Showing papers by "Sverre E. Kjeldsen published in 2015"
Saarland University1, French Institute of Health and Medical Research2, National and Kapodistrian University of Athens3, Sahlgrenska University Hospital4, Utrecht University5, University of Milano-Bicocca6, University of Oslo7, Oslo University Hospital8, Queen Mary University of London9, Hebrew University of Jerusalem10, University of Valencia11, Sapienza University of Rome12, University of Bern13
TL;DR: Clinical evidence in support of RDN as an effective interventional technique in patients with resistant hypertension is conflicting; a number of observational studies and three randomized, controlled trials support both safety and efficacy of this new therapy but some smaller studies and the large, single-blind, randomized, sham-controlled symplicity HTN-3 trial failed to show superiority ofRDN when compared with medical therapy alone.
Abstract: Approximately 8–18% of all patients with high blood pressure (BP) are apparently resistant to drug treatment.1,2 In this situation, new strategies to help reduce BP are urgently needed but the complex pathophysiology of resistant hypertension makes this search difficult. Not surprisingly in this context, the latest non-drug treatment which triggered controversy is catheter-based renal denervation (RDN).3,4 The method uses radiofrequency energy, or alternatively ultrasound or chemical denervation, to disrupt renal nerves within the renal artery wall, thereby reducing sympathetic efferent and sensory afferent signalling to and from the kidneys.5,6 Various experimental models of hypertension strongly support this concept7,8 and available evidence also suggests that sympathetic nervous system activation contributes to the development and progression of hypertension and subsequently to target organ damage.7–11 Historical observations have shown that surgical sympathectomy can reduce BP as well as morbidity and mortality in patients with uncontrolled hypertension.12,13 However, the clinical evidence in support of RDN as an effective interventional technique in patients with resistant hypertension is conflicting. A number of observational studies and three randomized, controlled trials (Symplicity HTN-2, Prague-15, and DENERHTN) support both safety and efficacy of this new therapy14–22 but some smaller studies and the large, single-blind, randomized, sham-controlled symplicity HTN-3 trial failed to show superiority of RDN when compared with medical therapy alone.23–25
Whatever the shortcomings of individual trials may be, the possibility remains that the observed BP responses were due to placebo response, the Hawthorne effect, regression to the mean, unknown co-interventions or other bias.26 The design, conduct, and interpretation …
166 citations
TL;DR: In selected rHT patients maintained on antihypertensive drugs, RDN with the SYMPLICITY systems does not significantly decrease BP but is safe, and future trials with next-generation catheters should aim at identifying responders in patients with evidence of sympathetic nervous overactivity.
Abstract: Objective The blood pressure (BP)-lowering effect of renal sympathetic nervous denervation (RDN) in resistant hypertension (rHT) shows large variation among studies Methods We meta-analyzed summary statistics of randomized clinical trials on RDN in rHT For continuous outcomes, we assessed heterogeneity by Cochran's Q test and used random-effect models weighted for the inverse of the variance We assessed safety by assessing the risk of major adverse events from stratified contingency tables Results Of 5652 patients screened in seven trials, 985 (174%) qualified and were randomized to control (n = 397) or RDN with SYMPLICITY™ catheters (n = 588) Follow-up was 6 months In both control and RDN patients, antihypertensive treatment was continued or optimized At enrolment, age averaged 581 years, systolic/diastolic office and 24 h BP 1685/933 mmHg and 1518/861 mmHg, respectively, and estimated glomerular filtration rate (eGFR) 793 ml/min/173 m² For BP outcomes, there was heterogeneity
64 citations
TL;DR: Accumulated SBP ⩽130 mm Hg is associated with a lower risk of new-onset AF in hypertensive patients with ECG left ventricular hypertrophy, suggesting that more aggressive BP control may reduce therisk of new AF.
Abstract: 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.
64 citations
TL;DR: In LIFE patients, higher in-treatment BP6–24months variability was independently of mean BP6-24months associated with later CEP and stroke, but not with MI or TOD after 24 months.
Abstract: 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.
51 citations
TL;DR: Monitoring data from monitoring phases of large outcome trials in hypertension show that inertia, the lack of titration of study drugs to higher dosing levels or drug combinations according to the study protocols, is a major cause of not reaching BP targets in the trials.
