Showing papers by "Sverre E. Kjeldsen published in 2012"
TL;DR: This position statement intends to facilitate a better understanding of the effectiveness, safety, limitations and issues still to be addressed with RDN.
Abstract: Experts from the European Society of Hypertension prepared this position paper in order to summarize current evidence, unmet needs and practical recommendations on the application of percutaneous transluminal ablation of renal nerves [renal denervation (RDN)] as a novel therapeutic strategy for the treatment of resistant hypertension. The sympathetic nervous activation to the kidney and the sensory afferent signals to the central nervous system represent the targets of RND. Clinical studies have documented that catheter-based RDN decreases both efferent sympathetic and afferent sensory nerve traffic leading to clinically meaningful systolic and diastolic blood pressure (BP) reductions in patients with resistant hypertension. This position statement intends to facilitate a better understanding of the effectiveness, safety, limitations and issues still to be addressed with RDN.
273 citations
TL;DR: It seems some classes are superior to others in the prevention of new-onset atrial fibrillation and prevention of stroke and new classes of anticoagulants that do not require international normalized ratio monitoring have been introduced with promising results.
Abstract: Hypertension is the most common cardiovascular disorder and atrial fibrillation is the most common clinically significant arrhythmia. Both these conditions frequently coexist and their prevalence increases rapidly with aging. There are different risk factors and clinical conditions predisposing to the development of atrial fibrillation, but due its high prevalence, hypertension is still the main risk factor for the development of atrial fibrillation. Several pathophysiologic mechanisms (such as structural changes, neurohormonal activation, fibrosis, atherosclerosis, etc.) have been advocated to explain the onset of atrial fibrillation. The presence of atrial fibrillation per se increases the risk of stroke but its coexistence with high blood pressure leads to an abrupt increase of cardiovascular complications. Different risk models are available for the risk stratification and the prevention of thromboembolism in patients with atrial fibrillation. In all of them hypertension is present and is an important risk factor. Antihypertensive treatment may contribute to reduce this risk, and it seems some classes are superior to others in the prevention of new-onset atrial fibrillation and prevention of stroke. Antithrombotic treatment with warfarin is effective in the prevention of thromboembolic events, although quite recently, new classes of anticoagulants that do not require international normalized ratio monitoring have been introduced with promising results.
196 citations
TL;DR: An increased HR is a long-term predictor of cardiovascular events in patients with high-risk hypertension and this effect was not modified by good blood pressure control.
Abstract: A high heart rate (HR) predicts future cardiovascular events. We explored the predictive value of HR in patients with high-risk hypertension and examined whether blood pressure reduction modifies this association. The participants were 15,193 patients with hypertension enrolled in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial and followed up for 5 years. The HR was assessed from electrocardiographic recordings obtained annually throughout the study period. The primary end point was the interval to cardiac events. After adjustment for confounders, the hazard ratio of the composite cardiac primary end point for a 10-beats/min of the baseline HR increment was 1.16 (95% confidence interval 1.12 to 1.20). Compared to the lowest HR quintile, the adjusted hazard ratio in the highest quintile was 1.73 (95% confidence interval 1.46 to 2.04). Compared to the pooled lower quintiles of baseline HR, the annual incidence of primary end point in the top baseline quintile was greater in each of the 5 study years (all p
155 citations
TL;DR: Upper normal blood pressures are long-term predictors of incident AF in initially healthy middle-aged men in a population-based study of middle-aging men.
Abstract: Hypertension is the most prevalent risk factor for incident atrial fibrillation (AF). Recently, even high normal blood pressures (BPs) have been established as predictive of AF in women. We aimed t...
137 citations
TL;DR: In this article, the Losartan intervention for endpoint reduction in hypertension study, a double-blind, randomized (losartan versus atenolol) parallel-group study, including 9193 patients with hypertension and electrocardiographic left ventricular hypertrophy, showed that PP was the strongest single blood pressure predictor of new-onset AF determined by the decrease in the -2 Log likelihood statistic.
