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Background: Drug concentration in blood or urine is an acknowledged method to detect nonadherence. Observational studies suggest that informing patients about low or absent serum drug levels improves blood pressure (BP). We performed a multicenter randomized clinical trial to test the hypothesis that therapeutic drug monitoring (TDM) could improve drug adherence and BP in patients with uncontrolled hypertension (HT)., Methods: Patients were ≥18 years on stable treatment with at least 2 antihypertensive agents. We planned to randomize 80 nonadherent patients with a systolic daytime ambulatory BP ≥135 mm Hg to TDM intervention or not. The control group and the study personnel who measured BP remained uninformed about serum drug measurements throughout. All patients and physicians were blinded for BPs. Lifestyle advice and detailed information on the disease process and the importance of BP treatment were given to both groups., Results: From 2017 to 2022, we randomized 46 diagnosed nonadherent from a total of 606 patients with uncontrolled HT. The TDM group had a 6.7 (±14.5) mm Hg reduction from 147.9 (±10.3) to 141.1 (±14.1) mm Hg, and the control group experienced a 7.3 (±13.2) mm Hg reduction from 147.1 (±9.2) to 139.1 (±17.4) mm Hg, P = 0.9 between groups. Adherence improved in both groups, 73% in the TDM group and 59% in the control group became adherent at 3 months, P = 0.51., Conclusions: In our prospective multicenter clinical trial of uncontrolled and nonadherent hypertensive patients, we found no additional effect of TDM on BP and drug adherence compared with standard care., Clinical Trials Registration: Trial Number NCT03209154, www.clinicaltrials.gov., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Background: Systolic blood pressure (BP) is a key predictor of cardiovascular events, but patients with peripheral artery disease (PAD) are rarely included in hypertension trials. The VALUE trial (Valsartan Antihypertensive Long-Term Use Evaluation) investigated the long-term effects of valsartan- or amlodipine-based treatments on cardiovascular outcomes in patients with hypertension with a high cardiovascular risk. The aim of this subanalysis was to clarify the relationship between achieved BP on treatment and cardiovascular outcomes in patients with hypertension with PAD., Methods: Patients were followed for 4 to 6 years, and BP was measured regularly. The primary end point was time to the first major adverse cardiovascular event, including myocardial infarction, stroke, cardiovascular death, and heart failure requiring hospitalization. Statistical analyses were performed using Cox regression, adjusting for various baseline covariates., Results: Of the 13 803 participants, 1898 (13.8%) had PAD. During a median follow-up of 4.5 years, patients with PAD had a 23% increased risk of major adverse cardiovascular events compared with patients without PAD. Patients with an achieved systolic BP <130 mm Hg and 130 to 139 mm Hg, compared with those with systolic BP ≥140 mm Hg, were associated with a decreased risk of a major adverse cardiovascular event (hazard ratio, 0.65 [95% CI, 0.43-0.97]; P =0.037; 0.85 [95% CI, 0.74-0.97]; P =0.016, respectively). Additionally, systolic BP <130 mm Hg was associated with a decreased risk of cardiovascular death (hazard ratio, 0.33 [95% CI, 0.12-0.92]; P =0.034). The incidence of the primary outcome did not differ between antihypertensive treatment regimens ( P =0.365)., Conclusions: Our results indicate that more intensive BP control is associated with a reduction in cardiovascular morbidity and mortality in patients with hypertensive PAD., Competing Interests: Disclosures G. Mancia reports honoraria from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, Menarini Group, Merck, Novartis, Recordati, Sandoz, Sanofi, and Servier outside the present work. S.E. Kjeldsen reports lecture honoraria from Emcure, Getz, JB Pharma, Merck Healthcare KGaA, Sanofi-Aventis, and Vector-Intas. M.A. Weber reports honoraria from Abbvie, Johnson & Johnson, Idorsia, Roche, Medtronic, ReCor, Ablative Solutions, Verve, and Omron. M. Vrsalovic reports honoraria from AstraZeneca, Viatris, and Berlin Chemie Menarini. The other authors report no conflicts.

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Purpose: Event-based clinical outcome trials have shown limited evidence to support guidelines recommendations to lower blood pressure (BP) to <130/80 mmHg in middle-aged and elderly hypertensive patients with diabetes mellitus or with general high cardiovascular (CV) risk. We addressed this issue by post-hoc analysing the risk of CV events in patients who participated in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial and compared the hypertensive patients with type 2 diabetes mellitus with all high-risk hypertensive patients., Materials and Methods: Patients were divided into 4 groups according to the proportion of on-treatment visits before the occurrence of an event (<25% to ≥75%) in which BP was reduced to <140/90 or <130/80 mmHg. Patients with diabetes mellitus ( n  = 5250) were compared with the entire VALUE population with high CV risk ( n  = 15,245)., Results: After adjustments for baseline differences between groups, a reduction in the proportion of visits in which BP was reduced to <140/90 mmHg, but not to <130/80 mmHg, was accompanied by a progressive increase in the risk of CV morbidity and mortality as well as stroke, myocardial infarction and heart failure in both diabetes mellitus and in all high-risk patients. Target BP <130/80 mmHg reduced stroke risk in the main population but not in the diabetes mellitus patients. Patients with diabetes mellitus had higher event rates for the primary cardiac endpoint and all-cause mortality driven by a higher rate of heart failure., Conclusion: In the high-risk hypertensive patients of the VALUE trial achieving more frequently BP <140/90 mmHg, but not <130/80 mmHg, showed principally the same protective effect on overall and cause-specific cardiovascular outcomes in patients with diabetes mellitus and in the general high-risk hypertensive population.

