A prediction of the renal and cardiovascular efficacy of aliskiren in ALTITUDE using short-term changes in multiple risk markers.

INTRODUCTION: We recently developed and validated in existing trials a novel algorithm (PRE score) to predict long-term drug efficacy based on short-term (month-6) drug-induced changes in multiple risk markers. To show the value of the PRE score for ongoing and planned clinical trials, we here report the predicted long-term cardio-renal efficacy of aliskiren in type 2 diabetes, which was investigated in the ALTITUDE trial, but unknown at the time this study was conducted. METHODS: We established the relation between multiple risk markers and cardio-renal endpoints (as defined in ALTITUDE) using a background database from past clinical trials. The short-term effect of aliskiren on multiple risk markers was taken from the AVOID trial. A PRE score was developed by multivariate Cox analysis in the background population and was then applied to the baseline and month-6 measurements of the aliskiren treatment arm of the AVOID trial to predict cardio-renal risk. The net risk difference at these time-points, after correction for placebo effects, was taken to indicate the estimated long-term cardio-renal risk change. RESULTS: Based on the PRE score, we predicted that aliskiren treatment in ALTITUDE would confer a relative risk change of -7.9% (95% CI -2.5 to -13.4) for the cardio-renal endpoint, a risk change of -5.1% (-1.2 to -9.0) for the CV endpoint and a non-significant risk change of -19.9% (-42.1 to +2.1) for the renal endpoint. CONCLUSIONS: PRE score estimations suggested that aliskiren has only a marginal additive protective effect on cardio-renal endpoints. These predictions were validated by the results of the ALTITUDE trial, confirming the potential of the PRE score to prospectively predict drug efficacy on cardio-renal outcomes.

Impact of overweight and obesity on cardiac benefit of antihypertensive treatment.

BACKGROUND AND AIMS: Increased body mass index (BMI) has been associated with increased cardiovascular morbidity and mortality in hypertension. Less is known about the impact of BMI on improvement in left ventricular (LV) structure and function during antihypertensive treatment. METHODS AND RESULTS: Annual BMI, echocardiograms and cardiovascular events were recorded in 875 hypertensive patients with LV hypertrophy during 4.8 years randomized treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography substudy. Patients were grouped by baseline BMI into normal (n = 282), overweight (n = 405), obese (n = 150) and severely obese groups (n = 38) (BMI ≤24.9, 25.0-29.9, 30.0-34.9, and ≥35.0 kg/m(2), respectively). At study end, residual LV hypertrophy was present in 54% of obese and 79% of severely obese patients compared to 31% of normal weight patients (both p < 0.01). In regression analyses, adjusting for initial LV mass/height(2.7), higher BMI predicted less LV hypertrophy reduction and more reduction in LV ejection fraction (both p < 0.05), independent of blood pressure reduction, diabetes and in-study weight change. During follow-up, 91 patients suffered cardiovascular death, myocardial infarction or stroke. In Cox regression analysis 1 kg/m(2) higher baseline BMI predicted a 5% higher rate of cardiovascular events and 10% higher cardiovascular mortality over 4.8 years (both p < 0.05). CONCLUSIONS: In hypertensive patients in the LIFE study, increased BMI was associated with less reduction of LV hypertrophy and less improvement in LV systolic function which may contribute to the observed higher cardiovascular event rate of treated hypertensive patients.

Changes in electrocardiographic left ventricular hypertrophy and risk of major cardiovascular events in isolated systolic hypertension: the LIFE study.

The predictive value of changes in the severity of electrocardiographic left ventricular hypertrophy (ECG-LVH) during antihypertensive therapy remains unclear in isolated systolic hypertension (ISH). In a Losartan Intervention For Endpoint reduction in hypertension substudy, we included 1320 patients aged 54-83 years with systolic blood pressure (BP) of 160-200 mm Hg, diastolic BP <90 mm Hg and ECG-LVH by Cornell voltage-duration product and/or Sokolow-Lyon voltage criteria, randomized to losartan- or atenolol-based treatment with a mean follow-up of 4.8 years. The composite end point of cardiovascular death, non-fatal myocardial infarction (MI) or stroke occurred in 179 (13.6%) patients. In Cox regression models controlling for treatment, Framingham risk score, as well as baseline and in-treatment BP, less severe in-treatment ECG-LVH by Cornell product and Sokolow-Lyon voltage was associated with 17 and 25% risk reduction for the composite end point (adjusted hazard ratio (HR) 0.83, 95% confidence interval (95% CI:) 0.75-0.92, P=0.001 per 1050 mm × ms (1 s.d.) lower Cornell product; and HR 0.75, 95% CI: 0.65-0.87, P<0.001 per 10.5 mm (1 s.d.) lower Sokolow-Lyon voltage). In parallel analyses, lower Cornell product and Sokolow-Lyon voltage were associated with lower risks of cardiovascular mortality and MI, and lower Sokolow-Lyon voltage with lower risk of stroke. Lower Cornell product and Sokolow-Lyon voltage during antihypertensive therapy are associated with lower likelihoods of cardiovascular events in patients with ISH.