Abstract: Previous studies have found pulse pressure (PP), a marker of arterial stiffness, to be an independent predictor of atrial fibrillation (AF) in general and hypertensive populations. We examined whether PP predicted new-onset AF in comparison with other blood pressure components in the Losartan Intervention For Endpoint reduction in hypertension study, a double-blind, randomized (losartan versus atenolol), parallel-group study, including 9193 patients with hypertension and electrocardiographic left ventricular hypertrophy. In 8810 patients with neither a history of AF nor AF at baseline, Minnesota coding of electrocardiograms confirmed new-onset AF in 353 patients (4.0%) during mean 4.9 years of follow-up. In multivariate Cox regression analyses, baseline and in-treatment PP and baseline and in-treatment systolic blood pressure predicted new-onset AF, independent of baseline age, height, weight, and Framingham Risk Score; sex, race, and treatment allocation; and in-treatment heart rate and Cornell product. PP was the strongest single blood pressure predictor of new-onset AF determined by the decrease in the -2 Log likelihood statistic, in comparison with systolic blood pressure, diastolic blood pressure, and mean arterial pressure. When evaluated in the same model, the predictive effect of systolic and diastolic blood pressures together was similar to that of PP. In this population of patients with hypertension and left ventricular hypertrophy, PP was the strongest single blood pressure predictor of new-onset AF, independent of other risk factors.
58 citations
TL;DR: It is concluded that high concentrations of these relatively pure anthocyanins do not reduce BP in healthy men with a high normal BP.
Abstract: High intakes of flavonoids are associated with reduced cardiovascular risk, and flavonoids such as cocoa and soy protein isolate have shown beneficial effects on blood pressure (BP). Anthocyanins constitute a flavonoid subgroup consumed in regular diets, but few studies have assessed the antihypertensive potential of anthocyanins. We aimed to assess whether high concentrations of relatively pure anthocyanins reduce BP and alter cardiovascular and catecholamine reactivity to stress. A total of 31 healthy men between 35-51 years of age with screening BP >140/90 mm Hg, not on antihypertensive or lipid-lowering medication, were randomised in a double-blind crossover study to placebo versus 320-mg anthoycanins twice daily. Treatment duration was 4 weeks, with a 4-week washout. Sitting and supine BP measurements, ambulatory BP recording and stress reactivity were assessed and analyzed by a paired sample t-test. In all, 27 patients completed all visits. Sitting systolic BP (primary endpoint) was 133 mm Hg after placebo versus 135 mm Hg after anthocyanin treatment (P=0.25). Anthocyanins did neither affect semiautomatic oscillometric BP measurements in the sitting or supine position nor 24-h ambulatory BP. No significant differences in stress reactivity were found across treatment periods. Overall, we conclude that high concentrations of these relatively pure anthocyanins do not reduce BP in healthy men with a high normal BP.
56 citations
TL;DR: The findings support the suggestion from SCAST that blood pressure reduction may be harmful and that routine blood pressure-lowering treatment should probably be avoided in the acute phase.
Abstract: Background and Purpose—The Scandinavian Candesartan Acute Stroke Trial (SCAST) found no benefits of candesartan in acute stroke. In the present analysis we aim to investigate the effect of change in blood pressure during the first 2 days of stroke on the risk of early adverse events and poor outcome. Methods—SCAST was a multicenter, randomized controlled, double-blind trial of candesartan in acute stroke. The trial recruited 2029 patients presenting within 30 hours of acute stroke and with systolic blood pressure (SBP) ≥140 mm Hg. Treatment was given for 7 days. Change in blood pressure was defined as the difference in SBP between baseline and Day 2 and was used to divide patients into groups with increase/no change, a small decrease, moderate decrease, or large decrease in SBP. The primary effect parameter was early adverse events (recurrent stroke, stroke progression, and symptomatic hypotension) during the first 7 days, analyzed using logistic regression, with the group with a small decrease in SBP as ...
