Showing papers by "Sverre E. Kjeldsen published in 2007"

2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Abstract: 2007 Guidelines for the Management of Arterial Hypertension : The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the Management of Arterial Hypertension.

Abstract: Authors/Task Force Members: Giuseppe Mancia, Co-Chairperson (Italy), Guy De Backer, Co-Chairperson (Belgium), Anna Dominiczak (UK), Renata Cifkova (Czech Republic), Robert Fagard (Belgium), Giuseppe Germano (Italy), Guido Grassi (Italy), Anthony M. Heagerty (UK), Sverre E. Kjeldsen (Norway), Stephane Laurent (France), Krzysztof Narkiewicz (Poland), Luis Ruilope (Spain), Andrzej Rynkiewicz (Poland), Roland E. Schmieder (Germany), Harry A.J. Struijker Boudier (Netherlands), Alberto Zanchetti (Italy)

2007 Guidelines for the management of arterial hypertension

Abstract: For several years the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) decided not to produce their own guidelines on the diagnosis and treatment of hypertension but to endorse the guidelines on hypertension issued by the World Health Organization (WHO) and International Society of Hypertension (ISH)1,2 with some adaptation to reflect the situation in Europe. However, in 2003 the decision was taken to publish ESH/ESC specific guidelines3 based on the fact that, because the WHO/ISH Guidelines address countries widely varying in the extent of their health care and availability of economic resource, they contain diagnostic and therapeutic recommendations that may be not totally appropriate for European countries. In Europe care provisions may often allow a more in-depth diagnostic assessment of cardiovascular risk and organ damage of hypertensive individuals as well as a wider choice of antihypertensive treatment. The 2003 ESH/ESC Guidelines3 were well received by the clinical world and have been the most widely quoted paper in the medical literature in the last two years.4 However, since 2003 considerable additional evidence on important issues related to diagnostic and treatment approaches to hypertension has become available and therefore updating of the previous guidelines has been found advisable. In preparing the new guidelines the Committee established by the ESH and ESC has agreed to adhere to the principles informing the 2003 Guidelines, namely 1) to try to offer the best available and most balanced recommendation to all health care providers involved in the management of hypertension, 2) to address this aim again by an extensive and critical review of the data accompanied by a series of boxes where specific recommendations are given, as well as by a concise set of practice recommendations to be published soon thereafter as already done in 2003; …

2007 ESH-ESC guidelines for the management of arterial hypertension - The task force for the management of arterial hypertension of the European society of hypertension (ESH) and of the European society of cardiology (ESC)

Abstract: Authors/Task Force Members: Giuseppe Mancia, Co-Chairperson (Italy), Guy De Backer, Co-Chairperson (Belgium), Anna Dominiczak (UK), Renata Cifkova (Czech Republic) Robert Fagard (Belgium), Giuseppe Germano (Italy), Guido Grassi (Italy), Anthony M. Heagerty (UK), Sverre E. Kjeldsen (Norway), Stephane Laurent (France), Krzysztof Narkiewicz (Poland), Luis Ruilope (Spain), Andrzej Rynkiewicz (Poland), Roland E. Schmieder (Germany), Harry A.J. Struijker Boudier (Netherlands), Alberto Zanchetti (Italy)

Regression of Electrocardiographic Left Ventricular Hypertrophy During Antihypertensive Therapy and Reduction in Sudden Cardiac Death The LIFE Study

Abstract: Regression of electrocardiographic left ventricular hypertrophy during antihypertensive therapy and reduction in sudden cardiac death : the LIFE Study.

Regression of electrocardiographic left ventricular hypertrophy is associated with less hospitalization for heart failure in hypertensive patients

Abstract: Regression of left ventricular hypertrophy (LVH) has been associated with reductions in various cardiovascular outcomes, but heart failure outcomes have not been carefully studied. Okin and colleag...

Exceptional early blood pressure control rates: The ACCOMPLISH trial

Abstract: Background. ACCOMPLISH is a “new‐generation” hypertension trial assessing single‐tablet combination therapy for initial treatment of high‐risk hypertension. At baseline, 97% of subjects were treate...