Clustered metabolic abnormalities blunt regression of hypertensive left ventricular hypertrophy: the LIFE study.

BACKGROUND AND AIMS: Clusters of metabolic abnormalities resembling phenotypes of metabolic syndrome predicted outcome in the LIFE study, independently of single risk markers, including obesity, diabetes and baseline ECG left ventricular hypertrophy (LVH). We examined whether clusters of two or more metabolic abnormalities (MetAb, including obesity, high plasma glucose without diabetes, low HDL-cholesterol) in addition to hypertension were associated to levels of ECG LVH reduction comparable to that obtained in hypertensive subjects without or with only one additional metabolic abnormality (no-MetAb). METHODS AND RESULTS: We studied 5558 non-diabetic participants without MetAb (2920 women) and 1235 with MetAb (751 women) from the LIFE-study cohort. MetAb was defined by reported LIFE criteria, using partition values from the ATPIII recommendations. Time-trends of Cornell voltage-duration product (CP) over 5 years was assessed using a quadratic polynomial contrast, adjusting for age, sex, prevalent cardiovascular disease and treatment arm (losartan or atenolol). At baseline, despite similar blood pressures, CP was greater in the presence than in the absence of MetAb (p<0.0001). During follow-up, despite similar reduction of blood pressure, CP decreased less in patients with than in those without MetAb, even after adjustment for the respective baseline values (both p<0.002). Losartan was more effective than atenolol in reducing CP independently of MetAb. CONCLUSIONS: Clusters of metabolic abnormalities resembling phenotypes of metabolic syndrome are related to greater initial ECG LVH in hypertensive patients with value of blood pressure similar to individuals without metabolic abnormalities, and are associated with less reduction of ECG LVH during antihypertensive therapy, potentially contributing to the reported adverse prognosis of metabolic syndrome.

Impact of diabetes on treatment-induced changes in left ventricular structure and function in hypertensive patients with left ventricular hypertrophy. The LIFE study.

BACKGROUND AND AIM: Diabetes is associated with left ventricular hypertrophy (LVH) and impaired systolic function in hypertensive patients, but less is known about its impact on LVH regression and functional improvement during antihypertensive treatment. METHODS AND RESULTS: We performed annual echocardiography in 730 non-diabetic and 93 diabetic patients (aged 55-80 years) with hypertension and electrocardiographic LVH during 4.8-year losartan- or atenolol-based treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Baseline mean blood pressure (BP) and LV mass did not differ between groups. Diabetic patients had higher body mass index and pulse pressure, and lower LV ejection fraction, midwall shortening, stress-corrected midwall shortening, and estimated glomerular filtration rate (all p<0.05), and were more likely to have albuminuria. Despite comparable BP reduction in diabetic and non-diabetic groups during treatment (33/18 vs. 28/16mmHg (ns)), diabetes was associated with higher prevalence of persistent LVH (47 vs. 39%, p<0.05). In multivariate analyses, diabetes independently predicted less LV mass reduction and less improvement in stress-corrected LV midwall shortening (both p<0.01). CONCLUSION: Among hypertensive patients with LVH, diabetes is associated with more residual LVH and less improvement in systolic LV function by echocardiography over 4.8 years of antihypertensive treatment.

New risk markers may change the HeartScore risk classification significantly in one-fifth of the population.

