| 1. |
- Eijkelkamp, W. B., et al.
(författare)
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Renal function and risk for cardiovascular events in type 2 diabetic patients with hypertension: the RENAAL and LIFE studies
- 2007
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Ingår i: J Hypertens. - 0263-6352. ; 25:4, s. 871-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether a threshold exists for cardiovascular risk in type 2 diabetic patients with hypertension, the association between renal function and cardiovascular risk was examined across the entire physiological range of serum creatinine. DESIGN AND METHODS: The RENAAL and LIFE studies enrolled 1513 and 1195 patients with type 2 diabetes and hypertension, respectively. The relationship between baseline serum creatinine and the risk for a composite outcome of myocardial infarction, stroke or cardiovascular death was examined using Cox regression models. To adjust for heterogeneity between studies and treatment groups, these factors were included as strata when applicable. The analyses were conducted with adjustment for age, gender, smoking, alcohol use, blood pressure, heart rate, total and high-density lipoprotein (HDL) cholesterol, hemoglobin, albuminuria and prior cardiovascular disease. RESULTS: The hazard ratios across the baseline serum creatinine categories < 0.9 mg/dl, 0.9-1.2 mg/dl, 1.2-1.6 mg/dl, 1.6-2.8 mg/dl and >or= 2.8 mg/dl were 0.51 (95% confidence interval 0.34, 0.74), 0.74 (0.55, 1.00), 1.00 (reference), 1.24 (0.96, 1.59) and 1.67 (1.17, 2.91), respectively. Baseline serum creatinine (per mg/dl) strongly predicted the composite cardiovascular endpoint in LIFE [2.82(1.74,4.56), P < 0.001], RENAAL [1.41(1.12,1.79), P < 0.001], as well as the combined studies [1.51(1.21,1.87), P < 0.001]. CONCLUSION: A progressively higher risk for the composite cardiovascular endpoint was observed with incremental baseline serum creatinine in type 2 diabetic patients with hypertension, even within the normal range. Thus, there appears to be no serum creatinine threshold level for an increased cardiovascular risk. Baseline serum creatinine was a major independent risk factor for cardiovascular disease (www.ClinicalTrials.gov number NCT00308347).
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| 2. |
- Carr, A. A., et al.
(författare)
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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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Ingår i: Am J Cardiol. - : Elsevier BV. - 0002-9149. ; 96:11, s. 1530-6
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Wiik, B. P., et al.
(författare)
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Serum uric acid is associated with new-onset diabetes in hypertensive patients with left ventricular hypertrophy: The LIFE Study
- 2010
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Ingår i: American Journal of Hypertension. - : Nature Publishing Group. - 0895-7061 .- 1941-7225. ; 23:8, s. 845-851
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is unclear whether serum uric acid (SUA) is associated with development of new-onset diabetes (NOD) in patients with hypertension and left ventricular hypertrophy (LVH). The aim of the present investigation was to test the hypothesis that SUA predicts development of NOD in these patients. METHODS: In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, a double-masked, parallel-group design, 9,193 patients with hypertension and electrocardiographic LVH were randomized to losartan- or atenolol-based antihypertensive treatment and followed for a mean of 4.9 years. At baseline, 7,489 patients with available SUA measurements did not have diabetes mellitus and were thus at risk of its development during the study. We used Cox regression analyses to investigate whether SUA predicted development of NOD. RESULTS: NOD developed in 522 of 7,489 patients. The association between baseline SUA and development of NOD was significant (hazard ratio (HR) 1.29 per s.d. (1.3 mg/dl), 95% confidence interval (CI) 1.18-1.42, P < 0.001) after adjustment for treatment with losartan vs. atenolol, baseline serum glucose, urinary albumin/creatinine ratio, estimated glomerular filtration rate and Framingham risk score, time-varying systolic and diastolic blood pressure, and time-varying LVH by Cornell voltage-duration product and Sokolow-Lyon voltage. In parallel analyses, baseline quartiles of SUA were significantly associated with increasing NOD (HR 1.28, 95% CI 1.18-1.40, P < 0.001). Time-varying SUA was also associated with NOD (HR 1.10 per s.d. [1.3 mg/dl], 95% CI 1.02-1.19, P = 0.015). CONCLUSION: Our analysis suggests that SUA is an independent risk marker for NOD in hypertensive patients with LVH.
