Reductions in albuminuria and in electrocardiographic left ventricular hypertrophy independently improve prognosis in hypertension: the LIFE study

BACKGROUND: In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, reduced urine albumin/creatinine ratio (UACR) as well as regression of left ventricular hypertrophy have been associated with lower incidence of cardiovascular events. We wanted to investigate whether these prognostic improvements were independent. METHODS: In 6679 hypertensive patients included in the LIFE study, we measured UACR, left ventricular hypertrophy by electrocardiography, serum cholesterol, plasma glucose and blood pressure after 2 weeks of placebo treatment and again after 1 year of anti-hypertensive treatment with either an atenolol- or a losartan-based regimen. During this first year of treatment, 77 patients encountered a non-fatal stroke or myocardial infarction and were excluded to avoid bias. During the next 3-4 years, 610 composite endpoints [cardiovascular death (n = 228), fatal or non-fatal myocardial infarction or stroke] were recorded. RESULTS: In Cox regression analyses, the composite endpoint was after adjustment for treatment allocation predicted by baseline logUACR [hazard ratio (HR) = 1.16 per 10-fold increase, P < 0.05], 1-year logUACR (HR = 1.29 per 10-fold increase), baseline Sokolow-Lyon voltage (HR = 1.01 per mm, both P < 0.001) and 1-year Cornell product (HR = 1.01 per 100 mm x ms, P < 0.01). Cardiovascular death was predicted by 1-year logUACR (HR = 1.59, P < 0.001), baseline Sokolow-Lyon voltage (HR = 1.01, P = 0.06) and 1-year Cornell product (HR = 1.02, P < 0.001). Both were predicted independent of age, Framingham risk score, current smoking, history of cardiovascular disease and diabetes. Gender, serum cholesterol, plasma glucose and blood pressure did not enter the models. CONCLUSIONS: Baseline UACR and Sokolow-Lyon voltage, as well as in-treatment UACR and Cornell product, added to the risk prediction independent of traditional risk factors, indicating that albuminuria and left ventricular hypertrophy reflect different aspects of cardiovascular damage and are modifiable cardiovascular risk factors.     

Aortic valve sclerosis and albuminuria predict cardiovascular events independently in hypertension: a losartan intervention for endpoint-reduction in hypertension (LIFE) substudy

BACKGROUND: Aortic valve (AV) sclerosis and urine albumin/creatinine ratio (UACR) are both markers of atherosclerosis. We aimed to investigate whether they predicted cardiovascular (CV) events independently in patients with hypertension and electrocardiographic left ventricular (LV) hypertrophy. METHODS: After 2 weeks of placebo treatment, clinical, laboratory, and echocardiographic variables were assessed in 960 hypertensive patients from the LIFE Echo substudy who had electrocardiographic LV hypertrophy. Morning urine albumin and creatinine were measured calculating UACR. The presence of AV sclerosis was defined as valve thickening or calcification. Fifteen patients with mild AV stenosis were excluded. The patients were followed for 60 +/- 4 months and the composite endpoint (CEP) of CV death, nonfatal stroke, or nonfatal myocardial infarction was recorded. RESULTS: A value of UACR above the median value of 1.406 was associated with higher incidence of CEP and CV death in patients with AV sclerosis (CEP: 18.8% v 9.0% P < 0.05, CV death: 7.1% v 0.7% P < 0.01) and in patients without AV sclerosis (CEP: 14.0% v 4.9% P < 0.001, CV death: 5.1% v 1.1% P < 0.01). In Cox regression analysis, AV sclerosis predicted CEP (hazard ratio [HR] = 1.52, P < .05), but not CV death (HR = 1.30 [0.62 to 2.70], NS) independently of logUACR (HR = 1.70 and HR = 3.25, both P < .001). After adjusting for the Framingham Risk Score, CV disease, diabetes, smoking, and treatment allocation, AV sclerosis predicted CEP (HR = 1.5, P < .05) but not CV death (HR = 1.4, NS) independently of logUACR (HR = 1.2, P = .09 and HR = 1.94, P < .05). CONCLUSIONS: In hypertensive patients with electrocardiographic LV hypertrophy, AV sclerosis predicted CEP but not CV death independently of UACR after adjusting for CV risk factors and treatment allocation, indicating that AV sclerosis and UACR might be markers of different aspects of the atherosclerotic process.     