The study aim was to determine whether urine albumin/creatinine ratio (UACR), high-sensitivity C-reactive protein (hsCRP) or N-terminal pro-brain natriuretic peptide (Nt-proBNP) added to risk prediction based on HeartScore and history of diabetes or cardiovascular disease. A Danish population sample of 2460 individuals was divided in three groups: 472 subjects receiving cardiovascular medication or having history of diabetes, prior myocardial infarction or stroke, 559 high-risk subjects with a 10-year risk of cardiovascular death above 5% as estimated by HeartScore, and 1429 low-moderate risk subjects with estimated risk below 5%. During the following 9.5 years the composite end point of cardiovascular death, non-fatal myocardial infarction or stroke (CEP) occurred in 204 subjects. CEP was predicted in all three groups by UACR (HRs: 2.1, 2.1 and 2.3 per 10-fold increase, all P<0.001) or by hsCRP (HRs: 1.9, 1.9 and 1.7 per 10-fold increase, all P<0.05), but not by Nt-proBNP (HRs: 1.1, 2.6 and 3.7 per 10-fold increase, last two P<0.001) (P<0.05 for interaction). In the low-moderate risk group, pre-specified gender adjusted (men/women) cutoff values of UACR> or =0.73/1.06 mg mmol(-1) or hsCRP> or =6.0/7.3 mg l(-1) identified a subgroup of 16% who experienced one-third of the CEPs. In the patient group, combined absence of high UACR and high Nt-proBNP> or =110/164 pg ml(-1) (men/women) identified a subgroup of 52% who experienced only 15% of the CEPs. Additional use of UACR and hsCRP in subjects with low-moderate risk and UACR and Nt-proBNP in subjects with known diabetes of cardiovascular disease changed HeartScore risk classification significantly in 19% of the population.

Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients with left ventricular hypertrophy and diabetes.

In type 2 diabetes the degree of albuminuria is strongly related to progression of diabetic renal disease, as well as to the risk for cardiovascular complications. If normoalbuminuria is maintained, the risk of diabetic nephropathy is very low. In individuals with microalbuminuria, the rate of decline in glomerular filtration rate is closely related to the degree of albuminuria, and regression to normoalbuminuria slows down the rate of decline in renal function. Data from the LIFE-diabetes subgroup showed that levels of albuminuria well below what is usually defined as microalbuminuria, strongly predicted risk for cardiovascular complications. This indicates that when albuminuria is used as a risk predictor for cardiovascular events, so called normal values should be redefined. Traditional values for normo-micro-macroalbuminuria are primarily defined as predictors for the risk of development of diabetic nephropathy. In the LIFE-diabetes subgroup we found that reduction in albuminuria was more pronounced in losartan-based as compared with atenolol-based treatment. The benefit in favor of losartan was partly related to its major influence on albuminuria. Individuals with the highest baseline values of albuminuria had the greatest benefit in terms of reduction in cardiovascular morbidity and mortality on losartan as compared with atenolol. The level of albuminuria during treatment was closely related to the risk for cardiovascular events. We conclude that tiny amounts of albuminuria, well below traditional levels for microalbuminuria, predict cardiovascular morbidity and mortality. Reduction in albuminuria during treatment translates to reduction in cardiovascular events. Monitoring of albuminuria should be an integrated part of management of hypertension in diabetic as well as nondiabetic patients.

Impact of the metabolic syndrome on the predictive values of new risk markers in the general population.

Although the metabolic syndrome (MetS) is positively associated with high-sensitivity C-reactive protein (hsCRP), negatively associated with N-terminal pro-brain natriuretic peptide (Nt-proBNP) and inconsequently related to urine albumin/creatinine ratio (UACR) they are all associated with cardiovascular events. Therefore, we wanted to determine the influence of MetS on the predictive values of UACR, hsCRP and Nt-proBNP. On the basis of the definition of MetS by the International Diabetes Federation, a Danish population sample of 1983 apparently healthy subjects was divided into three groups: 530 subjects without any elements of MetS, 1093 subjects with some elements of MetS and 360 subjects with MetS. During the following 9.5 years the composite end point of cardiovascular death, non-fatal myocardial infarction or stroke (composite cardiovascular end point, CEP) occurred in 204 subjects. In Cox-regression analyses adjusting for age, gender and smoking, all three cardiovascular risk markers predicted CEP independently of MetS. Despite no significant interaction with MetS, high log(hsCRP) was associated with CEP primarily in subjects without any elements of MetS (hazard ratio (HR)=4.5 (1.5-14.0), P<0.01), log(Nt-proBNP) primarily in subjects with some elements of MetS (HR=3.0 (1.6-5.6), P<0.01), and logUACR independently of elements of MetS. Pre-specified gender-adjusted (men/women) cutoff values of hsCRP > or = 6.0/7.3 mg l(-1) predicted CEP in subjects without elements of MetS with positive and predictive values of 11.5 and 98%, respectively. UACR > or = 0.73/1.06 mg mmol(-1) predicted CEP in subjects with MetS with positive and predictive values of 23.5 and 93%, respectively. In apparently healthy subjects, high hsCRP was associated with CEP primarily in subjects without MetS, high Nt-proBNP in subjects with elements of MetS and UACR independently of MetS.