56 citations
TL;DR: The need for randomized evaluation of treatment to more aggressive vs. conventional SBP targets is supported, aschieved SBP 130 mmHg or less is not associated with lower cardiovascular risk and is associated with a significantly increased risk of death and trend towards increased cardiovascular mortality.
Abstract: Background:Hypertensive patients with ECG left-ventricular hypertrophy (LVH) are at increased risk of cardiovascular morbidity and mortality, and regression of ECG LVH is associated with improved cardiovascular outcomes. Although tighter control of systolic blood pressure (SBP) has been associated w
50 citations
TL;DR: Within the authors' lean baseline cohort of healthy middle-age men, a BMI of ≥28 kg/m(2) and weight gain of ≥10 kg from age 25 to midlife were long-term predictors of incident AF in men with physical fitness below the population median.
Abstract: The incidence of both atrial fibrillation (AF) and obesity is increasing in the community, and lifestyle intervention is recommended. We aimed to test whether the predictive effect of body mass index (BMI) and weight change from age 25 years to midlife on incident AF were influenced by physical fitness. In 1972 to 1975, 2,014 healthy middle-age men conducted a bicycle exercise electrocardiographic test as a part of a cardiovascular survey program, defining physical fitness as work performed divided by body weight. During 35 years of follow-up, 270 men developed AF, documented by scrutiny of the health files in all Norwegian hospitals. Risk estimation was analyzed using Cox proportional hazard models and tested for age-adjusted physical fitness above and below the median. The mean BMI of 24.6 kg/m 2 defined a lean baseline cohort. The men with a baseline BMI of ≥28 kg/m 2 (11%) compared to a BMI 2 had a 1.68-fold risk of AF (95% confidence interval 1.14 to 2.40) and men reporting weight gain of ≥10 kg (24%) compared to weight loss (11%) of 1.66-fold (95% confidence interval 1.00 to 2.89), respectively. The dichotomy into men with age-adjusted physical fitness above and below the median, demonstrated statistically significant risk associations only for men with low fitness. The overall risk of AF was reduced by 23% in the fit men. In conclusion, within our lean baseline cohort of healthy middle-age men, a BMI of ≥28 kg/m 2 and weight gain of ≥10 kg from age 25 to midlife were long-term predictors of incident AF in men with physical fitness below the population median. The fit men had an overall slightly reduced risk of AF.
40 citations
TL;DR: The data suggest that cTnT is a better predictor of long-term mortality after CABG surgery than CK-MB, and similar results were found when the biomarkers were analyzed together in a Cox model adjusting for European System for Cardiac Operative Risk Evaluation.
37 citations
TL;DR: Regression of time-varying Cornell product was associated with similar reductions in risk of new-onset HF and the combined endpoint of HF or death in ISH and non-ISH patients.
TL;DR: Benazepril coupled to amlodipine was a more effective antihypertensive treatment than when coupled to hydrochlorothiazide in non-Black patients to reduced kidney disease progression, and Blacks have a modestly higher increased risk for more advanced increases in serum creatinine than non-Blacks.
TL;DR: Independent of prior cardiovascular history or baseline BP, hypertensive patients requiring combination therapy, which includes a thiazide diuretic for BP control, have a poorer cardiovascular prognosis than those controlled by monotherapy and only a nonsignificantly lower event rate than noncontrolled patients.
Abstract: Objectives:To determine whether blood pressure (BP) control in hypertensive patients achieved with combination drug therapy provides the same cardiovascular benefits as with single-agent therapy.Background:Drug combinations, most often including hydrochlorothiazide (HCTZ), are now recommended for ro
TL;DR: The higher risk of SCD inblack patients persists after adjusting for the higher prevalence of risk factors in black patients, in- treatment blood pressure, and the established predictive value of in-treatment electrocardiographic left ventricular hypertrophy and heart rate for SCD for this population.
