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Cited by 1,153Blood Pressure and Hypertension StudiesHormonal Regulation and HypertensionSodium Intake and Health

Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association

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Carey, Robert M., Calhoun, David A., Bakris, George L., Brook, Robert D., Daugherty, Stacie L., Dennison-Himmelfarb, Cheryl R., Egan, Brent M., Flack, John M. +11 more·2018·Hypertension
DOI 10.1161/hyp.0000000000000084PMC PMC6530990
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Abstract

Resistant hypertension (RH) is defined as above-goal elevated blood pressure (BP) in a patient despite the concurrent use of 3 antihypertensive drug classes, commonly including a long-acting calcium channel blocker, a blocker of the renin-angiotensin system (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a diuretic. The antihypertensive drugs should be administered at maximum or maximally tolerated daily doses. RH also includes patients whose BP achieves target values on ≥4 antihypertensive medications. The diagnosis of RH requires assurance of antihypertensive medication adherence and exclusion of the “white-coat effect” (office BP above goal but out-of-office BP at or below target). The importance of RH is underscored by the associated risk of adverse outcomes compared with non-RH. This article is an updated American Heart Association scientific statement on the detection, evaluation, and management of RH. Once antihypertensive medication adherence is confirmed and out-of-office BP recordings exclude a white-coat effect, evaluation includes identification of contributing lifestyle issues, detection of drugs interfering with antihypertensive medication effectiveness, screening for secondary hypertension, and assessment of target organ damage. Management of RH includes maximization of lifestyle interventions, use of long-acting thiazide-like diuretics (chlorthalidone or indapamide), addition of a mineralocorticoid receptor antagonist (spironolactone or eplerenone), and, if BP remains elevated, stepwise addition of antihypertensive drugs with complementary mechanisms of action to lower BP. If BP remains uncontrolled, referral to a hypertension specialist is advised.

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Written from the paper’s full text.

TL;DR

This AHA scientific statement updates the definition, evaluation, and management of resistant hypertension, emphasizing confirmed medication adherence and out-of-office BP to exclude pseudoresistance. It recommends lifestyle optimization, long-acting thiazide-like diuretics, mineralocorticoid receptor antagonists, and stepwise add-on therapy, while highlighting major evidence gaps.

Key findings

  • RH is defined as above-goal BP despite concurrent use of 3 antihypertensive classes at maximum or maximally tolerated doses, commonly a long-acting CCB, a renin-angiotensin system blocker, and a diuretic; it also includes patients controlled on ≥4 medications. Diagnosis requires confirming adherence and excluding the white-coat effect.
  • Apparent treatment-resistant hypertension (aTRH) occurs in ≈12%–15% of population-based and 15%–18% of clinic-based treated hypertensive adults, and in 34%–39% of clinical trial populations.
  • RH is associated with worse outcomes: in >200,000 patients with incident hypertension, RH conferred 47% higher risk of death, MI, heart failure, stroke, or CKD over median 3.8 years; in >400,000 patients, RH was linked to 32% increased end-stage renal disease, 24% increased ischemic heart events, 46% increased heart failure, 14% increased stroke, and 6% increased death.
  • Management includes maximizing lifestyle interventions, using long-acting thiazide-like diuretics (chlorthalidone or indapamide), adding a mineralocorticoid receptor antagonist (spironolactone or eplerenone), and stepwise addition of complementary antihypertensives; switching from hydrochlorothiazide to the same daily dose of chlorthalidone yields an additional SBP reduction of 7–8 mm Hg, and primary aldosteronism prevalence is ≈20% in confirmed RH.

Methods

  • Design: An updated American Heart Association scientific statement/consensus document, not primary research; it synthesizes evidence since the 2008 AHA RH statement.
  • Data or sample: No original study sample; it draws on population-, clinic-, and trial-based reports, prior guidelines, and cited literature, with tables and figures.
  • Main analysis: Narrative expert synthesis and recommendations for detection, evaluation, and management; no systematic review, meta-analysis, or formal primary data analysis is described.

Limitations

  • Stated: Knowledge gaps include the need for true RH prevalence accounting for inaccurate BP measurement, white-coat effect, and nonadherence; unclear pathophysiology; limited genetics/pharmacogenetics; uncertain optimal BP target and sodium intake; and investigational device therapy.
  • Stated: Evidence specific to improving adherence in RH is sparse; diet intervention trials in RH are absent; and no trials of alternative approaches in RH have been performed.
  • Evident from the text: As a scientific statement, recommendations rely on expert consensus and indirect evidence, with many cited RH studies being observational, small, or lacking rigorous randomized confirmation.

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Integrity signals

Registry

Crossref · 10.1161/hyp.0000000000000084

Cites

420 of 420 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

0 of 411 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    In another study of more than 400,000 patients, compared with patients without resistant hypertension, patients with resistant hypertension had a 32% increased risk of developing end-stage renal disease.

    “In another study of >400 000 patients, compared with patients without RH, patients with RH had a 32% increased risk of developing end-stage renal disease, a 24% increased risk of an ischemic heart event, a 46% increased risk of heart failure, a 14% increased risk of stroke, and a 6% increased risk of death.29”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Sim JJ, Bhandari SK, Shi J, Reynolds K, Calhoun DA, Kalantar-Zadeh K, Jacobsen SJ. Comparative risk of renal, cardiovascular, and mortality outcomes in controlled, uncontrolled resistant, and nonresistant hypertension. Kidney Int. 2015; 88: 622– 632. doi: 10.1038/ki.2015.142 25945406 PMC4556588 source

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  • Premisecitation

    In that study, patients with resistant hypertension had a 24% increased risk of an ischemic heart event.

    “In another study of >400 000 patients, compared with patients without RH, patients with RH had a 32% increased risk of developing end-stage renal disease, a 24% increased risk of an ischemic heart event, a 46% increased risk of heart failure, a 14% increased risk of stroke, and a 6% increased risk of death.29”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Sim JJ, Bhandari SK, Shi J, Reynolds K, Calhoun DA, Kalantar-Zadeh K, Jacobsen SJ. Comparative risk of renal, cardiovascular, and mortality outcomes in controlled, uncontrolled resistant, and nonresistant hypertension. Kidney Int. 2015; 88: 622– 632. doi: 10.1038/ki.2015.142 25945406 PMC4556588 source

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  • Premisecitation

    Prevalent apparent treatment-resistant hypertension occurs in a higher percentage of population- and clinic-based samples when an at-risk group is selected, such as patients with treated hypertension and chronic kidney disease.

    “Prevalent aTRH occurs in a higher percentage of the population- and clinic-based samples when an at-risk group is selected, for example, patients with treated hypertension and chronic kidney disease (CKD).16,19”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [16] Tanner RM, Calhoun DA, Bell EK, Bowling CB, Gutiérrez OM, Irvin MR, Lackland DT, Oparil S, Warnock D, Muntner P. Prevalence of apparent treatment-resistant hypertension among individuals with CKD. Clin J Am Soc Nephrol. 2013; 8: 1583– 1590. doi: 10.2215/CJN.00550113 23868902 PMC3805064 source

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    • cites [19] Thomas G, Xie D, Chen HY, Anderson AH, Appel LJ, Bodana S, Brecklin CS, Drawz P, Flack JM, Miller ER 3rd, Steigerwalt SP, Townsend RR, Weir MR, Wright JT Jr, Rahman M; CRIC Study Investigators. Prevalence and prognostic significance of apparent treatment resistant hypertension in chronic kidney disease: report from the Chronic Renal Insufficiency Cohort Study. Hypertension. 2016; 67: 387– 396. doi: 10.1161/HYPERTENSIONAHA.115.06487 26711738 PMC4713320 source

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  • Premisecitation

    Among treated adults with hypertension, prevalent apparent treatment-resistant hypertension occurs in 15% to 18% of clinic-based samples.

    “Among treated adults with hypertension, prevalent aTRH occurs in ≈12% to 15% of population-based13–16 and 15% to 18% of clinic-based reports.17–20”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [17] Borghi C, Tubach F, De Backer G, Dallongeville J, Guallar E, Medina J, Perk J, Roy C, Banegas JR, Rodriguez-Artalejo F, Halcox JP. Lack of control of hypertension in primary cardiovascular disease prevention in Europe: results from the EURIKA study. Int J Cardiol. 2016; 218: 83– 88. doi: 10.1016/j.ijcard.2016.05.044 27232917 source

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    • cites [18] de la Sierra A, Segura J, Banegas JR, Gorostidi M, de la Cruz JJ, Armario P, Oliveras A, Ruilope LM. Clinical features of 8295 patients with resistant hypertension classified on the basis of ambulatory blood pressure monitoring. Hypertension. 2011: 57; 898– 902. 21444835 source

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    • cites [19] Thomas G, Xie D, Chen HY, Anderson AH, Appel LJ, Bodana S, Brecklin CS, Drawz P, Flack JM, Miller ER 3rd, Steigerwalt SP, Townsend RR, Weir MR, Wright JT Jr, Rahman M; CRIC Study Investigators. Prevalence and prognostic significance of apparent treatment resistant hypertension in chronic kidney disease: report from the Chronic Renal Insufficiency Cohort Study. Hypertension. 2016; 67: 387– 396. doi: 10.1161/HYPERTENSIONAHA.115.06487 26711738 PMC4713320 source

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    • cites [20] Egan BM, Zhao Y, Li J, Brzezinski WA, Todoran TM, Brook RD, Calhoun DA. Prevalence of optimal treatment regimens in patients with apparent treatment-resistant hypertension based on office blood pressure in a community-based practice network. Hypertension. 2013; 62: 691– 697. doi: 10.1161/HYPERTENSIONAHA.113.01448 23918752 PMC4066303 source

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  • Premisecitation

    In that retrospective study, differences in cardiovascular disease events were driven largely by a higher risk for the development of chronic kidney disease.

    “Differences in CVD events in this study were driven largely by a higher risk for the development of CKD.23”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Daugherty SL, Powers JD, Magid DJ, Tavel HM, Masoudi FA, Margolis KL, O’Connor PJ, Selby JV, Ho PM. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation. 2012; 125: 1635– 1642. doi: 10.1161/CIRCULATIONAHA.111.068064 22379110 PMC3343635 source

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  • May combine two claims. 72
  • Classified as probably not a substantial claim. 14

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    Premisecitation

    Resistant hypertension is not associated with increased adverse clinical events in patients with heart failure with reduced ejection fraction and may lower the risk for heart failure-related rehospitalization.

    “Conversely, RH is not associated with increased adverse clinical events in patients with heart failure with reduced ejection fraction and may lower the risk for heart failure-related rehospitalization.36”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Jin CN, Liu M, Sun JP, Fang F, Wen YN, Yu CM, Lee AP. The prevalence and prognosis of resistant hypertension in patients with heart failure. PLoS One. 2014; 9: e114958. doi: 10.1371/journal.pone.0114958 25490405 PMC4260939 source

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    Premisecitation

    In another study of more than 118,000 treated hypertensive adults, blood pressure control was associated with significantly lower rates of incident stroke and coronary heart disease with no difference in rates of incident heart failure.

    “In another study of >118 000 treated hypertensive adults, including >40 000 individuals with RH and 460 000 observation-years, BP control was associated with significantly lower rates of incident stroke and coronary heart disease with no difference in rates of incident heart failure.37”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] Egan BM, Kai B, Wagner CS, Henderson JH, Chandler AH, Sinopoli A. Blood pressure control provides less cardiovascular protection in adults with than without apparent treatment-resistant hypertension. J Clin Hypertens (Greenwich). 2016; 18: 817– 824. doi: 10.1111/jch.12773 26856795 PMC5837039 source

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    Premisecitation

    Physiological aberrations in resistant hypertension include vascular disease/dysfunction as evidenced by high rates of peripheral and carotid artery atherosclerosis, impaired endothelial function, reduced arterial compliance, and raised systemic vascular resistance, all of which may be more pronounced in resistant hypertension compared with non-resistant hypertension.