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.     

Progressive hypertrophy regression with sustained pressure reduction in hypertension: the Losartan Intervention For Endpoint Reduction study

OBJECTIVE : To examine the time course of left ventricular (LV) geometric response to blood pressure (BP) control during 2 years of systematic antihypertensive treatment. DESIGN : A total of 754 hypertensive patients with left ventricular hypertrophy (LVH) by Cornell voltage-duration product or Sokolow-Lyon voltage criteria on a screening electrocardiogram had their LV mass measured by echocardiogram at enrolment in the Losartan Intervention For Endpoint Reduction (LIFE) trial, and after 12 and 24 months of blinded therapy with losartan-based or atenolol-based regimens. SETTING : The LIFE trial, in which hypertensive patients with electrocardiographic LVH (Cornell voltage-duration product > 2440 mm x ms and/or Sokolow-Lyon voltage criteria SV1 + RV5-6 > 38 mm) were randomized to >or= 4 years double-blinded treatment with losartan or atenolol. PARTICIPANTS : A total of 754 LIFE participants with serial echocardiographic measurements of LV geometry. INTERVENTIONS : None. MAIN OUTCOME MEASURES : LV wall thicknesses, diameter and mass, and its indices. RESULTS : Mean systolic/diastolic BP fell from 173/95 to 150/84 mmHg after 1 year (P < 0.001) and to 148/83 mmHg at year 2 (P = not significant). Mean echocardiographic LV mass fell from 233 g at baseline to 206 g after 1 year (P < 0.001, adjusted for change in systolic BP) and to 195 g at year 2 (P < 0.001 versus year 1), with a parallel decrease in indexed LV mass [from 56.1 to 49.7 g/m2.7 (P < 0.001), to 47.1 g/m2.7 (P < 0.001 versus year 1)]. Relative wall thickness decreased from 0.41 at baseline to 0.37 at year 1 (P < 0.001), to 0.36 at year 2 (P < 0.001 versus year 1). As a result, there were serial decreases in prevalences of eccentric LVH [44 to 38%, and to 30% (P < 0.001 versus year 1)] and concentric LVH [24 to 7% (P < 0.001), to 2% (P < 0.05 versus year 1)], and increases in the proportion with normal LV geometry [22 to 50% (P < 0.001), and to 64% (P < 0.01 versus year 1)]. CONCLUSIONS : Sustained BP reduction in hypertensive patients with target organ damage causes continued decrease in echocardiographic LV mass and prevalence of anatomic LVH for at least 2 years despite only small BP decreases after the first year of blinded therapy. These data document cardiac benefit of sustained BP control and suggest that maximum LVH regression with effective antihypertensive treatment requires at least 2 years.     

Does long-term losartan- vs atenolol-based antihypertensive treatment influence collagen markers differently in hypertensive patients? A LIFE substudy

BACKGROUND: The aim of this study was to investigate the effects of losartan- vs atenolol-based antihypertensive treatment on circulating collagen markers beyond the initial blood pressure (BP) reduction. METHODS: In 204 patients with hypertension and left ventricular (LV) hypertrophy we measured serum concentration of carboxy-terminal telopeptide of type I procollagen (ICTP), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), amino-terminal propeptide of type I procollagen (PINP) and LV mass by echocardiography at baseline and annually during 4 years of losartan- or atenolol-based antihypertensive treatment; 185 patients completed the study. RESULTS: Beyond the first year of treatment systolic and diastolic BP, LV mass index (LVMI) as well as collagen markers did not change significantly and were equal in the two treatment groups. Changes in PICP during first year of treatment were related to subsequent changes in LV mass index after 2 and 3 years of treatment (r=0.28 and r=0.29, both p<0.05) in patients randomized to losartan, but not atenolol. CONCLUSION: Long-term losartan- vs atenolol-based antihypertensive treatment did not influence collagen markers differently, making a BP-independent effect of losartan on collagen markers unlikely. However, initial reduction in circulating PICP may predict later regression of LV hypertrophy during losartan-based antihypertensive treatment.     

Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: losartan intervention for endpoint reduction in hypertension study

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.     

Left ventricular mass regression in the LIFE study: effect of previous antihypertensive treatment

BACKGROUND: Whether to include only those patients who have not had prior hypertension treatment in clinical trials of left ventricular (LV) mass reduction is controversial. Accordingly, our aim was to study the relationship between prior treatment and both baseline and 1-year echocardiographic LV mass in subjects enrolled in the Losartan Intervention For Endpoint reduction (LIFE) study. METHODS: We studied clinical and baseline echocardiographic data on 960 patients with electrocardiographically confirmed left ventricular hypertrophy enrolled in the electrocardiographic substudy of the LIFE study, 847 of whom had LV mass remeasured after 1 year of blinded treatment. The majority (75%) of these patients had prior medical treatment for hypertension. RESULTS: In multivariable regression analysis, controlling for age, sex, blood pressure (BP), body mass index, and indices of pump and myocardial function, prior antihypertensive treatment was not associated with either greater LV mass or relative wall thickness on the baseline study. Moreover, there was no significant difference between the 637 subjects who were previously treated and the 210 who were not treated with regard to the mean reduction in systolic or diastolic pressures (-25 +/- 17 v -24 +/- -16 and -13 +/- 9 mm Hg v -12 +/- 9 mm Hg), LV mass (-27 +/- 38 v -29 +/- 34 g), or LV mass/body surface area (-14 +/- 20 v -15 +/- 18 g/m(2)), all P >.05. CONCLUSIONS: Prior treatment is not associated with either greater LV mass or greater relative wall thickness when age, body mass index, sex, systolic BP, heart rate, or indices of LV volume load and systolic function are taken into account. In addition, prior treatment is not associated with lesser degrees of LV mass reduction. For design of future clinical trials, restriction of inclusion criteria to only previously untreated patients does not appear to be necessary when the selection criterion is electrocardiographically determined left ventricular hypertrophy.     

High-sensitivity C-reactive protein is only weakly related to cardiovascular damage after adjustment for traditional cardiovascular risk factors

BACKGROUND: The independent prognostic value of high-sensitivity C-reactive protein (hsCRP) has been questioned, and consequently we decided to investigate whether hsCRP was associated with subclinical cardiovascular (CV) damage independently of traditional CV risk factors. METHODS: In a population-based sample of 2028 apparently healthy individuals without prior stroke or myocardial infarction not receiving any CV, anti-diabetic or lipid-lowering treatment, aged 41, 51, 61 or 71 years, we measured in 1993 serum hsCRP, traditional CV risk factors (lifestyle, metabolic and hemodynamic) and assessed subclinical CV damage [atherosclerotic plaques in the carotid arteries, pulse wave velocity (PWV), urine albumin/creatinine ratio (UACR), left ventricular (LV) mass and ejection fraction]. RESULTS: Adjusting for age and gender in multiple regression analyses, higher log(hsCRP) was associated with higher logPWV (beta = 0.15) and log(left ventricular mass index) (LVMI) (beta = 0.09, both P < 0.001), LV relative wall thickness (beta = 0.07, P < 0.01), logUACR (beta = 0.04, P = 0.06) and more atherosclerotic plaques (beta = 0.06, P < 0.05). However, higher log(hsCRP) was only weakly associated with higher logPWV(beta = 0.06, P < 0.05) and more atherosclerotic plaques (beta = 0.04, P = 0.06) when adjusting for other significant CV risk factors, such as daily smoking (beta = 0.18), female gender (beta = -0.17), older age (beta = 0.11), lower log(high density lipoprotein cholesterol) (beta = -0.11, all P < 0.001); wider waist (beta = 0.17), higher body mass index (beta = 0.14), higher heart rate (beta = 0.06, all P < 0.01); and higher log(plasma glucose) (beta = 0.05, P < 0.05) (adj. R2 = 0.19, P < 0.001). CONCLUSION: After adjustment for traditional CV risk factors hsCRP was only associated with PWV and atherosclerotic plaques, indicating a possible effect of low-grade inflammation on macrovascular damage. The close relationship between traditional CV risk factors and hsCRP suggested that hsCRP was an integrated CV risk marker early in the development of atherosclerosis.     

