New perspectives on the definition, diagnosis, and treatment of true arterial hypertension

ABSTRACT Introduction Office blood pressure measurements (OBPM), still used today for diagnosis and management of hypertension, fail to reveal clinically important features of the mostly predictable blood pressure (BP) 24 h pattern, and lead to >45% of individuals being misclassified. Current hypertension guidelines do not provide recommendation on when-to-treat, despite multiple prospective clinical trials documenting improved normalization of 24 h BP pattern and significant reduction in cardiovascular disease (CVD) events when hypertension medications are ingested at bedtime rather than upon waking. Areas covered In this review, the authors discuss current evidence on the: (i) most relevant attributes of the 24 h BP pattern deterministic of CVD risk; (ii) asleep systolic BP (SBP) mean as the most significant therapeutic target for CVD risk reduction; (iii) ingestion-time differences in pharmacodynamics of BP-lowering medications as reported with high consistency in multiple clinical trials; and (iv) enhanced prevention of CVD events achieved by bedtime hypertension chronotherapy. Expert opinion Several prospective trials consistently document asleep SBP mean and sleep-time relative SBP decline (dipping) constitute highly significant CVD risk factors, independent of OBPM. Bedtime, compared to customary upon-waking, hypertension chronotherapy reduces risk of major CVD events. Collectively, these findings call for new definition of true hypertension and, accordingly, its proper diagnosis and management.

[1]  S. Prabhu,et al.  Chronobiological Influence Over Cardiovascular Function: The Good, the Bad, and the Ugly. , 2020, Circulation research.

[2]  R. Hermida,et al.  Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial. , 2019, European heart journal.

[3]  F. Cosentino,et al.  The 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. , 2019, European heart journal.

[4]  Yoshihiko Kanno,et al.  The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019) , 2019, Hypertension Research.

[5]  M. Smolensky,et al.  Diagnosis and management of hypertension: around-the-clock ambulatory blood pressure monitoring is substantially more effective and less costly than daytime office blood pressure measurements , 2019, Chronobiology international.

[6]  E. O’Brien,et al.  Association of Office and Ambulatory Blood Pressure With Mortality and Cardiovascular Outcomes. , 2019, JAMA.

[7]  Kui Yang,et al.  Valsartan chronotherapy reverts the non-dipper pattern and improves blood pressure control through mediation of circadian rhythms of the renin-angiotensin system in spontaneous hypertension rats , 2019, Chronobiology international.

[8]  T. Lüscher Dangerous encounters: triggers of fatal ventricular arrhythmias and safety of interventional treatment strategies. , 2018, European heart journal.

[9]  D. Thompson,et al.  Randomized Crossover Trial of the Impact of Morning or Evening Dosing of Antihypertensive Agents on 24-Hour Ambulatory Blood Pressure: The HARMONY Trial , 2018, Hypertension.

[10]  G. Bakris,et al.  Has the Sun Set on Nighttime Dosing in Uncomplicated Hypertension? , 2018, HYPERTENSION.

[11]  Thomas Kahan,et al.  [2018 ESC/ESH Guidelines for the management of arterial hypertension. The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH)]. , 2018, Giornale italiano di cardiologia.

[12]  S. Shea,et al.  Chronotherapy for Hypertension , 2018, Current Hypertension Reports.

[13]  G. Lip,et al.  2018 ESC/ESH Guidelines for the management of arterial hypertension. , 2018, European heart journal.

[14]  R. Hermida,et al.  Asleep blood pressure: significant prognostic marker of vascular risk and therapeutic target for prevention , 2018, European heart journal.

[15]  Jackson T. Wright,et al.  2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. , 2018, Journal of the American College of Cardiology.

[16]  Alexander G Logan,et al.  Hypertension Canada's 2018 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults and Children. , 2018, The Canadian journal of cardiology.

[17]  R. Hermida,et al.  Risk of incident chronic kidney disease is better reduced by bedtime than upon-awakening ingestion of hypertension medications , 2018, Hypertension Research.

[18]  J. Jeppesen,et al.  Office blood pressure or ambulatory blood pressure for the prediction of cardiovascular events , 2017, European heart journal.

[19]  M. Smolensky,et al.  Circadian mechanisms of 24-hour blood pressure regulation and patterning. , 2017, Sleep medicine reviews.

[20]  R. Hermida Sleep-time ambulatory blood pressure as a prognostic marker of vascular and other risks and therapeutic target for prevention by hypertension chronotherapy: Rationale and design of the Hygia Project , 2016, Chronobiology international.

[21]  M. Smolensky,et al.  Chronotherapy with conventional blood pressure medications improves management of hypertension and reduces cardiovascular and stroke risks , 2016, Hypertension Research.

