Elevated asleep blood pressure and non-dipper 24h patterning best predict risk for heart failure that can be averted by bedtime hypertension chronotherapy: A review of the published literature.

Several prospective studies consistently report elevated asleep blood pressure (BP) and blunted sleep-time relative systolic BP (SBP) decline (non-dipping) are jointly the most significant prognostic markers of cardiovascular disease (CVD) risk, including heart failure (HF); therefore, they, rather than office BP measurements (OBPM) and ambulatory awake and 24 h BP means, seemingly are the most worthy therapeutic targets for prevention. Published studies of the 24 h BP pattern in HF are sparse in number and of limited sample size. They report high prevalence of the abnormal non-dipper/riser 24 h SBP patterning. Despite the established clinical relevance of the asleep BP, past as do present hypertension guidelines recommend the diagnosis of hypertension rely on OBPM and, when around-the-clock ambulatory BP monitoring (ABPM) is conducted to confirm the elevated OBPM, either on the derived 24 h or "daytime" BP means. Additionally, hypertension guidelines do not advise the time-of-day when BP-lowering medications should be ingested, in spite of known ingestion-time differences in their pharmacokinetics and pharmacodynamics. Between 1976 and 2020, 155 unique trials of ingestion-time differences in the effects of 37 different single and 14 dual-combination hypertension medications, collectively involving 23,972 patients, were published. The vast majority (83.9%) of them found the at-bedtime/evening in comparison to upon-waking/morning treatment schedule resulted in more greatly enhanced: (i) reduction of asleep BP mean without induced sleep-time hypotension; (ii) reduction of the prevalence of the higher CVD risk non-dipper/riser 24 h BP phenotypes; (iii) improvement of kidney function, reduction of cardiac pathology, and with lower incidence of adverse effects. Most notably, no single published randomized trial found significantly better BP-lowering, particularly during sleep, or medical benefits of the most popular upon-waking/morning hypertension treatment-time scheme. Additionally, prospective outcome trials have substantiated that the bedtime relative to the upon-waking, ingestion of BP-lowering medications not only significantly reduces risk of HF but also improves overall CVD event-free survival time.

Optimización del control telemático de la presión arterial en atención primaria en España (Iniciativa Óptima): resultados de un estudio Delphi / Optimizing blood pressure control through telemedicine in Primary Care in Spain (Iniciativa Óptima): Results from a Delphi study

Objetivo: Representantes de los grupos de trabajo de hipertensión o enfermedad cardiovascular de las Sociedades Españolas de Médicos de Atención Primaria (MAP) [SEMERGEN], de Medicina Familiar y Comunitaria [semFYC] y de Médicos Generales y de Familia [SEMG] realizaron un estudio Delphi para validar con un panel de MAP expertos en hipertensión una propuesta de recomendaciones para optimizar la teleconsulta en pacientes hipertensos. Materiales y métodos: Estudio Delphi basado en un cuestionario online con 59 recomendaciones, elaborado en base a la bibliografía relacionada disponible y a la experiencia clínica aportada por los autores. Resultados: Un total de 118 MAP participaron en dos rondas del cuestionario (98,3% de los invitados), alcanzándose el consenso en 53/62 sentencias (85%). El equipo de Atención Primaria debe seleccionar a los pacientes hipertensos candidatos a realizar la consulta telemática proactivamente, informando de la cita con antelación. Al iniciar la consulta telemática, se recomienda explicar el motivo y los objetivos de la misma, y realizar la anamnesis preguntando por signos y síntomas de empeoramiento de la enfermedad, tratamientos actuales y adherencia a los mismos. En pacientes con una automedida de la presión arterial (AMPA) ≤135/85mmHg se recomienda pautar una nueva cita telemática en 3-6meses. Por el contrario, en pacientes asintomáticos que reporten una AMPA ≥135/85mmHg se recomienda la monitorización ambulatoria de la presión arterial, modificar el tratamiento, o derivar al paciente a visita presencial o al hospital en caso de signos o síntomas de alarma. Conclusiones: La teleconsulta puede complementar la consulta presencial, constituyendo un elemento más a tener en cuenta para el adecuado control de los pacientes hipertensos.(AU)