Purpose: Available data of event-based clinical outcomes trials show that little evidence supports the guidelines recommendations to lower blood pressure (BP) to <130/80 mmHg in middle-aged and elderly people with type 2 diabetes mellitus and hypertension. We addressed this issue by post-hoc analysing the risk of cardiovascular (CV) events in mostly elderly high-risk hypertensive patients with type 2 diabetes mellitus participating in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial., Material and Methods: Patients ( n  = 5250) were divided into 4 groups according to the proportion of on-treatment visits before the occurrence of an event (<25% to ≥ 75%) in which BP was reduced to <140/90 or <130/80 mmHg., Results: After adjustment for baseline demographic differences between groups, a reduction in the proportion of visits in which BP achieved <140/90 mmHg accompanied a progressive increase in the risk of CV mortality and morbidity as well as of cause-specific events such as stroke, myocardial infarction and heart failure. A progressive reduction in the proportion of visits in which BP was reduced <130/80 mmHg did not have any effect on CV risks., Conclusion: In mostly elderly high-risk hypertensive patients with type 2 diabetes mellitus participating in the VALUE trial, achieving more frequently BP <140/90 mmHg showed a marked protective effect on overall and all cause-specific cardiovascular outcomes. This was not the case for a more frequent achievement of the more intensive BP target, i.e. <130/80 mmHg.

Blood pressure-lowering drugs have different blood pressure-lowering profiles. We studied if differences in blood pressure mean and variability can explain the differences in risks of cardiovascular events and death among 15 245 high-risk hypertensive patients randomized to valsartan or amlodipine and followed for 4.2 years in the VALUE trial (Valsartan Antihypertensive Long-Term Use Evaluation). We selected patients with ≥3 visits and performed Cox regression analyses, defining mean blood pressure as a time-dependent covariate and visit-to-visit and within-visit blood pressure variability as the SD. Of 14 996 eligible patients, participants in the valsartan group had higher systolic mean blood pressure by 2.2 mm Hg, higher visit-to-visit systolic variability by 1.4 mm Hg, and higher within-visit systolic variability by 0.2 mm Hg ( P values <0.0001). The higher risks of myocardial infarction and stroke in the valsartan group was attenuated after adjustment for mean and variability of systolic blood pressure, from HR 1.19 (95% CI, 1.02-1.39) to 1.11 (0.96-1.30) and from HR 1.13 (0.96-1.33) to 1.00 (0.85-1.18), respectively. The lower risk of congestive heart failure in the valsartan group was accentuated after adjustment, from HR 0.86 (0.74-1.00) to 0.76 (0.65-0.89). A smaller effect was seen on risk of death, from 1.01 (0.92-1.12) to 0.94 (0.85-1.04). In conclusion, the higher risks of myocardial infarction and stroke in patients randomized to valsartan versus amlodipine were related to the drugs' different blood pressure modulating profiles. The risk of congestive heart failure with valsartan was lower, independent of the less favorable blood pressure modulating profile.

There is no consensus on the definition of an exaggerated increase in systolic blood pressure (SBP) during exercise. The aim was to explore a potential threshold for exercise SBP associated with increased risk of coronary heart disease in healthy men using repeated exercise testing. Two thousand fourteen healthy white male employees were recruited into the Oslo Ischemia Study during early 1970s. At follow-up 7 years later, 1392 men were still considered healthy. A bicycle exercise test at 100 W workload was performed at both visits. Cox regression analyses were performed with increasing cutoff levels of peak exercise SBP at 100 W workload (SBP100W) from 160 mm Hg to 200 mm Hg, adjusted for cardiovascular risk factors and physical fitness. Participants with SBP100W below cutoff level at both baseline and first follow-up were compared with participants with SBP100W equal to or above cutoff level at both visits. Compared with participants with SBP100W below all cutoff levels between 165 and 195 mm Hg, coronary heart disease risk was increased among participants with SBP100W equal to or above cutoff at all levels. There was no evidence of a distinct threshold level for coronary heart disease risk, and the relation between SBP100W and coronary heart disease appears linear. When investigating exercise SBP at moderate workload measured at 2 exercise tests in healthy middle-aged white men, there is increasing risk of coronary heart disease with increasing exercise SBP independent of SBP at rest. The association is linear from the low range of exercise SBP, and there is no sign of a distinct threshold level for increased coronary disease risk.