TL;DR: Earlier use of antihypertensive FDC (including first-line) may help to shrink the current gap between antihyertensive use and BP target control achieved, and suggest that physicians may need to readdress their approach to anti Hypertensive treatment.
Abstract: Objective:To contemplate how initial antihypertensive therapy with fixed-dose combinations (FDC) might be incorporated into clinical practice, based on a compilation of evidence comparing FDCs with monotherapy and loose-dose combinations in varying patient populations.Methods:A non-systematic search of PubMed (from 2007 to 2012) was performed for randomized, controlled trials in order to capture the evidence on FDC versus monotherapy and loose-dose combinations as first-line therapy. The literature search focused on calcium channel blocker (CCB)–renin angiotensin system (RAS) blocker combinations. Additionally, any relevant papers known to the authors were included. International recommendations from published hypertension treatment guidelines were also consulted.Results:The results of this literature review identified two emergent issues. Firstly, there is a discord between antihypertensive use and actual blood pressure (BP) control achieved – despite an increase in the use of antihypertensives o...
TL;DR: High-density lipoprotein cholesterol (HDL) is a strong predictor of long term risk of CHD, fatal CHD and fatal CVD in healthy middle-aged men and physical fitness or its changes had no impact on the ability of HDL to predict CHD.
TL;DR: A greater in-treatment HR on the serial electrocardiograms predicts a greater risk of incident HF during antihypertensive treatment, independent of the covariates, in patients with hypertension with Electrocardiographic left ventricular hypertrophy.
Abstract: An elevated heart rate (HR) at rest at baseline is associated with an increased risk of incident heart failure (HF) and with greater cardiovascular event rates in patients with chronic HF. However, despite the high attributable risk of hypertension for HF, whether the in-treatment HR predicts incident HF in patients with treated hypertension has not been evaluated. The HR was evaluated on annual electrocardiograms from 9,024 patients with hypertension without HF who were treated with losartan- or atenolol-based regimens. During a mean follow-up of 4.7 ± 1.1 years, HF developed in 285 patients (3.2%). On multivariate Cox analyses adjusted for randomized treatment, the baseline risk factors for HF, baseline and in-treatment blood pressure, QRS duration, and electrocardiographic left ventricular hypertrophy, a greater in-treatment HR predicted a 45% greater adjusted risk of new HF for every 10-beats/min increase in the HR (95% confidence interval [CI] 34% to 57%) or a 159% greater risk of HF in patients with the persistence or development of a HR of ≥84 beats/min (95% CI 88% to 257%). In contrast, with adjustment for the same covariates, the baseline HR as a continuous variable was a significantly less powerful predictor of new HF (hazard ratio 1.15 per 10 beats/min, 95% CI 1.03 to 1.28) and a baseline HR of ≥84 beats/min did not predict new HF (hazard ratio 1.00, 95% CI 0.63 to 1.58). In conclusion, a greater in-treatment HR on the serial electrocardiograms predicts a greater risk of incident HF during antihypertensive treatment, independent of the covariates, in patients with hypertension with electrocardiographic left ventricular hypertrophy. These findings support serial HR assessment to improve the risk stratification of patients with hypertension.
TL;DR: There are probably no important pharmacogenetic interactions for BP reduction with use of beta-blockers, diuretics or diltiazem, and nominally significant associations for rs12946454 and rs11191548 are true signals and could be of possible clinical relevance for deciding treatment of polygenic essential hypertension.