Aim: Members of the working groups on hypertension or cardiovascular disease of the Spanish Societies of Primary Care Physicians (PCPs) [SEMERGEN], Family and Community Medicine [semFYC] and General and Family Physicians [SEMG], conducted a Delphi study to validate with a panel of PCPs with expertise in hypertension several recommendations to optimize teleconsultation in hypertensive patients. Materials and methods: Delphi study based on an online questionnaire with 59 recommendations based on the available evidence and the clinical experience of the authors. Results: 118 PCPs participated in two rounds of the questionnaire (98.3% of the invited physicians), reaching consensus in 53/62 statements (85%). The Primary Care team must proactively select the hypertensive patients suitable for telematic consultation and contact them to set up an appointment. Telematic consultation must begin explaining the reason and aims pursued, continuing with anamnesis, which must explore signs and symptoms of disease worsening, current treatments and level of adherence. In patients with a home blood pressure measurement (HBPM) ≤135/85mmHg, it is recommended to schedule a new telematic appointment in 3-6months. On the contrary, asymptomatic patients with a HBPM ≥135/85mmHg should undergo ambulatory blood pressure monitoring, treatment modification or, in case of warning signs or symptoms, referral to a face-to-face visit or to emergency department. Conclusions: Teleconsultation can complement face-to-face consultation, constituting an additional tool for the appropriate follow-up of hypertensive patients.(AU)

[Optimizing blood pressure control through telemedicine in Primary Care in Spain (Iniciativa Óptima): Results from a Delphi study]. / Optimización del control telemático de la presión arterial en atención primaria en España (Iniciativa Óptima): resultados de un estudio Delphi.

AIM: Members of the working groups on hypertension or cardiovascular disease of the Spanish Societies of Primary Care Physicians (PCPs) [SEMERGEN], Family and Community Medicine [semFYC] and General and Family Physicians [SEMG], conducted a Delphi study to validate with a panel of PCPs with expertise in hypertension several recommendations to optimize teleconsultation in hypertensive patients. MATERIALS AND METHODS: Delphi study based on an online questionnaire with 59 recommendations based on the available evidence and the clinical experience of the authors. RESULTS: 118 PCPs participated in two rounds of the questionnaire (98.3% of the invited physicians), reaching consensus in 53/62 statements (85%). The Primary Care team must proactively select the hypertensive patients suitable for telematic consultation and contact them to set up an appointment. Telematic consultation must begin explaining the reason and aims pursued, continuing with anamnesis, which must explore signs and symptoms of disease worsening, current treatments and level of adherence. In patients with a home blood pressure measurement (HBPM) ≤135/85mmHg, it is recommended to schedule a new telematic appointment in 3-6months. On the contrary, asymptomatic patients with a HBPM ≥135/85mmHg should undergo ambulatory blood pressure monitoring, treatment modification or, in case of warning signs or symptoms, referral to a face-to-face visit or to emergency department. CONCLUSIONS: Teleconsultation can complement face-to-face consultation, constituting an additional tool for the appropriate follow-up of hypertensive patients.

Cardiovascular disease risk stratification by the Framigham score is markedly improved by ambulatory compared with office blood pressure.

INTRODUCTION AND OBJECTIVES: Ambulatory blood pressure (BP) better predicts cardiovascular disease (CVD) outcomes than office BP measurements (OBPM). Nonetheless, current CVD risk stratification models continue to rely on exclusively daytime OBPM along with traditional factors, eg, age, sex, smoking, dyslipidemia, and/or diabetes. METHODS: Data from 19 949 participants of the primary care-based Hygia Project assessed by 48-hour ambulatory BP monitoring (ABPM) and without prior CVD events were used to compare the diagnostic accuracy, discrimination, and performance of the original Framingham risk score (RSOFG) and its adjusted version to the Hygia Project study population (RSAFG) with that of a novel CVD risk stratification model constructed by replacing OBPM with ABPM-derived prognostic parameters (RSABPM). RESULTS: During the follow-up, lasting up to 12.7 years, 1854 participants experienced a primary CVD outcome of CVD death, myocardial infarction, coronary revascularization, heart failure, stroke, transient ischemic attack, angina pectoris, or peripheral artery disease. Asleep systolic BP (SBP) mean and sleep-time relative SBP decline were the only joint significant ABPM-derived predictive factors of CVD risk and were therefore used to substitute for in-clinic SBP in the RSABPM model. The RSABPM model, in comparison with the RSOFG and RSAFG models, showed significantly improved calibration, diagnostic accuracy, discrimination, and performance (always P<.001). The RSAFG-derived event-probabilities of 57.3% of the participants were outside the 95% confidence limits of the event probability determined by the RSABPM model. CONCLUSIONS: These collective findings reveal important limitations of CVD risk stratification when based upon OBPM, as in the Framingham score, and corroborate the clinical value of around-the-clock ABPM to properly diagnose true hypertension and reliably stratify CVD vulnerability.

