| 1. |
- Devereux, R. B., et al.
(författare)
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Prognostic significance of left ventricular mass change during treatment of hypertension
- 2004
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Ingår i: Jama. - 1538-3598. ; 292:19, s. 2350-6
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Increased baseline left ventricular (LV) mass predicts cardiovascular (CV) complications of hypertension, but the relation between lower LV mass and outcome during treatment for hypertension is uncertain. OBJECTIVE: To determine whether reduction of LV mass during antihypertensive treatment modifies risk of major CV events independent of blood pressure change. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort substudy of the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) randomized clinical trial, conducted from 1995 to 2001. A total of 941 prospectively identified patients aged 55 to 80 years with essential hypertension and electrocardiographic LV hypertrophy had LV mass measured by echocardiography at enrollment in the LIFE trial and thereafter were followed up annually for a mean (SD) of 4.8 (1.0) years for CV events. MAIN OUTCOME MEASURES: Composite end point of CV death, fatal or nonfatal myocardial infarction, and fatal or nonfatal stroke. RESULTS: The composite end point occurred in 104 patients (11%). The multivariable Cox regression model showed a strong association between lower in-treatment LV mass index and reduced rate of the composite CV end point (hazard ratio [HR], 0.78 per 1-SD (25.3) decrease in LV mass index; 95% confidence interval [CI], 0.65-0.94; P = .009) over and above that predicted by reduction in blood pressure. There were parallel associations between lower in-treatment LV mass index and lower CV mortality (HR, 0.62; 95% CI, 0.47-0.82; P = .001), stroke (HR, 0.76; 95% CI, 0.60-0.96; P = .02), myocardial infarction (HR, 0.85; 95% CI, 0.62-1.17, P = .33), and all-cause mortality (HR, 0.72; 95% CI, 0.59-0.88, P = .002), independent of systolic blood pressure and assigned treatment. Results were confirmed in analyses adjusting for additional CV risk factors, electrocardiographic changes, or when only considering events after the first year of study treatment. CONCLUSION: In patients with essential hypertension and baseline electrocardiographic LV hypertrophy, lower LV mass during antihypertensive treatment is associated with lower rates of clinical end points, additional to effects of blood pressure lowering and treatment modality.
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| 2. |
- Devereux, R. B., et al.
(författare)
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Regression of hypertensive left ventricular hypertrophy by losartan compared with atenolol: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial
- 2004
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Ingår i: Circulation. - 1524-4539. ; 110:11, s. 1456-62
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: An echocardiographic substudy of the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial was designed to test the ability of losartan to reduce left ventricular (LV) mass more than atenolol. METHODS AND RESULTS: A total of 960 patients with essential hypertension and LV hypertrophy (LVH) on screening ECG were enrolled at centers in 7 countries and studied by echocardiography at baseline and after 1, 2, 3, 4, and 5 years' randomized therapy. Clinical examination and blinded readings of echocardiograms in 457 losartan-treated and 459 atenolol-treated participants with > or =1 follow-up measurement of LV mass index (LVMI) were used in an intention-to-treat analysis. Losartan-based therapy induced greater reduction in LVMI from baseline to the last available study than atenolol with adjustment for baseline LVMI and blood pressure and in-treatment pressure (-21.7+/-21.8 versus -17.7+/-19.6 g/m2; P=0.021). Greater LVMI reduction with losartan was observed in women and men, participants >65 or <65 years of age, and with mild or more severe baseline hypertrophy. The difference between treatment arms in LVH regression was due mainly to reduced concentricity of LV geometry in both groups and lesser increase in LV internal diameter in losartan-treated patients. CONCLUSIONS: Antihypertensive treatment with losartan, plus hydrochlorothiazide and other medications when needed for pressure control, resulted in greater LVH regression in patients with ECG LVH than conventional atenolol-based treatment. Thus, angiotensin receptor antagonism by losartan has superior efficacy for reversing LVH, a cardinal manifestation of hypertensive target organ damage.
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| 3. |
- Kizer, J. R., et al.