Objective: We investigated the association between exercise SBP at a moderate workload and long-term risk of coronary heart disease (CHD) in men who were healthy when assessed by two bicycle exercise tests 7 years apart., Methods: During 1972-1975, apparently healthy men (n = 1999) were initially enrolled following thorough medical examination and ECG-monitored bicycle exercise test. Participants (n = 1392) who were healthy also at a second exercise test 7 years later were included in the present study. They were divided into quartiles, Q1-Q4, according to the highest SBP during the initial 6 min of the exercise test on a moderate workload of 100 W (SBP100W) at 7 years and followed for up to 28 years. Adjusted Cox regression was used to estimate CHD risk defined as first occurrence of angina pectoris, nonfatal myocardial infarction or CHD mortality., Results: During follow-up, 452 of the 1392 men suffered incident CHD, and unadjusted, there was increased risk of CHD with increasing SBP100 W, with significant differences between Q1-Q4. In the multivariate analysis adjusting for classical coronary risk factors, including SBP at rest, there was increased risk of CHD in Q3 (SBP100 W above 180 mmHg) and Q4 (SBP100 W above 200 mmHg) compared with Q1 (≤160 mmHg, lowest SBP100 W), hazard ratios 1.42 (CI 1.07-1.90) and 1.93 (CI 1.38-2.70), respectively., Conclusion: Healthy middle-aged men had increased long-term risk of CHD with exercise SBP above 180 mmHg at moderate workload. The prognostic impact of SBP above 180 mmHg at exercise is independent of classical coronary risk factors and blood pressure at rest.

The Systolic Blood Pressure Intervention Trial (SPRINT) suggested a favourable effect of lowering blood pressure to < 120/80 mmHg in high-risk hypertensive patients; however, new American guidelines in 2017 have not followed SPRINT but lowered its recommended treatment target to < 130/80 mmHg. We aimed to review the latest research from large randomised controlled trials and observational analyses in order to investigate the evidence for new treatment targets. We assessed recent data from the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD) study, the International Verapamil-Trandolapril Study (INVEST), the Telmisartan, Ramipril or Both in Patients at High Risk for Vascular Events trial (ONTARGET)/the Telmisartan Randomised AssessmenNt Study in aCE iNtolerant participants with cardiovascular Disease (TRANSCEND) study and The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study. These studies confirm a positive effect on cardiovascular protection with blood pressure lowering treatment to between 120-140 mmHg in patients with and without diabetes, but no additional effect of lowering blood pressure to < 120 mmHg; possibly too aggressive treatment may increase both cardiovascular morbidity and mortality. Thus, a target blood pressure < 130/80 mmHg appears appropriate in most high-risk hypertensive patients. Additionally, early and sustained BP control below this target is required for optimal cardiovascular protection.

Background: The SPRINT study demonstrated that targeting systolic blood pressure (SBP) less than 120 mmHg was associated with lower cardiovascular event and mortality rates. In the LIFE study, however, a lower achieved SBP was associated with increased mortality. Mean baseline SBP in SPRINT was 140 mmHg and a third of the population had a baseline SBP 132 mmHg or less, raising the question of whether the lower baseline SBP in SPRINT could in part account for these differences., Methods: All-cause mortality during 4.8 ± 0.9 years follow-up was examined in relation to tertiles of achieved on-treatment average SBP in patients with baseline SBP of 25th percentile or less versus greater than 25th percentile value of 164 mmHg in 7998 nondiabetic hypertensive patients with ECG left ventricular hypertrophy randomly assigned to losartan-based or atenolol-based treatment. Average on-treatment SBP less than 142 mmHg (lowest tertile) and average SBP 142 mmHg to less than 152 mmHg (middle tertile) were compared with average SBP at least 152 mmHg (highest tertile and reference group)., Results: In the overall population, there was a significant interaction between baseline SBP 164 mmHg or less and average on-treatment SBP less than 142 mmHg in Cox analysis (χ = 15.48, P < 0.001). Among patients with baseline SBP greater than 164 mmHg, in multivariate Cox analyses adjusting for other potential predictors of mortality and a propensity score for having baseline SBP 164 mmHg or less and compared with average on-treatment SBP at least 152 mmHg, average on-treatment SBP less than 142 mmHg was associated with 32% higher mortality (hazard ratio 1.32, 95% CI 1.01-1.65), whereas average SBP of 142 mmHg to less than 152 mmHg was associated with 24% lower mortality (hazard ratio 0.76, 95% CI 0.59-0.98). In contrast, among patients with baseline SBP 164 mmHg or less, both average on-treatment SBP less than 142 mmHg (hazard ratio 0.60, 95% CI 0.36-0.99) and average SBP of 142 mmHg to less than 152 mmHg (hazard ratio 0.51, 95% CI 0.30-0.89) were associated with significantly lower mortality compared with average SBP of at least 152 mmHg., Conclusion: Achievement of an average SBP less than 142 mmHg was associated with reduced mortality in patients with baseline SBP 164 mmHg or less but with increased mortality in those with higher baseline SBP in LIFE. These findings suggest that the lower mortality associated with a lower targeted SBP in SPRINT may not be applicable to patients with considerably higher baseline SBP than SPRINT patients. Further study is necessary to better understand these findings., Clinical Trials Registration: http://clinicaltrials.gov/ct/show/NCT00338260?order=1.

