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Special populations

TL;DR — The general treatment rules hold in most subgroups, and the informative exceptions are few but sharp. In chronic kidney disease, SPRINT's prespecified CKD subgroup (n=2,646) showed the same benefit as the whole trial (primary composite HR 0.81, 95% CI 0.63–1.05; all-cause death HR 0.72, 0.53–0.99) with no excess of the main kidney outcome, only a slightly faster eGFR slope after the first six months (−0.47 vs −0.32 mL/min/1.73 m²/year) (Cheung 2017, PMID 28642330) — which is why KDIGO 2021 recommends systolic <120 mm Hg by standardised office measurement (KDIGO 2021, PMID 33637192). In diabetes, ACCORD-BP's null result has been superseded by ESPRIT and BPROAD (Liu 2024, PMID 38945140; Bi 2025, PMID 39555827). In Black adults, the ALLHAT racial subgroup analysis found chlorthalidone superior to lisinopril for stroke (RR 1.40 for lisinopril, 95% CI 1.17–1.68) and combined cardiovascular disease (1.19, 1.09–1.30), with significant race interactions, but no race interaction for the amlodipine comparison — an evidence-based difference in drug ranking, not a biological essentialism (Wright 2005, PMID 15811979). In frail and very old people the evidence genuinely thins, and it is the one place where net harm is plausible (Falk 2024, PMID 39688187; Sheppard 2023, PMID 37075078).

Chronic kidney disease

Question Evidence
Does intensive control help? SPRINT CKD subgroup: composite HR 0.81 (95% CI 0.63–1.05), all-cause death HR 0.72 (0.53–0.99), no interaction with CKD status (p ≥0.30) (Cheung 2017, PMID 28642330)
Does it harm the kidney? Main kidney composite HR 0.90 (0.44–1.83); eGFR slope after 6 months −0.47 vs −0.32 mL/min/1.73 m²/yr (Cheung 2017, PMID 28642330); post-hoc SPRINT/ACCORD analysis of kidney outcomes (Xu 2025, PMID 41117098)
Mortality in CKD at intensive targets Favourable in meta-analysis (Aggarwal 2019, PMID 31067189); systematic review of CKD targets (Tada 2025, PMID 40542174)
What does guidance say? KDIGO 2021: systolic <120 mm Hg by standardised office measurement for most adults with CKD not on dialysis, excluding children and transplant recipients; a dedicated chapter on measurement because the pivotal trials used standardised protocols (KDIGO 2021, PMID 33637192; Cheung 2021, PMID 33637203; Tomson 2021, PMID 34152826)
Is that target contested? Yes, chiefly on measurement grounds and applicability (Carriazo 2022, PMID 35498896; Mann 2021, PMID 34398316; See 2025, PMID 39725407; Park 2023, PMID 37538023)

AASK is the historical anchor for Black adults with hypertensive kidney disease: 1,094 participants randomised to usual (mean arterial pressure 102–107 mm Hg) or low (≤92 mm Hg) targets and to metoprolol, ramipril or amlodipine. Control to <140/90 mm Hg rose from 20.0% to 78.9% in the low-target group versus 21.5% to 41.8% in the usual-target group, achieving a sustained ~12 mm Hg separation in a population widely described as hard to control (Wright 2002, PMID 12123409). Long-term follow-up showed benefit from the lower target confined largely to those with baseline proteinuria (Bloch 2011, PMID 21366854), and AASK cardiovascular outcomes were reported separately (Norris 2006, PMID 17059993). Masked hypertension is markedly more common in CKD and prognostically important (Babu 2019, PMID 31111326; Burnier 2023, PMID 37053276; Ku 2019, PMID 30898362; Hamrahian 2017, PMID 27873228), and non-dipping predicts progression (Park 2024, PMID 37452154; Borrelli 2023, PMID 35709922).

Dialysis is a distinct problem: pressure is volume-dependent, intradialytic and interdialytic readings diverge, and home rather than pre-dialysis measurement is the better guide (Agarwal 2009, PMID 19246891; Agarwal 2009, PMID 19528362; Bansal 2021, PMID 32800842; Georgianos 2018, PMID 30084190; Miskulin 2017, PMID 28264150). Intradialytic hypertension is a recognised phenotype (Theofilis 2023, PMID 37231809), resistant hypertension in dialysis has its own epidemiology (Georgianos 2024, PMID 38227447), and ambulatory pressure predicts mortality in this group (Mayer 2018, PMID 30045925; Liu 2022, PMID 34433762). In kidney transplant recipients, office measurement performs poorly against ambulatory monitoring (Korogiannou 2021, PMID 34311458) and true resistant hypertension reaches 56.0% (95% CI 52.7–59.3) (Noubiap 2019, PMID 30087099).