Impact of New-Onset Diabetes Mellitus on Cardiac Outcomes in the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) Trial Population

Abstract: There has been a lot of interest about new-onset diabetes mellitus in recent hypertension trials, but the implications of diabetes development on cardiac outcomes have not been known. In the Valsartan Antihypertensive Long-Term Use Evaluation trial, 15 245 high-risk patients were followed for an average of 4.2 years. At baseline, 5250 patients were diabetic by the 1999 World Health Organization criteria, and among the 9995 nondiabetic patients, 1298 patients developed diabetes during follow-up. We have investigated the influence of diabetes development on outcomes in the Valsartan Antihypertensive Long-Term Use Evaluation trial. The patients with diabetes at baseline and new-onset diabetes were compared with patients who did not develop diabetes by a Cox regression model with adjustment for prespecified covariates (age, diabetes status, left ventricular hypertrophy, baseline coronary heart disease, and randomized study treatment). Patients with diabetes at baseline had the highest cardiac morbidity defined as myocardial infarction and heart failure with a hazard ratio of 2.20 (95% CI: 1.95 to 2.49). The patients with new-onset diabetes had significantly higher cardiac morbidity, especially more congestive heart failure, than those without diabetes, with a hazard ratio of 1.43 (95% CI: 1.16 to 1.77). This indicates that patients who develop diabetes during antihypertensive treatment have cardiac morbidity intermediate between diabetic subjects and those subjects who never had diabetes and that it is of importance to find these patients at risk of diabetes development and optimize lifestyle and medical treatment.

Baseline characteristics in the Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial: A hypertensive population at high cardiovascular risk

Abstract: ACCOMPLISH is the first trial designed to compare the effects on major fatal and non-fatal cardiovascular endpoints of two forms of antihypertensive combination therapy: benazepril plus hydrochlorothiazide and amlodipine plus benazepril in hypertensive patients at high cardiovascular risk. Enrollment for this trial is now complete and this report describes the clinical characteristics of the study cohort. Patients with hypertension and a previous history of cardiovascular events, strokes or diabetes mellitus were randomized to double-blind treatment with either of the two combination regimens. The data in this report detail the clinical history and demographic characteristics in patients immediately prior to randomization to study drugs. A total of 11,454 patients were randomized. Mean age (+/-SD) was 68.4+/-6.9 years, 60% were men, and 1360 (12%) were African American. Mean body mass index (BMI) was 31.0+/-6.3 kg/m(2). At study entry, 46% of patients had a history of acute coronary syndromes, coronary artery bypass grafts or percutaneous coronary interventions; 13% had a history of stroke. A history of diabetes mellitus was reported in 6928 (60%) of patients. Mean blood pressure at baseline (on prior hypertension therapy) was 145.4/80.0 mmHg; only 38% of patients had a BP less than 140/90 mmHg. Overall, 97% of patients had received previous antihypertensive treatment (74% on at least two drugs); 53% were on oral diabetes therapy or insulin, 68% on anti-lipid therapy and 63% on anti-platelet agents. In summary, the ACCOMPLISH trial has recruited hypertensive patients at high risk of cardiovascular morbidity and mortality. It is noteworthy that the mean BMI of 31 in this cohort is clearly above the accepted diagnostic criterion of obesity and that 60% of patients are diabetic, possibly reflecting secular trends in clinical disease.

In-Treatment Resolution or Absence of Electrocardiographic Left Ventricular Hypertrophy Is Associated With Decreased Incidence of New-Onset Diabetes Mellitus in Hypertensive Patients: The Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) Study