Abstract: OBJECTIVE:: We aimed to test whether eight common recently identified single-nucleotide polymorphisms (SNPs), strongly associated with blood pressure (BP) in the population, also have impact on the degree of BP reduction by antihypertensive agents with different mechanisms. METHODS:: In 3863 Swedish hypertensive patients, we related number of unfavorable alleles of each SNP (i.e. alleles associated with higher baseline BP) to the magnitude of BP reduction during 6 months of monotherapy with either a beta-blocker, a thiazide diuretic or diltiazem. RESULTS:: For six SNPs (rs16998073, rs1378942, rs3184504, rs1530440, rs16948048, rs17367504) no pharmacogenetic interactions were suggested, whereas two SNPs showed nominal evidence of association with treatment response: PLCD3-rs12946454 associated with more SBP (beta = 1.53 mmHg per unfavorable allele; P = 0.010) and DBP (beta = 0.73 mmHg per unfavorable allele; P = 0.014) reduction in patients treated with diltiazem, in contrast to those treated with beta-blockers or diuretics wherein no treatment response association was found. CYP17A1-rs11191548 associated with less DBP reduction (beta = -1.26 mmHg per unfavorable allele; P = 0.018) in patients treated with beta-blockers or diuretics, whereas there was no treatment response association in diltiazem-treated patients. However, if accounting for multiple testing, the significant associations for rs12946454 and rs11191548 were attenuated. CONCLUSION:: For a majority of these, eight recently identified BP-associated SNPs, there are probably no important pharmacogenetic interactions for BP reduction with use of beta-blockers, diuretics or diltiazem. Whether the nominally significant associations for rs12946454 and rs11191548 are true signals and could be of possible clinical relevance for deciding treatment of polygenic essential hypertension should be further tested. (Less)
TL;DR: The evaluation of an individual attributable risk forms the basis of clinical guidelines for the prevention of cardiovascular diseases worldwide, and a recalibrated Framingham cardiovascular risk prediction equation will provide similar results to the equations developed from Asian cohorts.
Abstract: Epidemiological estimates (1,2) indicate that more than a quarter of the adult world population are hypertensive: an approximate one billion people with diagnosed and undiagnosed hypertension, a fi...
TL;DR: Patients with diabetes mellitus have a high risk of cardiovascular disease, and the latter is the leading cause of premature mortality in diabetic patients, and intensive lifestyle intervention and often combinations of different antihypertensive drugs must be initiated.
Abstract: Patients with diabetes mellitus have a high risk of cardiovascular disease, and the latter is the leading cause of premature mortality in diabetic patients. Treatment of risk factors and comorbidities, such as hypertension, is very important and may effectively prevent cardiovascular events. The blood pressure goal in diabetic patients should be below 140/90 mmHg, probably down to 130-135/85 mmHg, although the evidence for this is scarce. To reach this blood pressure goal, intensive lifestyle intervention and often combinations of different antihypertensive drugs must be initiated. In combination treatment, a blocker of the renin-angiotensin system should be included, and according to the results of the ACCOMPLISH trial, a combination of a renin-angiotensin system blocker and a calcium channel blocker should probably be the first choice.
TL;DR: The data suggest that alcohol intake above this level may be marginally deleterious, while no effect of smoking on risk of AF was detected in hypertensive patients with LVH and there were no significant interactions between high alcohol intake and either smoking or gender on the risk of getting AF.
Abstract: Background The incidence of new-onset atrial fibrillation (AF) is increased by uncontrolled hypertension, and antihypertensive treatment reduces new-onset AF However, it is unclear whether alcohol intake and smoking influence the risk of new-onset AF during antihypertensive treatment Methods In the Losartan Intervention For Endpoint reduction in Hypertension (LIFE) study, a double-blinded, randomized, parallel-group study, 9193 hypertensive patients with electrocardiogram (ECG)-documented left ventricular hypertrophy (LVH), randomized to once-daily losartan- or atenolol-based antihypertensive therapy were followed for a mean of 48 years At baseline, 8831 patients (54% women, mean age 67 years, mean blood pressure 174/98 mmHg after placebo run-in) had neither a history of AF nor AF on ECG, and they were thus at risk of developing this condition during the study Results New-onset AF occurred in 353 (4%) patients Univariate Cox analyses showed that intake of alcohol > 10 units/week compared
TL;DR: The beneficial effect of losartan versus atenolol-based antihypertensive treatment on pulse pressure, HDL-C, UACR, and Cornell and Sokolow–Lyon voltage were not more pronounced in patients older than67 years compared to patients younger than 67 years.