Hypertension is the strongest or one of the strongest risk factors for almost all different cardiovascular diseases acquired during life, including coronary disease, left ventricular hypertrophy and valvular heart diseases, cardiac arrhythmias including atrial fibrillation, cerebral stroke and renal failure. The continuous relationship between blood pressure and cardiovascular and renal events makes the distinction between high normal blood pressure and hypertension based on arbitrary cut-off values for blood pressures. Overall the prevalence of hypertension in different European countries appears to be around 30-45% of the general population, with a steep increase with ageing. The prevention of cardiovascular disease and treatment recommendations should be related to quantification of total cardiovascular risk which could be estimated from several different models. However the impact of age on risk is so strong that young adults (particularly women) are unlikely to reach high-risk levels even when they have more than one major risk factor and a clear increase in relative risk. Therefore age-adjusted models, models assessing relative risks compared to others of same age and models including thorough assessments of target organ damage and ambulatory 24h blood pressure are needed together with national models because of the large variations between countries., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Sympathetic tone is one of the main determinants of blood pressure (BP) variability and treatment-resistant hypertension. The aim of our study was to assess changes in BP variability after renal denervation (RDN). In addition, on an exploratory basis, we investigated whether baseline BP variability predicted the BP changes after RDN., Methods: We analyzed 24-h BP recordings obtained at baseline and 6 months after RDN in 167 treatment-resistant hypertension patients (40% women; age, 56.7 years; mean 24-h BP, 152/90 mmHg) recruited at 11 expert centers. BP variability was assessed by weighted SD [SD over time weighted for the time interval between consecutive readings (SDiw)], average real variability (ARV), coefficient of variation, and variability independent of the mean (VIM)., Results: Mean office and 24-h BP fell by 15.4/6.6 and 5.5/3.7 mmHg, respectively (P < 0.001). In multivariable-adjusted analyses, systolic/diastolic SDiw and VIM for 24-h SBP/DBP decreased by 1.18/0.63 mmHg (P ≤ 0.01) and 0.86/0.42 mmHg (P ≤ 0.05), respectively, whereas no significant changes in ARV or coefficient of variation occurred. Furthermore, baseline SDiw (P = 0.0006), ARV (P = 0.01), and VIM (P = 0.04) predicted the decrease in 24-h DBP but not 24-h SBP after RDN., Conclusion: RDN was associated with a decrease in BP variability independent of the BP level, suggesting that responders may derive benefits from the reduction in BP variability as well. Furthermore, baseline DBP variability estimates significantly correlated with mean DBP decrease after RDN. If confirmed in younger patients with less arterial damage, in the absence of the confounding effect of drugs and drug adherence, baseline BP variability may prove a good predictor of BP response to RDN.

We identified sociodemographic, medical, and psychosocial factors associated with unfavorable blood pressure (BP) control in 1012 patients, hospitalized with myocardial infarction and/or a coronary revascularization procedure. This cross-sectional study collected data from hospital records, a comprehensive self-report questionnaire, clinical examination, and blood samples after 2-36 (mean 17) months follow-up. Forty-six percent had unfavorable BP control (≥140/90 [80 in diabetics] mm Hg) at follow-up. Low socioeconomic status and psychosocial factors did not predict unfavorable BP control. Patients with unfavorable BP used on average 1.9 (standard deviation 1.1) BP-lowering drugs at hospital discharge, and the proportion of patients treated with angiotensin inhibitors and beta-blockers decreased significantly (P < .001) from discharge to follow-up. Diabetes (odds ratio [OR] 2.4), higher body mass index (OR 1.05 per 1.0 kg/m 2 ), and older age (OR 1.04 per year) were significantly associated with unfavorable BP control in adjusted analyses. Only age (standardized beta [β] 0.24) and body mass index (β 0.07) were associated with systolic BP in linear analyses. We conclude that BP control was insufficient after coronary events and associated with obesity and diabetes. Prescription of BP-lowering drugs in hypertensive patients seems suboptimal. Overweight and intensified drug treatment thus emerge as the major factors to target to improve BP control., (Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Objective: There is an association between exercise systolic blood pressure (SBP) and cardiovascular disease and mortality. The aim of this study was to investigate this association, with 35 years of follow-up., Methods: Through 1972-75, 2014 healthy, middle-aged men underwent thorough medical examination and a bicycle exercise test. 1999 participants completed six minutes at 100 W. SBP was measured manually, both before the test and every two minutes during the test. Highest SBP measured during the first six minutes (SBP100W) was used in further analyses., Results: Participants were divided into quartiles (Q) based on their SBP100W; Q1: 100-160 mm Hg (n = 457), Q2: 165-175 mm Hg (n = 508), Q3: 180-195 mm Hg (n = 545) and Q4: 200-275 mm Hg (n = 489). After 35-years follow-up, there was a significant association between exercise SBP at baseline and cardiovascular disease and mortality. In the multivariate analysis adjusting for resting SBP, age, smoking status, total serum cholesterol and family history of coronary heart disease, as well as physical fitness, there is a 1.39-fold (CI: 1.00-1.93, p = 0.05) increased risk of cardiovascular mortality in Q4 compared to Q1. When not adjusting for physical fitness, there is a 1.29-fold (CI: 1.03-1.61, p = 0.02) increase in risk of cardiovascular disease between Q1 and Q4., Conclusions: The results of this study suggest that the association between exercise SBP at moderate workload and cardiovascular disease and mortality in middle-aged men extends through as long as 35 years and into old ages.

