Showing papers by "Sverre E. Kjeldsen published in 2003"
TL;DR: The reductions in major cardiovascular events with atorvastatin are large, given the short follow-up time, and may have implications for future lipid-lowering guidelines.
3,436 citations
01 Jun 2003
TL;DR: The Committee has tried to avoid giving rigid rules that would constrain judgement on the management of individual patients differing in their personal, medical and cultural characteristics.
2,534 citations
TL;DR: This large prospective study of hypertensive patients with left ventricular hypertrophy found that increasing albuminuria is associated with a graded increase in risk, and any threshold identified would be much lower than the threshold traditionally defined in diabetic populations.
Abstract: An increased urine albumin–creatinine ratio (UACR) is associated with increasing cardiovascular risk in hypertensive patients with left ventricular hypertrophy. The authors found no UACR values whe...
558 citations
TL;DR: Losartan-based antihypertensive therapy resulted in greater regression of ECG LVH by Cornell voltage-duration product and Sokolow-Lyon voltage criteria than did atenolol-based therapy, and these findings support the value of angiotensin receptor blockade with losartan for reversing ECGLVH.
Abstract: Background— Electrocardiographic left ventricular hypertrophy (LVH) predicts cardiovascular morbidity and mortality, and regression of ECG LVH may predict improved prognosis in hypertensive patients. However, uncertainty persists as to how best to regress ECG LVH. Methods and Results— Regression of ECG LVH with losartan versus atenolol therapy was assessed in 9193 hypertensive patients with ECG LVH by Sokolow-Lyon voltage or Cornell voltage-duration product criteria enrolled in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) Study. Patients had ECGs at study baseline and after 6 months, 1, 2, 3, 4, and 5 years of blinded losartan-based or atenolol-based therapy. After 6 months’ follow-up, adjusting for baseline ECG LVH levels, baseline and in-treatment systolic and diastolic pressures, and for diuretic therapy, losartan-based therapy was associated with greater regression of both Cornell product (adjusted means, −200 versus −69 mm · ms, P<0.001) and Sokolow-Lyon voltage (−2.5 versu...
264 citations
TL;DR: The VALUE study is executed in regular clinical settings and 92% of the patients received antihypertensive drugs at baseline and the achieved BP control exceeds values reported in most published large-scale trials.
107 citations
TL;DR: A subgroup analysis in the LIFE study was performed to determine whether angiotensin II AT1-receptor antagonism with losartan reduces cardiovascular morbidity and mortality, compared with active therapy with established -blockerbased therapy, in hypertensive participants with electrocardiogram-defined LVH.
Abstract: In hypertensive patients without clinically evident vascular disease, losartan and atenolol were equally effective in reducing blood pressure, but losartan was more effective in preventing cardiova...
74 citations
Journal Article•
54 citations
TL;DR: In healthy non-diabetic and non-hypertensive men, strong associations were found between fasting blood glucose and blood pressure at rest and during exercise and to development of elevated blood pressure after 7-years follow-up.
Abstract: ObjectiveTo assess whether fasting blood glucose is independently related to blood pressure at rest and during exercise, and to development of elevated blood pressureDesignCross-sectional and prospective cohort study of 2014 apparently healthy middle-aged menMethodsThe baseline survey included car
32 citations
TL;DR: The Joint National Committee (JNC) seventh report states that thiazide-type diuretics should be used for drug treatment in most patients with uncomplicated hypertension, either alone or combined with antihypertensive drugs from other classes.
Abstract: (2003). Editorial: Recent hypertension guidelines: JNC-7 and 2003 ESH/ESC. Blood Pressure: Vol. 12, No. 4, pp. 196-197.
22 citations
TL;DR: High thickness of the common carotid arteries was associated with LV hypertrophy and high deceleration time of early diastolic transmitral flow, and high MFVR wasassociated with low ratio between early and atrial LV filling peak flow velocity, which may suggest that systemic vascularhypertrophy contributes to abnormal diastsolic LV relaxation in patients with hypertension and electrocardiographic LV hyperTrophy.
