Hypertension

Details

Hypertension is the most prevalent and modifiable cardiovascular risk factor, affecting 46.7% of US adults (2017–2020 NHANES). It is a leading cause of stroke, heart failure, atrial fibrillation, CKD, dementia, and all-cause mortality. Two major 2024/2025 guidelines have updated its management — the 2024 ESC Guidelines and the 2025 AHA/ACC Guidelines — with important differences in classification, risk assessment tools, and treatment targets (see ESC vs AHA comparison below).

ESC 2024 vs AHA 2025 — Key Guideline Differences

(sources/ht-esc-2024, rating: very high; sources/HT-AHA-2025, rating: very high)

Epidemiology

• Prevalence: overall 46.7%; highest in Black adults (56–57%), age 75–80 (83–85%), men (49.5%). (sources/HT-AHA-2025, rating: very high)
• HT is antecedent in 71% of HF cases; highest attributable risk factor for new-onset AF.
• Only 23% of all US adults with hypertension achieve BP control (<130/80 mmHg). (sources/rnd-aha-2024, rating: high)

Classification

ESC 2024 (3-category system): (sources/ht-esc-2024, rating: very high)

• HBPM hypertension: ≥135/85 mmHg; ABPM 24h: ≥130/80 mmHg; ABPM daytime: ≥135/85 mmHg; ABPM night-time: ≥120/70 mmHg
• Diagnosis requires out-of-office confirmation (HBPM or ABPM) or repeated office BP on a second visit
• Elevated BP category triggers risk stratification — not automatic treatment

AHA 2025 (4-category system): (sources/HT-AHA-2025, rating: very high)

• Diagnosis requires average of ≥2 readings on ≥2 separate occasions. (sources/HT-AHA-2025, rating: very high)

ESC 2024 Risk Stratification for Elevated BP

For patients with elevated BP (SBP 120–139 / DBP 70–89 mmHg): (sources/ht-esc-2024, rating: very high)

• Automatic high-risk (treat if BP ≥130/80 after 3 months lifestyle): moderate/severe CKD, established CVD (CAD, stroke, PAD, HF), HMOD, diabetes mellitus, familial hypercholesterolaemia
• Use SCORE2 (age 40–69) or SCORE2-OP (age ≥70): ≥10% 10-year CVD risk = treat
• Borderline 5–<10%: consider sex-specific risk modifiers (gestational DM, gestational HT, pre-eclampsia, preterm delivery, stillbirth, recurrent miscarriage); shared modifiers (South Asian ethnicity, premature ASCVD family history, socioeconomic deprivation, autoimmune disorders, HIV, severe mental illness)
• If still uncertain: CAC score, carotid/femoral plaque, hs-cTnT/BNP, pulse wave velocity
• <5% CVD risk OR BP 120–129/70–79: lifestyle only; reassess in 1 year
• Age <40: HMOD assessment preferred (SCORE2 not validated in this age group)
• See concepts/Hypertension-HMOD for full HMOD assessment thresholds

AHA 2025 Risk Assessment — PREVENT™ Score

• PREVENT™ (Predicting Risk of CVD EVENTs) derived from 3.2 million individuals (1992–2022); contemporary, diverse, race-free model. (sources/HT-AHA-2025, rating: very high)
• Estimates total CVD (MI + stroke + HF), not just ASCVD; applicable ages 30–79; includes eGFR, statin use, and social deprivation index (SDI).
• PCEs overpredicted risk ~2-fold; PREVENT has excellent calibration across race/ethnic groups.
• Treatment threshold: PREVENT ≥7.5% (lowered from PCE ≥10%) — initiate medication at SBP ≥130 mmHg. (sources/HT-AHA-2025, rating: very high)
• See concepts/ASCVD-Risk-Assessment for full PREVENT methodology.