Diabetes

Once the exception, now not. ACCORD-BP found no significant composite benefit from a <120 mm Hg target (HR 0.88, 95% CI 0.73–1.06) though stroke fell (0.59, 0.39–0.89) (ACCORD 2010, PMID 20228401). ESPRIT included 4,359 people with diabetes and found no heterogeneity of the intensive-target effect by diabetes status (Liu 2024, PMID 38945140); BPROAD randomised 12,821 people with type 2 diabetes and found HR 0.79 (0.69–0.90) for the primary composite, with more symptomatic hypotension and hyperkalaemia but similar serious adverse events (Bi 2025, PMID 39555827). Meta-analyses have followed (Ioannidou 2023, PMID 37257222; Saad 2025, PMID 40769802; Akhtar 2026, PMID 41266861). Renin-angiotensin blockers retain their place for albuminuric kidney disease in diabetes (Wu 2013, PMID 24157497). Frailty modifies the risk–benefit in diabetes as elsewhere (Nguyen 2021, PMID 34035077; Wenjie 2025, PMID 39915072). DASH4D shows dietary intervention works in this group, driven mainly by sodium reduction (Pilla 2025, PMID 40489102). The 2026 AHA/ACC/ADA/ASN cardiovascular-kidney-metabolic guideline now treats the overlap as a single management domain (Ndumele 2026, PMID 42265997; Writing Committee 2026, PMID 42263157). Detailed diabetes management lives in type-2-diabetes.

Older and frail adults

  • Benefit persists. BPLTTC age-stratified analysis: HR per 5 mm Hg systolic reduction 0.91 (95% CI 0.87–0.96) at 75–84 years, with larger absolute risk reductions in older groups; only the ≥85 stratum (n=4,788) was null (0.99, 0.87–1.12), and the authors recommend removing age-based thresholds from guidelines (BPLTTC 2021, PMID 34461040).
  • Trial evidence. HYVET, in 3,845 people aged ≥80 with systolic ≥160 mm Hg, reduced all-cause death 21% (95% CI 4–35) and heart failure 64% (42–78) with fewer serious adverse events than placebo (Beckett 2008, PMID 18378519). STEP enrolled 60–80-year-olds and favoured intensive treatment (Zhang 2021, PMID 34491661; Song 2025, PMID 41105077). Cochrane's 2024 update finds lower targets reduce stroke (RR 1.33 favouring the lower target, high certainty) with unclear mortality effect (Falk 2024, PMID 39688187).
  • Harm concentrates in frailty. Serious adverse events associated with antihypertensive treatment rise with age and frailty in cohort analysis (Sheppard 2023, PMID 37075078); antihypertensive initiation was associated with fracture risk in nursing-home residents (Dave 2024, PMID 38648065) and with falls and other serious events in people with dementia (Fujiwara 2025, PMID 40961130). Earlier syntheses found no excess falls or cognitive impairment but real excess hypotension, syncope and pill burden (Weiss 2017, PMID 28114673).
  • Deprescribing. OPTIMISE randomised 569 people aged ≥80 on ≥2 antihypertensives with systolic <150 mm Hg to medication reduction or usual care and met its non-inferiority margin for short-term blood-pressure control (Sheppard 2020, PMID 32453368). RETREAT-FRAIL then randomised 1,048 frail nursing-home residents aged ≥80 with systolic <130 mm Hg to protocolised step-down or usual care for a median potential 38.4 months: all-cause death was 61.7% versus 60.2% (adjusted HR 1.02, 95% CI 0.86–1.21), systolic pressure rose 4.1 mm Hg more (95% CI 1.9–5.7), and adverse events did not apparently differ (Benetos 2025, PMID 40879421; NCT03453268). A separate 522-participant long-term-care deprescribing trial has completed follow-up but had no PubMed-indexed result at the 2026-09-01 audit (Carr 2026, PMID 41689048; NCT05047731). TONE data address orthostatic symptoms (Juraschek 2022, PMID 34718403).