Abstract: Vascular hypertrophy and insulin resistance have been associated with abnormal left ventricular (LV) geometry in population studies. We wanted to investigate the influence of vascular hypertrophy and insulin resistance on LV hypertrophy and its function in patients with hypertension. In 89 patients with essential hypertension and electrocardiographic LV hypertrophy, we measured blood pressure; insulin sensitivity by hyperinsulinaemic euglucaemic clamp; minimal forearm vascular resistance (MFVR) by plethysmography; intima-media cross-sectional area of the common carotid arteries (IMA) by ultrasound; and LV mass, relative wall thickness (RWT), systolic function and diastolic filling by echocardiography after two weeks of placebo treatment. LV mass index correlated to IMA/height (r=0.36, P=0.001), serum insulin (r=−0.25, P<0.05), plasma glucose (r=−0.34, P<0.01), and showed a tendency towards a correlation to insulin sensitivity (r=0.21, P=0.051), but was unrelated to MFVR. Deceleration time of early diastolic transmitral flow positively correlated to IMA/height (r=0.30, P<0.01). The ratio between early and atrial LV filling peak flow velocity negatively correlated to MFVRmen (r=−0.30, P<0.05). Endocardial and midwall systolic LV function were not related to vascular hypertrophy, plasma glucose, serum insulin or insulin sensitivity. In conclusion, insulin resistance was not related to LV hypertrophy or reduced LV function. However, high thickness of the common carotid arteries was associated with LV hypertrophy and high deceleration time of early diastolic transmitral flow. High MFVR was associated with low ratio between early and atrial LV filling peak flow velocity. This may suggest that systemic vascular hypertrophy contributes to abnormal diastolic LV relaxation in patients with hypertension and electrocardiographic LV hypertrophy.
16 citations
TL;DR: Data suggest that hemorheology may be involved in the uric acid metabolism in borderline as well as in established hypertensives, and may possibly be a link between SUA and cardiovascular risk.
Abstract: Serum uric acid (SUA) but also hemorheological parameters such as hematocrit (Hct) and whole blood viscosity (WBV) are markers of cardiovascular risk. Increased blood cell volume is one of the known causes of hyperuricemia. We therefore aimed to investigate the relationship between SUA and hemorheology in untreated borderline hypertensive young men (n = 67) and in subjects with established hypertension and left ventricular hypertrophy (n = 40) examined when they had been without treatment for 2 weeks. We found positive correlations between SUA and Hct (r = 0.46, p < 0.0001), hemoglobin (Hgb) (r = 0.40, p = 0.001), mean blood pressure (BP) (r = 0.39, p = 0.001) and body weight (r = 0.26, p = 0.036) in the borderline hypertensive young men. No relation between SUA and glucose disposal rate (GDR) assessed with hyperinsulinemic isoglycemic glucose clamp appeared (r = -0.06, p = 0.633). Multiple regression analysis showed that 33% of the variation in SUA could be explained by BP and Hct. We also found positive correlations between SUA and Hgb (r = 0.40, p = 0.011) and body weight (r = 0.42, p = 0.006) and an inverse trend with GDR (r = -0.27, p = 0.087) in the subjects with established hypertension. Multiple regression showed that 32% of the variation in SUA was explained by Hgb and body weight. These data suggest that hemorheology may be involved in the uric acid metabolism in borderline as well as in established hypertensives. Hemorheology may possibly be a link between SUA and cardiovascular risk. There was no relation between SUA and insulin resistance in these hypertensive groups.
TL;DR: In this long-term cardiovascular end point study in patients with moderate to severe hypertension and left ventricular hypertrophy, statins were not optimally administered and cholesterol levels were poorly controlled.
TL;DR: Clinical trials over the last decade that focused on the impact of anti-hypertensive agents and the subsequent occurrence of stroke were reviewed, finding that reductions in stroke risk that extend beyond blood pressure reduction are needed.
Abstract: (2003). Hypertension treatment and stroke prevention. Blood Pressure: Vol. 12, No. 5-6, pp. 264-268.
TL;DR: It appears that benefit has been shown in elderly patients for at least one representative agent of several drug classes (i.e. diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme inhibitors and angiotENSin receptor antagonists) and initiation of antihypertensive treatment in elderly Patients should follow the general guidelines.
Abstract: The 2003 European Society of Hypertension–European Society of Cardiology Guidelines for the management of arterial hypertension [1] conclude that there is little doubt from randomized controlled trials that elderly patients benefit from antihypertensive treatment in terms of reduced cardiovascular morbidity and mortality, irrespective of whether they have systolic–diastolic hypertension or isolated systolic hypertension [2,3]. It appears that benefit has been shown in elderly patients for at least one representative agent of several drug classes (i.e. diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists) [1]. Initiation of antihypertensive treatment in elderly patients should follow the general guidelines. Many patients will have other risk factors, target organ damage and associated cardiovascular conditions, to which the choice of the first drug should be tailored.