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.     

Impact of age on left ventricular hypertrophy regression during antihypertensive treatment with losartan or atenolol (the LIFE study)

To assess the influence of age on changes in left ventricular (LV) mass and geometry during antihypertensive treatment, we related age to clinical and echocardiographic findings before and after 4 years of antihypertensive treatment in a subset of 560 hypertensive patients without known concurrent disease in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, which randomized patients to blinded losartan- or atenolol-based treatment. Patients >/=65 years (older group) included more women and patients with isolated systolic hypertension or albuminuria (all P<0.05). Compared to patients <65 years, older patients had higher pulse pressure, LV mass, and prevalence of concentric hypertrophy at baseline (78 vs 69 mmHg, 234 vs 224 g, and 28 vs 16%, respectively, all P<0.01), while the mean blood pressure did not differ. Over 4 years, reductions in LV mass and the mean blood pressure were similar in both groups, but older patients more often had residual hypertrophy (31 vs 15%, P<0.001) with a preponderance of eccentric geometry. In multivariate analysis of 4-year change in LV mass controlling for baseline mass, larger hypertrophy reduction was associated with losartan treatment, while age, gender, body mass index, and 4-year change in pulse pressure and albuminuria did not enter (Multiple R (2)=0.40, P<0.001). Thus, in up-to-80-year-old hypertensive patients with left ventricular hypertrophy, age did not significantly attenuate hypertrophy reduction during antihypertensive treatment, although residual hypertrophy was more prevalent in older patients as a consequence of higher initial LV mass.     

Antihypertensive effect of felodipine associated with persistent sympathetic activation and minimal regression of left ventricular hypertrophy.

Twenty patients whose systemic hypertension was not controlled with chronic beta-blocker therapy were studied to evaluate the acute (first dose), short-term (4 weeks) and chronic (6 to 12 months) effects of the calcium antagonist felodipine on blood pressure (BP), left ventricular (LV) anatomy and function and on plasma norepinephrine. The first dose of felodipine rapidly reduced total peripheral resistance and BP, associated with significant increases in heart rate, cardiac output and plasma norepinephrine. During chronic therapy, at the end of the dosing interval (12 hours), significant decreases in BP persisted with minimal changes in the other variables. However, even after 1 year of therapy BP after dosing again rapidly decreased associated with 50 to 100% increases in plasma norepinephrine and small increases in heart rate and cardiac output. Despite the marked decreases in systolic BP, LV wall thickness and mass showed only small decreases (LV mass -- 17 +/- 7 g/m2 after 1 year) and significant LV hypertrophy persisted after 1 year. Both average systolic BP and plasma norepinephrine were significant determinants of LV mass over the duration of the study. It is concluded that during chronic treatment with the twice-daily tablet formulation of felodipine, major daily fluctuations in BP persist associated with persisting sympathetic hyperactivity. The latter may play a role in the modest regression of LV hypertrophy despite 30 to 40 mm Hg decreases in systolic BP for 1 year.     

Arterial plasma noradrenaline predicts left ventricular mass independently of blood pressure and body build in men who develop hypertension over 20 years