    “Physiological aberrations in RH include vascular disease/dysfunction as evidenced by high rates of peripheral39 and carotid artery atherosclerosis,42 impaired endothelial function,51,52 reduced arterial compliance, and raised systemic vascular resistance,40 all of which may be more pronounced in RH compared with non-RH.”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [39] Acharya T, Tringali S, Singh M, Huang J. Resistant hypertension and associated comorbidities in a Veterans Affairs population. J Clin Hypertens (Greenwich). 2014; 16: 741– 745. doi: 10.1111/jch.12410 25243893 PMC8031950 source

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    • cites [40] Bakhtar O, Ference BA, Hedquist LA, Levy PD, Flack JM. Relationship of resistant hypertension and treatment outcomes with total arterial compliance in a predominantly African American hypertensive cohort. J Clin Hypertens (Greenwich). 2012; 14: 618– 622. doi: 10.1111/j.1751-7176.2012.00653.x 22947360 PMC8108755 source

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    • cites [42] Cuspidi C, Macca G, Sampieri L, Michev I, Salerno M, Fusi V, Severgnini B, Meani S, Magrini F, Zanchetti A. High prevalence of cardiac and extracardiac target organ damage in refractory hypertension. J Hypertens. 2001; 19: 2063– 2070. 11677373 source

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    • cites [51] De la Sierra A, Larrousse M, Oliveras A, Armario P, Hernàndez-del Rey R, Poch E, Roca-Cusachs A. Abnormalities of vascular function in resistant hypertension. Blood Press. 2012; 21: 104– 109. 22017418 source

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    • cites [52] Quinaglia T, Martins LC, Figueiredo VN, Santos RC, Yugar-Toledo JC, Martin JF, Demacq C, Pimenta E, Calhoun DA, Moreno H Jr. Nondipping pattern relates to endothelial dysfunction in patients with uncontrolled resistant hypertension. J Hum Hypertens. 2011; 25: 656– 664. doi: 10.1038/jhh.2011.43 21544090 source

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  • May combine two claims.

    Interpretationreasoning

    Although blood pressure control is associated with a lower risk for some cardiovascular disease outcomes, it is possible that the benefit of blood pressure lowering may be less in patients with resistant hypertension compared with patients with non-resistant hypertension.

    “Although BP control is associated with a lower risk for some CVD outcomes, it is possible that the benefit of BP lowering may be less in patients with RH compared with patients with non-RH.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Blood pressure control reduced the risk of incident stroke, coronary heart disease, or heart failure by 13% among those with resistant hypertension compared with a 31% lower risk of these outcomes among patients without resistant hypertension.

    “BP control reduced the risk of incident stroke, coronary heart disease, or heart failure by 13% among those with RH compared with a 31% lower risk of these outcomes among patients without RH.37”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] Egan BM, Kai B, Wagner CS, Henderson JH, Chandler AH, Sinopoli A. Blood pressure control provides less cardiovascular protection in adults with than without apparent treatment-resistant hypertension. J Clin Hypertens (Greenwich). 2016; 18: 817– 824. doi: 10.1111/jch.12773 26856795 PMC5837039 source

      Not checked in the free run.

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    Premisecitation

    Demographic correlates of resistant hypertension include black race, older age, and male sex.

    “Demographic correlates of RH include black race, older age, and male sex.38”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Sim JJ, Bhandari SK, Shi J, Liu IL, Calhoun DA, McGlynn EA, Kalantar-Zadeh K, Jacobsen SJ. Characteristics of resistant hypertension in a large, ethnically diverse hypertension population of an integrated health system. Mayo Clin Proc. 2013; 88: 1099– 1107. doi: 10.1016/j.mayocp.2013.06.017 24079679 PMC3909733 source

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    Premisecitation

    Obesity, left ventricular hypertrophy, albuminuria, diabetes mellitus, chronic kidney disease, higher Framingham 10-year risk score, and obstructive sleep apnea are more common in resistant hypertension than non-resistant hypertension.

    “Obesity,39–41 left ventricular hypertrophy,42 albuminuria,14,43 diabetes mellitus,14,38,39 CKD,38,39,44 higher Framingham 10-year risk score,39 and obstructive sleep apnea (OSA)45,46 are more common in RH than non-RH.”
    Quote in the paperNot a substantial claim0 of 8 sources checked
    • cites [39] Acharya T, Tringali S, Singh M, Huang J. Resistant hypertension and associated comorbidities in a Veterans Affairs population. J Clin Hypertens (Greenwich). 2014; 16: 741– 745. doi: 10.1111/jch.12410 25243893 PMC8031950 source

      Not checked in the free run.

    • cites [40] Bakhtar O, Ference BA, Hedquist LA, Levy PD, Flack JM. Relationship of resistant hypertension and treatment outcomes with total arterial compliance in a predominantly African American hypertensive cohort. J Clin Hypertens (Greenwich). 2012; 14: 618– 622. doi: 10.1111/j.1751-7176.2012.00653.x 22947360 PMC8108755 source

      Not checked in the free run.

    • cites [41] Holecki M, Duława J, Chudek J. Resistant hypertension in visceral obesity. Eur J Intern Med. 2012; 23: 643– 648. doi: 10.1016/j.ejim.2012.04.012 22939810 source

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    • cites [42] Cuspidi C, Macca G, Sampieri L, Michev I, Salerno M, Fusi V, Severgnini B, Meani S, Magrini F, Zanchetti A. High prevalence of cardiac and extracardiac target organ damage in refractory hypertension. J Hypertens. 2001; 19: 2063– 2070. 11677373 source

      Not checked in the free run.

    • cites [43] Oliveras A, Armario P, Hernández-Del Rey R, Arroyo JA, Poch E, Larrousse M, Roca-Cusachs A, de la Sierra A. Urinary albumin excretion is associated with true resistant hypertension. J Hum Hypertens. 2010; 24: 27– 33. doi: 10.1038/jhh.2009.35 19421225

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    • cites [44] Oliveras A, de la Sierra A. Resistant hypertension: patient characteristics, risk factors, co-morbidities and outcomes. J Hum Hypertens. 2014; 28: 213– 217. doi: 10.1038/jhh.2013.77 23985879

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    • cites [45] Demede M, Pandey A, Zizi F, Bachmann R, Donat M, McFarlane SI, Jean-Louis G, Ogedegbe G. Resistant hypertension and obstructive sleep apnea in the primary-care setting. Int J Hypertens. 2011; 2011: 340929. doi: 10.4061⁄2011/340929 21755035 PMC3132606

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    • cites [46] Bhandari SK, Shi J, Molnar MZ, Rasgon SA, Derose SF, Kovesdy CP, Calhoun DA, Kalantar-Zadeh K, Jacobsen SJ, Sim JJ. Comparisons of sleep apnoea rate and outcomes among patients with resistant and nonresistant hypertension. Respirology. 2016; 21: 1486– 1492. doi: 10.1111/resp.12840 27427469

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  • May combine two claims.

    Interpretationreasoning

    Together, these studies suggest that resistant hypertension is associated with an increased risk of adverse outcomes and represents an important public health problem.

    “Together, these studies suggest that RH is associated with an increased risk of adverse outcomes and represents an important public health problem.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Bedtime dosing of once-daily antihypertensive agents (relative to morning or twice-daily dosing) appears to significantly affect diurnal blood pressure patterns because there are fewer patients with nondipping of blood pressure and >24-hour blood pressure control and higher rates of nocturnal normalization of blood pressure.

    “Bedtime dosing of once-daily antihypertensive agents (relative to morning or twice-daily dosing) appears to significantly affect diurnal BP patterns because there are fewer patients with nondipping of BP and >24-hour BP control and higher rates of nocturnal normalization of BP62 with this dosing strategy.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [62] Hermida RC, Ríos MT, Crespo JJ, Moyá A, Domínguez-Sardiña M, Otero A, Sánchez JJ, Mojón A, Fernández JR, Ayala DE; Hygia Project Investigators. Treatment-time regimen of hypertension medications significantly affects ambulatory blood pressure and clinical characteristics of patients with resistant hypertension. Chronobiol Int. 2013; 30: 192– 206. doi: 10.3109/07420528.2012.701460 23098160 source

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    Premisecitation

    Adequate adherence necessary for patients to experience benefit from full exposure to prescribed pharmacological therapy is generally defined as taking at least 80% of doses, although the scientific basis for this cutoff is unclear.

    “Adequate adherence necessary for patients to experience benefit from full exposure to prescribed pharmacological therapy is generally defined as taking at least 80% of doses, although the scientific basis for this cutoff is unclear.102”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [102] Hyman DJ, Pavlik V. Medication adherence and resistant hypertension. J Hum Hypertens. 2015; 29: 213– 218. doi: 10.1038/jhh.2014.73 25209307 source

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  • May combine two claims.

    Interpretationreasoning

    The diagnosis of resistant hypertension is predicated on the patient's adherence to the prescribed regimen, and failure to identify inadequate adherence contributes to overestimation of the prevalence of true resistant hypertension.

    “In fact, the diagnosis of RH is predicated on the patient’s adherence to the prescribed regimen, and failure to identify inadequate adherence contributes to overestimation of the prevalence of “true” RH.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Medication adherence is an important determinant of hypertension control.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A disproportionately higher prevalence of resistant hypertension among blacks has been suggested to reflect a contribution by genetic factors, but environmental or psychosocial determinants of blood pressure control are also possible.

    “A disproportionately higher prevalence of RH among blacks67,68 has been suggested to reflect a contribution by genetic factors, but environmental or psychosocial determinants of BP control are also possible.69”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [67] Cushman WC, Ford CE, Cutler JA, Margolis KL, Davis BR, Grimm RH, Black HR, Hamilton BP, Holland J, Nwachuku C, Papademetriou V, Probstfield J, Wright JT Jr, Alderman MH, Weiss RJ, Piller L, Bettencourt J, Walsh SM; ALLHAT Collaborative Research Group. Success and predictors of blood pressure control in diverse North American settings: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). J Clin Hypertens (Greenwich). 2002; 4: 393– 404. 12461301 source

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    • cites [68] Howard VJ, Tanner RM, Anderson A, Irvin MR, Calhoun DA, Lackland DT, Oparil S, Muntner P. Apparent treatment-resistant hypertension among individuals with history of stroke or transient ischemic attack. Am J Med. 2015; 128: 707– 714.e2. doi: 10.1016/j.amjmed.2015.02.008 25770032 PMC4475646

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    • cites [69] Shallcross AJ, Butler M, Tanner RM, Bress AP, Muntner P, Shimbo D, Ogedegbe G, Sims M, Spruill TM. Psychosocial correlates of apparent treatment-resistant hypertension in the Jackson Heart Study. J Hum Hypertens. 2017; 31: 474– 478. doi: 10.1038/jhh.2016.100 28124682 PMC7432960

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    Premisecitation

    Blood pressure has a genetic basis, as evidenced by its heritability in family-based studies, with estimates for long-term average blood pressure that as much as 50% to 60% of blood pressure variability can be attributed to additive genetic factors.

    “BP has a genetic basis, as evidenced by its heritability in family-based studies,63–65 with estimates for long-term average BP that as much as 50% to 60% of BP variability can be attributed to additive genetic factors.66”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [63] Hottenga JJ, Boomsma DI, Kupper N, Posthuma D, Snieder H, Willemsen G, de Geus EJ. Heritability and stability of resting blood pressure. Twin Res Hum Genet. 2005; 8: 499– 508. doi: 10.1375/183242705774310123 16212839

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    • cites [64] Snieder H, Harshfield GA, Treiber FA. Heritability of blood pressure and hemodynamics in African- and European-American youth. Hypertension. 2003; 41: 1196– 1201. doi: 10.1161/01.HYP.0000072269.19820.0D 12719445

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    • cites [65] Kupper N, Willemsen G, Riese H, Posthuma D, Boomsma DI, de Geus EJ. Heritability of daytime ambulatory blood pressure in an extended twin design. Hypertension. 2005; 45: 80– 85. doi: 10.1161/01.HYP.0000149952.84391.54 15557390

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    • cites [66] Levy D, DeStefano AL, Larson MG, O’Donnell CJ, Lifton RP, Gavras H, Cupples LA, Myers RH. Evidence for a gene influencing blood pressure on chromosome 17: genome scan linkage results for longitudinal blood pressure phenotypes in subjects from the Framingham Heart Study. Hypertension. 2000; 36: 477– 483. 11040222

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    Premisecitation

    Resistant hypertension has been linked to metabolic derangements, including hyperuricemia, aldosterone excess, and suppressed circulating renin levels (approximately 60% of those with resistant hypertension have suppressed renin levels).