[22]  K. Kario,et al.  Prognostic Effect of the Nocturnal Blood Pressure Fall in Hypertensive Patients: The Ambulatory Blood Pressure Collaboration in Patients With Hypertension (ABC-H) Meta-Analysis. , 2016, Hypertension.

[23]  D. Webb,et al.  Methods of a large prospective, randomised, open-label, blinded end-point study comparing morning versus evening dosing in hypertensive patients: the Treatment In Morning versus Evening (TIME) study , 2016, BMJ Open.

[24]  R. Hermida,et al.  Bedtime ingestion of hypertension medications reduces the risk of new-onset type 2 diabetes: a randomised controlled trial , 2016, Diabetologia.

[25]  M. Smolensky,et al.  Ambulatory Blood Pressure Monitoring (ABPM) as the reference standard for diagnosis of hypertension and assessment of vascular risk in adults , 2015, Chronobiology international.

[26]  M. Smolensky,et al.  Ambulatory Blood Pressure Monitoring (ABPM) as THE reference standard to confirm diagnosis of hypertension in adults: Recommendation of the 2015 U.S. Preventive Services Task Force (USPSTF) , 2015, Chronobiology international.

[27]  F. Miller,et al.  Ethical complexities in standard of care randomized trials: A case study of morning versus nighttime dosing of blood pressure drugs , 2015, Clinical trials.

[28]  M. Smolensky,et al.  Nocturnal light pollution and underexposure to daytime sunlight: Complementary mechanisms of circadian disruption and related diseases , 2015, Chronobiology international.

[29]  Jiguang Wang Chinese Hypertension Guidelines , 2015, Pulse.

[30]  Evelyn P Whitlock,et al.  Diagnostic and Predictive Accuracy of Blood Pressure Screening Methods With Consideration of Rescreening Intervals: A Systematic Review for the U.S. Preventive Services Task Force , 2015, Annals of Internal Medicine.

[31]  G. Parati,et al.  Evening versus morning dosing of antihypertensive drugs in hypertensive patients with sleep apnoea: a cross-over study , 2015, Journal of hypertension.

[32]  P. Palatini,et al.  Time of administration important? Morning versus evening dosing of valsartan , 2015, Journal of hypertension.

[33]  M. Smolensky,et al.  Bedtime hypertension chronotherapy: concepts and patient outcomes. , 2014, Current pharmaceutical design.

[34]  G. Pucci,et al.  Antihypertensive drug treatment and circadian blood pressure rhythm: a review of the role of chronotherapy in hypertension. , 2014, Current pharmaceutical design.

[35]  Jerrica E. Shuster,et al.  Treatment of Hypertension With Chronotherapy , 2014, The Annals of pharmacotherapy.

[36]  K. Kario,et al.  Prognostic impact from clinic, daytime, and night-time systolic blood pressure in nine cohorts of 13 844 patients with hypertension , 2014, Journal of hypertension.

[37]  Hong Yuan,et al.  Evening -Versus Morning- Dosing Drug Therapy for Chronic Kidney Disease Patients with Hypertension: A Systematic Review , 2014, Kidney and Blood Pressure Research.

[38]  J. Kostis,et al.  Evening Dosing of Antihypertensive Therapy to Reduce Cardiovascular Events: A Third Type of Evidence Based on a Systematic Review and Meta‐Analysis of Randomized Trials , 2014, Journal of clinical hypertension.

[39]  M. Gruchała,et al.  Mortality in hypertensive patients with coronary heart disease depends on chronopharmacotherapy and dipping status , 2014, Pharmacological reports : PR.

[40]  Brian M. Gryzlak,et al.  Efficacy and Safety of Nighttime Dosing of Antihypertensives: Review of the Literature and Design of a Pragmatic Clinical Trial , 2014, Journal of clinical hypertension.

[41]  F. Portaluppi,et al.  Circadian rhythms and medical diseases: does it matter when drugs are taken? , 2013, European journal of internal medicine.

[42]  E. Haus,et al.  2013 Ambulatory Blood Pressure Monitoring Recommendations for the Diagnosis of Adult Hypertension, Assessment of Cardiovascular and other Hypertension-associated Risk, and Attainment of Therapeutic Goals , 2013, Chronobiology international.

[43]  R. Hermida,et al.  Blunted Sleep-Time Relative Blood Pressure Decline Increases Cardiovascular Risk Independent of Blood Pressure Level—The “Normotensive Non-dipper” Paradox , 2013, Chronobiology international.

[44]  R. Hermida,et al.  Ambulatory Blood Pressure Monitoring: Importance of Sampling Rate and Duration—48 Versus 24 Hours—on the Accurate Assessment of Cardiovascular Risk , 2013, Chronobiology international.

[45]  R. Hermida,et al.  Cardiovascular Risk of Essential Hypertension: Influence of Class, Number, and Treatment-Time Regimen of Hypertension Medications , 2013, Chronobiology international.