(författare)
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Stroke reduction in hypertensive adults with cardiac hypertrophy randomized to losartan versus atenolol: the Losartan Intervention For Endpoint reduction in hypertension study
- 2005
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Ingår i: Hypertension. - 1524-4563. ; 45:1, s. 46-52
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Tidskriftsartikel (refereegranskat)abstract
- The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study showed that treatment with the angiotensin II type-1 receptor antagonist losartan reduces overall stroke risk compared with conventional therapy with the beta-blocker atenolol. We conducted secondary analyses in LIFE to determine the extent to which the cerebrovascular benefits of losartan apply to different clinical subgroups and stroke subtypes and to assess the dependence of these benefits on baseline and time-varying covariates. Among 9193 hypertensive patients with electrocardiographic evidence of left ventricular hypertrophy, random allocation to losartan-based treatment lowered the risk of fatal (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.43 to 0.96; P=0.032) and atherothrombotic stroke (HR, 0.72; 95% CI, 0.59 to 0.88; P=0.001) compared with atenolol-based therapy. Although comparable risk reductions occurred for hemorrhagic and embolic stroke, these were not statistically significant. The number of neurological deficits per stroke was similar, but there were fewer strokes in the losartan group for nearly every level of stroke severity. Effects were consistent in all clinical subgroups except for those defined by age and ethnicity. The benefits of losartan on all strokes were independent of baseline and time-varying risk factors, including blood pressure. The number needed to treat for 5 years to prevent 1 stroke was 54 for the average participant, declining to 25, 24, and 9 for patients with cerebrovascular disease, isolated systolic hypertension, and atrial fibrillation, respectively. In conclusion, substantial cerebrovascular benefit could be realized with the institution of losartan-based therapy over conventional therapy among hypertensive patients with left ventricular hypertrophy across the spectrum of cardiovascular risk.
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| 4. |
- 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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| 5. |
- Ibsen, H., et al.
(författare)
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Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: losartan intervention for endpoint reduction in hypertension study
- 2005
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Ingår i: Hypertension. - 1524-4563. ; 45:2, s. 198-202
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Tidskriftsartikel (refereegranskat)abstract
- Few data are available to clarify whether changes in albuminuria over time translate to changes in cardiovascular risk. The aim of the present study was to examine whether changes in albuminuria during 4.8 years of antihypertensive treatment were related to changes in risk in 8206 patients with hypertension and left ventricular hypertrophy in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Urinary albumin/creatinine ratio (UACR) was measured at baseline and annually. Time-varying albuminuria was closely related to risk for the primary composite end point (ie, when UACR decreased during treatment, risk was reduced accordingly). When the population was divided according to median baseline value (1.21 mg/mmol) and median year 1 UACR (0.67 mg/mmol), risk increased stepwise and significantly for the primary composite end point from those with low baseline/low year 1 (5.5%), to low baseline/high year 1 (8.6%), to high baseline/low year 1 (9.4%), and to high baseline/high year 1 (13.5%) values. Similar significant, stepwise increases in risk were seen for the components of the primary composite end point (cardiovascular mortality, stroke, and myocardial infarction). The observation that changes in UACR during antihypertensive treatment over time translated to changes in risk for cardiovascular morbidity and mortality was not explained by in-treatment level of blood pressure. We propose that monitoring of albuminuria should be an integrated part of the management of hypertension. If albuminuria is not decreased by the patient's current antihypertensive and other treatment, further intervention directed toward blood pressure control and other modifiable risks should be considered.
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| 6. |
- Narayan, P., et al.
(författare)
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Association of hemoglobin delivery with left ventricular structure and function in hypertensive patients: Losartan Intervention for End Point Reduction in Hypertension Study
- 2006
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Ingår i: Hypertension. - 1524-4563. ; 47:5, s. 868-73
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have shown associations of high levels of hemoglobin (Hgb) or blood viscosity with cardiac events and with left ventricular (LV) hypertrophy (LVH). To assess the relations of LV mass and function with Hgb delivery (ie, the physiological carrier of oxygen), we calculated the product of Hgb concentration and Doppler-derived cardiac output in 864 hypertensive participants with electrocardiographic LVH (359 women) in the Losartan Intervention for End Point Reduction in Hypertension echocardiography substudy. Among women, Hgb delivery was positively related to internal dimension, septal and posterior wall thicknesses, LV mass, endocardial and midwall fractional shortening, and peak A wave velocity and negatively to total peripheral resistance index, E/A ratio, deceleration time, and the isovolumic relaxation time. Among men, Hgb delivery was positively related to LV internal dimension, LV mass, and A velocity, and negatively to LV midwall shortening, relative wall thickness, peripheral resistance index, and E/A ratio. In multivariable analyses that adjusted for age, diastolic blood pressure, body mass index, and total cholesterol, hemoglobin delivery in women was related positively to LV fractional shortening, midwall shortening, LV mass mitral valve A velocity, and LV internal dimension and negatively to mitral valve deceleration time and isovolumic relaxation time. Among men, Hgb delivery had positive independent relations to mitral valve A velocity, LV internal dimension, midwall shortening, and LV mass and negative relations to the E/A ratio and relative wall thickness. Thus, in hypertensive LVH, higher oxygen delivery capacity is associated with higher LV mass and impaired early diastolic LV filling.
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| 7. |
- Okin, P. M., et al.