    “RH has also been linked to metabolic derangements, including hyperuricemia,17 aldosterone excess,47 and suppressed circulating renin levels (≈60% of those with RH have suppressed renin levels).57”
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    • cites [17] Borghi C, Tubach F, De Backer G, Dallongeville J, Guallar E, Medina J, Perk J, Roy C, Banegas JR, Rodriguez-Artalejo F, Halcox JP. Lack of control of hypertension in primary cardiovascular disease prevention in Europe: results from the EURIKA study. Int J Cardiol. 2016; 218: 83– 88. doi: 10.1016/j.ijcard.2016.05.044 27232917 source

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    • cites [47] Gonzaga CC, Gaddam KK, Ahmed MI, Pimenta E, Thomas SJ, Harding SM, Oparil S, Cofield SS, Calhoun DA. Severity of obstructive sleep apnea is related to aldosterone status in subjects with resistant hypertension. J Clin Sleep Med. 2010; 6: 363– 368. 20726285 PMC2919667 source

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    • cites [57] Eide IK, Torjesen PA, Drolsum A, Babovic A, Lilledahl NP. Low-renin status in therapy-resistant hypertension: a clue to efficient treatment. J Hypertens. 2004; 22: 2217– 2226. 15480108

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    Premisecitation

    Individually, these variants explain ≤0.1% of blood pressure variability and, in aggregate, only 3% of total blood pressure variance.

    “Individually, these variants explain ≤0.1% of BP variability and, in aggregate, only 3% of total BP variance.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites 70–91

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    Premisecitation

    Common genetic variants influencing blood pressure have been identified at more than 300 independent loci but require scores to hundreds of thousands of individuals for their detection.

    “Common genetic variants influencing BP have been identified at >300 independent loci but require scores to hundreds of thousands of individuals for their detection.70–91”
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    • cites 70–91

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    Premisecitation

    These genetic variants typically have effects on the order of 1.0-mm Hg systolic blood pressure and 0.5-mm Hg diastolic blood pressure per blood pressure-raising allele.

    “These genetic variants typically have effects on the order of 1.0-mm Hg SBP and 0.5-mm Hg diastolic BP per BP-raising allele.”
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    • cites 70–91

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    Premisecitation

    The majority of genetic studies of resistant hypertension have been limited to candidate genes and have lacked adequate sample sizes to survive the multiple testing burden across the many such candidate gene studies performed.

    “The majority of genetic studies of RH have been limited to candidate genes and have lacked adequate sample sizes to survive the multiple testing burden across the many such candidate gene studies performed.92–96”
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    • cites [92] Yugar-Toledo JC, Martin JF, Krieger JE, Pereira AC, Demacq C, Coelho OR, Pimenta E, Calhoun DA, Júnior HM. Gene variation in resistant hypertension: multilocus analysis of the angiotensin 1-converting enzyme, angiotensinogen, and endothelial nitric oxide synthase genes. DNA Cell Biol. 2011; 30: 555– 564. doi: 10.1089/dna.2010.1156 21438754

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    • cites [93] Oliveira-Paula GH, Lacchini R, Coeli-Lacchini FB, Junior HM, Tanus-Santos JE. Inducible nitric oxide synthase haplotype associated with hypertension and responsiveness to antihypertensive drug therapy. Gene. 2013; 515: 391– 395. doi: 10.1016/j.gene.2012.12.059 23266817

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    • cites [94] Lynch AI, Irvin MR, Davis BR, Ford CE, Eckfeldt JH, Arnett DK. Genetic and adverse health outcome associations with treatment resistant hypertension in GenHAT. Int J Hypertens. 2013; 2013: 578578. doi: 10.1155/2013/578578 24288596 PMC3833110

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    • cites [95] Fontana V, McDonough CW, Gong Y, El Rouby NM, Sá AC, Taylor KD, Chen YD, Gums JG, Chapman AB, Turner ST, Pepine CJ, Johnson JA, Cooper-DeHoff RM. Large-scale gene-centric analysis identifies polymorphisms for resistant hypertension. J Am Heart Assoc. 2014; 3: e001398. doi: 10.1161/JAHA.114.001398 25385345 PMC4338734

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    • cites [96] Newton-Cheh C, Larson MG, Vasan RS, Levy D, Bloch KD, Surti A, Guiducci C, Kathiresan S, Benjamin EJ, Struck J, Morgenthaler NG, Bergmann A, Blankenberg S, Kee F, Nilsson P, Yin X, Peltonen L, Vartiainen E, Salomaa V, Hirschhorn JN, Melander O, Wang TJ. Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure. Nat Genet. 2009; 41: 348– 353. doi: 10.1038/ng.328 19219041 PMC2664511

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  • May combine two claims.

    Premisecitation

    Among 279 patients with resistant hypertension, brain natriuretic peptide was higher and plasma renin activity was lower than in control patients, supporting a component of relative volume excess, although 24-hour urinary sodium levels were not increased.

    “Among 279 patients with RH, brain natriuretic peptide was higher and PRA was lower than in control patients, supporting a component of relative volume excess (although 24-hour urinary sodium levels were not increased).159”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [159] Gaddam KK, Nishizaka MK, Pratt-Ubunama MN, Pimenta E, Aban I, Oparil S, Calhoun DA. Characterization of resistant hypertension: association between resistant hypertension, aldosterone, and persistent intravascular volume expansion. Arch Intern Med. 2008; 168: 1159– 1164. doi: 10.1001/archinte.168.11.1159 18541823 PMC2748247 source

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    Premisecitation

    Chronic renal insufficiency is a well-established cause of heightened salt sensitivity of blood pressure and has been repetitively linked to apparent treatment-resistant hypertension.

    “Further indirect evidence can be derived from large population studies in which chronic renal insufficiency, a well-established cause of heightened salt sensitivity of BP, has been repetitively linked to aTRH.13,38,152”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [13] Egan BM, Zhao Y, Axon RN, Brzezinski WA, Ferdinand KC. Uncontrolled and apparent treatment resistant hypertension in the United States, 1988–2008. Circulation. 2011: 124; 1046– 1058. 21824920 PMC3210066 source

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    • cites [38] Sim JJ, Bhandari SK, Shi J, Liu IL, Calhoun DA, McGlynn EA, Kalantar-Zadeh K, Jacobsen SJ. Characteristics of resistant hypertension in a large, ethnically diverse hypertension population of an integrated health system. Mayo Clin Proc. 2013; 88: 1099– 1107. doi: 10.1016/j.mayocp.2013.06.017 24079679 PMC3909733 source

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    • cites [152] de la Sierra A, Banegas JR, Oliveras A, Gorostidi M, Segura J, de la Cruz JJ, Armario P, Ruilope LM. Clinical differences between resistant hypertensives and patients treated and controlled with three or less drugs. J Hypertens. 2012; 30: 1211– 1216. 22525201 source

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  • May combine two claims.

    Premisecitation

    The dose-response association between alcohol and blood pressure may differ between men (linear) and women (J shaped) and can be modified by metabolic genes.

    “The dose-response association may differ between men (linear) and women (J shaped)164 and can be modified by metabolic genes.163”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [164] Briasoulis A, Agarwal V, Messerli FH. Alcohol consumption and the risk of hypertension in men and women: a systematic review and meta-analysis. J Clin Hypertens (Greenwich). 2012; 14: 792– 798. doi: 10.1111/jch.12008 23126352 PMC8108791 source

      Not checked in the free run.

    • cites [163] Chen L, Smith GD, Harbord RM, Lewis SJ. Alcohol intake and blood pressure: a systematic review implementing a mendelian randomization approach. PLoS Med. 2008; 5: e52. doi: 10.1371/journal.pmed.0050052 18318597 PMC2265305 source

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  • May combine two claims.

    Premisecitation

    Alcohol intake has been linked to increases in blood pressure and the risk for developing hypertension.

    “Alcohol intake has been linked to increases in BP and the risk for developing hypertension.162–164”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [162] McFadden CB, Brensinger CM, Berlin JA, Townsend RR. Systematic review of the effect of daily alcohol intake on blood pressure. Am J Hypertens. 2005; 18(pt 1): 276– 286. doi: 10.1016/j.amjhyper.2004.07.020 15752957

      Not checked in the free run.

    • cites [163] Chen L, Smith GD, Harbord RM, Lewis SJ. Alcohol intake and blood pressure: a systematic review implementing a mendelian randomization approach. PLoS Med. 2008; 5: e52. doi: 10.1371/journal.pmed.0050052 18318597 PMC2265305 source

      Not checked in the free run.

    • cites [164] Briasoulis A, Agarwal V, Messerli FH. Alcohol consumption and the risk of hypertension in men and women: a systematic review and meta-analysis. J Clin Hypertens (Greenwich). 2012; 14: 792– 798. doi: 10.1111/jch.12008 23126352 PMC8108791 source

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    Premisecitation

    Both reduced physical activity and lower physical fitness are independent risk factors for hypertension.

    “Both reduced physical activity and lower physical fitness are independent risk factors for hypertension.166–171”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [166] Shimbo D, Levitan EB, Booth JN 3rd, Calhoun DA, Judd SE, Lackland DT, Safford MM, Oparil S, Muntner P. The contributions of unhealthy lifestyle factors to apparent resistant hypertension: findings from the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study. J Hypertens. 2013; 31: 370– 376. doi: 10.1097/HJH.0b013e32835b6be7 23303356 PMC3838894 source

      Not checked in the free run.

    • cites [167] Diaz KM, Shimbo D. Physical activity and the prevention of hypertension. Curr Hypertens Rep. 2013; 15: 659– 668. doi: 10.1007/s11906-013-0386-8 24052212 PMC3901083 source

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    • cites [168] Carnethon MR, Evans NS, Church TS, Lewis CE, Schreiner PJ, Jacobs DR Jr, Sternfeld B, Sidney S. Joint associations of physical activity and aerobic fitness on the development of incident hypertension: coronary artery risk development in young adults. Hypertension. 2010; 56: 49– 55. doi: 10.1161/HYPERTENSIONAHA.109.147603 20516395 PMC2909350 source

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    • cites [169] Chase NL, Sui X, Lee DC, Blair SN. The association of cardiorespiratory fitness and physical activity with incidence of hypertension in men. Am J Hypertens. 2009; 22: 417– 424. doi: 10.1038/ajh.2009.6 19197248 source

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    • cites [170] Forman JP, Stampfer MJ, Curhan GC. Diet and lifestyle risk factors associated with incident hypertension in women. JAMA. 2009; 302: 401– 411. doi: 10.1001/jama.2009.1060 19622819 PMC2803081 source

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    • cites [171] Crump C, Sundquist J, Winkleby MA, Sundquist K. Interactive effects of physical fitness and body mass index on the risk of hypertension. JAMA Intern Med. 2016; 176: 210– 216. doi: 10.1001/jamainternmed.2015.7444 26784837 PMC4803286

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  • May combine two claims.

    Premisecitation

    Indirect methods, including patient self-report medication adherence assessment tools such as the Morisky Medication Adherence Scale and the Hill-Bone Compliance Scale, have demonstrated predictive validity in a variety of hypertensive populations and identify adherence risk factors that can be used to tailor messages targeting improved adherence.

    “Indirect methods, including patient self-report medication adherence assessment tools such as the Morisky Medication Adherence Scale107 and the Hill-Bone Compliance Scale,108 have demonstrated predictive validity in a variety of hypertensive populations and identify adherence risk factors that can be used to tailor messages targeting improved adherence.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [107] Morisky DE, Ang A, Krousel-Wood M, Ward HJ. Predictive validity of a medication adherence measure in an outpatient setting. J Clin Hypertens (Greenwich). 2008; 10: 348– 354. 18453793 PMC2562622

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    • cites [108] Kim MT, Hill MN, Bone LR, Levine DM. Development and testing of the Hill-Bone Compliance to High Blood Pressure Therapy Scale. Prog Cardiovasc Nurs. 2000; 15: 90– 96. 10951950 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A variety of environmental exposures, including loud noises, colder temperatures, higher altitudes, and air pollutants, promote high blood pressure.

    “Finally, a variety of environmental exposures, including loud noises (eg, traffic), colder temperatures (eg, winter), higher altitudes, and air pollutants, promote high BP.179”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [179] Brook RD, Weder AB, Rajagopalan S. “ Environmental hypertensionology” the effects of environmental factors on blood pressure in clinical practice and research. J Clin Hypertens (Greenwich). 2011; 13: 836– 842. doi: 10.1111/j.1751-7176.2011.00543.x 22051429 PMC8108751 source

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  • May combine two claims.

    Premisecitation

    Low-dose aspirin does not have COX-2-inhibiting or blood pressure-increasing effects, as indicated by results from the HOT study.

    “In contrast, low-dose aspirin does not have COX-2–inhibiting or BP-increasing effects, as indicated by results from the HOT study (Hypertension Optimal Treatment).191”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [191] Zanchetti A, Hansson L, Leonetti G, Rahn KH, Ruilope L, Warnold I, Wedel H. Low-dose aspirin does not interfere with the blood pressure-lowering effects of antihypertensive therapy. J Hypertens. 2002; 20: 1015– 1022. 12011664 source

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  • May combine two claims.