Journal Article•
TL;DR: The objective was to establish an experimental procedure and show direct results that unequivocally can be assigned as safe levels of blood pressure in patients with a history of heart disease.
Abstract: HOME BLOOD PRESSURE MONITORING Gianfranco Parati, Grzegorz Bilo, Sverre E Kjeldsen, Giuseppe Mancia Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Milan, Italy Centro Interuniversitario di Fisiologia Clinica e Ipertensione, Milan, Italy Department of Cardiology, S. Luca Hospital, Istituto Auxologico Italiano, Milan, Italy Department of Cardiology, Oslo University Hospital, Ullevaal, Oslo, Norway
Journal Article•
TL;DR: Losartan was very effective in reducing cardiovascular morbidity and mortality as compared to atenolol and will have a major impact on the choice of anti-hypertensive treatment for patients with hypertension and diabetes.
Abstract: INTRODUCTION The most suitable antihypertensive drug to reduce the risk of cardiovascular disease in patients with hypertension and diabetes is unclear. In a prespecified analysis of the LIFE-study we compared the effects of losartan and atenolol on cardiovascular morbidity and mortality in diabetic patients. MATERIAL AND METHODS A total of 1195 patients in the LIFE-study had diabetes at the time of the randomisation. The patients were randomised for double-blind treatment with losartan versus atenolol. The patients had ECG-verified left ventricular hypertrophy, mean age 67 years, blood pressure 177/96 mmHg after two weeks placebo run-in period. Patients were followed for at least four years (mean 4.7 years). The primary composite endpoint was cardiovascular death, stroke or myocardial infarction. RESULTS Blood pressure was reduced to 146/79 and 148/79 in losartan-treated patients and atenolol-treated patients, respectively. The primary endpoint occurred in 103 patients assigned losartan (n = 586) and 139 assigned atenolol (n = 609). Relative risk reduction 24% (p < 0.031). Cardiovascular mortality was reduced by 37% in favour of losartan (p < 0.028), and all cause mortality by 39% (p < 0.002). DISCUSSION Losartan was very effective in reducing cardiovascular morbidity and mortality as compared to atenolol. These results will have a major impact on the choice of anti-hypertensive treatment for patients with hypertension and diabetes.
Journal Article•
TL;DR: Losartan prevents to a higher degree cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated.
Abstract: Ugeskr Laeger 2003;165:456-9. Introduction: Left ventricular hypertrophy is a strong independent predictor of risk of cardiovascular morbidity and death. The aim of the LIFE-study was to establish whether treatment with the angiotensin-II AT 1-receptor antagonist, losartan, reduced cardiovascular events more effectively than treatment with the betablocker atenolol in patients with hypertension and left ventricular hypertrophy. Material and methods: The LIFE-study included 9193 patients with essential hypertension and ECG-verified left ventricular hypertrophy, age range 55-80 years, systolic blood pressure in sitting position 160-200 mmHg and/or diastolic blood pressure 95-115 mmHg. Patients were randomized to double-blind treatment with losartan versus atenolol. They were followed for at least four years and until 1040 patients had a primary cardiovascular event (cardiovascular death, myocardial infarction or stroke). Results: Blood pressure fell by 30.2/16.6 and 29.1/16.8 mmHg in the losartan and the atenolol group, respectively. The primary composite endpoint occurred in 508 losartan and 588 atenolol patients (relative risk 0.87, p=0.021). A total of 232 and 309, respectively, had fatal or non-fatal stroke (relative risk 0.75, p=0.001). There was no difference in myocardial infarction. New-onset diabetes was 25% less frequent on losartan. Side effects were less on losartan compared to atenolol. Discussion: Losartan prevents to a higher degree cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated.
TL;DR: There is no firm evidence that statins contribute to blood pressure reduction in hypertensive patients and the high and increasing use of statins in “usual care” of hypertensives with additional cardiovascular risk factors in the USA is explained.