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| 4. |
- Cicala, S., et al.
(författare)
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Are coronary revascularization and myocardial infarction a homogeneous combined endpoint in hypertension trials? The Losartan Intervention For Endpoint reduction in hypertension study
- 2010
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 28:6, s. 1134-1140
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Construction of prognostically relevant endpoints for clinical trials in hypertension has increasingly included coronary revascularization with myocardial infarction (MI) as manifestations of coronary artery disease. However, whether coronary revascularization and MI predict other cardiovascular events similarly is unknown. METHODS: We examined risks of cardiovascular death, all-cause death, and stroke following MI or coronary revascularization in hypertensive patients with left ventricular hypertrophy (LVH) enrolled in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE). We studied 9113 patients after excluding those who died within 7 days after MI or underwent coronary revascularization within 24 h after MI. RESULTS: In multivariate Cox regression adjusting for participating countries, time-varying systolic blood pressure, and Framingham risk score, hazard ratios for cardiovascular death, all-cause death, and stroke were, respectively, 4.5 (P<0.0001), 2.9 (P<0.0001), and 1.9 (P=0.003) in 321 patients with MI as first event. In similar models, coronary revascularization as first event (n=202) was not associated with increased risks of cardiovascular death, all-cause death, and stroke (P=0.06-0.86). CONCLUSION: During follow-up of hypertensive patients with LVH, occurrence of MI but not coronary revascularization as first cardiovascular event significantly increased risk of subsequent cardiovascular death, all-cause death, and stroke. In view of differences in prognostic implications, when the goal is to have a prognostically relevant composite endpoint for trials in hypertensive patients, caution should be used in combining coronary revascularization with MI.
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| 5. |
- de Simone, G., et al.
(författare)
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Body build and risk of cardiovascular events in hypertension and left ventricular hypertrophy: the LIFE (Losartan Intervention For Endpoint reduction in hypertension) study
- 2005
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Ingår i: Circulation. - 1524-4539. ; 111:15, s. 1924-31
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obesity may independently increase the risk of adverse events in hypertension with target-organ damage. We investigated whether body build was independently associated with higher cardiovascular risk and whether treatment with losartan relative to atenolol influenced the impact of body build on the primary composite end point of cardiovascular death, stroke, and myocardial infarction and on cardiovascular death in patients with hypertension and left ventricular hypertrophy in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. METHODS AND RESULTS: The population of 9079 patients was divided as follows: thin (body mass index [BMI] <20 kg/m2, 2%), normal weight (BMI 20 to 24.9, 24%), overweight (BMI 25 to 29.9, 45%), and obese (class I: BMI 30 to 34.9, 21%; class II: BMI 35 to 39.9, 6%; class III: BMI > or =40, 2%). Incident diabetes increased progressively with BMI and was somewhat higher in the atenolol arm. Differences in gender and race were detected among the body build groups. Rates (Cox proportional hazard analysis) of the primary composite end point did not differ among body build groups after adjustment for age, gender, race, smoking habit, prevalent cardiovascular disease, and left ventricular hypertrophy. Cardiovascular death was more frequent among thin (P<0.05) and pooled class II-III obesity (both P<0.04) than normal-weight groups. Risk was not attenuated significantly by losartan treatment, nor did it interfere with the greater benefit of losartan- as opposed to atenolol-based treatment. CONCLUSIONS: In the LIFE study, stratification for classes of body build identified increased risk of cardiovascular mortality in both thin and moderately-to-severely obese individuals. This risk was not attenuated significantly by losartan treatment, nor did it interfere with the greater benefit of losartan-based treatment as opposed to atenolol-based treatment.
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| 6. |
- Devereux, R. B., et al.