Does Timing of Antihypertensive Medication Dosing Matter?

PURPOSE OF REVIEW: Current hypertension guidelines do not provide recommendation on when-to-treat. Herein, we review the current evidence on ingestion-time differences of hypertension medications in blood pressure (BP)-lowering effects and prevention of cardiovascular disease (CVD) events. RECENT FINDINGS: The vast (81.6%) majority of the 136 published short-term treatment-time trials document benefits, including enhanced reduction of asleep BP and increased sleep-time relative BP decline (dipping), when hypertension medications and their combinations are ingested before sleep rather than upon waking. Long-term outcome trials further document bedtime hypertension therapy markedly reduces risk of major CVD events. The inability of the very small 18.4% of the published trials to substantiate treatment-time difference in effects is mostly explained by deficiencies of study design and conduct. Our comprehensive review of the published literature reveals no single study has reported better benefits of the still conventional, yet scientifically unjustified, morning than bedtime hypertension treatment scheme.

The Hygia Project and Hygia Chronotherapy Trial: insights of we clinical investigators on the impact of the embedded continuing medical education on primary-care practice and improved patient cardiovascular health.

The participating doctors of the Hygia Chronotherapy Trial (HCT) are aware of the criticisms of its published findings, which have been unjustifiably misrepresented in letters to the editors and commentaries, perhaps because of lack of understanding of the foundations of the Hygia Project, in which the HCT is nested. Thus, our purpose through this communication is to highlight the unique features of the Hygia Project and HCT in terms of: (i) organization, management, and quality control, (ii) physician training/continuing medical education, and (iii) impact on every-day primary-care clinical practice specifically improved patient care through 48 h ambulatory blood pressure monitoring to diagnose and optimally manage by bedtime hypertension chronotherapy true arterial hypertension to markedly improve the cardiovascular health of our patients.

Bedtime hypertension chronotherapy best reduces cardiovascular disease risk as corroborated by the Hygia Chronotherapy Trial. Rebuttal to European Society of Hypertension officials.

Reinhold Kreutz and colleagues in a recent editorial claim the Hygia Chronotherapy Trial lacks credibility because of deficient methods, thereby dismissing both the plausibility and clinical significance of its reported findings. They misstate and misrepresent crucial information, findings and conclusions unambiguously detailed in the published report of the Hygia Chronotherapy Trial. The purpose of this communication is to provide a complete rebuttal to each and every one of the misleading and scientifically unsupported claims by Kreutz et al. that calls into question their expertise to decry the merits, advantages, limitations and validity of correctly designed and conducted ambulatory blood pressure monitoring-based chronotherapy trials.

Ambulatory blood pressure monitoring-based definition of true arterial hypertension.