Abstract: Small, but well-conducted, clinical trials using statins in hypertensive subjects have indicated that blood pressure lowering may be one of many suggested pleiotrophic effects of statins [1]. However, preliminary results of the large Plaque Hypertension Lipid Lowering Italian Study (PHYLLIS) indicate that this benefit is not seen in welltreated hypertensives [2]. Thus, presently there is no firm evidence that statins contribute to blood pressure reduction in hypertensive patients. However, lowering cholesterol in individuals at high risk for developing cardiovascular disease has been shown to improve outcome [3–10] since there is often a clustering of risk factors including hypertension and concomitant dyslipidemia in such patient groups. Recently, two major trials in hypertensive subjects with additional cardiovascular risk factors have evaluated the potential benefits of statins on cardiovascular outcome. In the American Antihypertensive and Lipid Lowering treatment to prevent Heart Attack Trial (ALLHAT), hypertensive subjects with cholesterol levels above the recommended were included [11], whereas the AngloScandinavian Cardiac Outcomes Trial (ASCOT) excluded subjects with high cholesterol levels [12]. The ALLHAT study, however, was not successful in showing any major benefits of statin as add-on treatment in hypertensives with high risk for coronary heart disease [11]. Most likely, the failure of ALLHAT to demonstrate any positive result was due to the small separation of only approximately 0.5 mmol/l in total cholesterol level between patients randomized to statin vs those randomized to usual care. This failure in achieving the expected difference in cholesterol level could be explained by the high and increasing use of statins in “usual care” of hypertensives with additional cardiovascular risk factors in the USA. Until the ASCOT study results were presented [12], no trial had shown benefit of a statin as add-on treatment in hypertensives and no study had previously been done to evaluate the potential benefits of cholesterol lowering in the primary prevention of coronary heart disease in hypertensive subjects with average and below average levels of serum cholesterol. Of the 19342 hypertensive subjects (aged 40–79 years) initially randomized to one of two antihypertensive treatment strategies in ASCOT, 10305 subjects with total cholesterol levels 6.5 mmol/l were additionally randomized, using a double-blind factorial design, to either atorvastatin 10 mg or placebo [12]. Patients with total cholesterol level 6.5 mmol/l were recommended open statin treatment according to guidelines [11, 12]. Follow-up of the lipid-lowering arm of ASCOT was planned for an average of 5 years, and the primary composite end-point included non-fatal myocardial infarction and fatal coronary heart disease. A number of secondary and tertiary endpoints were pre-specified and included in subgroup analyses. The study was powered ( = 0.90) to detect a 30% reduction in the primary endpoint (p = 0.01) by an intention-to-treat analysis. The lipid arm of the study was stopped prematurely by the Steering Committee after a median follow-up period of 3.3 years, effective October 1, 2002, on the recommendation of the Data Safety Monitoring Board. This recommendation was based on a highly significant 36% reduction in the primary end-point. One hundred events (6.0 per 1000 patient-years) occurred in those randomized to atorvastatin compared with 154 events (9.4 per 1000 patient-years) in those receiving placebo (hazard ratio = 0.64, p = 0.0005). For the primary endpoint, life-table analyses revealed a divergence of the Kaplan–Meier curves already during the first year of follow-up. Several secondary and tertiary endpoints were also significantly reduced – combined fatal and non-fatal stroke by 27% (p = 0.023), total cardiovascular events by 21% (p = 0.0005) and total coronary events by 29% (p = 0.0005). There were 185 deaths (11.1 per 1000 patient-years) in the atorvastatin group and 212 deaths (12.8 per 1000 patient-years) in those receiving placebo (hazard ratio = 0.87, p = 0.165). The impact of atorvastatin on the primary endpoint of ASCOT was homogeneous across all subgroups. Non-cardiovascular mortality and cancer deaths were similar in the two treatment arms of the trial. Atorvastatin lowered total serum cholesterol by of 1.3 mmol/l compared with placebo at 12 months of follow-up. After 3 years of follow-up, the difference between the atorvastatin and placebo arms was 1.1 mmol/ l. This smaller difference was most likely explained by the open use of statin by 9% of those originally allocated placebo, and the 13% of non-statin users who had been randomized to atorvastatin. While it is obvious that the results of the lipid arm in the ALLHAT could not be taken as an evidence for the lack of benefits of pravastatin in hypertensives, the benefits of atorvastatin reported in ASCOT are substantial
TL;DR: The LIFE study suggests that the mechanism of stroke prevention with losartan extends beyond its blood-pressure-lowering effects, and a reduction in stroke was an important contributor to the benefit in the composite outcome observed in patients with diabetes or isolated systolic hypertension.