Diagnosis and BP Monitoring

Treatment Thresholds — ESC 2024

• Hypertension (≥140/90 mmHg): initiate lifestyle + pharmacotherapy promptly regardless of risk (Class I, A) (sources/ht-esc-2024, rating: very high)
• Elevated BP + high CVD risk (SCORE2 ≥10% or high-risk conditions): lifestyle 3 months then add drugs if BP ≥130/80 (Class I, A)
• Elevated BP + low/medium CVD risk (<10%): lifestyle only (Class I, B)
• Elevated BP in special populations (defer drugs to ≥140/90): pre-treatment symptomatic orthostatic hypotension, age ≥85 years, moderate-to-severe frailty, limited lifespan <3 years (Class IIa, B)
• Target SBP: 120–129 mmHg in most adults (Class I, A); ALARA principle if not tolerated (Class I, A)
• Lenient target: <140 mmHg (symptomatic orthostasis or age ≥85, Class IIa, C); <140/90 (severe frailty or lifespan <3 years, Class IIb, C)

Treatment Thresholds — AHA 2025

• All adults SBP ≥140 or DBP ≥90: initiate antihypertensives (COR 1, LOE A). (sources/HT-AHA-2025, rating: very high)
• CVD, diabetes, CKD, or PREVENT ≥7.5%: initiate if SBP ≥130 or DBP ≥80 (COR 1, LOE A).
• PREVENT <7.5%: initiate if SBP ≥130/DBP ≥80 persists after 3–6 month lifestyle trial (COR 1).
• Goal for all: SBP <130 mmHg; encourage <120 mmHg if tolerated (COR 1 for high-risk; COR 2b for lower-risk).

BP Monitoring Modalities

• HBPM + cointerventions (telehealth, medication titration): COR 1, LOE A for monitoring treatment response. (sources/HT-AHA-2025, rating: very high)
• ABPM: Confirms white-coat and masked hypertension; nighttime BP provides additional CVD risk information.
• Cuffless devices and smartwatches: COR 3: No Benefit — insufficient validation for clinical use; PPG-based devices show skin tone bias; ISO validation standard (ISO 81060-7) still in development as of 2026. See concepts/Cuffless-BP-Monitoring for full technology assessment. (sources/cuffless-bp-aha-2026, rating: high)

Management

Lifestyle

• DASH eating plan: Most effective single lifestyle intervention; −5 to −8 mmHg SBP. (sources/HT-AHA-2025, rating: very high)
• Sodium: <2300 mg/d recommended; ideal <1500 mg/d; ~1 mmHg SBP per 1 mmol reduction.
• Potassium-based salt substitutes: COR 2a — useful for home food preparers; caution in CKD and with RAASi/K-sparing diuretics.
• Exercise: Aerobic + resistance + isometric exercise all lower BP; isometric exercise: −5 to −10 mmHg SBP.
• Alcohol: Optimal goal abstinence; SBP rises with any level of intake.
• Weight loss: ~1/1 mmHg SBP/DBP per kg lost; ≥5% body weight reduction for meaningful effect.

Pharmacological

• First-line agents: Thiazide-type diuretics, long-acting dihydropyridine CCB, ACEi, ARB. (sources/HT-AHA-2025, rating: very high)
• Stage 2 HT or high CVD risk: Start 2 agents as single-pill combination (SPC) — preferred over separate pills (COR 1, LOE A); improves adherence and reduces time to control.
• Avoid: ACEi + ARB combination (hyperkalemia, AKI risk); non-DHP CCB + BB (bradycardia risk).
• Beta-blockers: Not first-line for uncomplicated HT; preferred if concomitant CCD, HFrEF, or arrhythmia.
• Up to 50% of patients non-adherent at 1 year; once-daily SPC dosing improves adherence.