Abstract: Background. Treatment of resistant hypertension has attained much attention during the past few years and naturally so has the prevalence of resistant hypertension. In the search for sources of such documentation, the lack of blood pressure (BP) control in randomized clinical outcome trials in hypertension has been used as indication of treatment-resistant hypertension. In the present study, we aimed at using previously unpublished information from monitoring of clinical trials in investigating the mechanism explaining why large fractions of patients in the trials remained uncontrolled for their high BP. Methods. We report insight information from LIFE (n = 9193), VALUE (n = 15,245), ASCOT (n = 19,257) and ACCOMPLISH (n = 11,506). Data stored during the course of the trials for monitoring purposes were scrutinized for fractions of patients with BP control, which was BP < 140/90 mmHg in all trials, and we identified monitoring data showing fractions of patients who had been uptitrated to the variou...
33 citations
TL;DR: This article summarizes the key discussion points and identifies knowledge gaps in this field that need to be addressed by additional research and summarizes the mechanisms of autonomic modulation.
Abstract: Several device-based approaches to autonomic nervous system modulation are under investigation for the treatment of resistant hypertension and heart failure (Table 1).1 This line of research has evolved from the recognition that these diseases originate or are worsened by excess sympathetic activity and loss of parasympathetic tone.9–13 Drug therapies, including β-blockers, α-blockers, and centrally acting antihypertensive drugs, can modulate these neurohormonal systems, but they are often insufficient to control blood pressure (BP) or are limited by side effects or nonadherence. Technological innovations have produced devices that modulate the autonomic nervous system, including renal denervation, carotid baroreceptor stimulation, vagal nerve stimulation, and spinal cord stimulation.
View this table:
Table 1.
Select Completed and Ongoing Clinical Trials of Autonomic Modulation Therapies in Hypertension and Heart Failure
In Europe, several autonomic modulation therapy devices have received the Conformite Europeenne mark.14 US Food and Drug Administration evaluation of these devices is ongoing. The need for adequately powered, randomized, controlled studies with longer follow-up to capture definitive evidence of safety and effectiveness has been noted.14–17
The 9th and 10th Global Cardiovascular Clinical Trialists Forum (Paris, France, December 2012 and December 2013) convened a panel of primary investigators of ongoing trials, along with biostatisticians, National Institutes of Health scientists, European, and United States regulators, and medical device and pharmaceutical industry scientists to discuss the strengths and limitations of current clinical trials, optimal designs for future trials, approvability of new devices, and considerations for integrating these technologies into practice. This article summarizes the key discussion points and identifies knowledge gaps in this field that need to be addressed by additional research.
The mechanisms of autonomic modulation are complex, and a comprehensive review of these mechanisms is outside the scope of this article. Briefly, all existing strategies aim to decrease central sympathetic outflow. Renal …
26 citations
TL;DR: 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.
Abstract: 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 dr
21 citations
TL;DR: In hypertensive patients with ECG left ventricular hypertrophy with existing or new atrial fibrillation, digoxin use is not associated with a significantly increased risk of all-cause mortality after adjusting for other independent predictors of death and for the factors associated with the propensity to use digoxin in this population.
Abstract: Background: Digoxin is widely used for rate control of atrial fibrillation. However, recent studies have reported conflicting results on the association of digoxin with mortality when used in patie ...
14 citations
TL;DR: The overall blood-pressure lowering effect of RDN seems rather limited and the characteristics of true responders are largely unknown, Accordingly, RDN is not ready for clinical practice.
Abstract: Renal sympathetic denervation (RDN) has been and is still proposed as a new treatment modality in patients with apparently treatment resistant hypertension (TRH), a condition defined as persistent blood pressure elevation despite prescription of at least 3 antihypertensive drugs including a diuretic. However, the large fall in blood pressure after RDN reported in the first randomized study, Symplicity HTN-2 and multiple observational studies has not been confirmed in five subsequent prospective randomized studies and may be largely explained by 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 blood-pressure lowering effect of RDN seems rather limited and the characteristics of true responders are largely unknown. Accordingly, RDN is not ready for clinical practice. In most patients with apparently TRH, drug monitoring and improvement of drug adherence may prove more effective and cost-beneficial to achieve blood pressure control. In the meantime, research should aim at identifying characteristics of those patients with truly TRH who may respond to RDN.
14 citations
TL;DR: 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.
Abstract: 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 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%)...
