergency — IV labetalol, hydralazine, or oral nifedipine within 30–60 min, plus magnesium for seizure prophylaxis if preeclamptic.

Pregnancy:

Safe agents in pregnancy:

Contraindicated in pregnancy:

Reproductive-age women not pregnant:

Lactation:

Pediatrics:

Complications and Adverse Outcomes of Uncontrolled HTN

— LVH → diastolic dysfunction → HFpEF → eventually HFrEF

— Accelerated CAD, MI, sudden cardiac death

— Atrial fibrillation (LA enlargement from elevated filling pressures)

— Aortic dissection (especially with poorly controlled SBP)

— Aortic aneurysm

— Ischemic stroke (most common cause: HTN)

— Hemorrhagic stroke — basal ganglia, thalamus, pons, cerebellum (Charcot-Bouchard microaneurysms)

— Lacunar infarcts → vascular dementia

— Hypertensive encephalopathy (in emergency)

— Hypertensive nephrosclerosis — 2nd leading cause of ESRD after diabetes

— Progressive proteinuria, declining eGFR

— Accelerated atherosclerosis of renal arteries

— Keith-Wagener-Barker grading:

· I: arteriolar narrowing

· II: AV nicking, copper wiring

· III: flame hemorrhages, cotton-wool spots, exudates

· IV: papilledema (emergency)

— PAD, claudication, abdominal aortic aneurysm

— Erectile dysfunction from vascular disease (and from some meds — thiazide, beta-blocker)

— Urgency: BP ≥180/120 without acute end-organ damage → oral therapy, lower over 24–48 h, avoid rapid IV reduction (risk watershed stroke)

— Emergency: BP ≥180/120 with end-organ damage (encephalopathy, MI, dissection, pulmonary edema, AKI, eclampsia, retinopathy IV) → IV agents in ICU, lower MAP 10–20% in first hour, then 5–15% over next 23 h

· Exception: aortic dissection → SBP <120 within 20 min; ischemic stroke → permissive HTN unless tPA candidate

Board pearl: In hypertensive urgency without end-organ damage, the correct outpatient action is restart or up-titrate oral meds and follow up in 24–72 hours — NOT IV labetalol, NOT ED transfer, NOT sublingual nifedipine (causes precipitous drops and strokes).

Step 3 management: Always calculate ASCVD risk and obtain UACR at every HTN follow-up — these track progression of subclinical end-organ injury.

Cardiac:

Cerebrovascular:

Renal:

Retinal:

Peripheral vascular:

Sexual dysfunction:

Hypertensive crises:

When to Escalate — Specialist Referral, ED, and Inpatient Triage

— True resistant HTN confirmed (3 drugs including diuretic at max tolerated dose with confirmed adherence and ABPM)

— Suspected or confirmed secondary HTN (after initial workup)

— Pregnancy with chronic HTN — co-manage with MFM

— Pediatric HTN

— Recurrent hypertensive emergencies

— Progressive CKD (eGFR <30 or rapidly declining)

— Intolerance to multiple drug classes

— Hypertensive emergency: BP ≥180/120 with any of:

· Chest pain (ACS, dissection)

· Acute neurologic deficit or severe headache with vision change

· Severe dyspnea/pulmonary edema

· AKI with rising Cr

· New visual disturbance with papilledema

· Pregnancy with severe features (≥160/110, headache, RUQ pain, vision changes)

· Cocaine/methamphetamine-induced

— Hypertensive urgency that fails outpatient management or unreliable follow-up

— Suspected pheochromocytoma crisis

— Urgency with significant comorbidity needing observation

— New diagnosis requiring expedited secondary workup with unstable readings

— Arterial line for continuous BP monitoring

— IV nicardipine, clevidipine, labetalol, esmolol, nitroprusside (limited use, cyanide toxicity), nitroglycerin (preferred in ACS/pulmonary edema)

— Cardiology if LVH, HFpEF, CAD

— Nephrology if eGFR <45 or albuminuria progressing

— Sleep medicine if STOP-BANG ≥3

— Endocrinology for confirmed primary aldosteronism, pheo, Cushing

— Dietitian for DASH coaching

CCS pearl: In a CCS case of BP 200/130 with new dyspnea and crackles, transfer to ICU, start IV nitroglycerin + IV furosemide, obtain CXR/BNP/troponin/ECG — this is hypertensive emergency with flash pulmonary edema, classic for renovascular disease.

Board pearl: "Asymptomatic severe HTN" (urgency) does not require ED transfer or rapid lowering — overcorrection causes ischemic stroke.