Background: Abnormal P-wave terminal force in lead V 1 (PTF-V 1 ) is an ECG marker of increased left atrial (LA) volume, elevated LA filling pressures and/or LA systolic dysfunction. Because left ventricular (LV) diastolic dysfunction is one of the potential mechanisms driving LA remodelling, we hypothesized that PTF-V 1 might be an additional ECG marker of diastolic dysfunction., Methods: LV diastolic function after 3 years' systematic antihypertensive treatment was examined in relation to baseline PTF-V 1 in 431 hypertensive patients undergoing protocol-driven blood pressure reduction who had baseline and year-3 ECG and echocardiographic data and a preserved LV ejection fraction (EF >45%) at year-3. Abnormal diastolic function was defined by the tenth or 90th percentile values from 405 normotensive, non-obese and non-diabetic adults without overt cardiovascular disease. Abnormal PTF-V 1, defined by the presence of a negative terminal P-wave in lead V1 ≥ 4000 μV·ms, was present in 167 patients (38.7%)., Results: Abnormal PTF-V 1 was associated with worse year-3 mean diastolic first third filling time (0.43 ± 0.08 vs 0.40 ± 0.07 sec, p = 0.039), first half filling time (0.55 ± 0.07 vs 0.53 ± 0.07 sec, p = 0.041), mitral valve A velocity (86 ± 27 vs 76 ± 19 cm/sec, p = 0.009) and mitral valve E/A ratio (0.85 ± 0.22 vs 0.94 ± 0.27, p = 0.007) after adjusting for other potential predictors of diastolic dysfunction including race, and heart rate, systolic blood pressure and severity of ECG LVH by Cornell product criteria at baseline. In parallel multivariate logistic regression analysis, abnormal PTF-V 1 was associated with significantly increased odds of abnormal mitral valve E/A ratio (OR 1.55, 95%CI 1.04-2.32 p = 0.032), and a trend toward higher odds of abnormal half filling time (OR 1.42, 95%CI 0.94-2.15, p = 0.098) at year-3 of follow-up., Conclusions: Abnormal P-wave terminal force in lead V 1 is associated with worse diastolic function and predicts abnormal LV diastolic behaviour in patients with preserved EF after 3 years of blood pressure reductive therapy.

The SPRINT study investigators used the un-observed automated office blood pressure measurement technique. When their achieved systolic blood pressure is corrected, target systolic blood pressure for most people remains unchanged: <140mmHg for prevention of cardiovascular diseases and death.

The European Society of Hypertension recommend the following main rules for treatment of hypertension in elderly and octogenarians: 1) In elderly hypertensives with SBP ≥ 160 mmHg there is solid evidence to recommend reducing SBP to between 140 mmHg and 150 mmHg. 2) In fit elderly patients less than 80 years old treatment may be considered at SBP ≥ 140 mmHg with a target SBP < 140 mmHg if treatment is well tolerated. 3) In fit individuals older than 80 years with an initial SBP ≥ 160 mmHg it is recommended to reduce SBP to between 150 mmHg and 140 mmHg. 4) In frail elderly patients, it is recommended to base treatment decisions on comorbidity and carefully monitor the effects of treatment. 5) Continuation of well-tolerated antihypertensive treatment should be considered when a treated individual becomes octogenarian. 6) All hypertensive agents are recommended and can be used in the elderly, although diuretics and calcium antagonists may be preferred in isolated systolic hypertension.