13 citations
TL;DR: RDN certainly deserves further investigation but is not ready for wide clinical application, so physicians should focus on improvement of drug adherence and skilful drug treatment adjustment, which allow reaching blood pressure target in the large majority of hypertensive patients.
TL;DR: The 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.
Abstract: 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 ...
TL;DR: 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.
Abstract: 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.
TL;DR: It is confirmed that renal denervation (RDN) with the Symplicity catheter is not the miracle treatment for resistant hypertension as initially suggested and the BP response to RDN cannot be reliably evaluated in an isolated manner because of the combination of two effects acting in opposite directions.
Abstract: Resistant hypertension is a very intricate clinical situation in which complex pathophysiological mechanisms, target–organ damage, external factors, and behavior of both physicians and patients closely interact. Therefore, it is not surprising that the results of several prospective, randomized controlled trials (RCT) 1–3 are in line with those of SYMPLICITY HTN–3, 4 and confirm that renal denervation (RDN) with the Symplicity catheter (Medtronic Inc, Minneapolis, MN) is not the miracle treatment for resistant hypertension as initially suggested. 5 Moreover, its efficacy, even in a subset of patients with resistant hypertension, remains to be clearly documented. Other RDN catheters using different methods for RDN will have to be tested in appropriately designed randomized controlled studies. The large heterogeneity of the blood pressure (BP)–lowering effects of RDN reported in the different trials is multifactorial, as extensively discussed by experts in the field in the scientific contribution published in this issue of Journal of the American Society of Hypertension. 6 We would like to emphasize here the major confounding influence of the ongoing oral antihypertensive treatment in each individual trial, which deserves a special attention since different strategies were used among the various trials. It should also be kept in mind that RDN was initially developed to achieve BP control in patients with uncontrolled hypertension despite being treated with multiple and complex antihypertensive treatment regimens, and not to replace the ongoing antihypertensive treatment. The aim of RDN is to neutralize the renal sympathetic hyperactivity, which is one among the various mechanisms implicated in the pathophysiology of resistance to antihypertensive treatment, including volume overload, aldosterone excess, endothelin–1 over–activity, increased arterial stiffness, or renal fibrosis, as well as external contributing factors such as excess dietary sodium and alcohol intake, obesity, interfering drugs or substance of abuse, drug–drug interactions, non–compliance to treatment, and physician inertia etc. 7 Therefore, the BP response to RDN cannot be reliably evaluated in an isolated manner without taking into account: (1) the intensity of the ongoing antihypertensive treatment in terms of both combinations of different classes of antihypertensive drugs as well as their doses prescribed by the physicians and (2) full compliance and adherence of the patients to the prescribed regimen. After RDN, any uncontrolled reduction of the antihypertensive treatment (drugs or doses) by either physicians, patients, or both will make more complex, and thus impede, a reliable evaluation of the BP response to RDN because of the combination of two effects acting in opposite directions: RDN
TL;DR: The data suggest that clamp-derived insulin sensitivity is not a stable feature in young men, and thatFamily history of hypertension and baseline triglycerides were associated with future insulin sensitivity, especially in men with a family history of diabetes, and irrespective of blood pressure status 17 years earlier.
Abstract: OBJECTIVE Low insulin sensitivity is closely related to both cardiovascular diseases and diabetes development. Still, correlates of insulin sensitivity have mainly been examined in cross-sectional studies. As far as we are aware, the longitudinal stability of insulin sensitivity in young men is largely unknown. We aimed for the first time to examine both the stability (tracking) and longitudinal predictors of future insulin sensitivity in healthy young men with and without a family history of diabetes or hypertension. METHODS We performed a 17-year follow-up study of a cohort of 100 healthy young men. Cardiovascular risk markers, including insulin sensitivity measured by the gold standard method--hyperinsulinaemic isoglycaemic glucose clamp--were examined both at baseline and at follow-up. RESULTS Baseline insulin sensitivity showed no significant correlation with insulin sensitivity at follow-up, whereas all other measured cardiovascular risk markers had significant correlation (tracking coefficients 0.4-0.7). In multiple regression analyses, family history of hypertension and baseline triglycerides remained the negative predictors of future insulin sensitivity. This was driven by the strong correlations in men with family history of diabetes. CONCLUSION Our data suggest that clamp-derived insulin sensitivity is not a stable feature in young men, and that family history of hypertension and baseline triglycerides were associated with future insulin sensitivity, especially in men with a family history of diabetes, and irrespective of blood pressure status 17 years earlier. These findings provide further insight into the development of insulin sensitivity and related diseases.