Abstract: Treatment of hypertensive patients with electrocardiographic left ventricular hypertrophy with losartan-based therapy is associated with lower incidence of diabetes mellitus and greater regression of hypertrophy than atenolol-based therapy. However, whether in-treatment resolution or continued absence of electrocardiographic hypertrophy is independently associated with decreased incidence of diabetes is unclear. Electrocardiographic hypertrophy was evaluated over time in 7998 hypertensive patients without diabetes at baseline in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study who were treated with losartan- or atenolol-based regimens and followed with serial electrocardiograms and blood pressure determinations. Electrocardiographic hypertrophy was defined using gender-adjusted Cornell voltage-duration product criteria >2440 mm.ms. During mean follow-up of 4.6+/-1.2 years, diabetes developed in 562 patients (7.0%). In a Cox model adjusting for treatment assignment, in-treatment resolution or continued absence of Cornell product hypertrophy was associated with a 38% lower risk of new diabetes (HR 0.62, 95% CI 0.50 to 0.78). After adjusting for the association of new diabetes with prior antihypertensive treatment, baseline glucose, and Framingham risk score, baseline and in-treatment systolic and diastolic pressure, HDL, uric acid, and body mass index, and the decreased incidence associated with losartan-based therapy, in-treatment continued absence, or resolution of Cornell product hypertrophy remained associated with a 26% lower risk of new diabetes (HR 0.74, 95% CI 0.58 to 0.93). Thus, compared with presence of hypertrophy by Cornell product criteria during antihypertensive treatment, resolution or continued absence of Cornell product hypertrophy is associated with a lower incidence of diabetes, even after adjusting for the impact of treatment with losartan and other risk factors for diabetes.

Clusters of metabolic risk factors predict cardiovascular events in hypertension with target-organ damage: the LIFE study

Abstract: The relation of metabolic syndrome (MetS) with cardiovascular outcome may be less evident when preclinical cardiovascular disease is present. We explored, in a post hoc analysis, whether MetS predicts cardiovascular events in hypertensive patients with electrocardiographic left ventricular hypertrophy (ECG-LVH) in the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study. MetS was defined by >or=2 risk factors plus hypertension: body mass index >or=30 kg/m(2), high-density lipoprotein (HDL)-cholesterol or=6.1 mmol/l (>or=110 mg/dl) fasting or >or=7.8 mmol/l (>or=140 mg/dl) nonfasting or diabetes. Cardiovascular death and the primary composite end point (CEP) of cardiovascular death, stroke and myocardial infarction were examined. In MetS (1,591 (19.3%) of 8,243 eligible patients), low HDL-cholesterol (72%), obesity (77%) and impaired glucose (73%) were similarly prevalent, with higher blood pressure, serum creatinine and Cornell product, but lower Sokolow-Lyon voltage (all P<0.001). After adjusting for baseline covariates, hazard ratios for CEPs and cardiovascular death (4.8+/-1.1 years follow-up) were 1.47 (95% confidence interval (CI), 1.27-1.71)- and 1.73 (95% CI, 1.38-2.17)-fold higher with MetS (both P<0.0001), and were only marginally reduced when further adjusted for diabetes, obesity, low HDL-cholesterol, non-HDL-cholesterol, pulse pressure and in-treatment systolic blood pressure and heart rate. Thus, MetS is associated with increased cardiovascular events in hypertensive patients with ECG-LVH, independently of single cardiovascular risk factors.

Prevention of new-onset atrial fibrillation and its predictors with angiotensin II-receptor blockers in the treatment of hypertension and heart failure

Abstract: Atrial fibrillation is the most frequent occurring sustained cardiac arrhythmia and it is related to common cardiac disease conditions. Hypertension increases the risk of atrial fibrillation by approximately two-fold and, because of the high prevalence of hypertension, it accounts for more cases of atrial fibrillation than any other risk factor. In recent years, there are two large hypertension trials (LIFE and VALUE) and two large heart failure trials (CHARM and Val-HeFT) reporting the beneficial effect of angiotensin II-receptor blockers (ARBs) on new-onset atrial fibrillation, beyond the blood pressure-lowering effect. Blockade of the renin-angiotensin system may prevent left atrial dilatation, atrial fibrosis, dysfunction and conduction velocity slowing. Some studies also indicate direct anti-arrhythmic properties. This review aims to consider the preventive effect of ARBs on new-onset atrial fibrillation observed in recent reports from these trials, and to discuss possible mechanisms of the beneficial effect of angiotensin II-receptor blockade.

The effect of baseline physical activity on cardiovascular outcomes and new-onset diabetes in patients treated for hypertension and left ventricular hypertrophy: the LIFE study.