(författare)
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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
- 2007
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Ingår i: Curr Med Res Opin. - : Taylor & Francis. - 1473-4877 .- 0300-7995. ; 23:2, s. 259-70
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare blood pressure response and antihypertensive medication use visit-by-visit from baseline in patients receiving losartan-based or atenolol-based therapy in the LIFE study. RESEARCH DESIGN: LIFE was a randomized, double-blind trial comparing losartan-based and atenolol-based treatment regimens on the primary composite endpoint of death, myocardial infarction (MI), or stroke in 9193 patients aged 55-80 years with hypertension and left ventricular hypertrophy. Systolic and diastolic, pulse, and mean arterial pressures, blood pressure responder rates, distribution of open-label antihypertensive agents utilized, and the proportion of patients on randomized treatment were determined for each group at each clinic visit over a follow-up period of at least 4 years. RESULTS: Overall blood pressure reductions were comparable in the losartan-based and atenolol-based treatment groups. The mean reductions in sitting trough systolic and diastolic blood pressures from baseline to the end of follow-up (or last visit before a primary endpoint event) were 30.2/16.6 mmHg in the losartan group and 29.1/16.8 mmHg in the atenolol group. The time-averaged difference in overall mean arterial pressure was similar between groups. The proportion of patients on individual dose combinations varied visit by visit but was generally comparable between groups. During the entire study, 56% (2579/4605) of losartan-treated patients received at least one dose of the combination of losartan 100 mg plus hydrochlorothiazide 12.5 mg and 51% of atenolol-treated patients received 100 mg of atenolol plus hydrochlorothiazide 12.5 mg at some time during the study. CONCLUSIONS: Differences in blood pressure or distribution of add-on medications between treatment groups were not evident in the LIFE trial and, thus, cannot account for the observed outcome difference in the primary endpoint of risk reduction of the composite of cardiovascular death, stroke and MI favoring losartan.
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| 7. |
- Fossum, E., et al.
(författare)
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The effect of losartan versus atenolol on cardiovascular morbidity and mortality in patients with hypertension taking aspirin: the Losartan Intervention for Endpoint Reduction in hypertension (LIFE) study
- 2005
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Ingår i: J Am Coll Cardiol. - : Elsevier BV. - 0735-1097. ; 46:5, s. 770-5
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We conducted a subgroup analysis in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study to determine whether aspirin interacted with the properties of losartan, an angiotensin-II receptor antagonist. BACKGROUND: Negative interactions between angiotensin-converting enzyme inhibitors and aspirin have been reported. There are no data reported from clinical trials about possible interactions between angiotensin-II receptor antagonists and aspirin. METHODS: The LIFE study assigned 9,193 patients with hypertension and left ventricular hypertrophy (LVH) to losartan- or atenolol-based therapy for a mean of 4.7 years, with 1,970 (21.4%) taking aspirin at baseline. The primary composite end point (CEP) included cardiovascular death, stroke, and myocardial infarction (MI). The present cohort was stratified by aspirin use at baseline. RESULTS: Blood pressures were reduced similarly in the losartan with aspirin (n = 1,004) and atenolol with aspirin (n = 966) groups. The CEP was reduced by 32% (95% confidence interval 0.55 to 0.86, p = 0.001) with losartan with aspirin compared to atenolol with aspirin, adjusted for Framingham risk score and LVH. The test for treatment versus aspirin interaction, excluding other covariates, was significant for the CEP (p = 0.016) and MI (p = 0.037). CONCLUSIONS: There was a statistical interaction between treatment and aspirin in the LIFE study, with significantly greater reductions for the CEP and MI with losartan in patients using aspirin than in patients not using aspirin at baseline. Further studies are needed to clarify whether this represents a pharmacologic interaction or a selection by aspirin use of patients more likely to respond to losartan treatment.
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| 8. |
- Fyhrquist, F., et al.
(författare)
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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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Ingår i: Hypertension. - 1524-4563. ; 45:4, s. 580-5
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Tidskriftsartikel (refereegranskat)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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| 9. |
- Hoieggen, A., et al.