TL;DR: The SYMPLICITY HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension) study was a randomized, sham-controlled clinical study of the blood pressure-lowering effects of renal sympathetic denervation, which included ambulatory BP measurements (ABPM) as part of the inclusion.
TL;DR: In patients with TRH, the overall BP lowering effect of RDN is not superior to control, and RDN should not be considered as a treatment modality of RHT in clinical practice.
Abstract: Objective: Renal sympathetic denervation (RDN) has been and is still proposed as a new treatment modality in patients with treatment resistant hypertension (TRH), a condition defined as persistent blood pressure (BP) elevation despite prescription of at least 3 antihypertensive drugs, including a diuretic. However, the randomized controlled evidence that RDN effectively lowers BP is scarce and contradictory. This study investigated the current effectiveness of RDN for TRH. Design and method: We performed a systematic review and meta-analysis of the randomized controlled trials (RCT) that reported office and ambulatory systolic BP in RDN and control (sham control or drug adjustment) groups at 6 months of follow-up in patients with TRH. Pooled effect sizes were derived, using a random-effects model. Results: The literature search identified five RCTs with 867 randomized patients. In the pooled analysis, RDN was not associated with a significant decrease, either in office systolic BP (weighted mean difference (WMD): - 4.21 mmHg, 95% confidence interval: -17.12 to 8.69, p = 0.52), or in 24-h ambulatory systolic BP (WMD: -1.94 mmHg, 95% confidence interval: -6.05 to 2.17 mmHg, p = 0.36) compared to control at 6-months of follow-up. Figure. No caption available. Conclusions: In patients with TRH, the overall BP lowering effect of RDN is not superior to control. Accordingly, RDN should not be considered as a treatment modality of RHT in clinical practice. Future research should identify the characteristics of patients who might respond to RDN, effective ablation dose and measure that could confirm that RDN do occur.
TL;DR: The findings indicate that a systolic blood pressure of 190 mmHg or more at moderate workload is associated with future risk of CHD among apparently healthy middle-aged men.
Abstract: Objective:A hypertensive response to exercise at moderate workload is associated with future risk of coronary heart disease (CHD) and mortality. Yet there is still no consensus regarding the cut-off value for an inappropriate increase in exercise systolic blood pressure. We have previously shown tha
TL;DR: B+A has superior CV protection over B+H in high‐risk hypertensive patients independent of baseline PP although the absolute treatment effect is enhanced in the higher tertiles of PP where event rates are higher.
Abstract: Pulse pressure (PP) is an independent risk factor for cardiovascular (CV) disease and death but few studies have investigated the effect of antihypertensive treatments in relation to PP levels before treatment. The Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial showed that the combination of benazepril+amlodipine (B+A) is superior to benazepril+hydrochlorothiazide (B+H) in reducing CV events. We aimed to investigate whether the treatment effects in the ACCOMPLISH trial were dependent on baseline PP. High-risk hypertensive patients (n=11,499) were randomized to double-blinded treatment with single-pill combinations of either B+A or B+H and followed for 36 months. Patients were divided into tertiles according to their baseline PP and events (CV mortality/myocardial infarction or stroke) were compared. Hazard ratios (HRs) for the treatment effect (B+A over B+H) were calculated in a Cox regression model with age, coronary artery disease, and diabetes mellitus as covariates and were compared across the tertiles. The event rate was increased in the high tertile of PP compared with the low tertile (7.2% vs 4.4% P<.01). In the high and medium PP tertiles, HRs were 0.75 (95% confidence interval [CI], 0.60-0.95; P=.018) and 0.74 (CI, 0.56-0.98, P=.034), respectively, in favor of B+A. There was no significant difference between the treatments in the low tertile and no significant differences in treatment effect when comparing the HRs between tertiles of PP. B+A has superior CV protection over B+H in high-risk hypertensive patients independent of baseline PP although the absolute treatment effect is enhanced in the higher tertiles of PP where event rates are higher.
TL;DR: High BP and high BP variability were independently and linearly associated with the development of neurologic deterioration in acute ischemic stroke.