Resistant Hypertension

• Definition: BP above goal on ≥3 drugs of complementary mechanisms (including diuretic at max tolerated dose) OR at goal on ≥4 drugs. (sources/rnd-aha-2024, rating: high)
• Prevalence: 8.5–20% of hypertensive US adults; 50% higher risk of MI/stroke/ESKD vs non-resistant HT.
• Evaluate for: white-coat effect, non-adherence, interfering medications, secondary HT causes.
• 4th agent (COR 1): Spironolactone 25–50 mg/d (if eGFR ≥45 mL/min); reduces SBP 6.6–8.7 mmHg; superior to alpha-blocker or bisoprolol as 4th agent.
• Alternatives if MRA not tolerated: amiloride, beta-blockers, alpha-blockers, clonidine, aprocitentan (dual ERA).
• Aldosterone Synthase Inhibitors (ASIs) — emerging add-on therapy: Two agents have demonstrated efficacy in RCTs:
  • Baxdrostat (BaxHTN phase 3, n=794, NEJM 2025): 1 mg and 2 mg once daily reduced office SBP by −8.7 and −9.8 mmHg (placebo-corrected) in uncontrolled and resistant HT (P<0.001). (sources/baxdrostat-baxhtn-nejm-2025, rating: very high)
  • Lorundrostat (ADVANCE-HTN phase 2b, n=285, NEJM 2025): 50 mg stable dose reduced 24-hour ambulatory SBP by −7.9 mmHg (placebo-adjusted; P=0.001) at 12 weeks; dose-adjustment arm −6.5 mmHg (P=0.006); 50 mg is the optimal dose; 53% Black participants. Key safety note: lorundrostat inhibits the MATE1 renal transporter → serum creatinine rises spuriously; cystatin C should be used for renal monitoring. (sources/lorundrostat-advancehtn-nejm-2025, rating: high)
  • ASIs block aldosterone production (CYP11B2) rather than the receptor, avoiding MRA counter-regulatory increases in aldosterone; principal safety concerns are dose-dependent hyperkalemia (K >5.5–6.0: 6–11%), hyponatremia (~20% with baxdrostat), and a reversible eGFR dip. Not yet incorporated into guidelines (AHA 2025); no head-to-head comparison with spironolactone; no cardiovascular outcomes data. See concepts/Aldosterone-Synthase-Inhibitors.

Renal Denervation (RDN)

• ESC 2024 (major upgrade from Class III in 2018 to Class IIb in 2024):
  • Resistant HT (uncontrolled on 3-drug combination): Class IIb, B — medium-to-high volume centre; patient preference; multidisciplinary assessment (sources/ht-esc-2024, rating: very high)
  • Increased CVD risk + uncontrolled on <3 drugs (patient preference): Class IIb, A
  • Remains Class III: as first-line intervention; eGFR <40 or secondary HT causes
  • Key concern: ~6 mmHg office SBP reduction (= 1 drug equivalent); no CVD outcomes trial; not cost-effective vs generic pharmacotherapy
• AHA 2025 — COR 2b — adjunctive treatment for carefully selected patients after lifestyle + medication optimisation. (sources/HT-AHA-2025, rating: very high)
• FDA approval (Nov 2023): Medtronic Symplicity Spyral (radiofrequency) and Recor Medical Paradise (intravascular ultrasound). (sources/rnd-aha-2024, rating: high)
• Efficacy: 4.7–8.5 mmHg daytime SBP reduction vs sham in drug-naive patients; 60–70% achieve ≥5 mmHg reduction; ultrasound-based RDN outperforms radiofrequency (RADIOSOUND-HTN).
• vs Spironolactone: RDN inferior or equivalent to spironolactone as 4th agent (DENERVHTA, Prague-15); combination MRA + RDN not yet studied.
• Safety: No kidney function impairment; serious adverse events <1%; renal artery stenosis 0.2%/year; no late safety signals at 3 years. No CVD outcomes trial data.

See concepts/Renal-Denervation for full procedure detail, device types, complete trial data, patient selection framework, and contraindications.

RNA Interference — Angiotensinogen Silencing (Zilebesiran)