    Premisecitation

    Epidemiological studies of high-dose estrogen use found mean elevations in systolic blood pressure of 3 to 6 mm Hg, with ≈5% of women developing new hypertension.

    “Epidemiological studies of high-dose estrogen use found mean elevations in SBP of 3 to 6 mm Hg, with ≈5% of women developing new hypertension.209”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [209] Woods JW. Oral contraceptives and hypertension. Hypertension. 1988; 11(pt 2): II11– II15. 3280486 source

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  • May combine two claims.

    Premisecitation

    Psychosocial stressors, negative personality traits, and reduced sleep duration/quality have been associated with high blood pressure.

    “Psychosocial stressors (eg, occupational stress, low social support), negative personality traits (anxiety, anger, depression), and reduced sleep duration/quality have also been associated with high BP176–178; however, data linking them specifically to RH are lacking.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [176] Trudel-Fitzgerald C, Gilsanz P, Mittleman MA, Kubzansky LD. Dysregulated blood pressure: can regulating emotions help? Curr Hypertens Rep. 2015; 17: 92. doi: 10.1007/s11906-015-0605-6 26520446 PMC4764066 source

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    • cites [177] Cuffee Y, Ogedegbe C, Williams NJ, Ogedegbe G, Schoenthaler A. Psychosocial risk factors for hypertension: an update of the literature. Curr Hypertens Rep. 2014; 16: 483. doi: 10.1007/s11906-014-0483-3 25139781 PMC4163921 source

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    • cites [178] Gangwisch JE. A review of evidence for the link between sleep duration and hypertension. Am J Hypertens. 2014; 27: 1235– 1242. doi: 10.1093/ajh/hpu071 24778107 PMC4229731 source

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    Premisecitation

    Cessation of estrogen use typically leads to a return to baseline blood pressure within 2 to 12 months, but proteinuria may persist.

    “Cessation of estrogen use typically leads to a return to baseline BP within 2 to 12 months, but proteinuria may persist.209,210”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [209] Woods JW. Oral contraceptives and hypertension. Hypertension. 1988; 11(pt 2): II11– II15. 3280486 source

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    • cites [210] Lim KG, Isles CG, Hodsman GP. Malignant hypertension in women of childbearing age and its relation to the contraceptive pill. Br Med J. 1987; 294: 1057– 1059. 3107691 PMC1246219 source

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  • May combine two claims.

    Premisecitation

    Only 41.5 cases of hypertension per 10 000 person-years could be attributed to oral contraceptive use, and this number rapidly declined with cessation of therapy.

    “However, only 41.5 cases of hypertension per 10 000 person-years could be attributed to oral contraceptive use, and this number rapidly declined with cessation of therapy.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [205] Chasan-Taber L, Willett WC, Manson JE, Spiegelman D, Hunter DJ, Curhan G, Colditz GA, Stampfer MJ. Prospective study of oral contraceptives and hypertension among women in the United States. Circulation. 1996; 94: 483– 489. 8759093 source

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  • May combine two claims.

    Premisecitation

    Sympathomimetic-induced hypertension may not be clinically significant in healthy patients, but these blood pressure levels can be concerning in individuals with comorbid conditions.

    “Although sympathomimetic-induced hypertension may not be clinically significant in healthy patients, these BP levels can be concerning in individuals with comorbid conditions.214–217”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [214] Fleming GA. The FDA, regulation, and the risk of stroke. N Engl J Med. 2000; 343: 1886– 1887. doi: 10.1056/NEJM200012213432510 11117982

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    • cites [215] Mersfelder TL. Phenylpropanolamine and stroke: the study, the FDA ruling, the implications. Cleve Clin J Med. 2001; 68: 208– 209, 213. 11263849

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    • cites [216] Cantu C, Arauz A, Murillo-Bonilla LM, Lopez M, Barinagarrementeria F. Stroke associated with sympathomimetics contained in over-the-counter cough and cold drugs. Stroke. 2003; 34: 1667– 1672. doi: 10.1161/01.STR.0000075293.45936.FA 12791938

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    • cites [217] Kernan WN, Viscoli CM, Brass LM, Broderick JP, Brott T, Feldmann E, Morgenstern LB, Wilterdink JL, Horwitz RI. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med. 2000; 343: 1826– 1832. doi: 10.1056/NEJM200012213432501 11117973

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  • May combine two claims.

    Premisecitation

    Antihypertensive medication interactions have typically not been shown with calcium channel blockers, and the effect of NSAID use on α- and β-blocker efficacy might also be minimal.

    “It is important to note that antihypertensive medication interactions have typically not been shown with CCBs,186 and the effect of NSAID use on α- and β-blocker efficacy might also be minimal.187”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [186] White WB. Cardiovascular effects of the cyclooxygenase inhibitors. Hypertension. 2007; 49: 408– 418. doi: 10.1161/01.HYP.0000258106.74139.25 17261646

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    • cites [187] Ishiguro C, Fujita T, Omori T, Fujii Y, Mayama T, Sato T. Assessing the effects of non-steroidal anti-inflammatory drugs on antihypertensive drug therapy using post-marketing surveillance database. J Epidemiol. 2008; 18: 119– 124. 18469490 PMC4771606

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  • May combine two claims.

    Premisecitation

    Oral contraceptives raise blood pressure and induce hypertension by increasing angiotensin biosynthesis.

    “Oral contraceptives raise BP and induce hypertension by increasing angiotensin biosynthesis.203,204”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [203] Prentice RL. On the ability of blood pressure effects to explain the relation between oral contraceptives and cardiovascular disease. Am J Epidemiol 1988; 127: 213– 219. 3337079

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    • cites [204] Rosenthal T, Oparil S. Oral contraceptives, hormones replacement therapy, and hypertension In: Lip G, Hall J, eds. Comprehensive Hypertension. New York, NY: Elsevier/Mosby; 2007: 865– 882.

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  • May combine two claims.

    Premisecitation

    Recombinant human erythropoietin can increase blood pressure by complex mechanisms in a dose-dependent fashion, resulting in hypertension in 20% to 33% of recipients.

    “Recombinant human erythropoietin can increase BP by complex mechanisms in a dose-dependent fashion, resulting in hypertension in 20% to 33% of recipients.221”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [221] Eschbach JW, Abdulhadi MH, Browne JK, Delano BG, Downing MR, Egrie JC, Evans RW, Friedman EA, Graber SE, Haley NR. Recombinant human erythropoietin in anemic patients with end-stage renal disease: results of a phase III multicenter clinical trial. Ann Intern Med. 1989; 111: 992– 1000. 2688507 source

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  • May combine two claims.

    Premisecitation

    Long-term use of erythropoietin promotes vascular smooth muscle cell growth, vascular remodeling, and medial hypertrophy, with maintained elevated blood pressure.

    “Long-term use of erythropoietin promotes vascular smooth muscle cell growth, vascular remodeling, and medial hypertrophy, with maintained elevated BP.222,223”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [222] Vaziri ND. Mechanism of erythropoietin-induced hypertension. Am J Kidney Dis. 1999; 33: 821– 828. 10213636 source

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    • cites [223] Raine AE, Roger SD. Effects of erythropoietin on blood pressure. Am J Kidney Dis. 1991; 18(suppl 2): 76– 83. 1928084

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  • May combine two claims.

    Premisecitation

    In contrast to reduced sleep time and quality, the increase in sympathetic activity associated with obstructive sleep apnea is a function of intermittent hypoxia; the short-term rise in blood pressure parallels the severity of oxygen desaturation at night.

    “In contrast to reduced sleep time and quality, the increase in sympathetic activity associated with OSA is a function of intermittent hypoxia; the short-term rise in BP parallels the severity of oxygen desaturation at night.256,257”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [256] Itani O, Jike M, Watanabe N, Kaneita Y Short sleep duration and health outcomes: a systematic review, meta-analysis, and meta-regression. Sleep Med. 2017; 32: 246– 256. doi: 10.1016/j.sleep.2016.08.006 27743803 source

      Not checked in the free run.

    • cites [257] Guralnick A, Bakris GL. Approaches for targeting blood pressure control in sleep disorders. Curr Opin Nephrol Hypertens. 2012; 21: 469– 474. doi: 10.1097/MNH.0b013e32835623f5 22820373

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  • May combine two claims.

    Premisecitation

    Tachycardia and blood pressure elevation are common clinical manifestations of cocaine use.

    “Tachycardia and BP elevation are common clinical manifestations of cocaine use.238”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [238] Das G Cardiovascular effects of cocaine abuse. Int J Clin Pharmacol Ther Toxicol. 1993; 31: 521– 528. 8294163

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    Premisecitation

    Systolic blood pressure, diastolic blood pressure, and heart rate increase the day after a sleep-deprived night compared with the day after a normal sleep; urinary excretion of norepinephrine is also increased.

    “SBP, diastolic BP, and heart rate increase the day after a sleep-deprived night compared with the day after a normal sleep; urinary excretion of norepinephrine is also increased.56,253–256”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [56] Kario K, Bhatt DL, Kandzari DE, Brar S, Flack JM, Gilbert C, Oparil S, Robbins M, Townsend RR, Bakris G. Impact of renal denervation on patients with obstructive sleep apnea and resistant hypertension: insights from the SYMPLICITY HTN-3 trial. Circ J. 2016; 80: 1404– 1412. doi: 10.1253/circj.CJ-16-0035 27118620 source

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    • cites [253] Lusardi P, Zoppi A, Preti P, Pesce RM, Piazza E, Fogari R. Effects of insufficient sleep on blood pressure in hypertensive patients: a 24-h study. Am J Hypertens. 1999; 12(pt 1): 63– 68. 10075386 source

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    • cites [254] Gangwisch JE, Heymsfield SB, Boden-Albala B, Buijs RM, Kreier F, Pickering TG, Rundle AG, Zammit GK, Malaspina D. Short sleep duration as a risk factor for hypertension: analyses of the first National Health and Nutrition Examination Survey. Hypertension. 2006; 47: 833– 839. doi: 10.1161/01.HYP.0000217362.34748.e0 16585410 source

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    • cites [255] Jin ZN, Wei YX. Meta-analysis of effects of obstructive sleep apnea on the renin-angiotensin-aldosterone system. J Geriatr Cardiol. 2016; 13: 333– 343. doi: 10.11909/j.issn.1671-5411.2016.03.020 27403143 PMC4921546

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    • cites [256] Itani O, Jike M, Watanabe N, Kaneita Y Short sleep duration and health outcomes: a systematic review, meta-analysis, and meta-regression. Sleep Med. 2017; 32: 246– 256. doi: 10.1016/j.sleep.2016.08.006 27743803 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Pseudopheochromocytoma is a syndrome characterized by paroxysmal hypertension with three distinct features: abrupt elevation of blood pressure, equally abrupt onset of distressful physical symptoms, and absence of reported fear or panic at the onset of attacks.

    “Once true pheochromocytoma is excluded, one should consider pseudopheochromocytoma, a syndrome characterized by the presence of paroxysmal hypertension with 3 distinct features: abrupt elevation of BP, equally abrupt onset of distressful physical symptoms, and absence of reported fear or panic at the onset of attacks.249”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [249] Mann SJ. Severe paroxysmal hypertension (pseudopheochromocytoma): understanding the cause and treatment. Arch Intern Med. 1999; 159: 670– 674. 10218745

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    Premisecitation

    The complications of amphetamines are comparable to those of cocaine and include hypertension and tachycardia.

    “The complications of amphetamines are comparable to those of cocaine and include hypertension and tachycardia.240”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [240] Chiang W, Goldfrank L. The medical complications of drug abuse. Med J Aust. 1990; 152: 83– 88. 2404189

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    Premisecitation

    Sympathetic activity is increased in sleep deprivation, restless leg syndrome, and obstructive sleep apnea.

    “Sympathetic activity is also increased in sleep deprivation, restless leg syndrome, and OSA.252–254”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [252] Sayk F, Teckentrup C, Becker C, Heutling D, Wellhoner P, Lehnert H, Dodt C. Effects of selective slow-wave sleep deprivation on nocturnal blood pressure dipping and daytime blood pressure regulation. Am J Physiol Regul Integr Comp Physiol. 2010; 298: R191– R197. doi: 10.1152/ajpregu.00368.2009 19907004 source

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    • cites [253] Lusardi P, Zoppi A, Preti P, Pesce RM, Piazza E, Fogari R. Effects of insufficient sleep on blood pressure in hypertensive patients: a 24-h study. Am J Hypertens. 1999; 12(pt 1): 63– 68. 10075386 source

      Not checked in the free run.