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

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.

Impairment of cardiac function in hypertensive patients with Type 2 diabetes: a LIFE study.

AIMS: Type 2 diabetic patients with hypertension have an increased left ventricular (LV) mass and impaired cardiac function compared to hypertensive patients without diabetes. However, it is unknown if the impaired cardiac function can be explained solely by LV hypertrophy, or is independently related to diabetes. The aim of the present study was to compare LV function between diabetic and non-diabetic hypertensive patients with electrocardiographic LV hypertrophy. METHODS: In 937 patients participating in the LIFE echocardiographic substudy, all echocardiograms were centrally evaluated by a core reading centre measuring LV mass, systolic and diastolic LV function. Known diabetes was present in 105 patients. RESULTS: Left ventricular mass was similar in diabetic and non-diabetic patients. Endocardial systolic LV function, estimated by LV ejection fraction, was reduced and indices of midwall systolic LV function were impaired in the diabetic patients. Diastolic LV filling pattern was impaired and arterial stiffness, measured by pulse pressure/stroke index, was increased in diabetic patients. CONCLUSIONS: Systolic and diastolic LV function in hypertensive patients with electrocardiographic LV hypertrophy and diabetes are impaired independent of LV mass, most likely reflecting the adverse effects of diabetes per se.

Markers of collagen synthesis is related to blood pressure and vascular hypertrophy: a LIFE substudy.

Cardiac fibrosis and high levels of circulating collagen markers has been associated with left ventricular (LV) hypertrophy. However, the relationship to vascular hypertrophy and blood pressure (BP) load is unclear. In 204 patients with essential hypertension and electrocardiographic LV hypertrophy, we measured sitting BP, serum collagen type I carboxy-terminal telopeptide (ICTP) reflecting degradation, procollagen type I carboxy-terminal propeptide (PICP) reflecting synthesis and LV mass by echocardiography after 2 weeks of placebo treatment and after 1 year of antihypertensive treatment with a losartan- or an atenolol-based regimen. Furthermore, we measured intima-media thickness of the common carotid arteries (IMT), minimal forearm vascular resistance (MFVR) by plethysmography and ambulatory 24-h BP in around half of the patients. At baseline, PICP/ICTP was positively related to IMT (r=0.24, P<0.05), MFVR(men) (r=0.35, P<0.01), 24-h systolic BP (r=0.24, P<0.05) and 24-h diastolic BP (r=0.22, P<0.05), but not to LV mass. After 1 year of treatment with reduction in systolic BP (175+/-15 vs 151+/-17 mmHg, P<0.001) and diastolic BP (99+/-8 vs 88+/-9 mmHg, P<0.001), ICTP was unchanged (3.7+/-1.4 vs 3.8+/-1.4 microg/l, NS) while PICP (121+/-39 vs 102+/-29 microg/l, P<0.001) decreased. The reduction in PICP/ICTP was related to the reduction in sitting diastolic BP (r=0.31, P<0.01) and regression of IMT (r=0.37, P<0.05) in patients receiving atenolol and to reduction in heart rate in patients receiving losartan (r=0.30, P<0.01). In conclusion, collagen markers reflecting net synthesis of type I collagen were positively related to vascular hypertrophy and BP load, suggesting that collagen synthesis in the vascular wall is increased in relation to high haemodynamic load in a reversible manner.

Long-term plasma catecholamines in patients with hypertension and left ventricular hypertrophy treated with losartan or atenolol: ICARUS, a LIFE substudy.