BACKGROUND: Increased sympathetic activity may be an underlying mechanism in cardiovascular disease. It has been hypothesized that the degree of left ventricular (LV) hypertrophy is partly related to the blood pressure level, and partly to neurohormonal factors. The aim of this study was to investigate predictors of LV mass, including arterial plasma noradrenaline as an index of sympathetic activity, with particular emphasis on subjects who developed hypertension over a period of 20 years. METHODS: In a 20-year prospective study of middle-aged men, sustained hypertensives (n = 22), new hypertensives (crossovers) (n = 17) and sustained normotensives (controls) (n = 17) were examined both at baseline and after 20 years of follow-up (at ages 42.1 +/- 0.5 and 62.3 +/- 0.6 years, respectively). Relationships between arterial plasma catecholamines, blood pressure and body mass index at baseline to left ventricular parameters by echocardiography at follow-up were investigated. RESULTS: Groups were homogeneous regarding age, gender, race and body build. The group of sustained hypertensives had significantly more LV hypertrophy (P = 0.025) and diastolic dysfunction (P = 0.010). Among the crossovers, LV mass index was positively correlated to arterial plasma noradrenaline (r = 0.50, P = 0.043) and body mass index (BMI) (r = 0.51, P = 0.039) and showed a positive trend with systolic blood pressure (SBP) at baseline. Arterial plasma noradrenaline (beta = 0.47) was found to predict LV mass index after 20 years independently of BMI (beta = 0.45) and SBP (beta = 0.22) at baseline (R adjusted = 0.345, P = 0.037). Such a relationship was not found in the controls or in the sustained hypertensives, of which 16 were treated with antihypertensive drugs. CONCLUSIONS: Arterial plasma noradrenaline at baseline, as an index of sympathetic activity, predicts LV mass at follow-up independently of systolic blood pressure and body build in middle-aged men who developed hypertension over a period of 20 years.     

Opposite effects of losartan and atenolol on natriuretic peptides in patients with hypertension and left ventricular hypertrophy: a LIFE substudy

BACKGROUND: Secretion of natriuretic peptides is related to cardiac wall stress and influenced by the renin-angiotensin system. Therefore, we investigated the influence of blood pressure (BP) reduction with losartan versus atenolol on N-terminal pro-atrial natriuretic peptide (Nt-proANP) and N-terminal pro-brain natriuretic peptide (Nt-proBNP). METHODS: In 183 patients with hypertension and electrocardiographic left ventricular (LV) hypertrophy, enrolled in the LIFE Study, we measured BP and serum Nt-proANP and Nt-proBNP by immunoassay after 2 weeks of placebo treatment and after 1, 2, 4, 6, 12, 24, 36 and 48 months of randomized treatment with losartan- or atenolol-based antihypertensive regimens. RESULTS: There was no significant difference in BP at any time point between the two treatment groups. In patients treated with losartan, median Nt-proANP decreased gradually throughout the study, reaching significance after 6 months of treatment (1125-1060 pmol/l, P < 0.001), and Nt-proBNP decreased within the first month (24.7-18.7 pmol/l, P < 0.01) and stayed reduced throughout the study. During losartan-based antihypertensive treatment, Nt-proANP and Nt-proBNP as a percentage of baseline values were correlated to reductions in systolic BP (r = 0.11, P < 0.01 and r = 0.10, P = 0.01) and diastolic BP (r = 0.17, P < 0.001 and r = 0.07, P = 0.09). In atenolol-treated patients, Nt-proANP (1100-1640 pmol/l, P < 0.001) and Nt-proBNP (20.0-37.7 pmol/l, P < 0.001) increased during the first month, and remained elevated throughout the study. During atenolol-based antihypertensive treatment, changes in Nt-proANP (r = -0.16, P < 0.001) and Nt-proBNP (r = -0.07, P = 0.08) were negatively related to change in heart rate. CONCLUSION: Nt-proANP and Nt-proBNP were reduced in parallel with BP in losartan-treated patients whereas they increased in parallel with decreased heart rate in atenolol-treated patients.     

Changes in midwall systolic performance and cardiac hypertrophy reduction in hypertensive patients