Daytime office blood pressure measurements (OBPM), still recommended and utilized today for diagnosis and management of hypertension and categorization of cardiovascular disease (CVD) risk, fail to reveal clinically important features of the mostly predictable BP 24 h pattern and leads to a large proportion of individuals being misclassified. Most clinical guidelines now recommend ambulatory BP monitoring (ABPM) be applied to adult patients to confirm the OBPM-based diagnosis of hypertension, based on the high prevalence of masked hypertension and masked normotension plus demonstrated significantly better CVD prognostic value of around-the-clock ABPM than daytime OBPM. Nonetheless, there is yet no consensus of which parameter(s) and ABPM thresholds to utilize to diagnose hypertension. Findings of large prospective ABPM-based CVD outcome trials permit prospective evaluation of treatment and other induced changes in OBPM and ABPM during follow-up on CVD risk by incorporating multiple periodic (at least annual) patient ABPM assessments. They indicate: 1) asleep systolic BP (SBP) mean and sleep-time relative SBP decline (dipping) together are the most significant and only BP-derived prognostic markers of CVD risk; accordingly, around-the-clock ABPM should be the recommended method to diagnose true arterial hypertension and accurately assess CVD risk; and (2) treatment-induced lowering of the asleep SBP mean and rise of the sleep-time relative SBP decline towards the normal dipper BP pattern are both significantly protective against CVD events, thus constituting novel therapeutic targets to substantially better reduce CVD risk compared to the traditional approach that targets control of daytime OBPM or awake BP mean.

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

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.

Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial.

AIMS: The Hygia Chronotherapy Trial, conducted within the clinical primary care setting, was designed to test whether bedtime in comparison to usual upon awakening hypertension therapy exerts better cardiovascular disease (CVD) risk reduction. METHODS AND RESULTS: In this multicentre, controlled, prospective endpoint trial, 19 084 hypertensive patients (10 614 men/8470 women, 60.5 ± 13.7 years of age) were assigned (1:1) to ingest the entire daily dose of ≥1 hypertension medications at bedtime (n = 9552) or all of them upon awakening (n = 9532). At inclusion and at every scheduled clinic visit (at least annually) throughout follow-up, ambulatory blood pressure (ABP) monitoring was performed for 48 h. During the 6.3-year median patient follow-up, 1752 participants experienced the primary CVD outcome (CVD death, myocardial infarction, coronary revascularization, heart failure, or stroke). Patients of the bedtime, compared with the upon-waking, treatment-time regimen showed significantly lower hazard ratio-adjusted for significant influential characteristics of age, sex, type 2 diabetes, chronic kidney disease, smoking, HDL cholesterol, asleep systolic blood pressure (BP) mean, sleep-time relative systolic BP decline, and previous CVD event-of the primary CVD outcome [0.55 (95% CI 0.50-0.61), P < 0.001] and each of its single components (P < 0.001 in all cases), i.e. CVD death [0.44 (0.34-0.56)], myocardial infarction [0.66 (0.52-0.84)], coronary revascularization [0.60 (0.47-0.75)], heart failure [0.58 (0.49-0.70)], and stroke [0.51 (0.41-0.63)]. CONCLUSION: Routine ingestion by hypertensive patients of ≥1 prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in improved ABP control (significantly enhanced decrease in asleep BP and increased sleep-time relative BP decline, i.e. BP dipping) and, most importantly, markedly diminished occurrence of major CVD events. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT00741585.

Asleep blood pressure: significant prognostic marker of vascular risk and therapeutic target for prevention.

Aims: Sleep-time blood pressure (BP) is a stronger risk factor for cardiovascular disease (CVD) events than awake and 24 h BP means, but the potential role of asleep BP as therapeutic target for diminishing CVD risk is uncertain. We investigated whether CVD risk reduction is most associated with progressive decrease of either office or ambulatory awake or asleep BP mean. Methods and results: We prospectively evaluated 18 078 individuals with baseline ambulatory BP ranging from normotension to hypertension. At inclusion and at scheduled visits (mainly annually) during follow-up, ambulatory BP was measured for 48 consecutive hours. During the 5.1-year median follow-up, 2311 individuals had events, including 1209 experiencing the primary outcome (composite of CVD death, myocardial infarction, coronary revascularization, heart failure, and stroke). The asleep systolic blood pressure (SBP) mean was the most significant BP-derived risk factor for the primary outcome [hazard ratio 1.29 (95% CI) 1.22-1.35 per SD elevation, P < 0.001], regardless of office [1.03 (0.97-1.09), P = 0.32], and awake SBP [1.02 (0.94-1.10), P = 0.68]. Most important, the progressive attenuation of asleep SBP was the most significant marker of event-free survival [0.75 (95% CI 0.69-0.82) per SD decrease, P < 0.001], regardless of changes in office [1.07 (0.97-1.17), P = 0.18], or awake SBP mean [0.96 (0.85-1.08), P = 0.47] during follow-up. Conclusion: Asleep SBP is the most significant BP-derived risk factor for CVD events. Furthermore, treatment-induced decrease of asleep, but not awake SBP, a novel hypertension therapeutic target requiring periodic patient evaluation by ambulatory monitoring, is associated with significantly lower risk for CVD morbidity and mortality.