Abstract: Background: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study has previously demonstrated a beneficial effect of losartan compared to atenolol-based antihypertensive tre ...
TL;DR: Low‐grade systolic murmurs in healthy middle‐aged individuals: innocent or clinically significant?
Abstract: . Bodegard J, Skretteberg PT, Gjesdal K, Pyorala K, Kjeldsen SE, Liestol K, Erikssen G, Erikssen J (Oslo University Hospital, Oslo; University of Oslo, Oslo; University of Eastern Finland, Kuopio; University of Oslo, Oslo; Oslo University Hospital, Oslo). Low-grade systolic murmurs in healthy middle-aged individuals: innocent or clinically significant? A 35-year follow-up study of 2014 Norwegian men. J Intern Med 2012; 271: 581–588.
Objective. To determine whether a low-grade systolic murmur, found at heart auscultation, in middle-aged healthy men influences the long-term risk of aortic valve replacement (AVR) and death from cardiovascular disease (CVD).
Setting and subjects. During 1972–1975, 2014 apparently healthy men aged 40–59 years underwent an examination programme including case history, clinical examination, blood tests and a symptom-limited exercise ECG test. Heart auscultation was performed under standardized conditions, and murmurs were graded on a scale from I to VI. No men were found to have grade V/VI murmurs. Participants were followed for up to 35 years.
Results. A total of 1541 men had no systolic murmur; 441 had low-grade murmurs (grade I/II) and 32 had moderate-grade murmurs (grade III/IV). Men with low-grade murmurs had a 4.7-fold [95% confidence interval (CI) 2.1–11.1] increased age-adjusted risk of AVR, but no increase in risk of CVD death. Men with moderate-grade murmurs had an 89.3-fold (95% CI 39.2–211.2) age-adjusted risk of AVR and a 1.5-fold (95% CI 0.8–2.5) age-adjusted increased risk of CVD death.
Conclusions. Low-grade systolic murmur was detected at heart auscultation in 21.9% of apparently healthy middle-aged men. Men with low-grade murmur had an increased risk of AVR, but no increase in risk of CVD death. Only 1.6% of men had moderate-grade murmur; these men had a very high risk of AVR and a 1.5-fold albeit non-significant increase in risk of CVD death.
TL;DR: A low serum K is independently associated with a greater likelihood and severity of Cornell product LVH during antihypertensive therapy.
Abstract: Background. Low serum potassium (K) is associated with increased blood pressure, impaired cardiac function and renal dysfunction. Although lower serum K is associated with cardiac hypertrophy in an ...
TL;DR: The novel ARNI concept is currently being tested in a large outcomes trial in patients with heart failure with reduced ejection fraction and may also have potential therapeutic value in heart failure patients with preserved ejectedion fraction.
Abstract: The Renin-Angiotensin–Aldosterone System (RAAS) is central to blood pressure (BP) control, and chronic activation of the system, as occurs in some hypertensive patients, leads to damage of target o...
TL;DR: Irrespective of treatment, patients in the USA and Caucasians achieved better SBP control, whereas higher baseline SBP and more previous antihypertensive medications indicated less control.
Abstract: Background. The ACCOMPLISH Trial investigated intensive antihypertensive combination treatment with benazepril + amlodipine (B+A) or benazepril + hydrochlorothiazide (B+H) on cardiovascular outcomes in patients with systolic hypertension. We analyzed the baseline predictors of achieving a systolic blood pressure (SBP) Nordic region) and Caucasian ethn...
01 Jan 2012
TL;DR: In this article, a double-blinded crossover study was conducted to evaluate whether a purified anthocyanin supplement improves cardiovascular metabolic risk factors and markers of inflammation and oxidative stress in prehypertensive participants, and whether plasma polyphenols are increased 1-3 h following intake.