    • cites [254] Gangwisch JE, Heymsfield SB, Boden-Albala B, Buijs RM, Kreier F, Pickering TG, Rundle AG, Zammit GK, Malaspina D. Short sleep duration as a risk factor for hypertension: analyses of the first National Health and Nutrition Examination Survey. Hypertension. 2006; 47: 833– 839. doi: 10.1161/01.HYP.0000217362.34748.e0 16585410 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Primary aldosteronism includes hypertension caused by volume expansion and sympathetic nervous system activation, hypokalemia, metabolic alkalosis, and advanced cardiovascular and renal disease.

    “The disorder includes hypertension caused by volume expansion and sympathetic nervous system activation, hypokalemia, metabolic alkalosis, and advanced cardiovascular and renal disease.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [289] Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016; 101: 1889– 1916. doi: 10.1210/jc.2015-4061 26934393 source

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    Premisecitation

    Correction of sleep apnea with continuous positive airway pressure reduces blood pressure in those who are adherent; however, because the systolic blood pressure reduction is only from 2 to 5 mm Hg, adjunctive medications are almost always needed.

    “Correction of sleep apnea with CPAP reduces BP in those who are adherent; however, because the SBP reduction is only from 2 to 5 mm Hg, adjunctive medications are almost always needed.260”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [260] Gottlieb DJ, Punjabi NM, Mehra R, Patel SR, Quan SF, Babineau DC, Tracy RP, Rueschman M, Blumenthal RS, Lewis EF, Bhatt DL, Redline S. CPAP versus oxygen in obstructive sleep apnea. N Engl J Med. 2014; 370: 2276– 2285. doi: 10.1056/NEJMoa1306766 24918372 PMC4172401 source

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    Premisecitation

    Increased sympathetic activity is seen in both animal models subjected exclusively to intermittent hypoxia and healthy human volunteers exposed to intermittent hypoxia in a "tent."

    “Indeed, increased sympathetic activity is seen in both animal models subjected exclusively to intermittent hypoxia258 and healthy human volunteers exposed to intermittent hypoxia in a “tent.”259”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [258] Dematteis M, Julien C, Guillermet C, Sturm N, Lantuejoul S, Mallaret M, Lévy P, Gozal E. Intermittent hypoxia induces early functional cardiovascular remodeling in mice. Am J Respir Crit Care Med. 2008; 177: 227– 235. doi: 10.1164/rccm.200702-238OC 17962641 source

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    • cites [259] Tamisier R, Pépin JL, Rémy J, Baguet JP, Taylor JA, Weiss JW, Lévy P. 14 Nights of intermittent hypoxia elevate daytime blood pressure and sympathetic activity in healthy humans. Eur Respir J. 2011; 37: 119– 128. doi: 10.1183/09031936.00204209 20525723 source

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    Premisecitation

    Sleep duration of <5 hours is associated with incident hypertension in subjects <60 years of age, whereas sleep duration of >9 hours per night is associated with incident hypertension in subjects >60 years.

    “Moreover, sleep duration of <5 hours is associated with incident hypertension in subjects <60 years of age, whereas sleep duration of >9 hours per night is associated with incident hypertension in subjects >60 years.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Primary aldosteronism is associated with left ventricular hypertrophy, diastolic dysfunction and heart failure, large artery stiffness, oxidative stress, widespread tissue inflammation and fibrosis, and increased resistance vessel remodeling compared with primary hypertension.

    “Primary aldosteronism is also associated with left ventricular hypertrophy, diastolic dysfunction and heart failure, large artery stiffness, oxidative stress, widespread tissue inflammation and fibrosis, and increased resistance vessel remodeling compared with primary hypertension.291–293”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [291] Savard S, Amar L, Plouin PF, Steichen O. Cardiovascular complications associated with primary aldosteronism: a controlled cross-sectional study. Hypertension. 2013; 62: 331– 336. doi: 10.1161/HYPERTENSIONAHA.113.01060 23753408 source

      Not checked in the free run.

    • cites [292] Bernini G, Galetta F, Franzoni F, Bardini M, Taurino C, Bernardini M, Ghiadoni L, Bernini M, Santoro G, Salvetti A. Arterial stiffness, intima-media thickness and carotid artery fibrosis in patients with primary aldosteronism. J Hypertens. 2008; 26: 2399– 2405. doi: 10.1097/HJH.0b013e32831286fd 19008719 source

      Not checked in the free run.

    • cites [293] Stehr CB, Mellado R, Ocaranza MP, Carvajal CA, Mosso L, Becerra E, Solis M, García L, Lavandero S, Jalil J, Fardella CE. Increased levels of oxidative stress, subclinical inflammation, and myocardial fibrosis markers in primary aldosteronism patients. J Hypertens. 2010; 28: 2120– 2126. doi: 10.1097/HJH.0b013e32833d0177 20683341 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Primary aldosteronism is accompanied by a major increase in cardiovascular disease and events compared with primary hypertension, including stroke (4.2-fold), myocardial infarction (6.5-fold), and atrial fibrillation (12.1-fold).

    “Because of the toxic effects of aldosterone on heart and blood vessels, primary aldosteronism is accompanied by a major increase in CVD and events compared with those observed in primary hypertension, including stroke (4.2-fold), myocardial infarction (6.5-fold), and atrial fibrillation (12.1-fold).290”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [290] Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol. 2005; 45: 1243– 1248. doi: 10.1016/j.jacc.2005.01.015 15837256

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  • May combine two claims.

    Premisecitation

    Obstructive sleep apnea is extremely common in patients with resistant hypertension, with prevalence rates as high as 70% to 90%, and when present, obstructive sleep apnea is often severe.

    “OSA is extremely common in patients with RH, with prevalence rates as high as 70% to 90%, and when present, OSA is often severe.272–277”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [272] Lloberes P, Lozano L, Sampol G, Romero O, Jurado MJ, Rios J, Untoria MD, Tovar JL. Obstructive sleep apnoea and 24-h blood pressure in patients with resistant hypertension. J Sleep Res. 2010; 19: 597– 602. doi: 10.1111/j.1365-2869.2010.00839.x 20545837

      Not checked in the free run.

    • cites [273] Logan AG, Perlikowski SM, Mente A, Tisler A, Tkacova R, Niroumand M, Leung RS, Bradley TD. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens. 2001; 19: 2271– 2277. 11725173 source

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    • cites [274] Min HJ, Cho YJ, Kim CH, Kim DH, Kim HY, Choi JI, Lee JG, Park S, Cho HJ. Clinical features of obstructive sleep apnea that determine its high prevalence in resistant hypertension. Yonsei Med J. 2015; 56: 1258– 1265. doi: 10.3349/ymj.2015.56.5.1258 26256968 PMC4541655

      Not checked in the free run.

    • cites [275] Muxfeldt ES, Margallo VS, Guimarâes GM, Salles GF. Prevalence and associated factors of obstructive sleep apnea in patients with resistant hypertension. Am J Hypertens. 2014; 27: 1069– 1078. doi: 10.1093/ajh/hpu023 24705438

      Not checked in the free run.

    • cites [276] Walia HK, Li H, Rueschman M, Bhatt DL, Patel SR, Quan SF, Gottlieb DJ, Punjabi NM, Redline S, Mehra R. Association of severe obstructive sleep apnea and elevated blood pressure despite antihypertensive medication use. J Clin Sleep Med. 2014; 10: 835– 843. doi: 10.5664/jcsm.3946 25126027 PMC4106935 source

      Not checked in the free run.

    • cites [277] Pratt-Ubunama MN, Nishizaka MK, Boedefeld RL, Cofield SS, Harding SM, Calhoun DA. Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant hypertension. Chest. 2007; 131: 453– 459. doi: 10.1378/chest.06-1442 17296647 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Among a series of 4494 patients referred to hypertension specialty clinics, 12.7% had secondary causes overall, of which 35% were associated with occlusive renovascular disease.

    “Among a series of 4494 patients referred to hypertension specialty clinics, 12.7% had secondary causes overall, of which 35% were associated with occlusive renovascular disease.306”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [306] Anderson GH Jr, Blakeman N, Streeten DH. The effect of age on prevalence of secondary forms of hypertension in 4429 consecutively referred patients. J Hypertens. 1994; 12: 609– 615. 7930562 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Apparent treatment-resistant hypertension was present in 40% of CRIC participants and was associated with higher cardiovascular event rates and mortality whether blood pressure was uncontrolled (≥140/90 mm Hg) with 3 antihypertensive agents (52.5%) or controlled with ≥4 agents (47.5%).

    “aTRH was present in 40% and was associated with higher cardiovascular event rates and mortality whether BP was uncontrolled (≥140/90 mm Hg) with 3 antihypertensive agents (52.5%) or controlled with ≥4 agents (47.5%).19”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Thomas G, Xie D, Chen HY, Anderson AH, Appel LJ, Bodana S, Brecklin CS, Drawz P, Flack JM, Miller ER 3rd, Steigerwalt SP, Townsend RR, Weir MR, Wright JT Jr, Rahman M; CRIC Study Investigators. Prevalence and prognostic significance of apparent treatment resistant hypertension in chronic kidney disease: report from the Chronic Renal Insufficiency Cohort Study. Hypertension. 2016; 67: 387– 396. doi: 10.1161/HYPERTENSIONAHA.115.06487 26711738 PMC4713320 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    From data from NHANES 1999 to 2010, the lifetime risk of developing moderate-stage chronic kidney disease from normal baseline kidney function is 54% for ages 30-49 years, 52% for ages 50-64 years, and 42% for age ≥65 years.

    “From data from NHANES 1999 to 2010, the lifetime risk of developing (or “progressing to”) moderate-stage CKD from normal baseline kidney function is 54% (age, 30–49 years), 52% (age, 50–64 years), and 42% (age ≥65 years).299”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [299] Hoerger TJ, Simpson SA, Yarnoff BO, Pavkov ME, Ríos Burrows N, Saydah SH, Williams DE, Zhuo X. The future burden of CKD in the United States: a simulation model for the CDC CKD Initiative. Am J Kidney Dis. 2015; 65: 403– 411. doi: 10.1053/j.ajkd.2014.09.023 25468386 PMC11000251 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Hypokalemia reduces aldosterone secretion and should be corrected with oral K+ supplements before testing for primary aldosteronism.

    “Hypokalemia, which reduces aldosterone secretion, should be corrected with oral K+ supplements before testing.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [289] Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016; 101: 1889– 1916. doi: 10.1210/jc.2015-4061 26934393 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Other data confirm that even when patients with chronic kidney disease were followed up in nephrology clinics, <15% had their blood pressure controlled to <130/80 mm Hg and <40% achieved a blood pressure of <140/90 mm Hg despite the use of 3 different antihypertensive agents.

    “Other data confirm that even when patients with CKD were followed up in nephrology clinics, <15% had their BP controlled to <130/80 mm Hg and <40% achieved a BP of <140/90 mm Hg despite the use of 3 different antihypertensive agents.304”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [304] Saelen MG, Prøsch LK, Gudmundsdottir H, Dyrbekk D, Helge Hunderi O, Arnesen E, Paulsen D, Skjønsberg H, Os I. Controlling systolic blood pressure is difficult in patients with diabetic kidney disease exhibiting moderate-to-severe reductions in renal function. Blood Press. 2005; 14: 170– 176. doi: 10.1080/08037050510008959 16036497 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Of the 86% with hypertension in CRIC, 67% were controlled to <140/90 mm Hg and 46% were controlled to <130/80 mm Hg, with a higher prevalence of uncontrolled hypertension in those with lower estimated glomerular filtration rate.

    “Of the 86% with hypertension, 67% were controlled to <140/90 mm Hg and 46% were controlled to <130/80 mm Hg, with a higher prevalence of uncontrolled hypertension in those with lower eGFR.302,303”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [302] Lash JP, Go AS, Appel LJ, He J, Ojo A, Rahman M, Townsend RR, Xie D, Cifelli D, Cohan J, Fink JC, Fischer MJ, Gadegbeku C, Hamm LL, Kusek JW, Landis JR, Narva A, Robinson N, Teal V, Feldman HI; Chronic Renal Insufficiency Cohort (CRIC) Study Group. Chronic Renal Insufficiency Cohort (CRIC) study: baseline characteristics and associations with kidney function. Clin J Am Soc Nephrol. 2009; 4: 1302– 1311. doi: 10.2215/CJN.00070109 19541818 PMC2723966

      Not checked in the free run.