• Mechanism: zilebesiran is a GalNAc-conjugated siRNA that silences hepatic angiotensinogen mRNA — the sole precursor of all angiotensin peptides — from a subcutaneous injection, acting upstream of ACE inhibitors and ARBs and therefore upstream of the compensatory reactivation that limits both. (sources/zilebesiran-ht-nejm-2023, rating: high)
• Phase 1 signal (n=107, four UK sites): single doses ≥200 mg lowered 24-hour ambulatory systolic pressure by >10 mmHg and diastolic by >5 mmHg by week 8, sustained to week 24; at 800 mg the week-24 change was −22.5/−10.8 mmHg (n=8, six without add-on therapy), with >90% angiotensinogen suppression. Daytime and night-time pressures fell equally. (sources/zilebesiran-ht-nejm-2023, rating: high)
• Dosing concept: the duration of action supports quarterly or twice-yearly administration — the first blood-pressure therapy that addresses non-adherence by removing the daily tablet rather than by simplifying it. This is the same platform and dosing logic as inclisiran (entities/Inclisiran).
• Effect is conditional on sodium intake: in Part B a low-salt diet alone lowered pressure by −9.1/−2.4 mmHg, 800 mg plus low-salt by −18.8/−8.4 mmHg, and a high-salt diet (5.75 g/day) returned pressure to baseline. The authors present this as a potential rescue mechanism for over-lowering, not as tested clinical management.
• Safety in the trial: no deaths, no unplanned hospitalisations and no intervention for hypotension, hyperkalaemia or renal deterioration; injection-site reactions (5 patients, mild, transient) were the only treatment-related event in more than two patients. Patients with diabetes, prior cardiovascular events, CKD, heart failure or age >65 years were excluded, and all had a ≥2-week washout. See entities/Zilebesiran for the full evidence and its limits.

Secondary Hypertension

• Present in 5–25% of cases (10–35% per ESC 2024); more common with resistant HT, Stage 2 HT, early onset.
• Most common causes: OSA (25–50% of resistant HT), primary aldosteronism (up to 12% at BP >180/110 mmHg), CKD, drug-induced, renovascular HT.
• ESC 2024 — ALL confirmed hypertensive patients: Screen with aldosterone-to-renin ratio (ARR) for primary aldosteronism (Class IIa, B) — not just resistant HT; hypokalemia absent in majority. (sources/ht-esc-2024, rating: very high)
• AHA 2025 — Resistant HT only: Screen for primary aldosteronism regardless of hypokalemia (COR 1, LOE B-NR). (sources/HT-AHA-2025, rating: very high)
• ARR interpretation varies with concurrent medications; beta-blockers, central agents, RAS blockers, and diuretics interfere (ESC 2024 Table 12); long-acting CCBs and alpha-blockers do not
• Continue most antihypertensives (except MRA) during initial aldosterone/renin screening if stopping not feasible.

Comorbidities

• Diabetes: ACEi/ARB recommended if eGFR <60 or albuminuria ≥30 mg/g (COR 1, upgraded from COR 2b); SBP goal <130 mmHg; encourage <120 mmHg if tolerated (COR 2b). (sources/HT-AHA-2025, rating: very high) — BPROAD trial (NEJM 2025; n=12,821 Chinese T2DM patients ≥50 years) now provides first adequately-powered RCT evidence: intensive SBP <120 mmHg vs standard <140 mmHg reduced major CVD events by 21% (HR 0.79; 95% CI 0.69–0.90; P<0.001); stroke HR 0.79; albuminuria HR 0.87; serious AEs equivalent; hyperkalemia 2.8% vs 2.0% requires monitoring. (sources/bp-dm-bproad-nejm-2025, rating: very high) See concepts/Blood-Pressure-Target-T2DM.
• CKD: SBP goal <130 mmHg; RAASi (ACEi or ARB, not both) if albuminuria ≥30 mg/g; eGFR dip ≤30% acceptable.
• Atrial fibrillation: HT has highest attributable risk for AF; BP goal <130/80 mmHg reduces AF incidence and MACE.
• HF prevention: HT antecedent in 71% of HF; SBP <130 mmHg reduces HF incidence.
• HFrEF: Uptitrate GDMT (ARNi/ACEi/ARB + BB + MRA + SGLT2i) as first-line BP strategy; add dihydropyridine CCB if needed; avoid non-DHP CCB (COR 3 Harm). See entities/HFrEF.
• HFpEF: RAASi (ARNi/MRA/ARB) preferred; SGLT2i; diuretics for volume; BB NOT recommended for BP control (negative chronotropy impairs diastolic filling). (sources/HT-AHA-2025, rating: very high)
• Dementia prevention: SBP goal <130 mmHg — COR 1 (upgraded from COR 2a); SPRINT-MIND legacy data show 7-year benefit. (sources/HT-AHA-2025, rating: very high)
• Aortic disease: BP <130/80 mmHg; BB preferred; abdominal aortic aneurysm rupture risk +30% per 10 mmHg.
• PAD: SBP <130/80 mmHg; ACEi/ARB first-line; no evidence antihypertensives worsen claudication.