Abstract: High intake of fruits and vegetables is associated with reduced cardiovascular risk. A number of fruits and vegetables are rich in anthocyanins, which constitute a subgroup of the flavonoids. Anthocyanins have demonstrated anti-inflammatory and anti-oxidative properties, and anthocyanin-rich interventions have indicated beneficial effects on blood pressure and other cardiovascular risk factors. We assessed whether a purified anthocyanin supplement improves cardiovascular metabolic risk factors and markers of inflammation and oxidative stress in prehypertensive participants, and whether plasma polyphenols are increased 1-3 h following intake. In all, 31 men between 35-51 years with screening blood pressure >140/90 mm Hg without anti-hypertensive or lipid-lowering medication, were randomized in a double-blinded crossover study to placebo versus 640 mg anthocyanins daily. Treatment durations were 4 weeks with a 4-week washout. High-density lipoprotein (HDL)-cholesterol and blood glucose were significantly higher after anthocyanin versus placebo treatment (P=0.043 and P=0.024, respectively). No effects were observed on inflammation or oxidative stress in vivo, except for von Willebrand factor, which was higher in the anthocyanin period (P=0.007). Several plasma polyphenols increased significantly 1-3 h following anthocyanin intake. The present study strengthens the evidence that anthocyanins may increase HDL-cholesterol levels, and this is demonstrated for the first time in prehypertensive and non-dyslipidemic men. However, no other beneficial effects in the short term were found on pathophysiological markers of cardiovascular disease.
TL;DR: In the group of patients with recurrent stroke, lower baseline heart rate was associated with better neurological outcomes as measured with the Barthel index, and increased mortality risk persisted after adjusting for multiple confounders including baseline blood pressure.
Abstract: Michael Bohm and co-workers1 have reported on the relationship of cardiovascular and neurological outcomes to baseline heart rate after ischaemic stroke in 20 165 patients (mean age 66.1, SD 8.6 years) with baseline heart rate data assigned to the treatment arms of the PRoFESS trial. Patients were grouped by quintiles of baseline heart rate and were evaluated for a primary outcome of recurrent stroke, a secondary outcome of the composite of recurrent stroke, myocardial infarction, or death from a vascular cause, and were further assessed for new or worsening heart failure and non-vascular death. Additional pre-defined endpoints were disability after recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed with the Mini-Mental State Examination (MMSE) score at 4 weeks after randomization and at the penultimate visit.
Although there was no significant relationship of recurrent stroke, new myocardial infarction, or the composite secondary endpoint to baseline heart rate, these findings further support the strong relationship of heart rate to mortality. Patients in the two highest quintiles of heart rate (77–82 and >82 b.p.m.) were at higher risk for total death [hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.19–1.69; and HR 1.74, 95% CI 1.48–2.06, P 82 b.p.m., HR 1.66, 95% CI 1.29–2.13, P = 0.0016) was also strongly associated with higher baseline heart rate. Importantly, increased mortality risk persisted after adjusting for multiple confounders including baseline blood pressure. Perhaps most interesting, in the group of patients with recurrent stroke, lower baseline heart rate was associated with better neurological outcomes as measured with the Barthel index …
01 Jan 2012
TL;DR: A comprehensive meta-analysis of the results of 147 randomized trials involving 464,000 people in the context of epidemiological data from 958,000People indicated that the proportional reduction in cardiovascular disease events is the same or similar regardless of pretreatment blood pressure and the presence of cardiovascular disease.