Perception of health and understanding of cardiovascular risk among patients with recently diagnosed diabetes and/or metabolic syndrome.

BACKGROUND: Cardiovascular (CV) disease mortality is increased in diabetes mellitus (DM) and metabolic syndrome (MS), conditions which share CV risk factors. AIM: The purpose of this study was to assess understanding of CV risk by patients with DM and/or MS diagnosed less than 1 year before and seen in primary care. Perception by these patients of their health state is also analysed. DESIGN: A multicentre, observational study in subjects diagnosed with DM diagnosed less than 1 year before and/or with MS, in whom agreement between CV risk perceived by patients and assessed by physicians was analysed. METHODS: Medical registry data and a survey of health status and perceived risk by patients and physicians. Agreement of patient perception of CV risk with perception of the physician in charge and with the CV risk established with clinical registry data was assessed. Self-perceived health status was also studied. RESULTS: A total of 150 physicians recruited 681 patients (71.5% with DM and 28.5% with MS) aged 60.8 ± 10.8 years (55.8% males). Good or excellent health were reported by 41.3% and 0.9%, respectively. Inability to give an estimate of CV risk was found in 39.8%. Agreement between the CV risks perceived by patients and evaluated by chart was poor: kappa index 0.145 (95% CI 0.101-0.189), p < 0.001. Agreement between CV risk perceived by patients and clinical data in the medical registry was weak: kappa index 0.165 (95% CI 0.117-0.213), p < 0.001. CONCLUSIONS: Patients with recently diagnosed DM and/or with MS have a poor awareness of their CV risk and 42.2% of them think that they have good or excellent health.

Treatment-time regimen of hypertension medications significantly affects ambulatory blood pressure and clinical characteristics of patients with resistant hypertension.

Patients with resistant hypertension (RH) are at greater risk for stroke, renal insufficiency, and cardiovascular disease (CVD) events than are those for whom blood pressure (BP) is responsive to and well controlled by therapeutic interventions. Although all chronotherapy trials have compared the effects on BP regulation of full daily doses of medications when ingested in the morning versus at bedtime, prescription of the same medications in divided doses twice daily (BID) is frequent. Here, we investigated the influence of hypertension treatment-time regimen on the circadian BP pattern, degree of BP control, and relevant clinical and laboratory medicine parameters of RH patients evaluated by 48-h ambulatory BP monitoring (ABPM). This cross-sectional study evaluated 2899 such patients (1701 men/1198 women), 64.2 ± 11.8 (mean ± SD) yrs of age, enrolled in the Hygia Project. Among the participants, 1084 were ingesting all hypertension medications upon awakening (upon-awakening regimen), 1436 patients were ingesting the full daily dose of ≥1 of them at bedtime (bedtime regimen), and 379 were ingesting split doses of ≥1 medications BID upon awakening and at bedtime (BID regimen). Patients of the bedtime regimen compared with the other two treatment-time regimens had lower likelihood of microalbuminuria and chronic kidney disease; significantly lower albumin/creatinine ratio, glucose, total cholesterol, and low-density lipoprotein (LDL) cholesterol; plus higher estimated glomerular filtration rate and high-density lipoprotein (HDL) cholesterol. The bedtime regimen was also significantly associated with lower asleep systolic (SBP) and diastolic (DBP) BP means than the upon-awakening and BID regimens. The sleep-time relative SBP and DBP decline was significantly attenuated by the upon-awakening and BID regimens (p < .001), resulting in significantly higher prevalence of non-dipping in these two treatment-time regimen groups (80.5% and 77.3%, respectively) than in the bedtime regimen (54.4%; p < .001 between groups). Additionally, the prevalence of the riser BP pattern, associated with highest CVD risk, was much greater, 31.0% and 29.8%, respectively, among patients of the upon-awakening and BID-treatment regimens, compared with the bedtime regimen (17.6%; p < .001 between groups). Patients of the bedtime regimen also showed significantly higher prevalence of properly controlled ambulatory BP (p < .001) as a result of a greater proportion of them showing complete control of asleep SBP and DBP means. Our findings demonstrate significantly lower asleep SBP and DBP means and attenuated prevalence of blunted nighttime BP decline, i.e., lower prevalence of CVD risk markers, in RH patients ingesting the full daily dose of ≥1 hypertension medications at bedtime than in those ingesting all of them upon awakening or ≥1 of them as split doses BID. In RH, ingesting the same medications BID neither improves ambulatory BP control nor reduces the prevalence of non-dipping, and cannot be considered chronotherapy. Collectively, findings of this study indicate that a bedtime hypertension medication regimen, in conjunction with proper patient evaluation by ABPM to corroborate the diagnosis of true RH and avoid treatment-induced nocturnal hypotension, should be the therapeutic scheme of choice for patients who, by conventional cuff methods (and in the absence of ABPM) and the morning-treatment regimen, have been mistakenly judged to be resistant to therapy.