    • cites [303] Muntner P, Anderson A, Charleston J, Chen Z, Ford V, Makos G, O’Connor A, Perumal K, Rahman M, Steigerwalt S, Teal V, Townsend R, Weir M, Wright JT Jr; Chronic Renal Insufficiency Cohort (CRIC) Study Investigators. Hypertension awareness, treatment, and control in adults with CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2010; 55: 441– 451. doi: 10.1053/j.ajkd.2009.09.014 19962808 PMC2866514

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The prevalence of confirmed primary aldosteronism among 1656 hypertensive Chinese patients with resistant hypertension was only 7.1%, indicating significant variation in prevalence in different populations.

    “However, the prevalence of confirmed primary aldosteronism among 1656 hypertensive Chinese patients with RH was only 7.1%, indicating significant variation in prevalence in different populations.297”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [297] Sang X, Jiang Y, Wang W, Yan L, Zhao J, Peng Y, Gu W, Chen G, Liu W, Ning G. Prevalence of and risk factors for primary aldosteronism among patients with resistant hypertension in China. J Hypertens. 2013; 31: 1465– 1471. doi: 10.1097/HJH.0b013e328360ddf6 24006040

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    An alternative simulation for a 30-year-old individual estimated a residual lifetime risk of 59.1% for estimated glomerular filtration rate <60 mL⋅min−1⋅1.73 m−2.

    “An alternative simulation for a 30-year-old individual estimated a residual lifetime risk of 59.1% for estimated glomerular filtration rate (eGFR) <60 mL⋅min−1⋅1.73 m−2.300”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [300] Grams ME, Sang Y, Levey AS, Matsushita K, Ballew S, Chang AR, Chow EK, Kasiske BL, Kovesdy CP, Nadkarni GN, Shalev V, Segev DL, Coresh J, Lentine KL, Garg AX; Chronic Kidney Disease Prognosis Consortium. Kidney-failure risk projection for the living kidney-donor candidate. N Engl J Med. 2016; 374: 411– 421. doi: 10.1056/NEJMoa1510491 26544982 PMC4758367

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    β-adrenergic receptor blockers, central α2-receptor agonists, and renin inhibitors suppress plasma renin activity, and ACE inhibitors, ARBs, non-potassium-sparing diuretics, and dihydropyridine calcium channel blockers increase plasma renin activity, thus altering plasma aldosterone/renin ratio values.

    “For example, β-adrenergic receptor blockers, central α2-receptor agonists, and renin inhibitors suppress PRA, and ACE inhibitors, ARBs, non-potassium-sparing diuretics, and dihydropyridine CCBs increase PRA, thus altering plasma ARR values.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [289] Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016; 101: 1889– 1916. doi: 10.1210/jc.2015-4061 26934393 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Restoring main renal artery patency with endovascular stenting is likely to reduce arterial blood pressure, albeit with a residual requirement for antihypertensive drug therapy.

    “Although initial treatment usually includes systematically advancing medical therapy, restoring main renal artery patency with endovascular stenting is also likely to reduce arterial BP, albeit with a residual requirement for antihypertensive drug therapy.316”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [316] Weinberg I, Keyes MJ, Giri J, Rogers KR, Olin JW, White CJ, Jaff MR. Blood pressure response to renal artery stenting in 901 patients from five prospective multicenter FDA-approved trials. Catheter Cardiovasc Interv. 2014; 83: 603– 609. doi: 10.1002/ccd.25263 24307609 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    It is probable that excessive activation of mineralocorticoid receptors plays a prominent role in Cushing syndrome hypertension and adequate diuretic therapy will likely be a cornerstone of successful therapy.

    “Nevertheless, it is probable that excessive activation of mineralocorticoid receptors plays a prominent role and thus adequate diuretic therapy will likely prove to be a cornerstone of successful therapy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Catechol O-methyl transferase releases normetanephrine and metanephrine from pheochromocytoma/paraganglioma tumors, measured as plasma free metanephrines with sensitivity 96%-100% and specificity 89%-98%, or urinary fractionated metanephrines with sensitivity 86%-97% and specificity 86%-95%.

    “Catechol 0-methyl transferase releases normetanephrine and metanephrine from the tumors, measured as plasma free (sensitivity, 96%−100%; specificity, 89%−98%) or urinary fractionated (sensitivity, 86%−97%; specificity, 86%−95%) metanephrines.321”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [321] Schwartz GL. Screening for adrenal-endocrine hypertension: overview of accuracy and cost-effectiveness. Endocrinol Metab Clin North Am. 2011; 40: 279– 294, vii. doi: 10.1016/j.ecl.2011.02.001 21565667 PMC3094544 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Although high BP may be common among patients with Cushing syndrome, it is unlikely that Cushing syndrome is prevalent in the overall population of patients with resistant hypertension.

    “This suggests that although high BP (perhaps even severe forms) may be common among patients with Cushing syndrome, it is unlikely that it is prevalent in the overall population of patients with RH.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [326] Martins LC, Conceição FL, Muxfeldt ES, Salles GF. Prevalence and associated factors of subclinical hypercortisolism in patients with resistant hypertension. J Hypertens. 2012; 30: 967– 973. doi: 10.1097/HJH.0b013e3283521484 22406465

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Persistent hypertension after coarctation repair may be secondary to increased sympathetic tone, so β-blockers may be most useful for BP control.

    “Because persistent hypertension may be secondary to increased sympathetic tone, β-blockers may be most useful for BP control.333”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [333] Moltzer E, Mattace Raso FU, Karamermer Y, Boersma E, Webb GD, Simoons ML, Danser AH, van den Meiracker AH, Roos-Hesselink JW. Comparison of candesartan versus metoprolol for treatment of systemic hypertension after repaired aortic coarctation. Am J Cardiol. 2010; 105: 217– 222. doi: 10.1016/j.amjcard.2009.08.674 20102922

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Most patients with renovascular disease tolerate ACE inhibitor or ARB therapy without adverse renal effects, but a modest fraction (10%−20%) will develop an unacceptable rise in serum creatinine, particularly with volume depletion.

    “Most patients with renovascular disease tolerate ACE inhibitor or ARB therapy without adverse renal effects,311 but a modest fraction (10%−20%) will develop an unacceptable rise in serum creatinine, particularly with volume depletion.312”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [311] Evans KL, Tuttle KR, Folt DA, Dawson T, Haller ST, Brewster PS, He W, Jamerson K, Dworkin LD, Cutlip DE, Murphy TP, D’Agostino RB Sr, Henrich W, Cooper CJ. Use of renin-angiotensin inhibitors in people with renal artery stenosis. Clin J Am Soc Nephrol. 2014; 9: 1199– 1206. doi: 10.2215/CJN.11611113 24903387 PMC4078968

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    • cites [312] Chrysochou C, Foley RN, Young JF, Khavandi K, Cheung CM, Kalra PA. Dispelling the myth: the use of renin-angiotensin blockade in atheromatous renovascular disease. Nephrol Dial Transplant. 2012; 27: 1403– 1409. doi: 10.1093/ndt/gfr496 21993376

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Although small cohort studies suggest high BP is highly prevalent (often exceeding 80%) among patients with Cushing syndrome, the overall frequency of hypertension among patients with Cushing syndrome remains to be accurately characterized.

    “Although a variety of relatively small cohort studies suggest that high BP is highly prevalent (often exceeding 80%),324,325 the overall frequency of hypertension, mild or severe, among patients with Cushing syndrome remains to be accurately characterized.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [324] Cicala MV, Mantero F. Hypertension in Cushing’s syndrome: from pathogenesis to treatment. Neuroendocrinology. 2010; 92(suppl 1): 44– 49. doi: 10.1159/000314315 20829617 source

      Not checked in the free run.

    • cites [325] Singh Y, Kotwal N, Menon AS. Endocrine hypertension: Cushing’s syndrome. Indian J Endocrinol Metab. 2011; 15(suppl 4): S313– S316. doi: 10.4103/2230-8210.86973 22145133 PMC3230089 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Restenosis may develop in 15% to 24% of treated patients after endovascular procedures for renal artery stenosis but may not always be associated with worsening hypertension or kidney function.

    “Restenosis may develop in 15% to 24% of treated patients but may not always be associated with worsening hypertension or kidney function.319”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [319] Boateng FK, Greco BA. Renal artery stenosis: prevalence of, risk factors for, and management of in-stent stenosis. Am J Kidney Dis. 2013; 61: 147– 160. doi: 10.1053/j.ajkd.2012.07.025 23122491

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Patients with operated coarctation of the aorta are likely to have hypertension in adulthood and are at risk for premature CVD, including myocardial infarction, aortic aneurysm, stroke, and heart failure.

    “Patients with operated coarctation of the aorta are likely to have hypertension in adulthood and are at risk for premature CVD, including myocardial infarction, aortic aneurysm (ascending or descending), stroke, and heart failure.329–331”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [329] Choudhary P, Canniffe C, Jackson DJ, Tanous D, Walsh K, Celermajer DS. Late outcomes in adults with coarctation of the aorta. Heart. 2015; 101: 1190– 1195. doi: 10.1136/heartjnl-2014-307035 25810155

      Not checked in the free run.

    • cites [330] Canniffe C, Ou P, Walsh K, Bonnet D, Celermajer D. Hypertension after repair of aortic coarctation: a systematic review. Int J Cardiol. 2013; 167: 2456– 2461. doi: 10.1016/j.ijcard.2012.09.084 23041096

      Not checked in the free run.

    • cites [331] Vriend JW, Mulder BJ. Late complications in patients after repair of aortic coarctation: implications for management. Int J Cardiol. 2005; 101: 399– 406. doi: 10.1016/j.ijcard.2004.03.056 15907407

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Low-intensity physical activity, 6 minutes hourly over an 8-hour period, in sedentary individuals lowered BP (14/8 mm Hg) and can improve metabolic syndrome variables.

    “Low-intensity physical activity, 6 minutes hourly over an 8-hour period, in sedentary individuals lowered BP (14/8 mm Hg) and can improve metabolic syndrome variables.355–359”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [355] Dempsey PC, Sacre JW, Larsen RN, Straznicky NE, Sethi P, Cohen ND, Cerin E, Lambert GW, Owen N, Kingwell BA, Dunstan DW. Interrupting prolonged sitting with brief bouts of light walking or simple resistance activities reduces resting blood pressure and plasma noradrenaline in type 2 diabetes. J Hypertens. 2016; 34: 2376– 2382. doi: 10.1097/HJH.0000000000001101 27512975 source

      Not checked in the free run.

    • cites [356] Dempsey PC, Larsen RN, Sethi P, Sacre JW, Straznicky NE, Cohen ND, Cerin E, Lambert GW, Owen N, Kingwell BA, Dunstan DW. Benefits for type 2 diabetes of interrupting prolonged sitting with brief bouts of light walking or simple resistance activities. Diabetes Care. 2016; 39: 964– 972. doi: 10.2337/dc15-2336 27208318 source

      Not checked in the free run.

    • cites [357] Dunstan DW, Kingwell BA, Larsen R, Healy GN, Cerin E, Hamilton MT, Shaw JE, Bertovic DA, Zimmet PZ, Salmon J, Owen N. Breaking up prolonged sitting reduces postprandial glucose and insulin responses. Diabetes Care. 2012; 35: 976– 983. doi: 10.2337/dc11-1931 22374636 PMC3329818 source

      Not checked in the free run.

    • cites [358] Larsen RN, Kingwell BA, Sethi P, Cerin E, Owen N, Dunstan DW. Breaking up prolonged sitting reduces resting blood pressure in over-weight/obese adults. Nutr Metab Cardiovasc Dis. 2014; 24: 976– 982. doi: 10.1016/j.numecd.2014.04.011 24875670 source

      Not checked in the free run.

    • cites [359] Pescatello LS, Murphy D, Costanzo D. Low-intensity physical activity benefits blood lipids and lipoproteins in older adults living at home. Age Ageing. 2000; 29: 433– 439. 11108416 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A treadmill walking exercise program in 1 study was safe and effective for lowering BP in patients with resistant hypertension.

    “As previously outlined, a treadmill walking exercise program in 1 study was safe and effective for lowering BP in patients with RH.173”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [173] Dimeo F, Pagonas N, Seibert F, Arndt R, Zidek W, Westhoff TH. Aerobic exercise reduces blood pressure in resistant hypertension. Hypertension. 2012; 60: 653– 658. doi: 10.1161/HYPERTENSIONAHA.112.197780 22802220 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A recent small pilot study (n=16) demonstrated that a water-based aerobic exercise program may be safe and effective for lowering BP in patients with resistant hypertension.