Hypertension is a major risk factor for morbidity and mortality. Plasma catecholamines are linked to the pathogenesis of hypertension. Pharmacological intervention, including treatment with beta-blockers, reduces cardiovascular mortality and morbidity. In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, the angiotensin receptor blocker losartan significantly reduced cardiovascular end points compared to the beta-blocker atenolol. Thus, for the first time, one drug was shown to be superior to another in hypertension. The present substudy examined the effects of atenolol vs losartan treatment on plasma catecholamines at rest and during hyperinsulinaemia in a cohort of 86 LIFE patients. Plasma adrenaline increased significantly from placebo treatment at baseline to year 1 of treatment (P<0.0001), and also during hyperinsulinaemia (P<0.0001). Plasma noradrenaline did not change significantly from placebo treatment at baseline to year 1, but increased significantly during hyperinsulinaemia both at baseline and at year 1 (P<0.0001 for both). There were no differences in plasma catecholamines or the relative changes between the two treatment arms at any stage. In a subset of 42 patients examined also at years 2 and 3, these findings were confirmed during long-term treatment. Thus, losartan had an effect on plasma catecholamines comparable to that with the beta-blocker atenolol in patients with hypertension and left ventricular hypertrophy at rest and during hyperinsulinaemia. We find it unlikely that a difference in sympathetic activity explains the outcome benefits of losartan over atenolol in the LIFE study.

Regression of electrocardiographic left ventricular hypertrophy predicts regression of echocardiographic left ventricular mass: the LIFE study.

The electrocardiogram (ECG) is widely used for detection of left ventricular hypertrophy (LVH). However, whether changes in ECG LVH during antihypertensive therapy predict changes in LV mass remains unclear. Baseline and year-1 ECGs and echocardiograms were assessed in 584 hypertensive patients with ECG LVH by Sokolow-Lyon or Cornell voltage-duration product criteria at entry into the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic substudy. A >/=25% decrease in Cornell product defined regression of ECG LVH; a <25% decrease defined no significant regression; and an increase defined progression of ECG LVH. Regression of echocardiographic LVH was defined by a >/=20% reduction in LV mass. After 1 year of therapy, 155 patients (27%) had regression of ECG LVH, 286 (49%) had no significant change, and 143 (25%) had progression of ECG LVH. Compared with patients with progression of ECG LVH, patients with no significant decrease and patients with regression of ECG LVH had stepwise greater absolute decreases in LV mass (-16+/-33 vs -29+/-37 vs -32+/-41 g, P<0.001), greater percent reductions in LV mass (-5.7+/-14.6 vs -11.3+/-13.6 vs -12.3+/-15.6%, P<0.001), and were more likely to decrease LV mass by >/=20% (11.2 vs 24.8 vs 36.1%, P<0.001), even after adjusting for possible effects of baseline and change in systolic and diastolic pressures. Compared with progression of ECG LVH, regression of the Cornell product ECG LVH is associated with greater reduction in LV mass and a greater likelihood of regression of anatomic LVH.

24-h Ambulatory blood pressure in patients with ECG-determined left ventricular hypertrophy: left ventricular geometry and urinary albumin excretion-a LIFE substudy.

This study was undertaken to evaluate the relationships among left ventricular (LV) geometric patterns and urinary albumin excretion in patients with hypertension and electrocardiographic (ECG) LV hypertrophy. In 143 patients with stage II-III hypertension, 24-h ambulatory blood pressure (BP) monitoring, single urine albumin determination, and echocardiography were performed after 14 days of placebo treatment. Mean age was 68+/-7 years, 35% were women, body mass index was 28+/-5 kg/m(2), LV mass index (LVMI) was 125+/-26 g/m(2), and 24% had microalbuminuria. The mean office BP was 176+/-15/99+/-8 mmHg and the mean daytime ambulatory BP was 161+/-18/92+/-12 mmHg. Ambulatory BP, but not office BP, was higher among albuminuric compared to normoalbuminuric patients. In patients with established hypertension, daytime pulse pressure and office BP were different in the four patterns of LV geometry, with the highest pressure in those with abnormal geometry. Furthermore, microalbuminuria was more frequent in hypertensive patients with LV hypertrophy than in those with either normal geometry or concentric remodelling. White coat hypertensives (10%) showed lower LVMI and no microalbuminuria compared to patients with established hypertension. There were no differences in the prevalence of nondippers (26%) among the four LV geometric patterns or in microalbuminuria. In conclusion, increased daytime pulse pressure and office BP were associated with increased prevalence of abnormal LV geometry. Microalbuminuria was more frequent in groups with concentric and eccentric LV hypertrophy. Ambulatory BP, but not office BP, was higher in albuminuric than normoalbuminuric patients. With regard to the relationship among BP, LV geometric patterns, and urine albumin excretion in this population, 24-h ambulatory BP did not provide additional information beyond the office BP.