Refer to hypertension specialist or nephrology when:

Send to ED / direct admission:

Inpatient floor admission (not ICU) may suffice for:

ICU admission for emergency with:

Outpatient consultations to consider longitudinally:

Key Differentials — Other Causes of Elevated BP Within the Same Category

— White-coat HTN: elevated office, normal HBPM/ABPM — ~15–20% of office-diagnosed HTN; annual ABPM, lifestyle, no drugs

— Masked HTN: normal office, elevated HBPM/ABPM — higher CV risk than sustained HTN; treat as essential HTN

— Pseudohypertension: stiff, non-compressible arteries in very elderly; Osler maneuver positive (palpable radial after cuff inflation above SBP) — intra-arterial measurement may be needed

— Pseudo-resistance: apparent resistant HTN due to:

· Improper cuff size (small cuff on obese arm)

· Nonadherence (highest-yield cause — confirm via pill counts, pharmacy refill, witnessed dose, urine drug levels)

· Suboptimal dosing or wrong drug class

· White-coat effect in treated patient

— Primary aldosteronism — hypokalemia, metabolic alkalosis, suppressed renin, high aldosterone

— Renovascular HTN — flash pulmonary edema, AKI on ACEi, abdominal bruit, asymmetric kidneys

— Pheochromocytoma — paroxysmal HA, palpitations, diaphoresis; elevated metanephrines

— Cushing syndrome — central obesity, striae, glucose intolerance, hypokalemia

— OSA — snoring, daytime sleepiness, nocturnal HTN pattern (non-dipping on ABPM)

— Hyperthyroidism — isolated systolic HTN, tachycardia, weight loss

— Hyperparathyroidism — hypercalcemia

— Coarctation — radial-femoral delay, rib notching on CXR, BP differential between arms and legs

— CKD/renal parenchymal disease — elevated Cr, proteinuria

Key distinction: Masked HTN is more dangerous than white coat — it carries CV risk equal to or higher than sustained office HTN because patients go untreated. Screen with HBPM/ABPM when office BP is normal but the patient has end-organ damage or family history.

Board pearl: Nonadherence is the single most common cause of apparent treatment resistance — Step 3 stems often plant a clue like "occasionally misses doses" before asking for the next step (answer: confirm adherence, not add a 4th drug).

Differential within "elevated office BP" before committing to essential HTN diagnosis:

Secondary HTN to distinguish from essential:

Key Differentials — Other-Category Conditions That Mimic or Worsen HTN

— NSAIDs — sodium retention, blunted antihypertensive efficacy; raises SBP 3–5 mmHg

— Decongestants — pseudoephedrine, phenylephrine

— Stimulants — amphetamines, methylphenidate, cocaine, MDMA

— Oral contraceptives — estrogen-containing

— Glucocorticoids — prednisone, dexamethasone

— VEGF inhibitors — bevacizumab, sorafenib, sunitinib (classic on oncology stems)

— Calcineurin inhibitors — cyclosporine, tacrolimus (post-transplant patient)

— Erythropoiesis-stimulating agents

— Licorice (glycyrrhizic acid → apparent mineralocorticoid excess)

— Herbals — ephedra, ma huang, yohimbe, ginseng

— SNRIs — venlafaxine

— Alcohol (acute and chronic), heavy caffeine, tobacco

— Acromegaly — coarse features, large hands, OSA, HTN, DM

— Hyperthyroidism — isolated systolic HTN, wide pulse pressure

— Hyperparathyroidism — hypercalcemia, often mild HTN

— Congenital adrenal hyperplasia (11β- and 17α-hydroxylase deficiencies) — HTN with hypokalemia in young patient

— Pain, anxiety, urinary retention, alcohol withdrawal — treat the underlying cause

— Increased intracranial pressure (Cushing reflex: HTN + bradycardia + irregular respirations) — neurosurgical emergency, never just treat BP

— Autonomic dysreflexia in spinal cord injury (T6 or above) — paroxysmal HTN triggered by bladder distention or fecal impaction

— Panic disorder, hyperthyroidism, stimulant use, MAOI-tyramine interaction

Key distinction: In a spinal cord injury patient with sudden severe HTN and bradycardia, autonomic dysreflexia — first step is sit the patient upright and relieve the trigger (catheterize bladder, check for impaction); IV antihypertensives only if trigger removal fails.

Board pearl: Always reconcile OTC and supplement use at every BP visit — discontinuing an offending agent often eliminates the need for additional pharmacotherapy.