Aims: There is strong evidence for the association of high blood pressure (BP) with depressed renal function. Although high BP at baseline is associated with greater progression of chronic kidney disease (CKD), randomized trials in CKD patients have found no significant relationship between more intensive BP control and glomerular filtration rate (GFR) decline. However, the relationship of GFR and change in GFR over time to lower achieved systolic BP (SBP) in hypertensive patients undergoing treatment is unclear., Methods and Results: Baseline estimated GFR (eGFR) and change in eGFR during follow-up were examined in relation to average on-treatment SBP in 8778 hypertensive patients with ECG left ventricular hypertrophy (LVH) randomly assigned to losartan- or atenolol-based treatment. GFR was estimated using the Modification of Diet in Renal Disease study equation. Patients with average on-treatment SBP ≤130 mmHg (lowest quintile at last measurement) and average SBP between 131 and 141 mmHg were compared with patients with average SBP ≥142 mmHg (median SBP at last measurement). Patients with an average on-treatment SBP ≤130 mmHg had significantly lower baseline eGFR than those with average SBP between 131 and 141 or average SBP ≥142 mmHg (65.5 ± 14.3 vs. 69.3 ± 14.3 vs. 69.0 ± 14.5 mL/min/1.73 m2, P < 0.001 using analysis of covariance adjusting for age, sex, race, randomized treatment, prior antihypertensive treatment, history of diabetes, myocardial infarction, ischaemic heart disease or heart failure, smoking status, baseline serum glucose, total and HDL cholesterol, albuminuria, and baseline LVH by Cornell product and Sokolow-Lyon voltage). However, the decrease in eGFR between baseline and Year 4 was significantly lower among patients with average SBP ≤130 mmHg (-6.3 ± 10.3 vs. -7.9 ± 11.1 vs. -9.2 ± 10.6 mL/min/1.73 m2, P = 0.001 when adjusting for the same variables and for change in Cornell product and Sokolow-Lyon voltage between baseline and Year 4). These differences in eGFR change persisted even after adjusting for baseline eGFR, and there were no significant interactions with randomized treatment, sex, race, or baseline presence of proteinuria., Conclusion: Lower average on-treatment SBP (≤130 mmHg) was associated with a lower baseline eGFR but with a slower reduction in eGFR during 4-year follow-up in hypertensive patients with ECG LVH, independent of other possible risk factors for decreased GFR. Further study is necessary to determine whether randomized treatment to lower SBP goals is more protective of renal function than treatment to standard SBP goals., Clinical Trial Registration: http://clinicaltrials.gov/ct/show/NCT00338260?order=1; unique identifier: NCT00338260.

DISTINCT was an 8-week, double-blind, randomized study to investigate the antihypertensive efficacy and safety of various nifedipine gastrointestinal treatment system (GITS)/candesartan cilexetil (N/C) dose combinations, vs respective monotherapies or placebo, in patients with diastolic blood pressure (DBP) ≥95 to <110 mm Hg. The current prespecified analysis compared BP reduction in participants with mild vs moderate baseline hypertension (ie, systolic [S]BP <160 mm Hg vs ≥160 mm Hg and DBP <100 mm Hg vs ≥100 mm Hg). A total of 1362 patients were analyzed by descriptive statistics. In all patient subgroups investigated, the NC combinations (ie, N: 20, 30, or 60 mg; C: 4, 8, 16, or 32 mg daily) provided greater SBP and DBP lowering and higher rates of BP control (defined as BP <140/90 mm Hg) than respective monotherapies or placebo, with greatest absolute BP reductions observed in the moderately elevated SBP or DBP subgroups. A trend to dose-response relationship was observed in each subgroup. In each SBP and DBP subgroup, treatment-related vasodilatory events (flushing, headache, or edema) were less frequent for patients receiving NC combination therapy than N monotherapy. These analyses support the use of calcium antagonist and angiotensin receptor blocker combination therapy in patients with both mild and moderate hypertension, for whom effective BP normalization and good drug tolerance would greatly reduce the risk of cardiovascular events., (© 2016, The American College of Clinical Pharmacology.)

Previous studies have debated the notion that low blood pressure (BP) during treatment, particularly diastolic (DBP), is associated with increased risk of cardiovascular disease. We evaluated the impact of low BP on cardiovascular outcomes in a high-risk population of 15,244 hypertensive patients, almost half of whom had a history of coronary artery disease (CAD). In the prospective Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, patients were randomized to valsartan or amlodipine regimens and followed for 4.2 years (mean) with no difference in the primary cardiovascular endpoint. A Cox proportional hazards model was used to evaluate the relationship between average on-treatment BP and clinical outcomes. The relationship between BP and cardiovascular events was adjusted for age, gender and body mass index, and baseline qualifying risk factors and diseases (smoking, high total cholesterol, diabetes mellitus, proteinuria, CAD, previous stroke and left ventricular hypertrophy). DBP ≥ 90 mmHg, compared with < 90 mmHg, was associated with increased incidence of the primary cardiovascular endpoint (all cardiac events); however, DBP < 70 mmHg, compared with ≥ 70 mmHg, was not associated with increased incidence after covariate adjustment (no J-shaped curve). Similar results were observed for death, myocardial infarction (MI), heart failure and stroke, considered separately. Nadir for MI was at DBP of 76 mmHg and for stroke 60 mmHg. The ratio of MI to stroke increased with lower DBP. In CAD patients the MI to stroke ratio was more pronounced than in patients without CAD but there was no significant J-curve in either group. Systolic BP ≥ 150 but not < 130 mmHg, compared with 130-149 mmHg, similarly was associated with increased risk for primary outcome. In conclusion, patients in BP strata ≥ 150/90 mmHg, but not patients in BP strata < 130/70 mmHg, were at increased risk for adverse outcomes in this hypertensive, high-risk population. Although benefit in preventing MI in relation to preventing stroke levels off for the lowest BPs, these data provide no support for a J-curve in the treatment of high-risk hypertensive patients . The increase in the ratio of MI to stroke with lower DBP indicates target organ heterogeneity in that the optimal on-treatment DBP for cerebroprotection is below that for cardioprotection.

