[Show abstract][Hide abstract] ABSTRACT: The blood pressure (BP)-lowering effect of renal sympathetic nervous denervation (RDN) in resistant hypertension (rHT) shows large variation among studies.
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.
Of 5652 patients screened in seven trials, 985 (17.4%) 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 58.1 years, systolic/diastolic office and 24 h BP 168.5/93.3 mmHg and 151.8/86.1 mmHg, respectively, and estimated glomerular filtration rate (eGFR) 79.3 ml/min/1.73 m². For BP outcomes, there was heterogeneity among trials. Pooled effects (control minus RDN) were -4.9/-3.5 mmHg (95% confidence interval, -20.9 to 11.1/-8.9 to 1.9) for office BP, -2.8/-1.5 mmHg (-6.5 to 0.8/-3.3 to 0.4) for 24 h BP and 0.81 ml/min/1.73 m² (-1.69 to 3.30) for eGFR. Removing one trial at a time produced confirmatory results. Adverse events occurred in 7.4% and 9.9% of control and RDN patients, respectively (p = 0.24).
In selected rHT patients maintained on antihypertensive drugs, RDN with the SYMPLICITY systems does not significantly decrease BP but is safe. Future trials with next-generation catheters should aim at identifying responders in patients with evidence of sympathetic nervous overactivity.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
Journal of Hypertension 06/2015; DOI:10.1097/HJH.0000000000000632 · 4.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 that exercise blood pressure at 100W workload (SBP100W) > 200 mmHg is associated with increased risk of CHD and mortality. We now aimed to investigate the possible association between SBP100W >/= 190mmHg and risk of CHD over up to 28 years follow-up.
Of the 1999 apparently healthy, middle-aged men who underwent thorough medical examination and laboratory testing, including a symptom-limited bicycle ergometer test, during 1972-1975, 1392 men were still healthy at survey 2 seven years later and completed a workload of 100 W at both surveys. Systolic blood pressure was measured near completion of the 100W stage (SBP100W). By comparing subjects having SBP100W >/=190 mmHg at baseline, follow-up or both(n=365) with subjects having SBP100W < 190 mmHg at both surveys (n = 1027), we estimated the risk of CHD (angina pectoris, non-fatal myocardial infarction and death from coronary heart disease).
The combined endpoint of CHD occurred in 452 of the 1392 men; 243 events among the 365 men with SBP100W >/= 190 mmHg. When adjusting for survey 1 smoking status, age, systolic blood pressure at rest, total cholesterol and family history of coronary heart disease, there was a 1.38-fold (CI 1.11-1.71, p < 0.005) increased risk of CHD. When further adjusting for physical fitness, SBP100W >/=190mmHg was associated with a 1.35-fold (1.08-1.65) increased risk of CHD.
Our 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.(Figure is included in full-text article.).
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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).
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 is included in full-text article.).
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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 is included in full-text article.) 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: 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 patients with atrial fibrillation. Moreover, the relationship of digoxin use to mortality in hypertensive patients with atrial fibrillation has not been examined.
All-cause mortality was examined in relation to in-treatment digoxin use in 937 hypertensive patients with ECG left ventricular hypertrophy in atrial fibrillation at baseline (n = 134) or who developed atrial fibrillation during follow-up (n = 803), randomly assigned to losartan or atenolol-based treatment, in post-hoc analysis of a substudy of the Losartan Intervention For Endpoint Reduction in hypertension (LIFE) trial. During 4.7 ± 1.1 years of mean follow-up, 167 patients died (17.8%) and 372 (39.7%) were treated with digoxin. In univariate Cox analyses, in-treatment digoxin use, entered as a time-varying covariate, was associated with a 61% higher risk of dying (hazard ratio 1.61, 95% confidence interval 1.18-2.19, P = 0.003). After adjusting for other univariate predictors of death in this population, including age, diabetes, history of ischemic heart disease, stroke, or heart failure, baseline Cornell product, QRS duration, heart rate, serum glucose, creatinine and high-density lipoprotein cholesterol, and a propensity score for digoxin use entered as standard covariates, and for in-treatment heart rate, pulse pressure, and Sokolow-Lyon voltage treated as time-varying covariates, digoxin use was no longer a significant predictor of mortality (hazard ratio 1.04, 95% confidence interval 0.73-1.48, P = 0.839).
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. These findings suggest that factors other than digoxin use may account for the increased mortality found with digoxin use in some studies.
Journal of Hypertension 03/2015; 33(7). DOI:10.1097/HJH.0000000000000559 · 4.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the Oslo cardiovascular study of 1972–3 a 5-year randomized trial in mild to moderate hypertension was performed. Several changes in treatment practices have been recommended since that time. We followed the mortality patterns up to 40 years.
European Journal of Internal Medicine 02/2015; 26(2). DOI:10.1016/j.ejim.2015.01.013 · 2.30 Impact Factor
[Show abstract][Hide abstract] 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.
Frontiers in Physiology 02/2015; 6. DOI:10.3389/fphys.2015.00009 · 3.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite the availability of effective pharmacological treatments to aid the control of blood pressure, the global rate of uncontrolled blood pressure remains high. As such, further measures are required to improve blood pressure control. Recently, several national and international guidelines for the management of hypertension have been published. These aim to provide easily accessible information for healthcare professionals and patients to aid the diagnosis and treatment of hypertension. In this review, we have compared new and current guidelines from the American and International Societies of Hypertension; the American Heart Association, American College of Cardiology and the US Center for Disease Control and Prevention; the panel appointed to the Eighth Joint National Committee; the European Societies of Hypertension and Cardiology; the French Society of Hypertension; the Canadian Hypertension Education Program; the National Institute for Health and Clinical Excellence (UK); the Taiwan Society of Cardiology and the Chinese Hypertension League. We have identified consensus opinion regarding best practises for the management of hypertension and have highlighted any discrepancies between the recommendations. In general there is good agreement between the guidelines, however, in some areas, such as target blood pressure ranges for the elderly, further trials are required to provide sufficient high-quality evidence to form the basis of recommendations.