Circadian pattern of ambulatory blood pressure in hypertensive patients with and without type 2 diabetes.

There is strong association between diabetes and increased risk of end-organ damage, stroke, and cardiovascular disease (CVD) morbidity and mortality. Non-dipping (<10% decline in the asleep relative to awake blood pressure [BP] mean), as determined by ambulatory BP monitoring (ABPM), is frequent in diabetes and consistently associated with increased CVD risk. The reported prevalence of non-dipping in diabetes is highly variable, probably due to differences in the study groups (normotensive subjects, untreated hypertensives, treated hypertensives), relatively small sample sizes, reliance only on a single, low-reproducibility, 24-h ABPM evaluation per participant, and definition of daytime and nighttime periods by arbitrary selected fixed clock-hour spans. Accordingly, we evaluated the influence of diabetes on the circadian BP pattern by 48-h ABPM (rather than for 24 h to increase reproducibility of results) during which participants maintained a diary listing times of going to bed at night and awakening in the morning. This cross-sectional study involved 12 765 hypertensive patients (6797 men/5968 women), 58.1 ± 14.1 (mean ± SD) yrs of age, enrolled in the Hygia Project, designed to evaluate prospectively CVD risk by ABPM in primary care centers of northwest Spain. Among the participants, 2954 (1799 men/1155 women) had type 2 diabetes. At the time of study, 525/3314 patients with/without diabetes were untreated for hypertension, and the remaining 2429/6497 patients with/without diabetes were treated. Hypertension was defined as awake systolic (SBP)/diastolic (DBP) BP mean ≥135/85 mm Hg, or asleep SBP/DBP mean ≥120/70 mm Hg, or BP-lowering treatment. Hypertensive patients with than without diabetes were more likely to be men and of older age, have diagnoses of microalbuminuria, proteinuria, chronic kidney disease, obstructive sleep apnea, metabolic syndrome, and/or obesity, plus higher glucose, creatinine, uric acid, and triglycerides, but lower cholesterol and estimated glomerular filtration rate. In patients with diabetes, ambulatory SBP was significantly elevated (p < .001), mainly during the hours of nighttime sleep and initial hours after morning awakening, independent of presence/absence of BP-lowering treatment. Ambulatory DBP, however, was significantly higher (p < .001) in patients without diabetes, mainly during the daytime. Differing trends for SBP and DBP between groups resulted in large differences in ambulatory pulse pressure (PP), it being significantly greater (p < .001) throughout the entire 24 h in patients with diabetes, even after correcting for age. Prevalence of non-dipping was significantly higher in patients with than without diabetes (62.1% vs. 45.9%; p < .001). Largest difference between groups was in the prevalence of the riser BP pattern, i.e., asleep SBP mean greater than awake SBP mean (19.9% vs. 8.1% in patients with and without diabetes, respectively; p < .001). Elevated asleep SBP mean was the major basis for the diagnosis of hypertension and/or inadequate BP control among patients with diabetes; thus, among the uncontrolled hypertensive patients with diabetes, 89.2% had nocturnal hypertension. Our findings document significantly elevated prevalence of a blunted nocturnal BP decline in hypertensive patients with diabetes. Most important, prevalence of the riser BP pattern, associated with highest CVD risk among all possible BP patterns, was more than twice as prevalent in diabetes. Patients with diabetes also presented significantly elevated ambulatory PP, reflecting increased arterial stiffness and enhanced CVD risk. These collective findings indicate that diabetes should be included among the clinical conditions for which ABPM is recommended for proper CVD risk assessment.