Background: Assessment of antihypertensive treatment is normally based on the mean value of a number of blood pressure (BP) measurements. However, it is uncertain whether high in-treatment visit-to-visit BP variability may be harmful in hypertensive patients with left ventricular hypertrophy (LVH)., Methods: In 8505 patients randomized to losartan vs. atenolol-based treatment in the LIFE study, we tested whether BP variability assessed as SD and range for BP6-24 months measured at 6, 12, 18 and 24 months of treatment was associated with target organ damage (TOD) defined by LVH on ECG and urine albumin/creatinine ratio at 24 months, and predicted the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction (MI) or stroke occurring after 24 months (CEP = 630 events)., Results: In multiple regression models adjusted for mean BP6-24 months and treatment allocation, neither high BP6-24 months SD nor wide range were related to TOD at 24 months, except for a weak association between Sokolow-Lyon voltage and DBP6-24 months SD and range (both β = 0.04, P < 0.01). Independently of mean BP6-24 months, treatment allocation, TOD and baseline characteristics in Cox regression models, CEP after 24 months was associated with DBP6-24 months SD [hazard ratio per 1 mmHg increase1.04, 95% confidence interval (95% CI) 1.01-1.06, P = 0.005], range (hazard ratio 1.02, 95% CI 1.01-1.03, P = 0.004), SBP6-24 months SD (hazard ratio 1.01, 95% CI 0.99-1.02, P = 0.07) and range (hazard ratio 1.006, 95% CI 1.001-1.01, P = 0.04). Adjusted for the same factors, stroke was associated with DBP6-24 months SD (hazard ratio 1.06, 95% CI 1.02-1.10, P = 0.001), range (hazard ratio 1.03, 95% CI 1.01-1.04, P = 0.001), SBP6-24 months SD (hazard ratio 1.02, 95% CI 1.002-1.04, P = 0.04) and range (hazard ratio 1.008, 95% CI 1.001-1.02, P = 0.05), but MI was not., Conclusion: In LIFE patients, higher in-treatment BP6-24 months variability was independently of mean BP6-24 months associated with later CEP and stroke, but not with MI or TOD after 24 months.

Background: In the BEtter control of BP in hypertensive pAtients monitored Using the HOTMAN sYstem study, we investigated whether utilizing noninvasive monitoring of hemodynamic parameters combined with a drug selection algorithm (integrated hemodynamic management - IHM) compared with conventional drug selection may improve uncontrolled hypertension in European Hypertension Excellence centers., Method: Uncontrolled (office SBP >140 mmHg and ambulatory daytime SBP >135 mmHg while taking ≥2 antihypertensive drugs) essential hypertensive patients were referred to five European Hypertension Excellence centers and, if eligible, were randomized to IHM-guided (n = 83) vs. conventional (control, n = 84) treatment adjustment in an investigator-initiated multicenter prospective randomized parallel groups controlled study., Results: The average number of antihypertensive drugs increased from 3.1 to 4.1 in both groups and differed only in a rise of the use of diuretics in the IHM groups (from 13 to 31%). Daytime SBP, defined as the primary endpoint, decreased markedly and to the same extent from baseline to 6 months in IHM (-15.8 ± 14.8 mmHg) and control (-15.4 ± 14.5 mmHg) groups (P = 0.87), with a similar behavior of office SBP (no between group differences, P = 0.18). Average number of adverse events was significantly lower in IHM than in controls (P = 0.008) but of the more general type and not necessarily related to drug treatment., Conclusion: Thus, noninvasive hemodynamic monitoring associated with a drug selection algorithm induced similar reductions in ambulatory daytime and office SBP compared with conventional drug selection in uncontrolled hypertensive patients referred to European Hypertension Excellence centers.Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT01482364.