    “A recent small pilot study (n=16) also demonstrated that a water-based aerobic exercise program may be safe and effective for lowering BP in this population.354”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [354] Guimaräes GV, Cruz LG, Tavares AC, Dorea EL, Fernandes-Silva MM, Bocchi EA. Effects of short-term heated water-based exercise training on systemic blood pressure in patients with resistant hypertension: a pilot study. Blood Press Monit. 2013; 18: 342– 345. doi: 10.1097/MBP.0000000000000000 24192849 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A DASH-style eating pattern, alcohol restriction to <10 g/d (women) and <20 g/d (men), and a variety of other dietary modifications can each yield significant reductions in BP among patients with hypertension.

    “A DASH-style eating pattern,174,175 alcohol restriction to <10 g/d (women) and <20 g/d (men),162–165 and a variety of other dietary modifications174 can each yield significant reductions in BP among patients with hypertension.”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [174] Appel LJ, Giles TD, Black HR, Izzo JL Jr, Materson BJ, Oparil S, Weber MA; American Society of Hypertension Writing Group. ASH position paper: dietary approaches to lower blood pressure. J Clin Hypertens (Greenwich). 2009; 11: 358– 368. doi: 10.1111/j.1751-7176.2009.00136.x 19583632 PMC8673392 source

      Not checked in the free run.

    • cites [175] Saneei P, Salehi-Abargouei A, Esmaillzadeh A, Azadbakht L. Influence of Dietary Approaches to Stop Hypertension (DASH) diet on blood pressure: a systematic review and meta-analysis on randomized controlled trials. Nutr Metab Cardiovasc Dis. 2014; 24: 1253– 1261. doi: 10.1016/j.numecd.2014.06.008 25149893 source

      Not checked in the free run.

    • cites [162] McFadden CB, Brensinger CM, Berlin JA, Townsend RR. Systematic review of the effect of daily alcohol intake on blood pressure. Am J Hypertens. 2005; 18(pt 1): 276– 286. doi: 10.1016/j.amjhyper.2004.07.020 15752957

      Not checked in the free run.

    • cites [163] Chen L, Smith GD, Harbord RM, Lewis SJ. Alcohol intake and blood pressure: a systematic review implementing a mendelian randomization approach. PLoS Med. 2008; 5: e52. doi: 10.1371/journal.pmed.0050052 18318597 PMC2265305 source

      Not checked in the free run.

    • cites [164] Briasoulis A, Agarwal V, Messerli FH. Alcohol consumption and the risk of hypertension in men and women: a systematic review and meta-analysis. J Clin Hypertens (Greenwich). 2012; 14: 792– 798. doi: 10.1111/jch.12008 23126352 PMC8108791 source

      Not checked in the free run.

    • cites [165] Hussain K, Arisari RA, Ferder L. Alcohol-induced hypertension: mechanism and prevention. World J Cardiol. 2014; 26: 245– 252. PMC4038773 24891935

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    There is concern that a U-shaped relationship may exist between sodium intake and CVD risk, with greatest risk reductions at moderate restriction of 173 to 217 mmol/d (4-5 g/d) despite BP continuing to decrease linearly with further reductions to <65 mmol/d (1.5 g/d).

    “There is concern that a U-shaped relationship may exist, with the greatest risk reductions being achieved by following only moderate restriction in sodium intake of 173 to 217 mmol/d (4–5 g/d) despite the fact that BP continues to decrease in a linear fashion with even further reductions to <65 mmol/d (1.5 g/d).349”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [349] Mente A, O’Donnell M, Rangarajan S, Dagenais G, Lear S, McQueen M, Diaz R, Avezum A, Lopez-Jaramillo P, Lanas F, Li W, Lu Y, Yi S, Rensheng L, Iqbal R, Mony P, Yusuf R, Yusoff K, Szuba A, Oguz A, Rosengren A, Bahonar A, Yusufali A, Schutte AE, Chifamba J, Mann JF, Anand SS, Teo K, Yusuf S; PURE, EPIDREAM and ONTARGET/ TRANSCEND Investigators. Associations of urinary sodium excretion with cardiovascular events in individuals with and without hypertension: a pooled analysis of data from four studies. Lancet. 2016; 388: 465– 475. doi: 10.1016/S0140-6736(16)30467-6 27216139

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The effect of pharmacologically aided weight loss on BP is mixed, with some medications showing modest benefits (eg, orlistat), whereas others (sibutramine) may even raise BP.

    “On the other hand, the effect of pharmacologically aided weight loss is mixed, with some medications showing modest benefits (eg, orlistat), whereas others (sibutramine) may even raise BP.348”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [348] Siebenhofer A, Jeitler K, Horvath K, Berghold A, Posch N, Meschik J, Semlitsch T. Long-term effects of weight-reducing drugs in people with hypertension. Cochrane Database Syst Rev. 2016: 3: CD007654. 26934640

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Approximately 70% of adults with resistant hypertension are candidates for mineralocorticoid receptor antagonists based on eGFR and serum K+, yet only a small fraction receive these effective agents.

    “Approximately 70% of adults with RH are candidates for mineralocorticoid receptor antagonists based on eGFR and serum K+, yet only a small fraction receive these effective agents.379”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [379] Egan BM, Li J. Role of aldosterone blockade in resistant hypertension. Semin Nephrol. 2014; 34: 273– 284. doi: 10.1016/j.semnephrol.2014.04.004 25016399 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Some data suggest that long-acting formulations of nifedipine may have slightly greater antihypertensive actions than amlodipine but are associated with more edema.

    “Some data suggest that long-acting formulations of nifedipine may have slightly greater antihypertensive actions than amlodipine but are associated with more edema.384–386”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [384] Byyny RL, Shannon T, Schwartz LA, Rotolo C, Jungerwirth S. Efficacy and safety of nifedipine coat-core versus amlodipine in patients with mild to moderate essential hypertension: comparison of 24-hour mean ambulatory diastolic blood pressure. J Cardiovasc Pharmacol Ther. 1997; 2: 77– 84. doi: 10.1177/107424849700200201 10684445

      Not checked in the free run.

    • cites [385] Kuga K, Xu DZ, Ohtsuka M, Aonuma K, Lau AH, Watanabe Y, Ohtsuka K. Comparison of daily anti-hypertensive effects of amlodipine and nifedipine coat-core using ambulatory blood pressure monitoring: utility of “hypobaric curve” and “hypobaric area.” Clin Exp Hypertens. 2011; 33: 231– 239. doi: 10.3109/10641963.2011.583968 21699449

      Not checked in the free run.

    • cites [386] Tanaka T, Miura S, Tanaka M, Uehara Y, Hirano T, Saku K. Efficacies of controlling morning blood pressure and protecting the kidneys by treatment with valsartan and nifedipine CR or valsartan and amlodipine (MONICA study). J Clin Med Res. 2013; 5: 432– 440. doi: 10.4021/jocmr1563w 24171055 PMC3808261

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Nitrates are preferred in heart failure because they help restore calcium (Ca2+) cycling and cardiac contractile performance and control superoxide production in isolated cardiomyocytes.

    “Nitrates are preferred in this setting because they help restore calcium (Ca2+) cycling and cardiac contractile performance and control superoxide production in isolated cardiomyocytes.393”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [393] Dulce RA, Yiginer O, Gonzalez DR, Goss G, Feng N, Zheng M, Hare JM. Hydralazine and organic nitrates restore impaired excitation-contraction coupling by reducing calcium leak associated with nitroso-redox imbalance. J Biol Chem. 2013; 288: 6522– 6533. doi: 10.1074/jbc.M112.412130 23319593 PMC3585085

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationreasoning

    It is probable that the characteristics of patients with resistant hypertension may change with refinement of the definition using lower BP thresholds.

    “It is probable that the characteristics of patients with RH may change with refinement of the definition using lower BP thresholds.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Reducing the BP target in the general hypertensive population will increase the prevalence of resistant hypertension.

    “Reducing the BP target in the general hypertensive population will no doubt increase the prevalence of RH.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In the 1940s, surgical sympathectomy demonstrated dramatic improvement in BP control and accompanying reduction in cardiac size, improved renal function, and a decrease in the rate of cerebrovascular events before the availability of antihypertensive drugs.

    “In the 1940s, surgical sympathectomy demonstrated dramatic improvement in BP control and accompanying reduction in cardiac size, improved renal function, and a decrease in the rate of cerebrovascular events before the availability of antihypertensive drugs.400”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [400] Evelyn KA, Alexander F, Cooper SR. Effect of sympathectomy on blood pressure in hypertension; a review of 13 years’ experience of the Massachusetts General Hospital. J Am Med Assoc. 1949; 140: 592– 602. 18131738 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The patients enrolled in SPYRAL HTN-OFF MED did not have resistant hypertension, and at best the study represents a proof-of-principle demonstration of the role of the renal sympathetic nervous system in hypertension.

    “However, the patients enrolled in this study did not have RH, and at best, this represents a proof-of-principle study demonstrating the role of the renal sympathetic nervous system in hypertension.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The role of device-based sympatholytic treatments, such as renal denervation and baroreceptor stimulation, awaits clarification.

    “The role of device-based sympatholytic treatments, as with renal denervation and baroreceptor stimulation, awaits clarification.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Validation of true benefit for device-based sympatholytic treatments has not been confirmed in rigorous, double-blind comparisons with sham intervention.

  • Classified as probably not a substantial claim.

    Interpretationnone given

    The lesser efficacy of hypertension control in resistant hypertension may be related to differences in the 24-hour blood pressure profile, pathophysiological mechanisms, or subclinical target organ injury.

    “The reason for the lesser efficacy of hypertension control in RH is unclear but could be related to differences in the 24-hour BP profile (eg, less nocturnal dipping or greater BP variability), differences in pathophysiological mechanisms, or greater degrees of subclinical target organ injury.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    CALM-FIM_EUR has demonstrated in patients with resistant hypertension that endovascular baroreflex amplification with the MobiusHD device substantially lowered BP with an acceptable safety profile.

    “CALM-FIM_EUR has recently demonstrated in patients with RH that endovascular baroreflex amplification with the MobiusHD device substantially lowered BP with an acceptable safety profile.413”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [413] Spiering W, Williams B, Van der Heyden J, van Kleef M, Lo R, Versmissen J, Moelker A, Kroon A, Reuter H, Ansel G, Stone GW, Bates M; CALM-FIM_EUR investigators. Endovascular baroreflex amplification for resistant hypertension: a safety and proof-of-principle clinical study. Lancet. 2017; 390: 2655– 2661. doi: 10.1016/S0140-6736(17)32337-1 28870716

      Not checked in the free run.

82 of 82

  • The paper relies on this without support.

    A large proportion of hypertensive adults fail to achieve recommended blood pressure targets on 3 antihypertensive medications or require at least 4 medications to achieve their targets despite conscientious clinical management.

    “Even with steady improvement during the past 30 years in hypertension awareness, treatment, and control rates, a large proportion of hypertensive adults, despite conscientious clinical management, still fail to achieve their recommended blood pressure (BP) treatment targets on 3 antihypertensive medications or require ≥4 medications to achieve their targets.”

  • The paper relies on this without support.

    Patients with resistant hypertension are more likely to have medication adverse effects, more likely to have a secondary cause of hypertension, and may benefit from special diagnostic or therapeutic approaches.

    “Moreover, they are more likely to have medication adverse effects, more likely to have a secondary cause of hypertension compared with hypertensive patients without drug resistance, and may benefit from special diagnostic or therapeutic approaches to control their BP.”

  • The paper relies on this without support.

    Medication adherence is an important determinant of hypertension control.

    “Medication adherence is an important determinant of hypertension control.”

  • The paper relies on this without support.

    Pharmacy databases for medication possession and refills provide a valid measure of adherence.

    “Pharmacy databases for medication possession and refills provide a valid measure of adherence.”

  • The paper relies on this without support.

    Measurement of pharmacodynamic parameters may have limited specificity.

    “Measurement of pharmacodynamic parameters (eg, heart rate for β-blockers, lack of rise of plasma renin activity [PRA] for renin-angiotensin inhibitors, N-acetyl-seryl-aspartyl-lysyl-proline measurements for ACE inhibitors) may have limited specificity.”

  • The paper relies on this without support.

    Witnessed medication taking followed by monitoring of effect on blood pressure has been effective in identifying suspected nonadherence in trials of novel treatment modalities.

    “Witnessed medication taking followed by monitoring of effect on BP has been effective in identifying suspected nonadherence in trials of novel treatment modalities, although this approach has not been widely used in general practice.”

  • The paper relies on this without support.

    Medication Event Monitoring System monitoring has superior sensitivity compared with other methods.

    “Medication Event Monitoring System monitoring of the date and time that a medication bottle is opened and closed has superior sensitivity compared with other methods, although ingestion of the medication is not confirmed.”

  • The paper relies on this without support.