Abstract: Fossum E, Gleim GW, Kjeldsen SE, Kizer JR, Julius S, Devereux RB, Brady WE, Hille DA, Lyle PA, Dahlof B (University of Oslo, Oslo, Norway, Merck Research Laboratories, West Point, PA; University of Michigan, Ann Arbor, MI, Comell University, New York, NY, USA; and University Hospital/Ostra, Goteborg, Sweden). The effect of baseline physical activity on cardiovascular outcomes and new-onset diabetes in patients treated for hypertension and left ventricular hypertrophy: the LIFE study. J Intern Med 2007; 262: 439-448. Objectives. Physical activity (PA) is a preventive strategy for cardiovascular disease and for managing cardiovascular risk factors. There is little information on the effectiveness of PA for the prevention of cardiovascular outcomes once cardiovascular disease is present. Thus, we studied the relationship between PA at baseline and cardiovascular events in a high-risk population. Design. A prespecified analyses of observational data in a prospective, randomized hypertension study. Setting. Losartan Intervention For Endpoint reduction in hypertension (LIFE) study Subjects. Hypertension and left ventricular hypertrophy (LVH) (n = 9193). Interventions. Losartan versus atenolol. Main outcome measures. Reported level of PA: never exercise, exercise ≤30 min twice per week, or exercise >30 min twice per week at baseline and after a mean of 4.8 years of treatment with losartan- versus atenolol-based therapy. Risk reductions were calculated by level of PA for the primary composite end-point and its components cardiovascular death, stroke and myocardial infarction, and also all-cause mortality and new-onset diabetes. Results. A modest level of PA (>30 min twice per week) was associated with significant reductions in risk for the primary composite end-point [adjusted hazard ratio (aHR) 0.70, P 30 min twice per week) in patients with hypertension and LVH in the LIFE study was associated with significant reductions in risk for the primary composite end-point and its components of cardiovascular death, stroke, and myocardial infarction, all-cause mortality, and new-onset diabetes.

Decreased levels of asymmetric dimethylarginine during acute hyperinsulinemia.

Abstract: Endothelial dysfunction is reflected by an impaired nitric oxide (NO)-mediated vasodilatation. Insulin resistance may be linked to endothelial dysfunction by several mechanisms, including disturbances in signaling pathways common to both insulin action and NO production. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, may contribute to endothelial dysfunction, and elevated ADMA levels have been associated with both insulin levels and the degree of insulin resistance. The direct link between insulin and ADMA, however, has not yet been established. In the present study, we aimed to investigate the effects of acute hyperinsulinemia on circulating ADMA and L-arginine levels and on forearm blood flow (FBF). Male volunteers, aged 21 to 24 years, with borderline hypertension were included in the study. The participants underwent a 90-minute hyperinsulinemic isoglycemic glucose clamp with insulin levels at the postprandial levels (n=20) or a saline infusion (control) (n=9). Fasting blood samples were drawn at baseline and after 90 minutes. Insulin infusion was accompanied by a reduction in ADMA (0.78 to 0.68 micromol/L, P<.01), which was significantly different (P=.001) from the increase seen in the saline control group (0.69 to 0.79 micromol/L, P<.05). The same profile was obtained for L-arginine with a significantly more pronounced decrease (P<.001) in the insulin clamp group (74 to 61 micromol/L, P<.001) than in the saline control group (59 to 57 micromol/L, P=.95). The FBF level and nitrate/nitrite (NOx) levels were not affected by any of the clamp procedures. Short-term administration of insulin was accompanied by a decrease in both ADMA and L-arginine levels, with no change in FBF, in our population of young men with borderline hypertension. The possible influence of insulin on ADMA levels in a chronic state of insulin resistance can, however, not be deduced from the present investigation.