Background and Purpose: Hypertensive patients with electrocardiographic left ventricular hypertrophy are at increased risk of all-cause and cardiovascular death. Lowering blood pressure (BP) after stroke reduces the risk of recurrent stroke, but recent data suggest that lower systolic BP (SBP) measured 5 years after stroke is associated with increased mortality. Whether lower SBP is associated with increased short-term mortality after stroke in hypertensive patients is unclear., Methods: All-cause and cardiovascular mortality were examined in relation to average on-treatment SBP after stroke in 541 hypertensive patients with electrocardiographic left ventricular hypertrophy randomly assigned to losartan- or atenolol-based treatment who had new strokes during follow-up. Patients with on-treatment SBP<144 mm Hg (lowest tertile) and SBP>157 (highest tertile) were compared with patients with average SBP between 144 and 157., Results: During 2.02±1.65 years mean follow-up after incident stroke, 170 patients (31.4%) died, 135 (25.0%) from cardiovascular causes. In multivariate Cox analyses, adjusting for significant univariate predictors of mortality, compared with average SBP between 144 and 157, an average SBP<144 was a significant predictor of all-cause (hazard ratio, 1.81; 95% confidence interval, 1.20-2.73) and cardiovascular mortality (hazard ratio, 1.60; 95% confidence interval, 1.02-2.54), whereas patients who had an average SBP>157 had no significant increased risk of death., Conclusions: Lower achieved SBP (<144 mm Hg) is associated with a significantly increased risk of cardiovascular and all-cause mortality after initial stroke in hypertensive patients during short-term follow-up. Further study is required to determine ideal SBP goals after stroke., Clinical Trial Registration: URL: http://clinicaltrials.gov/. Unique identifier: NCT00338260., (© 2015 American Heart Association, Inc.)

Unlabelled: There is a well-established association between hypertension and atrial fibrillation (AF); indeed, even upper normal systolic blood pressures (SBP) are long-term predictors of incident AF. These findings suggest that more aggressive BP control may reduce the risk of new AF. However, whether lower achieved SBP is associated with a lower incidence of AF remains unclear. The risk of new-onset AF was examined in relation to last in-treatment SBP before AF diagnosis or last in-study measurement in the absence of new AF in 8831 hypertensive patients with ECG left ventricular hypertrophy with no history of AF, in sinus rhythm on their baseline ECG, randomly assigned to losartan- or atenolol-based treatment. Patients with in-treatment SBP ≤130 mm Hg (lowest quintile at last measurement) and SBP between 131 and 141 mm Hg were compared with patients with in-treatment SBP ≥142 mm Hg (median SBP at last measurement). During follow-up of 4.6±1.1 years, new-onset AF was diagnosed in 701 patients (7.9%). In multivariate Cox analyses, compared with in-treatment SBP ≥142 mm Hg, in-treatment SBP ≤130 mm Hg entered as a time-varying covariate was associated with a 40% lower risk (95% confidence interval, 18%-55%) and in-treatment SBP of 131 to 141 mm Hg with a 24% lower risk (95% confidence interval, 7%-38%) of new AF. Thus, achieved SBP ≤130 mm Hg is associated with a lower risk of new-onset AF in hypertensive patients with ECG left ventricular hypertrophy. Further study is needed to determine whether targeting hypertensive patients without AF to lower SBP goals can reduce the burden of new AF in this high-risk population., Clinical Trial Registration: URL: http://clinicaltrials.gov. Unique identifier: NCT00338260., (© 2015 American Heart Association, Inc.)

Objective: Approximately 10-20% of the general population have masked hypertension. However, how best to identify affected individuals is uncertain, and what predicts future masked hypertension is largely unknown. This study aimed to identify longitudinal predictors of masked hypertension., Methods: A long-term follow-up study of 100 healthy young men who had normal (n = 28) or high (n = 72) screening blood pressure (BP) at the compulsory military draft was carried out. They were examined in a detailed and highly standardized way for cardiovascular risk markers at baseline and at follow-up after a mean of 17.4 years., Results: At follow-up, 40% had masked hypertension. Participants with high screening BP had a 4.8 times higher likelihood of having masked hypertension at follow-up compared to men with low screening BP (odds ratio 4.8, 95% confidence interval 1.7-13.5, p = 0.003). Furthermore, only 25% of the men with masked hypertension had high normal office BP at follow-up, and the remaining 75% would, according to guidelines, not be recommended ambulatory BP measurements, and thus go undiagnosed., Conclusion: Our data suggest that high screening BP at a young age is an important predictor of future masked hypertension in young men, and that BP measurement according to guidelines is insufficient to uncover masked hypertension.

Renal sympathetic denervation (RDN) has been proposed as a new treatment modality in patients with apparent treatment-resistant hypertension (TRH), a condition defined as persistent blood pressure (BP) elevation despite prescription of at least three anti-hypertensive drugs including a diuretic. However, the large fall in BP reported after RDN in Symplicity HTN-2, the first randomized study, and in multiple observational studies has not been confirmed in five subsequent prospective randomized studies. The reduction in BP may be mostly due to non-specific effects, such as improvement of drug adherence in initially poorly adherent patients (the Hawthorne effect), placebo effect and regression to the mean. The overall BP lowering effect of RDN seems rather limited and the characteristics of the true responders remain largely unknown. Accordingly, RDN is not ready for clinical practice. In most patients with TRH, drug monitoring and subsequent improvement of drug adherence may prove more effective and cost-effective to achieve BP control. In the meantime, research should aim at identifying characteristics of those few patients adherent to drug treatment who has TRH and may respond to RDN., (Published on behalf of the European Society of Cardiology. All rights reserved. ©The Author 2015. For permissions please email: journals.permissions@oup.com.)