Ethnicity and ancestry

The ALLHAT prespecified racial subgroup analysis (35% Black among 33,357 participants) is the strongest randomised evidence. There was no difference between groups for the primary coronary outcome in either subgroup. For amlodipine vs chlorthalidone, heart failure was higher with amlodipine in both groups (Black RR 1.46, 95% CI 1.24–1.73; non-Black 1.32, 1.17–1.49) with no race interaction (p=0.38). For lisinopril vs chlorthalidone, results differed by race: stroke RR 1.40 (1.17–1.68) in Black versus 1.00 (0.85–1.17) in non-Black participants (p=0.01 for interaction), and combined cardiovascular disease 1.19 (1.09–1.30) versus 1.06 (1.00–1.13) (p=0.04); adjusting for time-dependent blood pressure did not remove the difference (Wright 2005, PMID 15811979). The authors' conclusion is that thiazide-type diuretics remain the initial drug of choice in both groups — the interaction changes the penalty for choosing an ACE inhibitor first, not the first choice itself. Reviews of hypertension management in Black patients cover the practical implications and the trap of treating a social category as a biological one (Sulaica 2020, PMID 32276785). Polygenic-score work suggests genetic risk stratification may eventually do what race is currently used as a proxy for, but portability across ancestries is unsolved (Armstrong 2024, PMID 39441603; Kurniansyah 2022, PMID 35729114; Krieger 2026, PMID 42395874).

Neighbourhood deprivation and racial composition together explain 91–98% of spatial variation in diagnosed hypertension prevalence in one US county (Blazel 2024, PMID 39177999) — a reminder that most of the observed "racial difference" in hypertension outcomes is structural rather than pharmacological.

Other populations

Population Key points
People living with HIV High and rising hypertension prevalence; inflammation-associated; incidence and cardiovascular impact analysed within REPRIEVE (Martínez 2026, PMID 42067280; van Zoest 2017, PMID 28787286; Ou-Yang 2023, PMID 37025998; Chen 2024, PMID 39039244); screening performance of automated office measurement tested in this group (Lucinde 2025, PMID 40970526)
Children and adolescents AAP thresholds; tracking into adulthood strong, reversion unlikely after adolescence (Flynn 2017, PMID 28827377; Meng 2025, PMID 39495520; Mainieri 2024, PMID 39051576; Santi 2015, PMID 26049390); automated device accuracy is a specific problem (Stergiou 2017, PMID 28438903; Seeman 2021, PMID 34565278)
Young adults (18–39) 21.3% prevalence, 28.3% aware, 5.6% controlled in the US in 2021–2023 (Tang 2025, PMID 40156902); isolated systolic hypertension in the young is a distinct phenotype (Palatini 2018, PMID 29570514)
Perioperative Hypotension-avoidance versus hypertension-avoidance strategies in noncardiac surgery were compared randomly (Marcucci 2023, PMID 37094336)
Prior stroke Target evidence from SPS3 and ESPRIT; secondary prevention belongs to stroke (SPS3 2013, PMID 23726159; Liu 2024, PMID 38945140)
Depression and mental illness Associated with worse blood-pressure control (Raddaoui 2024, PMID 38545723)

Open questions

  • KDIGO recommends <120 mm Hg in CKD from a trial that excluded people with proteinuria >1 g/day and used unattended measurement. Does the recommendation hold in proteinuric CKD, and by what measurement method? (KDIGO 2021, PMID 33637192; Cheung 2017, PMID 28642330)
  • Where is the frailty threshold beyond which antihypertensive treatment is net-harmful? RETREAT-FRAIL directly randomised frail nursing-home residents and found neither lower mortality nor an apparent adverse-event difference from step-down treatment, but it enrolled only people with systolic <130 mm Hg already taking more than one drug (Benetos 2025, PMID 40879421). The unresolved gap is whether its null result generalises to less intensively treated frail adults and to target-setting rather than deprescribing.
  • OPTIMISE established 12-week feasibility, and RETREAT-FRAIL supplied a median 38.4 months of potential follow-up with mortality as the primary endpoint (Sheppard 2020, PMID 32453368; Benetos 2025, PMID 40879421). Which frail patients, if any, gain quality of life from deprescribing without accepting excess vascular risk remains unresolved.
  • The ALLHAT race interaction was for lisinopril but not amlodipine (Wright 2005, PMID 15811979). Is that a pharmacological fact about renin-angiotensin blockade in low-renin hypertension, or a proxy for something else — and would renin measurement do the job better?
  • Blood pressure in dialysis has no target established by outcome trial; home versus pre-dialysis measurement was tested only in a pilot (Bansal 2021, PMID 32800842).

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