Stroke

• Acute ICH (SBP 150–220 mmHg): Lower to 130–<140 mmHg for ≥7 days; avoid SBP <130 mmHg (COR 2a). (sources/HT-AHA-2025, rating: very high)
• Post-EVT reperfusion (large vessel occlusion) — SBP <140 mmHg within 72h — COR 3: HARM: ENCHANTED2/MT trial — intensive lowering to <140 mmHg after successful EVT (mTICI 2b/2c/3) increased death and disability; optimal post-EVT target is 140–180 mmHg for ≥72h. (sources/ais-aha-2026, rating: very high)
• Post-IVT (no EVT): Maintain <180/105 mmHg; SBP <140 mmHg target post-IVT — COR 3: No Benefit. (sources/ais-aha-2026, rating: very high)
• Secondary stroke prevention: SBP/DBP goal <130/80 mmHg (COR 1); thiazide/ACEi/ARB preferred. (sources/HT-AHA-2025, rating: very high)
• See entities/Ischemic-Stroke for full AIS management including EVT selection, thrombolysis, and acute BP targets.

Pregnancy

• Severe acute HT (≥160/110 mmHg): Treat to <160/110 mmHg within 30–60 min (COR 1). (sources/ht-pregnancy-aha-2022, rating: high)
• Chronic HT: Treat to <140/90 mmHg (COR 1) — CHAP trial confirmed treating mild chronic HT reduces adverse pregnancy outcomes without increasing SGA.
• Preeclampsia prevention: Low-dose aspirin 81–150 mg/day from 12–16 weeks for high-risk women (≥1 high or ≥2 moderate risk factors); reduces preeclampsia by 10–20%. (sources/ht-pregnancy-aha-2022, rating: high)
• Contraindicated (COR 3: Harm): Atenolol (fetal growth restriction), ACEi, ARB, direct renin inhibitors (fetal renal development), nitroprusside, MRA/spironolactone (antiandrogenic).
• Safe first-line agents: Labetalol, long-acting nifedipine, methyldopa — equivalent per Cochrane review. Severe acute HT: parenteral labetalol, parenteral hydralazine, or oral nifedipine — comparable.
• Controversy: US ACOG threshold ≥160/110 mmHg vs international consensus ≥140/90 mmHg; CHIPS trial supports tighter control (achieved 133/85 mmHg) without adverse fetal outcomes. (sources/ht-pregnancy-aha-2022, rating: high)
• Postpartum: ~60% of maternal deaths occur in first year postpartum; furosemide RCT: 60% reduction in persistent postpartum HT at day 7.
• History of HDP (long-term risk): Sex-specific CVD risk enhancer — HF HR 2.7, stroke HR 1.9, ESKD RR 6.6 after preeclampsia; annual BP/CVD risk assessment; early CVD risk factor control.
• See concepts/Hypertensive-Disorders-of-Pregnancy and concepts/Preeclampsia for full HDP detail.

Hypertensive crisis

The Hospital Authority handbook divides severe elevation by target-organ damage rather than by the number: hypertensive emergency is above 180/120 mmHg with new or worsening organ damage, hypertensive urgency is the same pressure without it and is treated orally. Without a compelling feature, systolic pressure falls by no more than 25% in the first hour, then to 160/100 over the next 2–6 hours, then cautiously towards normal over 24–48 hours. With dissection, eclampsia or phaeochromocytoma crisis the target is <140 mmHg within the hour, and <120 mmHg in dissection. Agent dosing, condition-specific choices and the drugs to avoid in each are on concepts/Hypertensive-Crisis. (sources/Handbook-HA-2024, rating: high)