[46]  M. Smolensky,et al.  Dipper and Non-Dipper Blood Pressure 24-Hour Patterns: Circadian Rhythm–Dependent Physiologic and Pathophysiologic Mechanisms , 2013, Chronobiology international.

[47]  José R Fernández,et al.  Cardiovascular Risk of Resistant Hypertension: Dependence on Treatment-Time Regimen of Blood Pressure–Lowering Medications , 2013, Chronobiology international.

[48]  M. Smolensky,et al.  Administration-Time Differences in Effects of Hypertension Medications on Ambulatory Blood Pressure Regulation , 2013, Chronobiology international.

[49]  Atlanta,et al.  A Trial of 2 Strategies to Reduce Nocturnal Blood Pressure in Blacks with Chronic Kidney Disease Clinical Trial: African American Study of Kidney Disease , 2022 .

[50]  Jun Zhang,et al.  Effect of Valsartan With Bedtime Dosing on Chronic Kidney Disease Patients With Nondipping Blood Pressure Pattern , 2013, Journal of clinical hypertension.

[51]  K. Kario,et al.  A Bedtime Dose of ARB Was Better than a Morning Dose in Improving Baroreflex Sensitivity and Urinary Albumin Excretion—The J-TOP Study , 2012, Clinical and experimental hypertension.

[52]  Francesco Portaluppi,et al.  Circadian rhythms and cardiovascular health. , 2012, Sleep medicine reviews.

[53]  R. Hermida,et al.  Bedtime dosing of antihypertensive medications reduces cardiovascular risk in CKD. , 2011, Journal of the American Society of Nephrology : JASN.

[54]  C. Wan,et al.  Evening versus morning dosing regimen drug therapy for hypertension. , 2011, The Cochrane database of systematic reviews.

[55]  Giuseppe Conte,et al.  Prognostic role of ambulatory blood pressure measurement in patients with nondialysis chronic kidney disease. , 2011, Archives of internal medicine.

[56]  R. Hermida,et al.  Decreasing sleep-time blood pressure determined by ambulatory monitoring reduces cardiovascular risk. , 2011, Journal of the American College of Cardiology.

[57]  R. Hermida,et al.  Influence of Time of Day of Blood Pressure–Lowering Treatment on Cardiovascular Risk in Hypertensive Patients With Type 2 Diabetes , 2011, Diabetes Care.

[58]  Rachel D. Vanderlaan,et al.  The primary benefits of angiotensin-converting enzyme inhibition on cardiac remodeling occur during sleep time in murine pressure overload hypertrophy. , 2011, Journal of the American College of Cardiology.

[59]  M. Smolensky,et al.  Circadian rhythms in blood pressure regulation and optimization of hypertension treatment with ACE inhibitor and ARB medications. , 2011, American journal of hypertension.

[60]  B. Okeahialam,et al.  Chronotherapy in Nigerian hypertensives , 2011, Therapeutic advances in cardiovascular disease.

[61]  H. Matsubara,et al.  The Bedtime Administration Ameliorates Blood Pressure Variability and Reduces Urinary Albumin Excretion in Amlodipine-Olmesartan Combination Therapy , 2010, Clinical and experimental hypertension.

[62]  E. O’Brien,et al.  Prognostic value of isolated nocturnal hypertension on ambulatory measurement in 8711 individuals from 10 populations , 2010, Journal of hypertension.

[63]  R. Hermida,et al.  INFLUENCE OF CIRCADIAN TIME OF HYPERTENSION TREATMENT ON CARDIOVASCULAR RISK: RESULTS OF THE MAPEC STUDY , 2010, Chronobiology international.

[64]  Francesco Portaluppi,et al.  Administration–time-dependent effects of blood pressure-lowering medications: basis for the chronotherapy of hypertension , 2010, Blood pressure monitoring.

[65]  K. Kario,et al.  Effect of dosing time of angiotensin II receptor blockade titrated by self-measured blood pressure recordings on cardiorenal protection in hypertensives: the Japan Morning Surge-Target Organ Protection (J-TOP) study , 2010, Journal of hypertension.

[66]  T. Ogihara,et al.  The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009) , 2009, Hypertension Research.

[67]  M. Sole,et al.  The Role of Clock Genes in Cardiometabolic Disease Diurnal physiology : core principles with application to the pathogenesis , diagnosis , prevention , and treatment of myocardial hypertrophy and failure , 2009 .

[68]  Charles A Czeisler,et al.  Effect of Light on Human Circadian Physiology. , 2009, Sleep Medicine Clinics.

[69]  N J Wald,et al.  Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies , 2009, BMJ : British Medical Journal.