Ambulatory blood pressure monitoring after 1 year on valsartan or amlodipine-based treatment: a VALUE substudy

Abstract: ObjectiveThe ambulatory blood pressure (ABP) monitoring substudy of the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial was carried out in a subset of patients from USA, Italy and Denmark. ABP was measured after 1 year in the trial, with the aim of evaluating comparability of ABP l

Improved insulin sensitivity by the angiotensin II–receptor blocker losartan is not explained by adipokines, inflammatory markers, or whole blood viscosity

Abstract: We have previously found improved insulin sensitivity after antihypertensive treatment with an angiotensin II-receptor blocker as compared with a calcium channel blocker in hypertensives. In this study, we compare the effect of these 2 principal different vasodilating agents on levels of adipokines, inflammatory variables, and whole blood viscosity in the same hypertensive patients with cardiovascular risk factors. We test whether potential differences in these variables might explain the difference seen in insulin sensitivity. Twenty-one hypertensive patients (11 women, 10 men) with mean age of 58.6 years and blood pressure of 160 +/- 3/96 +/- 2 mm Hg entered a 4-week run-in period with open-label amlodipine 5 mg. Thereafter, they were randomized double-blindly to additional treatment with amlodipine 5 mg or losartan 100 mg; and after 8 weeks of treatment, all patients underwent laboratory testing. After a 4-week washout phase with open-label treatment, the participants were crossed over to the opposite treatment regimen for 8 weeks before final examination. No significant differences were seen in the blood levels of adiponectin (7814 +/- 870 vs 8090 +/- 967 ng/mL), leptin (961 +/- 122 vs 965 +/- 147 pmol/L), resistin (11.7 +/- 1.0 vs 11.3 +/- 0.7 ng/mL), plasminogen activator inhibitor 1 activity (23.9 +/- 2.2 vs 25.1 +/- 2.2 U/mL), tumor necrosis factor alpha (1.35 +/- 0.11 vs 1.72 +/- 0.28 pg/mL), and high-sensitivity C-reactive protein (3.09 +/- 0.84 vs 2.09 +/- 0.42 mg/L) between treatment with amlodipine 10 mg or losartan 100 mg + amlodipine 5 mg, respectively. Although no significant differences in whole blood viscosity and blood pressure were observed between the 2 treatment regimens, a consistent trend toward lower viscosity was found at all shear rates as vasodilatory treatment was intensified (baseline to amlodipine 5 mg to amlodipine 10 mg to losartan 100 mg + amlodipine 5 mg). Our data do not support that effects on adipokines, inflammatory markers, and whole blood viscosity could explain improved insulin sensitivity seen on AT1-receptor blockade.

Amlodipine and valsartan: calcium channel blockers/angiotensin II receptor blockers combination for hypertension

Abstract: Despite the availability of numerous antihypertensive agents, many patients with hypertension fail to achieve the blood pressure goals set out in current guidelines. These patients remain at a high risk of cardiovascular morbidity and mortality and require effective treatment options to reduce that risk. Current guidelines recognize that many patients require multiple antihypertensive agents to achieve blood pressure goals. Numerous combination therapies are available, although there is currently no available fixed-dose alternative that combines the benefits of angiotensin receptor blockers and calcium channel blockers. This article explores the rationale for using multiple-mechanism therapy with the angiotensin receptor blocker valsartan and the calcium channel blocker amlodipine and discusses the clinical data supporting this novel approach to the treatment of hypertension.

