276.3 🏥 內科專科考前版

276.3.1 Mechanistic Deep Dive

276.3.1.1 Genetics of HTN

  • 1000 SNPs identified in GWAS

  • Polygenic risk score (PRS) modest predictor
  • Monogenic causes (rare): Liddle, Gordon, Geller, GRA, AME — all involve renal Na handling

276.3.1.2 Sympathetic Nervous System

  • ↑ central sympathetic outflow
  • Baroreflex resetting
  • Renal sympathetic activity (target for renal denervation)
  • Carotid body chemoreflex (target for emerging therapies)

276.3.1.3 RAAS in HTN

  • Renin (JG cells of kidney) → angiotensinogen (liver) → Ang I → ACE (lung) → Ang II
  • Ang II: vasoconstriction, aldosterone, AT1R signaling
  • Aldosterone: Na retention, K wasting, fibrosis
  • Local tissue RAAS in heart, vessels, brain

276.3.1.4 Endothelial Dysfunction

  • ↓ NO bioavailability
  • ↑ ET-1
  • ↑ ROS, ↓ antioxidants
  • ↑ inflammatory cytokines

276.3.1.5 Vascular Stiffness

  • Aging → collagen replacement of elastin
  • Pulse wave velocity (PWV) ↑ predicts CV events
  • Isolated systolic HTN in elderly = stiff arteries

276.3.2 Recent Trials & Updates

276.3.2.1 SPRINT (2015) — Landmark

  • N = 9361 non-DM HTN, SBP < 120 vs < 140
  • ↓ CV mortality 27%, ↓ all-cause mortality 25%
  • ↑ AKI, syncope, hypotension
  • Foundation for 2017 ACC/AHA < 130/80 target

276.3.2.2 STEP (2021)

  • N = 8511 Chinese elderly (60-80) HTN
  • Intensive (< 130) vs standard (< 140-150)
  • ↓ CV events
  • Confirms benefit in elderly

276.3.2.3 SYMPLICITY HTN-3 (2014) → New Era (2018-2024)

  • Initial neg trial of renal denervation
  • SPYRAL-HTN-OFF MED (2018): positive in off-medication
  • RADIANCE-HTN SOLO (2018): positive (ultrasound)
  • SPYRAL-HTN-ON MED (2020): positive on background meds
  • 2024 FDA approval for resistant HTN
  • RDN now a real option for resistant HTN

276.3.2.4 PATHWAY-2 (2015)

  • Resistant HTN: spironolactone > bisoprolol > doxazosin
  • Spironolactone now first-line 4th drug

276.3.2.5 Aprocitentan (Tryvio) — 2024

  • Dual ETA/ETB receptor antagonist
  • PRECISION trial 2023 showed BP reduction in resistant HTN
  • FDA approved 2024 for resistant HTN

276.3.3 High-Yield Specialist Points

276.3.3.1 Beyond Mercury — Modern BP Measurement

  • Validated oscillometric devices standard
  • AOBP (automated office BP): serial unattended readings
  • ABPM still gold standard (especially with HBPM)
  • 24-h ambulatory BP higher predictive value than office

276.3.3.2 Cardiovascular Risk Stratification

  • PCE (US) — ASCVD 10-year risk
  • SCORE2 + SCORE2-OP (Europe)
  • JBS3 (UK) — lifetime risk
  • Use to decide treatment threshold

276.3.3.3 Sodium / Diet

  • Na restriction (< 2.3 g/d AHA, < 1.5 g/d optimal) ↓ BP 5/3 mmHg
  • DASH diet ↓ BP 8-14 mmHg
  • Mediterranean diet
  • Potassium supplementation (4.7 g/d) — SSaSS 2021 (salt substitute ↓ stroke + death)

276.3.3.4 Hypertension + Pregnancy

  • See Ch276 / Ch278 for crisis management
  • Preeclampsia spectrum
  • Hyperaldosteronism worsens
  • Treatment: methyldopa, labetalol, nifedipine — avoid ACEi/ARB/MRA

276.3.3.5 Hyperaldosteronism Workup Pearls

  • ARR > 20 (ng/dL : ng/mL/h) suggests PA
  • Hold MRA 6 weeks; β-blocker 1 week; ACEi/ARB OK for screening
  • Confirmation: oral sodium load, saline infusion, captopril challenge, fludrocortisone
  • Adrenal CT may miss small adenoma → adrenal vein sampling
  • Surgical adrenalectomy for unilateral; MRA (spironolactone or eplerenone) for bilateral

276.3.3.6 Renal Artery Stenosis Trials

  • CORAL (2014) — stent + OMT no benefit over OMT for ARAS
  • Exception: FMD patients (angioplasty effective)
  • Severe HTN refractory + recurrent flash pulmonary edema may still benefit

276.3.4 Pearls

  • 2017 ACC/AHA at 130/80 vs 2023 ESC at 140/90 — both reasonable, Taiwan aligns with ACC/AHA
  • ABPM / HBPM confirms diagnosis + rules out white coat / masked HTN
  • Most common secondary HTN = primary aldosteronism — screen with ARR
  • Spironolactone 1st-line for resistant HTN (PATHWAY-2)
  • Renal denervation approved 2024 for resistant HTN after large positive trials
  • Aprocitentan (Tryvio, ETA/ETB antagonist) FDA-approved 2024 for resistant HTN
  • SPRINT drove 130/80 target; STEP confirmed in elderly Chinese
  • Salt substitute (75% NaCl + 25% KCl) ↓ stroke and mortality (SSaSS 2021)