Albuminuria predicts cardiovascular events independently of left ventricular mass in hypertension: a LIFE substudy.

We wanted to investigate whether urine albumin/creatinine ratio (UACR) and left ventricular (LV) mass, both being associated with diabetes and increased blood pressure, predicted cardiovascular events in patients with hypertension independently. After 2 weeks of placebo treatment, clinical, laboratory and echocardiographic variables were assessed in 960 hypertensive patients from the LIFE Echo substudy with electrocardiographic LV hypertrophy. Morning urine albumin and creatinine were measured to calculate UACR. The patients were followed for 60+/-4 months and the composite end point (CEP) of cardiovascular (CV) death, nonfatal stroke or nonfatal myocardial infarction was recorded. The incidence of CEP increased with increasing LV mass (below the lower quartile of 194 g to above the upper quartile of 263 g) in patients with UACR below (6.7, 5.0, 9.1%) and above the median value of 1.406 mg/mmol (9.7, 17.0, 19.0%(***)). Also the incidence of CV death increased with LV mass in patients with UACR below (0, 1.4, 1.3%) and above 1.406 mg/mmol (2.2, 6.4, 8.0%(**)). The incidence of CEP was predicted by logUACR (hazard ratio (HR)=1.44(**) for every 10-fold increase in UACR) after adjustment for Framingham risk score (HR=1.05(***)), history of peripheral vascular disease (HR=2.3(*)) and cerebrovascular disease (HR=2.1(*)). LV mass did not enter the model. LogUACR predicted CV death (HR=2.4(**)) independently of LV mass (HR=1.01(*) per gram) after adjustment for Framingham risk score (HR=1.05(*)), history of diabetes mellitus (HR=2.4(*)) and cerebrovascular disease (HR=3.2(*)). (*)P<0.05, (**)P<0.01, (***)P<0.001. In conclusion, UACR predicted CEP and CV death independently of LV mass. CV death was predicted by UACR and LV mass in an additive manner after adjustment for Framingham risk score and history of CV disease.

Association of left bundle branch block with left ventricular structure and function in hypertensive patients with left ventricular hypertrophy: the LIFE study.

Electrocardiographic (ECG) left bundle branch block (LBBB) is associated with left ventricular hypertrophy (LVH), but its relation to left ventricular (LV) geometry and function in hypertensive patients with ECG LVH is unknown. Echocardiograms were performed in 933 patients (548 women, mean age 66+/-7 years) with essential hypertension and LVH by baseline ECG in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. LBBB, defined by Minnesota code 7.1, was present in 47 patients and absent in 886 patients. Patients with and without LBBB were similar in age, gender, body mass index, blood pressure, prevalence of diabetes, and history of myocardial infarction. Despite similarly elevated mean LV mass (126+/-25 vs 124+/-26 g/m(2)) and relative wall thickness (0.41+/-0.07 vs 0.41+/-0.07, P=NS), patients with LBBB had lower LV fractional shortening (30+/-6 vs 34+/-6%), ejection fraction (56+/-10 vs 61+/-8%), midwall shortening (14+/-2 vs 16+/-2%), stress-corrected midwall shortening (90+/-13 vs 97+/-13%) (all P<0.001), and lower LV stroke index (38+/-7 vs 42+/-9 ml/m(2)) (P<0.05). Patients with LBBB also had reduced LV inferior wall and lower mitral E/A ratio (0.75+/-0.18 vs 0.87+/-0.38) (all P<0.05). The above univariate results were confirmed by multivariate analyses adjusted for gender, age, blood pressures, height, weight, body mass index, heart rate, and LV mass index. Among hypertensive patients at high risk because of ECG LVH, the presence of LBBB identifies individuals with worse global and regional LV systolic function and impaired LV relaxation without more severe LVH by echocardiography.