(författare)
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The impact of serum uric acid on cardiovascular outcomes in the LIFE study
- 2004
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Ingår i: Kidney Int. - 0085-2538. ; 65:3, s. 1041-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study demonstrated the superiority of a losartan-based regimen over atenolol-based regimen for reduction of cardiovascular (CV) morbidity and mortality. It has been suggested that the LIFE study results may be related to the effects of losartan on serum uric acid (SUA). SUA has been proposed as an independent risk factor for CV morbidity and death. METHODS: Cox regression analysis was used to assess relationship of SUA and treatment regimens with the LIFE primary composite outcome (CV death, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke). RESULTS: Baseline SUA was significantly associated with increased CV events [hazard ratio (HR) 1.024 (95% CI 1.017-1.032) per 10 micromol/L, P < 0.0001] in the entire study population. The association was significant in women [HR = 1.025 (1.013-1.037), P < 0.0001], but not in men [HR = 1.009 (0.998-1.019), P= 0.108]. After adjustment for Framingham risk score (FRS), SUA was no longer significant in the entire study population [HR = 1.006 (0.998-1.014), P= 0.122] or in men [HR = 1.006 (0.995-1.017), P= 0.291], but was significant in women [HR = 1.013 (1-1.025), P= 0.0457]. The baseline-to-end-of-study increase in SUA (standard deviation, SD) was greater (P < 0.0001) in atenolol-treated subjects (44.4 +/- 72.5 micromol/L) than in losartan-treated subjects (17.0 +/- 69.8 micromol/L). SUA as a time-varying covariate was strongly associated with events (P < 0.0001) in the entire population. The contribution of SUA to the treatment effect of losartan on the primary composite end point was 29% (14%-107%), P= 0.004. The association between time-varying SUA and increased CV risk tended to be stronger in women (P < 0.0001) than in men (P= 0.0658), although the gender-outcome interaction was not significant (P= 0.079). CONCLUSION: The increase in SUA over 4.8 years in the LIFE study was attenuated by losartan compared with atenolol treatment, appearing to explain 29% of the treatment effect on the primary composite end point. The association between SUA and events was stronger in women than in men with or without adjustment of FRS.
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| 10. |
- Ibsen, H., et al.
(författare)
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Does albuminuria predict cardiovascular outcome on treatment with losartan versus atenolol in hypertension with left ventricular hypertrophy? A LIFE substudy
- 2004
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Ingår i: J Hypertens. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352. ; 22:9, s. 1805-11
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To examine a possible relationship between baseline albuminuria and effect of losartan versus atenolol on cardiovascular (CV) events in hypertensive patients with left ventricular hypertrophy, the effect of losartan versus atenolol on albuminuria, and whether the benefits of losartan versus atenolol could be explained by influence of losartan on albuminuria. DESIGN: Double-blind, randomized, controlled trial of 4.8 years. SETTING: Out-patient setting. PATIENTS: A total of 8206 with hypertension and left ventricular hypertrophy. INTERVENTIONS: Losartan or atenolol, supplemented with diuretics and/or calcium antagonists to reach blood pressure < 140/90 mmHg MAIN OUTCOME MEASURES: The urine albumin/creatinine ratio, and the primary composite endpoint (CEP) of CV death, myocardial infarction, and stroke. RESULTS: The blood pressure was reduced similarly on losartan (30.2/16.6 mmHg) versus atenolol (29.1/16.8 mmHg). The risk of a primary CEP increased linearly from the lowest to the highest decile of baseline albuminuria. The benefits of losartan versus atenolol for the primary CEP and for stroke tended to be more pronounced among patients above the median value for baseline albuminuria (urine albumin/creatinine ratio, 1.28 mg/mmol). The decrease in albuminuria was significantly greater with losartan versus atenolol throughout the study (a decrease from baseline to year 2 of 33% losartan versus 25% atenolol). One-fifth of the difference in favor of losartan on the primary CEP was explained by the greater reduction in albuminuria on losartan. CONCLUSIONS: Baseline albuminuria is a powerful risk factor for CV events. Baseline albuminuria did not identify the group of patients with greatest benefit on losartan versus atenolol in LIFE. Reduction in albuminuria explained one-fifth of the benefits of losartan versus atenolol.
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