(författare)
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Regression of electrocardiographic left ventricular hypertrophy and decreased incidence of new-onset atrial fibrillation in patients with hypertension
- 2006
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Ingår i: Jama. - Chicago : American medical association. - 1538-3598 .- 0098-7484. ; 296:10, s. 1242-8
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Atrial fibrillation (AF) is associated with increased risk of mortality and cardiovascular events, particularly stroke, making prevention of new-onset AF a clinical priority. Although the presence and severity of electrocardiographic left ventricular hypertrophy (LVH) appear to predict development of AF, whether regression of electrocardiographic LVH is associated with a decreased incidence of AF is unclear. OBJECTIVE: To test the hypothesis that in-treatment regression or continued absence of electrocardiographic LVH during antihypertensive therapy is associated with a decreased incidence of AF, independent of blood pressure and treatment modality. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, parallel-group study conducted in 1995-2001 among 8831 men and women with hypertension, aged 55-80 years (median, 67 years), with electrocardiographic LVH by Cornell voltage-duration product or Sokolow-Lyon voltage, with no history of AF, without AF on the baseline electrocardiogram, and enrolled in the Losartan Intervention for Endpoint Reduction in Hypertension Study. INTERVENTIONS: Losartan- or atenolol-based treatment regimens, with follow-up assessments at 6 months and then yearly until death or study end. MAIN OUTCOME MEASURE: New-onset AF in relation to electrocardiographic LVH determined at baseline and subsequently. Electrocardiographic LVH was measured using sex-adjusted Cornell product criteria ({R(aVL) + S(V3) [+ 6 mm in women]} x QRS duration). RESULTS: After a mean (SD) follow-up of 4.7 (1.1) years, new-onset AF occurred in 290 patients with in-treatment regression or continued absence of Cornell product LVH for a rate of 14.9 per 1000 patient-years and in 411 patients with in-treatment persistence or development of LVH by Cornell product criteria for a rate of 19.0 per 1000 patient-years. In time-dependent Cox analyses adjusted for treatment effects, baseline differences in risk factors for AF, baseline and in-treatment blood pressure, and baseline severity of electrocardiographic LVH, lower in-treatment Cornell product LVH treated as a time-varying covariate was associated with a 12.4% lower rate of new-onset AF (adjusted hazard ratio [HR], 0.88; 95% CI, 0.80-0.97; P = .007) for every 1050 mm x msec (per 1-SD) lower Cornell product, with persistence of the benefit of losartan vs atenolol therapy on developing AF (HR, 0.83; 95% CI, 0.71-0.97; P = .01). CONCLUSIONS: Lower Cornell product electrocardiographic LVH during antihypertensive therapy is associated with a lower likelihood of new-onset AF, independent of blood pressure lowering and treatment modality in essential hypertension. These findings suggest that antihypertensive therapy targeted at regression or prevention of electrocardiographic LVH may reduce the incidence of new-onset AF.
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| 8. |
- Wachtell, K., et al.
(författare)
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In-treatment reduced left atrial diameter during antihypertensive treatment is associated with reduced new-onset atrial fibrillation in hypertensive patients with left ventricular hypertrophy: The LIFE Study
- 2010
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Ingår i: Blood Pressure. - 0803-7051. ; 19:3, s. 169-175
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: It is unclear whether improvement of left atrial (LA) and ventricular (LV) structure results in reduction in new-onset atrial fibrillation (AF). The aim of the present study was to examine whether changes in-treatment LA diameter were related to changes in risk of new-onset AF. METHODS: We followed 939 hypertensive patients with electrocardiographic LV hypertrophy randomized to atenolol or losartan-based regimens in the LIFE Study for a mean of 4.8 years with echocardiograms at enrolment and annually during treatment. RESULTS: New-onset AF occurred in 46 patients (10.2/1000 patient-years of follow-up). At baseline, patients with new-onset AF were older, had higher systolic blood pressure and heart rate as well as higher prevalence of LA dilatation, but had similar prevalences of LV hypertrophy and mitral or aortic valve disease. In univariate Cox analysis baseline LA diameter (HR=4.67 per cm increase [95% CI 2.86-7.65], p<0.001) and LV mass index (HR=1.11 per 10 g/m(2) increase [95% CI 1.02-1.22], p<0.05) both predicted new-onset AF. In multivariate analysis, increased baseline LA diameter increased the risk of new-onset AF (HR=5.16 per cm [95% CI 2.85-9.35], p<0.001) whereas reduction of in-treatment LA diameter reduced the risk (HR=0.21 per cm lower LA diameter during treatment [95% CI 0.14-0.32], p<0.001) with adjustment for in-treatment LV mass in-treatment systolic blood pressure, age and Framingham risk score. CONCLUSION: LA diameter at baseline and during antihypertensive treatment were equally strong predictors of new-onset AF independent of the level of arterial pressure, LV mass and other covariates. Prevention of AF during antihypertensive treatment may be improved by antihypertensive therapy that reduces LA size in addition to controlling blood pressure.