OBJECTIVE: To investigate changes in left ventricular (LV) performance, as evaluated by measurement of midwall LV fractional shortening (FS), after reduction of cardiac hypertrophy. DESIGN AND METHODS: Echocardiographic evaluation of LV anatomy and function was performed by M-mode echocardiography at baseline, after long-term antihypertensive therapy, and after treatment withdrawal in 68 asymptomatic hypertensive patients (50 males, 18 females, age range 22-62 years). Patients were divided according to the presence of LV hypertrophy (LVH) at baseline (LV mass index, LVMI, > or = 51 g/m(2.7)). RESULTS: At baseline patients with concentric (relative wall thickness > 0.44) LV hypertrophy (n = 38) or remodelling (n = 7) had reduced midwall shortening with respect to patients with normal LV geometry (n = 4) or eccentric LVH (n = 19); no differences were observed for endocardial FS. After long-term treatment (average 15 months), in 11 patients LV mass remained within normal limits, in 45 patients LVH reduction was obtained, while in 12 patients LV mass remained persistently elevated. Midwall FS was significantly increased in patients with reduction of LVH both during treatment and after withdrawal of treatment, while it remained significantly lower in patients with persistently elevated LV mass. Changes in midwall fractional shortening were independently associated with modifications in relative wall thickness (P < 0.00001), with changes in end-diastolic dimensions (P < 0.0001) and those of LVMI (P< 0.02) as shown by multivariate analysis. CONCLUSION: LV midwall systolic performance significantly improved after reduction of LVH, even in the presence of high blood pressure values. Modifications in relative wall thickness are more independently associated with changes, in LV diastolic dimensions and mass, to midwall improvement     

Electrocardiographic strain pattern and left ventricular diastolic function in hypertensive patients with left ventricular hypertrophy: the LIFE study

BACKGROUND: Whether the typical electrocardiographic (ECG) strain pattern (Strain, in leads V5 and/or V6), which is associated with left ventricular hypertrophy (LVH) and LV systolic dysfunction, is independently associated with LV diastolic dysfunction is unknown. METHODS: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study enrolled hypertensive patients with ECG-LVH, of whom 10% underwent Doppler echocardiography. LV diastolic function measures included peak mitral E and A wave velocities and their ratio (E/A); E wave deceleration time (EDT); atrial filling fraction (AFF); and isovolumic relaxation time (IVRT). Normal filling pattern was defined by E/A < 1 with EDT >or= 150 and or=60 ms; abnormal relaxation by E/A < 1 with EDT > 250 ms or IVRT > 100 ms; pseudonormal filling pattern by E/A >or= 1 associated with IVRT > 100 ms or EDT > 250 ms; restrictive pattern by E/A >or= 1 with IVRT < 100 ms and EDT < 250 ms. A combined index of LV systolic-diastolic function was also computed (isovolumic time/ejection time, modified myocardial performance index). Of LIFE echo substudy participants with all needed ECG and Doppler data (n = 791), 110 (14%) had Strain. RESULTS: Strain was associated with male gender, African-American race, diabetes, history of coronary heart disease (CHD), higher systolic blood pressure (BP), LV mass and relative wall thickness, and higher prevalences of echo-LV hypertrophy and wall motion abnormalities, and with slower heart rate (all P < 0.05). Age, diastolic BP and LV ejection fraction were similar in patients with or without Strain. Diastolic parameters, and prevalences of different LV filling patterns, did not differ significantly between patients with versus those without Strain (all P > 0.1), but modified myocardial performance index was higher with Strain (P < 0.05). Findings were consistent in multivariate analyses. The association of Strain with higher modified myocardial performance index was no longer statistically significant after accounting for LV systolic function and wall motion abnormalities. CONCLUSIONS: In hypertensive patients with ECG-LVH, the ECG Strain pattern did not identify independently those with more severe LV diastolic abnormalities.     

Urine albumin/creatinine ratio and echocardiographic left ventricular structure and function in hypertensive patients with electrocardiographic left ventricular hypertrophy: the LIFE study. Losartan Intervention for Endpoint Reduction