[70]  E. Muxfeldt,et al.  Prognostic influence of office and ambulatory blood pressures in resistant hypertension. , 2008, Archives of internal medicine.

[71]  R. Hermida,et al.  Chronotherapy with nifedipine GITS in hypertensive patients: improved efficacy and safety with bedtime dosing. , 2008, American journal of hypertension.

[72]  Kazuomi Kario,et al.  Ambulatory blood pressure is a better marker than clinic blood pressure in predicting cardiovascular events in patients with/without type 2 diabetes. , 2008, American journal of hypertension.

[73]  Jan A. Staessen,et al.  Daytime and Nighttime Blood Pressure as Predictors of Death and Cause-Specific Cardiovascular Events in Hypertension , 2008, Hypertension.

[74]  R. Minutolo,et al.  Changing the timing of antihypertensive therapy to reduce nocturnal blood pressure in CKD: an 8-week uncontrolled trial. , 2007, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[75]  Yan Li,et al.  Prognostic accuracy of day versus night ambulatory blood pressure: a cohort study , 2007, The Lancet.

[76]  Francesco Portaluppi,et al.  Role of sleep-wake cycle on blood pressure circadian rhythms and hypertension. , 2007, Sleep medicine.

[77]  Francesco Portaluppi,et al.  Circadian variation of blood pressure: the basis for the chronotherapy of hypertension. , 2007, Advanced drug delivery reviews.

[78]  Michael Bursztyn,et al.  Predictors of All-Cause Mortality in Clinical Ambulatory Monitoring: Unique Aspects of Blood Pressure During Sleep , 2007, Hypertension.

[79]  A. Dominiczak,et al.  2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) , 2007, European heart journal.

[80]  N. Cook Use and Misuse of the Receiver Operating Characteristic Curve in Risk Prediction , 2007, Circulation.

[81]  R. Hermida,et al.  Treatment of non-dipper hypertension with bedtime administration of valsartan , 2005, Journal of hypertension.

[82]  R. Hermida,et al.  Decrease in Urinary Albumin Excretion Associated With the Normalization of Nocturnal Blood Pressure in Hypertensive Subjects , 2005, Hypertension.

[83]  Alice Stanton,et al.  Superiority of Ambulatory Over Clinic Blood Pressure Measurement in Predicting Mortality: The Dublin Outcome Study , 2005, Hypertension.

[84]  R. Hermida,et al.  Chronotherapy Improves Blood Pressure Control and Reverts the Nondipper Pattern in Patients With Resistant Hypertension , 2008, Hypertension.

[85]  Peter W de Leeuw,et al.  Prognostic value of ambulatory blood-pressure recordings in patients with treated hypertension. , 2003, The New England journal of medicine.

[86]  Peter Sleight,et al.  Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. , 2003, JAMA.

[87]  M. Kikuya,et al.  Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study , 2002, Journal of hypertension.

[88]  U. de Faire,et al.  Comparative Effects of Ramipril on Ambulatory and Office Blood Pressures: A HOPE Substudy , 2001, Hypertension.

[89]  R. Hermida,et al.  Day-Night Variations in Blood Levels of Nitric Oxide, T-TFPI, and E-Selectin , 2001, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[90]  S. Yusuf,et al.  Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. , 2000 .

[91]  J A Staessen,et al.  Comparison of active treatment and placebo in older Chinese patients with isolated systolic hypertension , 1998, Journal of hypertension.

[92]  H. Black,et al.  Comparison of effects of controlled onset extended release verapamil at bedtime and nifedipine gastrointestinal therapeutic system on arising on early morning blood pressure, heart rate, and the heart rate-blood pressure product. , 1998, The American journal of cardiology.

[93]  Jan A Staessen,et al.  Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension , 1997, The Lancet.

[94]  G. Reboldi,et al.  Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension. , 1994, Hypertension.

[95]  Lianqun Cui,et al.  Effect of bedtime administration of blood-pressure lowering agents on ambulatory blood pressure monitoring results: A meta-analysis. , 2016, Cardiology journal.

[96]  Tsung-Hsien Lin,et al.  2015 guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society for the management of hypertension. , 2015, Journal of the Chinese Medical Association : JCMA.

[97]  K. Shimamoto The Japanese Society of Hypertension Guidelines for the Management of Hypertension 2014 (JSH2014) , 2014 .

[98]  R. Sothern,et al.  Temporal (circadian) and functional relationship between atrial natriuretic peptides and blood pressure. , 1995, Chronobiology international.

[99]  A. Angeli,et al.  Chronobiology of the Hypothalamic-Pituitary-Adrenal and Renin-Angiotensin-Aldosterone Systems , 1992 .

[100]  F. Halberg,et al.  Circadian characteristics of urinary epinephrine and norepinephrine from healthy young women in Japan and U.S.A. , 1986, Chronobiology international.