    Urine or blood measurement of drug or metabolites with mass spectroscopy reliably determines whether a drug is present or absent.

    “Urine or blood measurement of drug or metabolites with mass spectroscopy reliably determines whether a drug is present or absent but does not determine whether it was taken regularly or at a therapeutic level.”

  • The paper relies on this without support.

    There is no gold standard for measuring adherence.

    “There is no gold standard for measuring adherence.”

  • The paper relies on this without support.

    Indirect methods such as pill count, self-report, and prescription refill data are simple, inexpensive, and widely used, but can easily be manipulated to overestimate adherence.

    “Indirect methods such as pill count, self-report, and prescription refill data are simple, inexpensive, and widely used. However, they can easily be manipulated to overestimate adherence.”

  • The paper relies on this without support.

    A direct method such as urine or blood measurement of drug or metabolites is considered more robust but is relatively expensive, is of limited availability, and does not perfectly reflect level of adherence.

    “A direct method such as urine or blood measurement of drug or metabolites is considered more robust but is relatively expensive, is of limited availability, and does not perfectly reflect level of adherence.”

  • The paper relies on this without support.

    All methods for measuring adherence have limitations.

    “All methods have limitations, and ideally, accurate assessment of adherence should involve a combination of approaches.”

  • The paper relies on this without support.

    Factors contributing to poor adherence are myriad and multilevel.

    “Factors contributing to poor adherence are myriad and multilevel.”

  • The paper relies on this without support.

    Evidence specific to improving adherence in the resistant hypertension population is sparse.

    “Evidence specific to improving adherence in the RH population is sparse.”

  • The paper relies on this without support.

    No single intervention is uniquely effective, and a sustained approach using multiple strategies is likely to be most effective.

    “No single intervention is uniquely effective, and a sustained approach using multiple strategies, including health system solutions and those that target the individual patient’s barriers to adherence, is likely to be most effective.”

  • The paper relies on this without support.

    Cuff size, body and arm positions, and measurement environment affect the accuracy of blood pressure measurement.

    “However, cuff size, body and arm positions, and measurement environment are common features of auscultatory and oscillometric methods that affect the accuracy of BP measurement.”

  • The paper relies on this without support.

    Cuff-measured blood pressure may differ from intra-arterial pressure.

    “Cuff-measured BP may differ from intra-arterial pressure.”

  • The paper relies on this without support.

    Severe arterial stiffness or medial calcification of the brachial artery may result in inaccurate detection of Korotkoff sounds with auscultatory blood pressure measurement.

    “Severe arterial stiffness or medial calcification of the brachial artery may result in an inaccurate detection of Korotkoff sounds when BP is measured with the auscultatory method.”

  • The paper relies on this without support.

    The degree to which arterial stiffness or brachial artery calcification affects blood pressure measurement with oscillometric devices is suspected to be less pronounced.

    “The degree to which arterial stiffness or brachial artery calcification affects BP measurement with oscillometric devices has not been established but is suspected to be less pronounced.”

  • The paper relies on this without support.

    Short duration of hypertension and absence of diabetes mellitus or chronic kidney disease are associated with pseudoresistance from a white-coat effect.

    “Short duration of hypertension and the absence of diabetes mellitus or CKD are also associated with pseudoresistance from a white-coat effect.”

  • The paper relies on this without support.

    The white-coat effect can be easily identified by 24-hour ambulatory blood pressure monitoring.

    “The white-coat effect can be easily identified by 24-hour ABPM.”

  • The paper relies on this without support.

    Blood pressure measurement by automated office blood pressure attenuates the white-coat effect.

    “BP measurement by automated office BP attenuates the white-coat effect.”

  • The paper relies on this without support.

    Individuals may alter their blood pressure logs or underreport high or low blood pressure values.

    “However, it is important to consider that individuals may alter their BP logs or underreport high or low BP values.”

  • The paper relies on this without support.

    Suboptimal antihypertensive therapy accounts for a large subset of patients not achieving blood pressure targets.

    “Suboptimal antihypertensive therapy accounts for a large subset of patients not achieving BP targets (Figure 1).140”

  • The paper relies on this without support.

    Relatively large interindividual variations exist in salt sensitivity of blood pressure.

    “However, relatively large interindividual variations exist in “salt sensitivity” of BP.”

  • The paper relies on this without support.

    The effects of pharmacologic agents that increase blood pressure are highly individualized, with the majority of individuals manifesting little or no effect and others demonstrating severe elevations in blood pressure levels.

    “However, the effects of these agents are found to be highly individualized, with the majority of individuals manifesting little or no effect and others demonstrating severe elevations in BP levels.”

  • The paper relies on this without support.

    Sympathetic amines increase blood pressure by activation of the sympathetic nervous system.

    “Sympathetic amines increase BP by activation of the sympathetic nervous system.”

  • The paper relies on this without support.

    Cyclosporine and tacrolimus increase blood pressure by inducing systemic and renal vasoconstriction and sodium retention.

    “Cyclosporine and tacrolimus increase BP by inducing systemic and renal vasoconstriction and sodium retention.”

  • The paper relies on this without support.

    Chronic kidney disease is both a cause and a complication of poorly controlled hypertension.

    “CKD is both a cause and a complication of poorly controlled hypertension.”

  • The paper relies on this without support.

    Reduced kidney function results in impaired salt excretion, overactivation of the renin-angiotensin-aldosterone system, increased sympathetic nervous system activity, and altered medication efficacy.

    “Reduced kidney function results in impaired salt excretion, overactivation of the renin-angiotensin-aldosterone system, increased sympathetic nervous system activity, and altered medication efficacy.”

  • The paper relies on this without support.

    Pheochromocytoma and paraganglioma are rare even in the hypertensive population, with a prevalence estimated at 0.01% to 0.2%.

    “The chromaffin cell tumors, pheochromocytoma (adrenal catecholamine producing, 90%) and paraganglioma (extra-adrenal, sympathetic/parasympathetic derived, 10%), are rare even in the hypertensive population, with a prevalence estimated at 0.01% to 0.2%.”

  • The paper relies on this without support.

    One-third of pheochromocytoma/paraganglioma cases are inherited.

    “Given the high morbidity and mortality of not treating these tumors, the usual 3-year delay in diagnosis, and the fact that one-third are inherited, it is essential to consider the diagnosis in anyone referred for RH.”

  • The paper relies on this without support.

    Hypertensive patients frequently have elevated levels of catecholamine metabolites, especially in the presence of obesity and OSA and with the use of certain drugs such as tricyclic antidepressants.

    “Hypertensive patients frequently have elevated levels of catecholamine metabolites, especially in the presence of obesity and OSA and with the use of certain drugs such as tricyclic antidepressants.”

  • The paper relies on this without support.

    True resistant hypertension usually has multiple causes, including excessive dietary salt intake, obesity, CKD, and OSA.

    “True RH usually has multiple causes, including excessive dietary salt intake, obesity, CKD, and OSA.”

  • The paper relies on this without support.

    The specificity for a high aldosterone-to-renin ratio is low as a result of the common occurrence of low-renin states (eg, volume expansion, dietary salt excess or sensitivity).

    “The specificity for a high ARR is low as a result of the common occurrence of low-renin states (eg, volume expansion, dietary salt excess or sensitivity).”

  • The paper relies on this without support.

    Hydrochlorothiazide does not induce a predictable natriuresis below a GFR of 45 mL⋅min−1⋅1.73 m−2, but chlorthalidone induces natriuresis down to an eGFR of 30 mL⋅min−1⋅1.73 m−2.

    “Hydrochlorothiazide does not induce a predictable natriuresis below an GFR of 45 mL⋅min−1⋅1.73 m−2, but chlorthalidone induces natriuresis down to an eGFR of 30 mL⋅min−1⋅1.73 m−2.”

  • The paper relies on this without support.

    Most cases of resistant hypertension are linked to either volume excess, especially in CKD, or high sympathetic tone.

    “Because most cases of RH are linked to either volume excess, especially in CKD, or high sympathetic tone, establishment of the pathogenesis will optimally facilitate the choice of the fourth drug.”

  • The paper relies on this without support.

    With prolonged use at higher doses, gynecomastia and erectile dysfunction in men and menstrual irregularities in women may limit the use of spironolactone.

    “With prolonged use at higher doses, gynecomastia and erectile dysfunction in men and menstrual irregularities in women may limit the use of spironolactone.”

  • The paper relies on this without support.

    Because of its shorter half-life compared with spironolactone, eplerenone should be administered twice daily for optimal effect.

    “Because of its shorter half-life compared with spironolactone, eplerenone should be administered twice daily for optimal effect.”

  • The paper relies on this without support.

    Except for rare monogenetic causes, the pathophysiology of primary hypertension appears to be governed by a multiplicity of genes, each contributing only weak effects.

    “Except for the rare monogenetic causes, the pathophysiology of primary hypertension appears to be governed by a multiplicity of genes, each contributing only weak effects.”

  • The paper relies on this without support.

    The current approach to blood pressure control in resistant hypertension, focused on adding or substituting drugs or drug classes based on pharmacological principles, is only partially successful in true resistant hypertension.

    “Currently, the approach to BP control in RH has focused on the addition or substitution of drugs or drug classes based on meaningful pharmacological principles that are only partially successful in true RH.”

  • The paper relies on this without support.

    Validation of true benefit for device-based sympatholytic treatments has not been confirmed in rigorous, double-blind comparisons with sham intervention.

    “Although previously approved and used in different countries worldwide, validation of true benefit has not been confirmed in rigorous, double-blind comparisons with sham intervention.”
42 of 42

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The MR antagonist spironolactone is effective for treating patients with resistant hypertension who are usually overweight or obese and already on at least three antihypertensive drugs.

    “The landmark PATHWAY-2 trial85,86 clearly established that the MR antagonist spironolactone is effective for treating patients with resistant hypertension who are usually overweight or obese and already on at least three antihypertensive drugs87.”

    From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [87]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Patient count differs from the cited study title

    Minor

    The text describes the series cited as reference 306 as having 4494 patients, but the title of reference 306 says it included 4429 consecutively referred patients.

  • Obesity odds ratio falls outside its reported confidence interval

    Minor

    The reported odds ratio of 1.62 is outside its stated 95% confidence interval of 1.42-1.51. The interval therefore cannot describe that estimate.

2 of 2

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 3

  1. Proteus Digital Health. U.S. FDA accepts first digital medicine new drug application for Otsuka and Proteus Digital Health. http://www.proteus.com/press-releases/u-s-fda-accepts-first-digital-medicine-new-drug-application-for-otsuka-and-proteus-digital-health/. September 10 2015. Accessed January 5 2016.
  2. 10.1016/j.jval.2013.03.1631 · DOI · Paper page
  3. 10.1007/s11900 · DOI

Cited by

Sorted by citations

Related

Authors
Carey, R. M., Calhoun, D. A., Bakris, G. L., Brook, R. D., Daugherty, S. L., Dennison-Himmelfarb, C. R., Egan, B. M., Flack, J. M., Gidding, S. S., Judd, E., Lackland, D. T., Laffer, C. L., Newton-Cheh, C., Smith, S. M., Taler, S. J., Textor, S. C., Turan, T. N., White, W. B., & on behalf of the American Heart Association Professional/Public Education and Publications Committee of the Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Genomic and Precision Medicine; Council on Peripheral Vascular Disease; Council on Quality of Care and Outcomes Research; and Stroke Council
ORCID
Venue
Hypertension
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2018-11
Volume
72
Issue
5
Pages
e53-e90
ISSN
  • 0194-911X (ISSN-L)
  • 1524-4563
DOI
10.1161/hyp.0000000000000084
PMC
PMC6530990
OpenAlex
W2896865390
Semantic Scholar
7bc2c45787107f8db70d5450bd091d6280e73dd3
Cited by
1,153
References
420
Citations by year
2026: 164 · 2025: 159 · 2024: 154 · 2023: 183 · 2022: 151 · 2021: 129 · 2020: 120 · 2019: 82 · 2018: 8 · 2013: 1
FWCI
64.03
Type
journal article
Language
en
Open access
Locations
  • Hypertension (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (K23DK102660)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
  • Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
Keywords
resistant hypertension, blood pressure control, antihypertensive medication adherence, white coat effect, out-of-office blood pressure, secondary hypertension, target organ damage, thiazide-like diuretics, chlorthalidone, indapamide, mineralocorticoid receptor antagonists, spironolactone, eplerenone, renin-angiotensin system blockade, lifestyle modification
MeSH terms
American Heart Association, Antihypertensive Agents, Blood Pressure, Humans, Hypertension, United States, Disease Management

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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