Prevalence and clinical characteristics of isolated-office and true resistant hypertension determined by ambulatory blood pressure monitoring.

Hypertension is defined as resistant to treatment when a therapeutic plan including ≥3 hypertension medications failed to sufficiently lower systolic (SBP) and diastolic (DBP) blood pressures (BPs). Most individuals, including those under hypertension therapy, show a "white-coat" effect that could cause an overestimation of their real BP. The prevalence and clinical characteristics of "white-coat" or isolated-office resistant hypertension (RH) has always been evaluated by comparing clinic BP values with either daytime home BP measurements or the awake BP mean obtained from ambulatory monitoring (ABPM), therefore including patients with either normal or elevated asleep BP mean. Here, we investigated the impact of including asleep BP mean as a requirement for the definition of hypertension on the prevalence, clinical characteristics, and estimated cardiovascular (CVD) risk of isolated-office RH. This cross-sectional study evaluated 3042 patients treated with ≥3 hypertension medications and evaluated by 48-h ABPM (1707 men/1335 women), 64.2 ± 11.6 (mean ± SD) yrs of age, enrolled in the Hygia Project. Among the participants, 522 (17.2%) had true isolated-office RH (elevated clinic BP and controlled awake and asleep ambulatory BPs while treated with 3 hypertension medications), 260 (8.6%) had false isolated-office RH (elevated clinic BP, controlled awake SBP/DBP means, but elevated asleep SBP or DBP mean while treated with 3 hypertension medications), and the remaining 2260 (74.3%) had true RH (elevated awake or asleep SBP/DBP means while treated with 3 medications, or any patient treated with ≥4 medications). Patients with false, relative to those with true, isolated-office RH had higher prevalence of microalbuminuria and chronic kidney disease (CKD), significantly higher albumin/creatinine ratio (p < .001), significantly higher 48-h SBP/DBP means by 9.6/5.3 mm Hg (p < .001), significantly lower sleep-time relative SBP and DBP decline (p < .001), and significantly greater prevalence of a non-dipper BP profile (96.9% vs. 38.9%; p < .001). Additionally, the prevalence of the riser BP pattern, which is associated with highest CVD risk, was much greater, 40.4% vs. 5.0% (p < .001), among patients with false isolated-office RH. The estimated hazard ratio of CVD events, using a fully adjusted model including the significant confounding variables of sex, age, diabetes, chronic kidney disease, asleep SBP mean, and sleep-time relative SBP decline, was significantly greater for patients with false compared with those with true isolated-office RH (2.13 [95% confidence interval: 1.95-2.32]; p < .001). Patients with false isolated-office hypertension and true RH, however, were equivalent for the prevalence of obstructive sleep apnea, metabolic syndrome, obesity, diabetes, microalbuminuria, and chronic kidney disease, and they had an equivalent estimated hazard ratio of CVD events (1.04 [95% confidence interval: .97-1.12]; p = .265). Our findings document a significantly elevated prevalence of a blunted nighttime BP decline in patients here categorized as either false isolated-office RH and true RH, jointly accounting for 82.8% of the studied sample. Previous reports of much lower prevalence of true RH plus a nonsignificant increased CVD risk of this condition compared with isolated-office RH are misleading by disregarding asleep BP mean for classification. Our results further indicate that classification of RH patients into categories of isolated-office RH, masked RH, and true RH cannot be based on the comparison of clinic BP with either daytime home BP measurements or awake BP mean from ABPM, as so far customary in the available literature, totally disregarding the highly significant prognostic value of nighttime BP. Accordingly, ABPM should be regarded as a clinical requirement for proper diagnosis of true RH.