Drug-induced HTN (review every visit):

Endocrine mimics worth distinguishing:

Other conditions producing transient or sustained BP elevation:

Pseudo-pheo presentations:

Secondary Prevention, Long-Term Plan, and Bundled Risk Reduction

— Statin therapy:

· ASCVD risk ≥7.5–10% with risk-enhancers → moderate-intensity statin

· Established ASCVD, LDL ≥190, DM age 40–75 → statin per ACC/AHA

· Treat to LDL goal per current ACC/AHA (no fixed target but ≥50% reduction in high-risk)

— Aspirin: not routine for primary prevention (USPSTF 2022 limited to age 40–59 with ≥10% ASCVD risk and low bleed risk, individualized); yes for secondary prevention

— Diabetes screening: A1c every 3 years if normal, annually if pre-DM

— Tobacco cessation at every visit (5 A's), pharmacotherapy: varenicline, bupropion, NRT

— Weight management: BMI goal <25; consider GLP-1 RA if BMI ≥30 or ≥27 with comorbidity

— DASH/Mediterranean diet counseling; sodium <1500 mg/day

— Exercise: 150 min/wk moderate or 75 min vigorous

— Alcohol: ≤2 (men), ≤1 (women) drinks/day

— Vaccinations: annual influenza, pneumococcal, COVID, RSV per age

— Single-pill combinations (lisinopril/HCTZ, valsartan/amlodipine, olmesartan/amlodipine/HCTZ) improve adherence ~20%

— Once-daily dosing whenever possible

— 90-day refills, mail-order pharmacy

— Generic preference for cost

— Home BP monitoring with logbook or connected device (telehealth integration)

— Diabetes + HTN + albuminuria → ACEi/ARB + SGLT2i + statin + GLP-1 RA bundle

— HFrEF → GDMT quadruple therapy (ARNI/ACEi, beta-blocker, MRA, SGLT2i)

— Post-MI → beta-blocker + ACEi + statin + antiplatelet

Step 3 management: Discharge from any cardiac admission must include reconciled antihypertensives, statin, and a follow-up appointment within 7–14 days — transition-of-care omissions drive 30-day readmissions and are heavily tested.

Board pearl: SGLT2 inhibitors lower SBP ~3–5 mmHg as a bonus while providing CV/renal benefit — they're not labeled as antihypertensives but count toward control in diabetic HTN.

HTN management is incomplete without addressing the full ASCVD risk profile:

Medication adherence strategies:

Co-management for compelling indications:

Follow-Up, Monitoring, and Lifestyle Counseling Cadence

— Newly started or titrated: reassess in 2–4 weeks

— Stable, at goal: every 3–6 months

— After major change (new drug, dose, comorbidity): 2 weeks

— HBPM preferred between visits — 2 readings AM, 2 readings PM × 7 days before each appointment

— BMP at 1–2 weeks after starting/changing ACEi, ARB, diuretic, MRA — check K, Cr, Na

— Annual: BMP, UACR, fasting lipids, A1c

— Uric acid if on thiazide and history of gout

— Magnesium if persistent hypokalemia despite repletion

— BP at goal (<130/80 for most)

— Heart rate (especially on beta-blocker or non-DHP CCB)

— Weight, BMI, waist circumference

— Orthostatic vitals in elderly or symptomatic

— Adherence (refill history, pill count, side-effect screen)

— Lifestyle review: diet recall, exercise minutes, alcohol, sleep

— Demonstrate proper HBPM technique

— Explain that BP fluctuates and single high readings rarely require action

— Set written goals; use motivational interviewing

— Address barriers: cost (use $4 generics, GoodRx, 90-day mail), polypharmacy, side effects, health literacy

— Discuss when to call: BP ≥180/120, chest pain, neurologic symptoms, severe headache

— ECG if symptomatic or LVH on prior

— Echo if HF symptoms develop

— Repeat ASCVD risk calculation, statin discussion

CCS pearl: When titrating a diuretic on the CCS, always order a BMP at 1–2 weeks — missing this electrolyte check is penalized regardless of clinical outcome.

Board pearl: Home BP averages <5 mmHg lower than office; treat to home goal of <125/75 if using HBPM-derived targets in shared decision-making.