Abstract: The accumulated evidence from numerous trials in many thousands of individuals with high blood pressure indicates that, compared with placebo or control therapy, antihypertensive drug treatment reduces the risk of stroke, coronary heart disease and progression of renal impairment. Benefits are seen in systolic and diastolic hypertension, in mild-to-moderate hypertension, in all age groups, and they appear to be constant in proportion across the blood pressure range. People at all levels of risk benefit; therefore, the bigger the absolute risk, the greater the absolute benefit. A comprehensive meta-analysis of the results of 147 randomized trials involving 464,000 people in the context of epidemiological data from 958,000 people indicated that the proportional reduction in cardiovascular disease events is the same or similar regardless of pretreatment blood pressure and the presence or absence of cardiovascular disease. Thus, whatever the risk level, comorbidity, or special groups, the most important thing is to lower blood pressure properly. All the different common antihypertensive drugs and most drug combinations can be used if well tolerated.
TL;DR: Higher in-treatment heart rate on serial ECGs predicts greater risk of incident heart failure during antihypertensive treatment, independent of covariates, in hypertensive patients with ECG left ventricular hypertrophy.
Abstract: Five decades ago, the status of hypertension as a risk factor for cardiovascular disease was a matter of debate. After further studies and the introduction of antihypertensive medications, few doubt the important role of hypertension in increasing cardiovascular risk. Today a growing body of evidence emphasizes the relationship between heart rate, hypertension and cardiovascular disease, and the measurement of heart rate is becoming an important component of cardiovascular risk assessment. The strongest evidence for a relationship between heart rate and cardiovascular morbidity and mortality is in white, middle-aged men, since most studies have been done in this subgroup. A similar relationship has been described in women, but the association is weaker than in men. The association between heart rate and hypertension has been well documented in cross-sectional studies that have observed a constellation of elevated heart rate, cardiac output and increased plasma catecholamines, the socalled “ hyperkinetic state ” in persons with borderline hypertension. There is evidence that this hyperkinetic state precedes the development of sustained hypertension and can be used as a prognostic index. While the evidence that heart rate predicts hypertension and cardiovascular disease is strong, to date most of the data supporting this relationship have come from epidemiologic observations or cross-sectional studies with single measurements of heart rate at the beginning of the study (1 – 10). Two papers from large randomized clinical trials in hypertension with repeated measurements of heart rate that came online ahead of print on December 12, 2011 add substantial evidence to the heart-rate story in hypertension (11,12). The relationship of in-treatment heart rate over time based on annual electrocardiograms (ECGs) to incident heart failure was evaluated in 9024 hypertensive patients without heart failure at baseline who were treated with losartanor atenolol-based regimens in the losartan intervention for endpoint reduction in hypertension (LIFE) study (11). During 4.7 1.1 years mean follow-up, heart failure developed in 285 patients (3.2%). In multivariate Cox analyses that adjusted for randomized treatment, baseline risk factors for heart failure, baseline and intreatment blood pressure, QRS duration and ECG left ventricular hypertrophy, higher in-treatment heart rate predicted 45% higher adjusted risk of new heart failure for every 10 beats per minute (bpm) higher heart rate (95% confi dence interval (CI) 34 – 57%) or 159% higher risk of heart failure in patients with persistence or development of a heart rate 84 bpm (95% CI 88 – 257%). With adjustment for the same covariates, baseline heart rate as a continuous variable was a signifi cantly less powerful predictor of new heart failure (hazard ratio 1.15 per 10 bpm, 95% CI 1.03 – 1.28) and a baseline heart rate 84 bpm did not predict new heart failure (hazard ratio 1.00, 95% CI 0.63 – 1.58). Thus, higher in-treatment heart rate on serial ECGs predicts greater risk of incident heart failure during antihypertensive treatment, independent of covariates, in hypertensive patients with ECG left ventricular hypertrophy. These interesting data add to previous observations from LIFE that higher in-treatment heart rate over time is associated with increased risk of cardiovascular and all-cause mortality and incident atrial fi brillation in patients with hypertension and left ventricular hypertrophy (13,14). The predictive value of heart rate in patients with high risk hypertension was further evaluated in a pre-planned secondary analysis of data from the Valsartan antihypertensive long-term use evaluation (VALUE) Trial (12). Participants were 15 193 Blood Pressure, 2012; 21: 1–2