Abstract: E arly neurological deterioration is an indicator of poor outcome after acute ischemic stroke [1]. The condition can be caused by different mechanisms, for example progression of thrombus, development of cerebral edema and hemorrhagic transformation [2]; it affects up to a quarter of all acute stroke patients and raises the risk of death or disability two to three-fold [3]. In this issue of Journal of Hypertension, Chung et al. [4] report their data on the association between blood pressure (BP) and the development of early neurological deterioration. In their retrospective study, they observed a consecutive series of patients hospitalized for acute ischemic stroke within 24 h of onset. The primary outcome was the development of early neurological deterioration according to predefined criteria within the first 72 h of stroke onset. For systolic blood pressure (SBP) and diastolic blood pressure (DBP) variability, they used the difference between the maximum and minimum recordings, the standard deviation and the coefficient of variation. They also studied effects of maximum and mean SBP and DBP. Of 1161 patients, 210 (18%) developed early neurological deterioration. All BP parameters (except for the difference between maximum and minimum SBP) were linearly and significantly associated with early neurological deterioration, independent of mean BP and clinical variables. After adjustments for confounders, the odds for early neurological deterioration increased with 14–21% with an increase of one standard deviation in any of the BP parameters. The authors conclude that high BP and high BP variability were independently and linearly associated with the development of neurologic deterioration in acute ischemic stroke. BP may contribute to the development of early neurological deterioration and poor outcome by affecting cerebral perfusion. For example, reduced cerebral haemodynamic
Journal Article•
TL;DR: Visit-to-visit systolic blood pressure variability predicts stroke and cardiac events in high risk hypertensive patients receiving valsartan or amlodipine, and independent of mean BP.
Abstract: Objective: High blood pressure variability has been associated with an increased risk of cardiovascular events. We aimed to assess if increased visit-to-visit variability in systolic blood pressure increases the risk of stroke or cardiac events (fatal/non-fatal coronary or heart failure events) in the VALUE population. Design and method: The VALUE trial was a randomised-controlled, double-masked investigation of valsartan versus amlodipine in patients 50 years or older with hypertension and high risk of cardiovascular events. Mean follow-up time was 4.2 years. We calculated the standard deviation (SD) of mean systolic blood pressure from visits from 6 months onward, excluding patients with less than 2 visits, or stroke or cardiac events during the first 6 months. In the pooled treatment arms, we grouped SD in quintiles and compared the risk of stroke or cardiac events in the highest and the lowest quintile, using a Cox regression model, adjusting for a number of prognostic variables, including randomised treatment and mean BP from 6 months onwards. Results: Of 14.146 patients included, 1278 (9.0%) experienced a cardiac event and 473 (3.3%) experienced a stroke. Compared to patients with the lowest variability, those in the highest quintile had an increased risk of stroke or cardiac events (HR 1.4, 95% CI 1.0–1.8, p = 0.045 and HR 1.9, 95% CI 1.6–2.3, p < 0.0001, respectively, Figure). Conclusions: Visit-to-visit systolic BP variability predicts stroke and cardiac events in high risk hypertensive patients receiving valsartan or amlodipine, and independent of mean BP. Systolic blood pressure variability was a stronger predictor of cardiac events than of stroke. Figure. No caption available.
TL;DR: Drug treatment of mild hypertensive men initiated in the 1970s did not reduce mortality at first myocardial infarction or total mortality, however, during the period when large changes in hypertension treatment practices occurred into regimes with more use of combination therapies including metabolically neutral drugs at lower doses, beneficial effects on MI mortality could be observed.
01 Jan 2015
TL;DR: This chapter will offer some examples of this relationship mainly based on past work by the authors on organ damages of more common assessment in clinical practice as well as of a more clear prognostic value, i.e. left ventricular hypertrophy, increased urinary protein excretion or reduction of glomerular filtration rate and carotid intima-media thickening or plaques.
Abstract: A large number of studies in experimental animals and man show that angiotensin II, catecholamines and many other substances with cardiovascular and/or metabolic effects can favour alterations of organ function and structure independently on their ability to modify blood pressure (BP). There is, however, also a large body of evidence that these alterations are related to BP levels “per se” both in untreated and treated hypertensive patients. This chapter will offer some examples of this relationship mainly based on past work by the authors. The examples will largely focus on organ damages of more common assessment in clinical practice as well as of a more clear prognostic value, i.e. left ventricular hypertrophy, increased urinary protein excretion or reduction of glomerular filtration rate and carotid intima-media thickening or plaques. However, other types of organ damage will be also mentioned, albeit more briefly.