Personality may influence reactivity to stress

Abstract: Possible mechanisms behind psychophysiological hyperreactivity may be located at a cognitive-emotional level. Several personality traits have been associated with increased cardiovascular reactivity. Subjects with white coat hypertension, which may constitute a kind of hyperreactivity, are found to suppress their emotions and adapt to the surroundings to a larger extent than controls. We hypothesized in this study that a) stress reactivity is related to personality, and that b) responses to cold pressor test (CPT) and mental stress test (MST) are associated with different personality traits. 87 men were selected from the 1st, 50th and 99th percentile of a blood pressure screening. Cardiovascular and catecholamine responses to MST and CPT were recorded. Fifteen personality traits were assessed using the Karolinska Scale of Personality. Possible independent explanatory predictors for cardiovascular and catecholamine variables at baseline and during stress were analyzed in multiple linear regression analyses using a stepwise forward procedure. Multiple regression analyses showed that muscular tension (β = 0.298, p = 0.004), irritability (β = 0.282, p = 0.016), detachment (β = 0.272, p = 0.017), psychasthenia (β = 0.234, p = 0.031) and somatic anxiety (β = 0.225, p = 0.046) were significant explanatory variables of reactivity to CPT. During MST, verbal aggression (β = -0.252, 0.031) and detachment (β = 0.253, p = 0.044) were significant predictors of norepinephrine and diastolic blood pressure response, respectively. Based on KSP-trait quartiles, delta (Δ) systolic (p = 0.025) and Δ diastolic blood pressure (p = 0.003) during MST were related to detachment score, with the highest reactivity in the 4th quartile, while Δ norepinephrine was significantly related to muscular tension (p = 0.033). Δ systolic and Δ diastolic blood pressure responses to CPT were dependent on detachment (p = 0.049 and p = 0.011, respectively) and psychasthenia (p = 0.020 and p = 0.015), while high verbal aggression was associated with lower reactivity measured by Δ norepinephrine (p = 0.037). The present study indicates that stress reactivity is clearly related to different personality traits, without any single trait being dominant over others. Furthermore, personality seems to have as much, or even more, importance of predicting responses to CPT than responses to MST.

Blood pressure reduction and antihypertensive medication use in the losartan intervention for endpoint reduction in hypertension (LIFE) study in patients with hypertension and left ventricular hypertrophy.

Abstract: Blood pressure reduction and antihypertensive medication use in the losartan intervention for endpoint reduction in hypertension (LIFE) study in patients with hypertension and left ventricular hypertrophy.

The kidney and cardiovascular risk – Implications for management: A consensus statement from the European Society of Hypertension

Abstract: Cardiovascular and renal diseases share many of the same risk factors. In fact, renal failure is usually accompanied by an increased global cardiovascular risk. Thus, preservation of kidney function might simultaneously protect the heart and the brain and, conversely, addressing cardiovascular risk factors might safeguard the kidney. This review considers the evidence supporting this approach, focusing on the protective effect of blood-pressure lowering and the ancillary actions of antihypertensive agents on renal protection. We review recent evidence on renal protection in individuals with and without diabetes, and the importance of offering a high standard of care also to those with the metabolic syndrome or prediabetes in order to prevent initial forms of renal, and as a consequence, cardiovascular damage. Intervention may be appropriate even in individuals with high-normal blood pressure, if they already have early renal and/or cardiovascular risk markers. As a consequence of these insights, thresholds for starting antihypertensive therapy are gradually falling, whereas awareness of the need for an early intervention in patients at high risk of developing renal damage and simultaneously cardiovascular disease is growing.

The antioxidative effects of long-term treatment are more pronounced for carvedilol than for atenolol in post-myocardial infarction patients.

Abstract: Oxidative stress might exert deleterious cardiovascular effects. The aim of the present study was to compare the antioxidative effects of carvedilol and atenolol. Levels of oxidized low-density lipoprotein cholesterol (ox-LDL), vitamin E, and thiobarbituric acid reactive substances (TBARS) were measured. In a prospective, open, and end-point-blinded study, 232 patients with an acute myocardial infarction (AMI) were randomized to receive either carvedilol or atenolol at equipotent doses, and the previously mentioned 3 parameters were measured at baseline and after 12 months of active treatment, with changes during the study period being compared both within and between the groups. Ox-LDL decreased in both treatment modalities, from 40.5 +/- 15.6 to 35.0 +/- 13.8 U/L, P = 0.0001, in the carvedilol group and from 40.3 +/- 16.5 to 37.4 +/- 13.1 U/L, P = 0.044, in the atenolol group, with a significant between-group difference in the changes (P = 0.036). The levels of vitamin E did not change during carvedilol treatment (31.0 +/- 10.2 vs 31.7 +/- 11.1 micromol/L), but it decreased marginally in the atenolol group (30.8 +/- 12.1 vs 27.2 +/- 9.1 micromol/L, P = 0.056), with a significant between-group difference (P = 0.008). No significant change in TBARS was observed between the carvedilol and atenolol groups (P = 0.454). These results indicate that carvedilol has a more pronounced antioxidative effect than atenolol in post-AMI patients, which might be of clinical importance.