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| 9. |
- Wachtell, K., et al.
(författare)
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Regression of electrocardiographic left ventricular hypertrophy during antihypertensive therapy and reduction in sudden cardiac death: the LIFE Study
- 2007
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 1524-4539 .- 0009-7322. ; 116:7, s. 700-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sudden cardiac death (SCD) occurs more often in patients with ECG left ventricular (LV) hypertrophy. However, whether LV hypertrophy regression is associated with a reduced risk of SCD remains unclear. METHODS AND RESULTS: The Losartan Intervention for End Point Reduction in Hypertension (LIFE) study included 9193 patients 55 to 80 years of age with essential hypertension and ECG LV hypertrophy by gender-adjusted Cornell product (CP) (RaVL+SV(3) [+6 mm in women]). QRS duration>2440 mm x ms) and/or Sokolow-Lyon voltage (SLV) (SV1+RV(5/6)>38 mm). During follow-up (mean, 4.8 years), 190 patients (2%) experienced SCD. In time-dependent Cox analyses, absence of in-treatment LV hypertrophy was associated with a decreased risk of SCD: every 1-SD-lower in-treatment CP (1050 mm x ms) was associated with a 28% lower risk of SCD (hazard ratio [HR], 0.72; 95% CI, 0.66 to 0.79) and 1-SD-lower SLV (10.5 mm) with a 26% lower risk (HR, 0.74; 95% CI, 0.65 to 0.84). After adjustment for time-varying systolic and diastolic blood pressures, treatment allocation, age, gender, baseline Framingham risk score, ECG strain, heart rate, urine albumin/creatinine ratio, smoking, diabetes, congestive heart failure, coronary heart disease, atrial fibrillation, and occurrence of myocardial infarction, atrial fibrillation, heart failure, and noncardiovascular death, both in-treatment CP and SLV remained predictive of SCD: each 1-SD-lower CP was associated with a 19% lower risk of SCD (HR, 0.81; 95% CI, 0.73 to 0.90) and 1-SD-lower SLV with an 18% lower risk (HR, 0.82; 95% CI, 0.70 to 0.98). Absence of in-treatment LV hypertrophy by both SLV and CP was associated with a 30% lower risk of SCD (HR, 0.70; 95% CI, 0.54 to 0.92). CONCLUSIONS: Absence of in-treatment ECG LV hypertrophy is associated with reduced risk of SCD independently of treatment modality, blood pressure reduction, prevalent coronary heart disease, and other cardiovascular risk factors in hypertensive patients with LV hypertrophy.
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| 10. |
- Bella, J. N., et al.
(författare)
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Sex-related difference in regression of left ventricular hypertrophy with antihypertensive treatment: the LIFE study
- 2004
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Ingår i: J Hum Hypertens. - 0950-9240. ; 18:6, s. 411-6
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Tidskriftsartikel (refereegranskat)abstract
- While left ventricular (LV) structure and function differ between hypertensive women and men, it remains unclear whether sex affects regression of LV hypertrophy with antihypertensive treatment. We analysed paired echocardiograms in 500 men and 347 women enrolled in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study at baseline and after 12 months of antihypertensive treatment with either losartan or atenolol. At enrollment, 177 women and 242 men were randomized to losartan-based treatment and 161 women and 247 men were randomized to atenolol-based treatment (sex difference=NS). After 12 months of antihypertensive treatment, blood pressure was lowered similarly in women (152/83 from 174/97 mmHg) and men (149/85 from 173/99 mmHg; both P<0.001, sex difference=NS), without significant change in body weight in either sex. Cardiac output and pulse pressure/stroke volume were equivalently reduced in both sexes (-0.2 vs -0.1 l/min and both -0.20 mmHg/ml/m(2), respectively; both P=NS). Absolute LV mass change after 12 months of antihypertensive treatment was greater in men than in women (-30 vs -24 g, P=0.01). However, after adjusting for baseline LV mass and randomized study treatment, LV mass reduction was greater in women than in men (-33 vs -23 g, P=0.001). LV mass regression was greater in women, by 8.0+/-2.8 g, after adjusting for baseline LV mass and randomized study treatment. After consideration of baseline LV mass and randomized study treatment, antihypertensive treatment regressed LV hypertrophy more in women. Further studies are needed to identify the mechanisms and prognostic implications of this sex-related difference.
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