Follow-up cadence after initiation or titration:

Labs to monitor:

Targets to verify at each visit:

Counseling content (high-yield Step 3 elements):

Cardiac rehab referral indicated post-MI, post-CABG/PCI, HFrEF, stable angina — improves BP and overall outcomes

Annual reassessment:

Ethical, Legal, and Patient Safety Considerations

— SPRINT-style intensive control reduces CV events but increases AKI, syncope, electrolyte abnormalities

— Discuss trade-offs with elderly, frail, or polypharmacy patients; document

— A frail 85-year-old patient with limited life expectancy may rationally choose a goal of <140/90 over <130/80 — autonomy and informed refusal are appropriate

— Pregnancy and teratogenic drugs (ACEi/ARB): document counseling about contraception or drug switch in reproductive-age women — failure to document is a malpractice exposure

— Genetic testing for familial HTN syndromes (rare): genetic counseling

— Severe uncontrolled HTN with syncope or visual impairment may warrant driving restriction counseling — varies by state; document

— Workplace clearance (CDL drivers, pilots) requires BP <140/90 per DOT/FAA — patients may have financial incentives to underreport readings

— Hospital discharge medication reconciliation — resume home antihypertensives unless contraindicated; "withholding home meds at discharge" is a sentinel-event-level error

— Cross-cover and handoff — communicate target BPs and recent changes

— Post-discharge 7-day follow-up reduces 30-day readmissions

— Reconcile that the inpatient regimen (often more aggressive) is appropriate for outpatient continuation — overzealous discharge regimens cause outpatient syncope/falls

— Cost barriers: prescribe generic chlorthalidone, lisinopril, amlodipine, losartan — all on $4 lists

— Food deserts impair DASH adherence — refer to social work, SNAP

— Language: use professional interpreters, not family members

— Never act on a single elevated reading without remeasurement and proper technique

— Avoid sublingual nifedipine in any setting — banned for HTN urgency due to stroke risk

— Beware drug interactions: ACEi + K-sparing diuretic + K supplement → fatal hyperkalemia

Board pearl: Discharging a patient on a new beta-blocker without warning about abrupt discontinuation rebound tachycardia/ischemia is both a safety and consent failure — written instructions and a primary care follow-up within 1–2 weeks are mandatory.

Shared decision-making in BP targets:

Informed consent edge cases:

Mandatory reporting and safety:

Transition-of-care risks (heavily tested on Step 3):

Health equity and access:

Patient safety in the office:

High-Yield Associations and Rapid-Fire Clinical Facts

— Goal BP <130/80 for nearly all adults

— Treat Stage 1 with drugs if ASCVD risk ≥10%, DM, CKD, or ASCVD

— Initiate 2 drugs if SBP >20 or DBP >10 above goal

— 1 kg weight loss ≈ 1 mmHg SBP reduction

— DASH ≈ 11 mmHg SBP reduction

— Sodium <1500 mg ≈ 5 mmHg reduction

— ACEi cough → switch to ARB

— ACEi angioedema → switch to anything BUT ARB (ARB carries small residual risk; avoid if severe)

— Amlodipine edema → reduce dose or add ACEi/ARB (NOT diuretic)

— Verapamil → constipation, AV block

— Hydralazine → drug-induced lupus (anti-histone antibodies)

— Procainamide → also drug-induced lupus

— Minoxidil → hirsutism, pericardial effusion

— Methyldopa → Coombs-positive hemolytic anemia, hepatitis

— Thiazide → hyperGLUC (hyperGlycemia, hyperLipidemia, hyperUricemia, hyperCalcemia)

— Loop → hypoCa, hypoMg, hypoK, ototoxicity

— Spironolactone → gynecomastia (switch to eplerenone)

— Low renin, high aldosterone → primary aldosteronism (Conn)

— High renin, high aldosterone → renovascular HTN, secondary

— Low renin, low aldosterone → Liddle (ENaC gain-of-function), licorice, CAH, Cushing

— Diabetes + albuminuria → ACEi/ARB

— Post-MI → BB + ACEi

— HFrEF → ARNI + BB + MRA + SGLT2i

— BPH + HTN → add doxazosin

— Migraine + HTN → propranolol or candesartan

— Osteoporosis + HTN → thiazide

— AFib + HTN → beta-blocker or diltiazem/verapamil

— Pregnancy → labetalol, nifedipine, methyldopa, hydralazine

Key distinction: Conn syndrome (primary aldosteronism) gives low renin + high aldosterone; renovascular HTN gives high renin + high aldosterone — the renin level distinguishes them.

Board pearl: Liddle syndrome mimics aldosteronism clinically (HTN, hypokalemia, alkalosis) but has low aldosterone AND low renin — treat with amiloride/triamterene, not spironolactone.