Increased hematocrit before blood pressure in men who develop hypertension over 20 years.

Abstract: We have previously demonstrated that neurohormonal activity can predict left ventricular (LV) mass in men who developed hypertension over 20 years. The aim of the study was to investigate early markers of cardiac and hemorheological changes at baseline in these men, i.e., before a rise in blood pressure. Fifty-six middle-aged men were followed for 20 years; 22 were sustained hypertensives, 17 developed hypertension, and 17 were sustained normotensives. They were compared at baseline (42 years) and follow-up (62 years). We investigated Cornell voltage product and Sokolow-Lyon voltage, hematocrit (Hct), and echocardiographic LV parameters. There was no sign of LV hypertrophy by electrocardiography (ECG) at baseline. Baseline Hct discriminated between the groups ( P = .015) and correlated to diastolic blood pressure (DBP) at baseline ( r = 0.37, P = .006) and follow-up ( r = 0.31, P = .020). Regression analysis identified baseline Hct as an independent correlate of DBP in the cohort at baseline when they were untreated (β = .33, P = .013, R 2 = 0.25), and of borderline significance at follow-up (β = .26, P = .060, R 2 = 0.12) despite possible interference by antihypertensive drugs. Hct was elevated at baseline compatible with the hypothesis that pathogenic hemorheological processes could be activated at the outset and prior to cardiac changes in men who later develop hypertension.

Effect of hemoglobin levels on cardiovascular outcomes in patients with isolated systolic hypertension and left ventricular hypertrophy (from the LIFE study).

Abstract: The optimal hemoglobin level in patients with hypertension or heart failure is not yet defined. The aim of the present investigation was to examine the relation of hemoglobin with cardiovascular outcomes in high-risk patients with isolated systolic hypertension (ISH) and left ventricular hypertrophy (LVH). In 1,326 patients with ISH in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study, hemoglobin and cardiovascular outcomes were examined using Cox proportional hazard models. Baseline hemoglobin was negatively related to rate of cardiovascular death (hazard ratio 0.81 per 1 g/dl, 95% confidence interval [CI] 0.67 to 0.98, p = 0.032) after adjusting for baseline Framingham risk score, LVH, treatment, and estimated glomerular filtration rate. Hemoglobin decreased slightly during the study and the decrease was more pronounced in the losartan group (13.9 ± 1.3 to 13.6 ± 1.4 g/dl) than in the atenolol group (13.9 ± 1.2 to 13.8 ± 1.4 g/dl). Hemoglobin as a time-varying covariate was negatively associated with rate of cardiovascular death (hazard ratio 0.75, 95% CI 0.63 to 0.90, p <0.001) and stroke (hazard ratio 0.84, 95% CI 0.72 to 0.99, p = 0.040) after adjusting for baseline Framingham risk score, LVH, treatment, and estimated glomerular filtration rate. In conclusion, in this high-risk population with ISH and LVH, lower hemoglobin at baseline was associated with higher probability of cardiovascular death, and decrease in hemoglobin over time was associated with higher probability of cardiovascular death or stroke; this effect was attenuated by treatment with losartan.

Risk of diabetes in a real-world setting among patients initiating antihypertensive therapy with valsartan or amlodipine.

Abstract: In the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial, the risk of new-onset diabetes was reported to be 23% lower among patients initiating therapy with valsartan versus amlodipine. The objective of our study was to examine whether this finding is generalizable to 'real-world' clinical practice. A retrospective cohort design and a large US health insurance database were employed for analyses. Study subjects included all hypertensive patients, aged >or=35 years, who were free from diabetes and who initiated treatment with valsartan (n=9999) or amlodipine (n=18 698) between January 1999 and March 2005. Unadjusted absolute risks of diabetes were 21.4 (95% confidence interval (CI) 18.9-24.3) and 26.3 (95% CI 24.3-28.3) per 1000 patient-years for valsartan and amlodipine, respectively; the corresponding relative risk (RR) for valsartan was 0.82 (95% CI 0.70-0.94). Multivariate analyses - controlling for age, sex, presence of hypercholesterolemia, cardiovascular disease and kidney disease, and pretreatment medical care expenditures - yielded similar results (RR=0.79, 95% CI 0.68-0.92). Our study thus corroborates the finding from VALUE that diabetes risk is lower for patients who receive valsartan versus amlodipine, and extends this finding to a 'real-world' setting.