Hypertension in old age

• Isolated systolic hypertension predominates in older adults, and vascular stiffening makes them vulnerable to hypotension on postural change, after meals and during volume contraction — so antihypertensives carry a real fall risk.
• Targets: systolic <150 mmHg is described as strongly evidenced; 130–140 may be considered for the biologically young 65–80 with little comorbidity, while patients over 80 or with multiple comorbidity should stay at <150. Diastolic target <90 mmHg and not below 65 in coronary disease — risk rises between 61 and 70 and further at ≤60, attributed to diastolic-dependent myocardial perfusion.
• Start low and go slow — roughly half the younger-adult starting dose, with the target reached over weeks to months, because the first one to two months carry increased falls and hip fracture. Exercise clinical judgement over guideline in frail patients with limited life expectancy. (sources/Handbook-HA-2024, rating: high)

Contradictions / Open Questions

• The handbook's older-adult targets are far looser than the ESC 2024 and AHA 2025 goals on the same page. It sets <150 mmHg for everyone over 80 and considers 130–140 only for selected 65–80-year-olds, where the guidelines above give SBP 120–129 mmHg Class I/A in most adults and reserve a lenient <140 mmHg for age ≥85 or symptomatic orthostasis (Class IIa, C). A 2026-dated handbook and a 2024 guideline cannot both be right about the same 82-year-old, and the difference is one whole treatment threshold, not one of emphasis. (sources/Handbook-HA-2024, rating: high; sources/ht-esc-2024)
• ESC 2024 vs AHA 2025 — BP classification mismatch: ESC uses "elevated BP" for SBP 120–139/DBP 70–89 with the same lower threshold (120/70 mmHg) for both; AHA uses "elevated" for SBP 120–129 with DBP <80 mmHg only. A patient with SBP 125/DBP 82 mmHg is "elevated BP" by ESC but "Stage 1 hypertension" by AHA — producing different treatment thresholds. (sources/ht-esc-2024, rating: very high; sources/HT-AHA-2025, rating: very high)
• ESC 2024 vs AHA 2025 — Treatment target conflict: ESC mandates SBP 120–129 mmHg as a single Class I, A target for most adults; AHA lists <130 mmHg as the primary COR 1 goal with <120 mmHg as COR 2b. ESC's rationale is to eliminate the 130–139 mmHg intermediate zone that drives therapeutic inertia. (sources/ht-esc-2024, rating: very high; sources/HT-AHA-2025, rating: very high)
• Primary aldosteronism screening threshold: ESC 2024 recommends ARR screening in ALL confirmed hypertensive patients; AHA 2025 limits to resistant HT only. Current real-world screening rates ~2% of eligible patients — universal ESC screening aspirational without system-level implementation. (sources/ht-esc-2024, rating: very high)
• PREVENT vs ASCVD-only tools: PREVENT estimates total CVD (adds HF) whereas ASCVD-focused guidelines (cholesterol) still use ASCVD-only outputs — creates potential risk category mismatches for the same patient. (sources/HT-AHA-2025, rating: very high)
• Intensive BP target in T2DM (<120 mmHg): BPROAD (NEJM 2025; HR 0.79; P<0.001) definitively resolves ACCORD null result (HR 0.88; underpowered; factorial confound); first RCT support for SBP <120 mmHg over <140 mmHg in T2DM. Guideline <130 mmHg recommendation predated this evidence — update expected. (sources/bp-dm-bproad-nejm-2025, rating: very high)
• Optimal BP target in HFpEF: No RCT data directly establishing BP target; extrapolated from general hypertension trials.
• DBP J-curve: Post-hoc SPRINT data suggest J-curve for DBP and coronary events; no fixed lower limit established in RCTs; clinical monitoring recommended.
• RDN efficacy: Inconsistent across trials — early negative trials (SYMPLICITY HTN-3, REDUCE HTN:REINFORCE) vs positive newer trials with improved technique and standardised drug surveillance; no CVD outcomes data; inferior or equivalent to spironolactone as 4th agent in resistant HT. (sources/rnd-aha-2024, rating: high)
• RDN vs spironolactone sequencing: Should spironolactone always precede RDN in resistant HT? Combination MRA + RDN not yet studied.
• Aldosterone synthase inhibitors vs MRAs: BaxHTN (n=794, NEJM 2025) and ADVANCE-HTN (n=285, NEJM 2025) demonstrate ~7–10 mmHg placebo-corrected SBP reduction with baxdrostat/lorundrostat, comparable to spironolactone's 6.6–8.7 mmHg effect in resistant HT. However: (1) no head-to-head RCT compares ASIs with spironolactone; (2) no cardiovascular outcomes data exist for ASIs; (3) ASIs are not yet guideline-recommended. Whether ASIs should replace, precede, or supplement MRAs as add-on therapy in resistant HT is unresolved. Cross-trial comparisons of lorundrostat vs baxdrostat effect sizes are also confounded by different BP measurement methods (ambulatory vs office). (sources/baxdrostat-baxhtn-nejm-2025, rating: very high; sources/lorundrostat-advancehtn-nejm-2025, rating: high)
• Fixed-interval angiotensinogen silencing versus titratable oral therapy: Zilebesiran suppressed angiotensinogen by >90% for 24 weeks after one injection, but the trial tested no hypothesis, excluded diabetes, prior cardiovascular events, CKD, heart failure and everyone over 65, and applied no background RAAS blocker. Whether sustained angiotensinogen suppression helps or harms in the patients where RAAS blockade is most valuable — and most likely to cause hyperkalaemia — is unknown, and a quarterly depot cannot be titrated down within days if pressure falls. The high-salt reversal of the pressure effect is a mechanistic finding, not a validated rescue strategy. (sources/zilebesiran-ht-nejm-2023, rating: high)
• RDN reinnervation in humans: Animal models show partial/full reinnervation with persistent BP reduction; human durability data from registries only (no long-term sham-controlled data).
• Post-kidney transplant BP: No robust RCT evidence for specific targets or drug class preference.
• Asleep BP: Unclear whether isolated nocturnal hypertension (high asleep, normal awake BP) warrants treatment; no high-quality RCT evidence.

