| 1. |
- Carr, A. A., et al.
(author)
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Hospitalizations for new heart failure among subjects with diabetes mellitus in the RENAAL and LIFE studies
- 2005
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In: Am J Cardiol. - : Elsevier BV. - 0002-9149. ; 96:11, s. 1530-6
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Journal article (peer-reviewed)abstract
- We sought to study the risk factors for heart failure (HF) and the relation between antihypertensive treatment with losartan and the first hospitalization for HF in patients with diabetes mellitus in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) and Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) studies. We evaluated 1,195 patients with hypertension, left ventricular hypertrophy, and diabetes from the LIFE study and 1,513 patients with type 2 diabetes and nephropathy from the RENAAL study. The comparative treatments were atenolol in the LIFE study and placebo in the RENAAL study. Patients with a history of HF were excluded from this analysis. Losartan significantly reduced the incidence of first hospitalizations for HF versus placebo in the RENAAL study (hazard ratio 0.74, p=0.037) and versus atenolol in the LIFE study (hazard ratio 0.57, p=0.019). Patients enrolled in the RENAAL study were at a higher risk of developing HF (hazard ratio for RENAAL vs LIFE diabetics 3.0, p<0.0001). The significant, independent baseline risk factors for the development of HF in the RENAAL study were urinary albumin/creatinine ratio, age, peripheral vascular disease, the Cornell product, body mass index, and previous angina; in the LIFE study they were the Cornell product, previous myocardial infarction, peripheral vascular disease, baseline atrial fibrillation, alcohol use (inverse relation), and urinary albumin/creatinine ratio. The beneficial effect of losartan on the reduction of risk for hospitalization for new HF was demonstrated in patients who were at high renal and/or high cardiovascular risk.
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| 2. |
- Fossum, E., et al.
(author)
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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
- 2007
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In: J Intern Med. - : Wiley. - 0954-6820. ; 262:4, s. 439-48
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Journal article (peer-reviewed)abstract
- 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 = 9,193). INTERVENTIONS: Losartan versus atenolol. MAIN OUTCOME MEASURES: Reported level of PA: never exercise, 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 < 0.001) and its components, all-cause mortality (aHR 0.65, P < 0.001), and new-onset diabetes (aHR 0.66, P < 0.001). CONCLUSION: A modest level of self-reported PA (>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.
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| 3. |
- Kjeldsen, S. E., et al.
(author)
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The effects of losartan compared to atenolol on stroke in patients with isolated systolic hypertension and left ventricular hypertrophy. The LIFE study
- 2005
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In: J Clin Hypertens (Greenwich). - 1524-6175. ; 7:3, s. 152-8
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Journal article (peer-reviewed)abstract
- The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study reported that a losartan-based antihypertensive regimen reduced cardiovascular morbidity and mortality (composite of cardiovascular death, stroke, and myocardial infarction) more than therapy based on atenolol in patients with left ventricular hypertrophy and isolated systolic hypertension (ISH). Patients aged 55-80 years with blood pressures 160-200/<90 mm Hg were followed for a mean of 4.7 years. Blood pressure was similarly reduced in the losartan (n=660) and atenolol (n=666) ISH groups. There were 88 (6.6%) patients who experienced a stroke, 18 of which were fatal. Of patients experiencing strokes, 72.7% had an ischemic stroke. ISH patients in LIFE compared to the non-ISH group had a higher incidence of any stroke and embolic stroke, and similar incidences of fatal, atherosclerotic, and hemorrhagic/other strokes. The incidence of any stroke (40% risk reduction [RR], p=0.02), fatal stroke (70% RR, p=0.035), and atherothrombotic stroke (45% RR, p=0.022) was significantly lower in losartan-treated compared to the atenolol-treated patients. The 36% RR for embolic strokes in the losartan group was not statistically significantly (p=0.33) different from the atenolol group. These data suggest that losartan-based treatment is more effective than an atenolol-based treatment for patients with ISH and a high risk for stroke.
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| 4. |
- Dahlöf, Björn, 1953, et al.
(author)
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Atenolol as a comparator in outcome trials in hypertension: a correct choice in the past, but not for the future?