Atenolol as a comparator in outcome trials in hypertension: A correct choice in the past, but not for the future?

Abstract: Objective. Twelve years after the design of the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, which showed superiority of losartan‐ vs atenolol‐based therapy for cardio...

Arterial plasma vasopressin and aldosterone predict left ventricular mass in men who develop hypertension over 20 years.

Abstract: Left ventricular (LV) hypertrophy is related to blood pressure level and neurohormonal factors. The authors previously demonstrated that arterial norepinephrine levels predict LV mass in middle-aged men who developed hypertension through 20 years. The aim of this 20-year prospective study was to investigate arterial vasopressin, aldosterone, and renin as long-term predictors of LV mass. Normotensives (n=17), subjects who developed hypertension (n=17), and sustained hypertensives (n=22) were compared at baseline (42 years) and at follow-up (62 years). There were no significant differences in baseline vasopressin, aldosterone, or renin levels. The group with sustained hypertension had more LV hypertrophy (P=.025) at follow-up. Among new hypertensives, multiple regression analysis demonstrated that baseline arterial vasopressin (beta-0.53; P=.041) and aldosterone (beta-0.56;P=.032) independently explained LV mass index (R(2)=0.85; P=.035). In conclusion, baseline arterial vasopressin and aldosterone, but not renin, appear to predict LV mass in middle-aged men who developed hypertension over a 20-year period.

Tissue Doppler imaging describes diastolic function in men prone to develop hypertension over twenty years

Abstract: Aims Hypertension is one of several risk factors of cardiovascular disease and is associated with left ventricular (LV) systolic and diastolic dysfunction. A method for reliably detecting the onset of LV dysfunction before transition to irreversible damage of the myocardium would be of crucial importance in subjects with essential hypertension. Methods and results Subjects with clear differences in BP level, development and duration of the hypertensive disease were examined at the age of 60 yrs: normotensives (n ¼ 17), new hypertensives who developed hypertension over a 20 year period (n ¼ 15) and hypertensives (n ¼ 19). Relationships between conventional echocardiographic and tissue velocities imaging (TVI) parameters compared to LV parameters, and TVI as an estimate of LV function were explored. E 0 (TVI peak early diastolic velocity) (P ¼ 0.006) and E/E 0 (P ¼ 0.002) demonstrated differences in diastolic function between the groups. There were no significant differences regarding systolic myocardial velocities. E 0 correlated to S 0 (TDI peak systolic velocity) (r ¼ 0.32, P ¼ 0.026) and was independently predicted by S 0 (R 2 ¼ 0.24, P ¼ 0.025) in multivariate analysis. E 0 correlated negatively to LV mass index (r ¼ 20.34, P ¼ 0.012), also in multivariate regression analysis (R 2 ¼ 0.12, P ¼ 0.032).

Fixed combination of losartan and hydrochlorothiazide and reduction of risk of stroke.

Abstract: A fixed-dose combination of losartan/hydrochlorothiazide (HCTZ) therapy may be a logical choice for antihypertensive treatment, including for initial therapy in patients with blood pressure elevation >20/10 mmHg above treatment target. The renin–angiotensin– aldosterone–system-activating effect of hydrochlorothiazide augments the efficacy of blocking the angiotensin II type 1 (AT1) receptor with losartan. Some adverse effects associated with hydrochlorothiazide, including increased risk for new-onset diabetes mellitus, may be offset by losartan. Losartan was frequently administered with hydrochlorothiazide in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, in which there was a 25% risk reduction for stroke in the losartan-based compared with the atenolol-based treatment group. The efficacy, tolerability, and convenience of losartan/HCTZ combination therapy may increase patient compliance and lower risk for stroke, a devastating outcome in patients with hypertension.