Connections

• Related to concepts/Hypertension-HMOD — HMOD assessment framework; triggers treatment in elevated BP category
• Related to concepts/ASCVD-Risk-Assessment — PREVENT™ replaces PCEs; total CVD estimation
• Related to entities/Atrial-Fibrillation — highest attributable risk for new-onset AF
• Related to entities/Heart-Failure — antecedent in 71% HF; BP management across HF phenotypes
• Related to entities/HFrEF — GDMT-first BP strategy; non-DHP CCB contraindicated
• Related to entities/HFpEF — HT as major HFpEF driver; BB not for BP control in HFpEF
• Related to entities/Obstructive-Sleep-Apnea — secondary HT; 25–50% prevalence
• Related to concepts/LV-Diastolic-Function — hypertension → LVH → diastolic dysfunction
• Related to concepts/Cuffless-BP-Monitoring — 2025/2026 AHA position: not recommended for clinical use
• Related to entities/Ischemic-Stroke — post-EVT BP harm; secondary stroke prevention targets
• Related to concepts/Renal-Denervation — catheter-based adjunctive treatment for resistant/uncontrolled HT
• Related to concepts/Hypertensive-Disorders-of-Pregnancy — BP thresholds and targets in pregnancy
• Related to concepts/Preeclampsia — strongest independent predictor of future hypertension (OR 11.6)
• Related to concepts/Blood-Pressure-Target-T2DM — first RCT evidence for SBP <120 mmHg in T2DM
• Related to entities/Type-2-Diabetes — most common HTN comorbidity; BPROAD defines BP target
• Related to concepts/Aldosterone-Synthase-Inhibitors — emerging add-on therapy for resistant/uncontrolled HT; BaxHTN ~9 mmHg office SBP (NEJM 2025); ADVANCE-HTN −7.9 mmHg 24h ambulatory SBP (NEJM 2025)
• Related to entities/Zilebesiran — angiotensinogen siRNA given quarterly or twice yearly; adherence-independent RAAS suppression, phase 1 only

Sources

• sources/ht-esc-2024
• sources/HT-AHA-2025
• sources/ais-aha-2026
• sources/cuffless-bp-aha-2026
• sources/ht-pregnancy-aha-2022
• sources/rnd-aha-2024
• sources/bp-dm-bproad-nejm-2025
• sources/baxdrostat-baxhtn-nejm-2025
• sources/lorundrostat-advancehtn-nejm-2025
• sources/zilebesiran-ht-nejm-2023
• sources/Handbook-HA-2024