- 2007
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In: Blood Press. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 16:1, s. 6-12
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Journal article (peer-reviewed)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 cardiovascular outcomes, we reviewed the literature for the effect of beta-blockers compared with initial placebo or no treatment on reduction of cardiovascular events to re-evaluate atenolol as the comparator in the LIFE study. METHODS: A literature search was conducted in September 2006 for randomized, controlled trials comparing beta-blockers with/without diuretics with placebo or no treatment in patients with hypertension and without recent cardiovascular morbidity. We calculated risk reductions for combined cardiovascular events, cardiovascular death, stroke, and coronary heart disease from groups of trials using atenolol first-line and all beta-blockers first-line. RESULTS: Five studies met the criteria. Significant risk reductions for cardiovascular events and stroke occurred in groups receiving treatment with atenolol or all beta-blockers, and for cardiovascular death in the all beta-blocker analysis. In meta-analysis of beta-blocker vs placebo or no treatment trials, risk reductions were 19% for combined cardiovascular events (95% CI 0.73-0.91, p<0.001), 15% for cardiovascular death (0.73-0.99, p = 0.037), 32% for stroke (0.57-0.82, p<0.001), and 10% for coronary heart disease (0.78-1.04, p = 0.146). CONCLUSIONS: Beta-blocker-based antihypertensive therapy significantly reduces cardiovascular risk in hypertension compared with placebo or no treatment. Atenolol was an appropriate comparator in the LIFE study. As the results of the LIFE study and other recent trials demonstrate superiority of newer agents over atenolol, this agent is not an appropriate reference drug for future trials of cardiovascular risk in hypertension.
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| 5. |
- de Simone, G., et al.
(author)
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Clusters of metabolic risk factors predict cardiovascular events in hypertension with target-organ damage: the LIFE study
- 2007
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In: J Hum Hypertens. - : Springer Science and Business Media LLC. - 0950-9240. ; 21:8, s. 625-32
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Journal article (peer-reviewed)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 <1.0/1.3 mmol/l (<40/50 mg/dl) (men/women), glucose >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.
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| 6. |
- Fyhrquist, F., et al.
(author)
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Pulse pressure and effects of losartan or atenolol in patients with hypertension and left ventricular hypertrophy
- 2005
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In: Hypertension. - 1524-4563. ; 45:4, s. 580-5
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Journal article (peer-reviewed)abstract
- In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, the primary composite end point of cardiovascular death, stroke, and myocardial infarction was reduced by losartan versus atenolol in patients with hypertension and left ventricular hypertrophy. The objective of this post hoc analysis was to determine the influence of pulse pressure on outcome. Patients were divided into quartiles of baseline pulse pressure. Cox regression, including baseline Framingham risk score as a covariate, was used to compare risk in the quartiles. In the atenolol group, there were significantly higher risks in the highest versus lowest quartile for the composite end point 28% (confidence interval [CI], 2% to 62%; P=0.035), stroke 84% (CI, 32% to 157%; P<0.001), and total mortality 41% (CI, 7% to 84%; P=0.013). Risk for myocardial infarction was 44% higher (CI, -5% to 120%; P=0.089). The risks in the losartan group also increased with increasing quartile, but were lower than in the atenolol group, and differences between the highest and lowest quartiles were not significant: composite end point 12% (CI, -13% to 44%; P>0.2), stroke -5% (CI, -34% to 37%; P>0.2), myocardial infarction 30% (CI, -13% to 94%; P>0.2), and total mortality 32% (CI, -1% to 76%; P=0.062). In patients with hypertension and left ventricular hypertrophy in the LIFE study, there were significantly higher risks, adjusted for the Framingham risk score, for the primary composite end point, stroke, and total mortality in the highest versus lowest quartile of pulse pressure with atenolol-based treatment. The risks in the losartan group also increased with increasing pulse pressure quartile, but were lower than those in the atenolol group, and were not significant.
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| 7. |
- Gudbjartsson, Daniel F., et al.
(author)
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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- 2009
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:3, s. 342-347
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Journal article (peer-reviewed)abstract
- Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
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| 8. |
- Kjeldsen, S. E., et al.
(author)
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Targeting the renin-angiotensin system for the reduction of cardiovascular outcomes in hypertension: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers
- 2005
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In: Expert Opin Emerg Drugs. - 1744-7623. ; 10:4, s. 729-45
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Journal article (peer-reviewed)abstract
- Agents that counteract the negative impact of the renin-angiotensin-aldosterone system (RAAS) are effective antihypertensives and reduce the risk of developing Type 2 diabetes. Contrary to common perception, angiotensin-converting enzyme inhibitors do not share the apparent benefit of angiotensin II receptor blockers (ARBs) in reducing risk of cardiovascular-disease outcomes, particularly stroke, in randomised clinical trials. RAAS agents, especially ARBs, are well tolerated. Use of ARBs alone or in combination with other classes of antihypertensive agents to lower blood pressure and/or medications to control other conditions (e.g., insulin sensitivity) reduces risk of cardiovascular disease outcomes and Type 2 diabetes with excellent tolerability. Selected issues related to use of RAAS agents as antihypertensive therapies (e.g., Type 2 diabetes, global risk management, multiple drug therapy and coronary heart disease) are addressed.
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