Numerical pearls:

Drug-association quick hits:

Renin/aldosterone pattern recognition:

Compelling indication shortcuts:

Board Question Stem Patterns

— The screening stem: "55 y/o asymptomatic man, office BP 142/88 today. PMH unremarkable. Next step?" → Repeat measurement, confirm with HBPM/ABPM, then stage; don't jump to drugs on one reading

— The Stage 2 starter: "62 y/o BP 162/96 × 3 visits, A1c 7.2." → Initiate two drugs: ACEi/ARB (DM/albuminuria) + thiazide or CCB

— The Black adult monotherapy stem: "58 y/o Black woman, no DM/CKD, BP 148/92." → Thiazide or CCB first, not ACEi monotherapy

— The resistant HTN stem: "On lisinopril 40, amlodipine 10, chlorthalidone 25, BP still 152/94, K 3.9, adherent." → Add spironolactone 25 mg

— The ACEi cough: "Started lisinopril 6 weeks ago, persistent dry cough." → Switch to ARB

— The bilateral RAS stem: "Started lisinopril, Cr rose from 1.1 to 1.9 in 2 weeks." → Stop ACEi, image renal arteries (duplex/MRA)

— The Conn stem: "BP 168/102, K 2.8 on no diuretic, alkalosis." → Plasma aldosterone/renin ratio

— The pheo stem: "Episodic HA + palpitations + sweating + HTN spikes." → Plasma free metanephrines

— The OSA stem: "Resistant HTN, BMI 38, snores, daytime fatigue." → Sleep study

— The pregnancy switch: "32 y/o on lisinopril, β-hCG positive." → Stop lisinopril, start labetalol or nifedipine

— The hypertensive urgency stem: "180/115, asymptomatic, no end-organ damage." → Oral agent, follow up 24–72 h; NOT ED transfer, NOT IV labetalol, NOT sublingual nifedipine

— The hypertensive emergency: "BP 220/130 with papilledema, AKI, headache." → ICU, IV nicardipine, MAP reduction 10–20% in 1st hour

— The orthostatic elderly: "78 y/o on 4 antihypertensives, syncope while standing." → Reduce or stop offending agent, recheck orthostatics

— Adding a 4th drug before confirming adherence or excluding secondary causes

— Sublingual nifedipine

— Combining ACEi + ARB

— Furosemide for amlodipine edema

— ACEi in pregnancy

Step 3 management: Pattern recognition saves time — anchor on the lab clue (K, Cr, A1c) and the compelling indication before choosing the drug.

Classic Step 3 vignettes to recognize:

Common distractors to reject:

One-Line Recap

Essential hypertension is a chronic ambulatory disease in which BP ≥130/80 confirmed by out-of-office measurement is treated with lifestyle plus stepwise pharmacotherapy — typically initiating a thiazide, ACEi/ARB, or CCB (or two simultaneously in Stage 2), titrated every 2–4 weeks to a goal of <130/80, with compelling indications driving drug class, and secondary causes investigated when resistance, atypical features, or early-onset disease emerge.

Board pearl: The most missed Step 3 move is not adding a drug — it's confirming adherence, excluding white-coat/secondary causes, and discontinuing a contributing OTC before escalating therapy.

Step 3 management: Hypertension is won in the outpatient longitudinal follow-up, not in any single visit — adherence, lifestyle, and risk-factor bundling outperform isolated drug escalations over a decade of care.

Diagnose right: Confirm with HBPM or ABPM; obtain baseline BMP, UACR, lipids, A1c, ECG; calculate ASCVD risk to decide when Stage 1 needs drugs

Treat right: First-line = thiazide (chlorthalidone preferred), ACEi/ARB, or DHP CCB; start two if SBP >20 or DBP >10 above goal; choose by compelling indication (DM/CKD → ACEi/ARB; Black without HF/CKD → thiazide or CCB; post-MI → BB + ACEi; pregnancy → labetalol/nifedipine/methyldopa)

Escalate right: A + C + D, then add spironolactone for resistant HTN; investigate secondary causes (OSA, primary aldosteronism, renovascular, pheo) when resistant or atypical; never combine ACEi + ARB

Follow right: BMP at 1–2 weeks after initiation/titration; reassess BP every 2–4 weeks until controlled then every 3–6 months; bundle statin, glycemic control, weight, DASH, sodium, exercise, alcohol, and smoking cessation; reconcile NSAIDs, OCPs, and stimulants at every visit