Background Albuminuria, reflecting systemic microvascular damage, and left ventricular (LV) geometric abnormalities have both been shown to predict increased cardiovascular morbidity and mortality. However, the relationship between these markers of cardiovascular damage has not been evaluated in a large hypertensive population. Methods The urine albumin/creatinine ratio (UACR) and echocardiographic measures of LV structure and function were obtained in 833 patients with stage I to III hypertension and LV hypertrophy determined by electrocardiogram (ECG) (Cornell voltage-duration or Sokolow-Lyon voltage criteria) after 14 days of placebo treatment. Results Patients' mean ages were 66 years, 42% were women, 23% had microalbuminuria, and 5% had macroalbuminuria. Patients with eccentric or concentric LV hypertrophy had higher prevalences of microalbuminuria (average 26%-30% vs 9%, P < .001) and macroalbuminuria (6%-7% vs <1%, P < .001). Furthermore, patients with microalbuminuria and macroalbuminuria had a significantly higher LV mass and lower endocardial and midwall fractional shortening. Patients with abnormal diastolic LV filling parameters had a significantly increased prevalence of microalbuminuria. In univariate analyses, UACR correlated positively to LV mass, systolic blood pressure, age (all P < .001) and pulse pressure/stroke volume and negatively to relative wall thickness (both P < .01) and endocardial (P < .05) and midwall shortening (P < .001) but not to diastolic filling parameters. In multiple regression analysis higher UACR was associated with higher LV mass (β = .169, P < .001) independently of older age (β = .095, P < .01), higher systolic pressure (β = .163), black race (β = .186), and diabetes (β = .241, all P < .001). Conclusions In hypertensive patients with ECG LV hypertrophy, abnormal LV geometry and high LV mass are associated with high UACR independent of age, systolic blood pressure, diabetes, and race, suggesting parallel cardiac and microvascular damage. (Am Heart J 2002;143:319-26.)     

Losartan versus atenolol on 24-hour ambulatory blood pressure. A LIFE substudy

Objective. The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study showed that losartan-based treatment reduced risk of the composite endpoint of cardiovascular death, stroke and myocardial infarction compared with atenolol-based treatment in patients with hypertension and left ventricular hypertrophy with similar office blood pressure (BP) reduction. Our aim was to investigate the effect of losartan- and atenolol-based treatment on 24-h ambulatory BP and heart rate (HR) in LIFE. Methods: In 110 patients, 24-h ambulatory BP and heart rate were recorded at baseline and 1 year after randomization. Results: Ambulatory BP was comparably reduced throughout the 24-h period after 1 year of losartan- vs atenolol-based antihypertensive treatment. Office and ambulatory BP were comparably reduced in the follow-up period. Early morning surge in BP was similar between groups. Non-dipping status was more frequent in the losartan group (p = 0.01). From baseline to Year 1 the 24-h HR profile for the losartan group was unchanged, but, as expected, there was a significant decrease in daytime HR in the atenolol group, which was not as large during early night-time. Conclusion: There were no differences in 24-h BP burden and HR that could explain the difference in outcome in favor of losartan vs atenolol in the LIFE study.     

Sex-related difference in regression of left ventricular hypertrophy with antihypertensive treatment: the LIFE study

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.     

老年及高龄高血压患者尿微量白蛋白与大动脉僵硬度的相关性研究

目的探讨老年及高龄高血压患者尿微量白蛋白(MAU)和大动脉僵硬度的关系。方法入选高血压患者384例,应用Complior自动脉搏波传导速度(PWV)分析仪测定颈股动脉PWV(C-FPWV)。依据MAU/肌酐(UACR)将患音分为NMAU组297例和MAU组87例;另按年龄分为老年组(60～79岁)264例和高龄组(≥80岁)120例。分别对各组临床资料进行比较,并进行多元回归分析。结果 MAU组的年龄、高血压病程、体重指数、TG、LDL-C、肌酐、尿酸、收缩压、舒张压、脉压、平均动脉压和C-FPWV明显高于NMAU组(P<0.05,P<0.01)。高龄组UACR和C-PWV明显高于老年组(P<0.05)。所有患者中,年龄、log高血压病程、脉压、logUACR、体重指数、男性是C-FPWV影响因素(R~2=0.592,P<0.05,P<0.01),高龄组中,脉压、年龄、logUACR是C FPWV影响因素(R~2=0.484,P<0.05)。结论老年及高龄高血压患者的UACR对C-FPWV有预测意义,独立于年龄、脉压等心血管危险因素,应定期监测UACR。     

Change of left ventricular geometric pattern after 1 year of antihypertensive treatment: the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study

Background Patients with hypertension have different types of left ventricular (LV) geometry, but the impact of blood pressure (BP) reduction on LV geometry change during antihypertensive treatment remains unclear. Methods Two-dimensional and M-mode echocardiograms were recorded at baseline in 853 unmedicated patients with stage II to III hypertension and LV hypertrophy determined by electrocardiography (Cornell voltage duration ≥2440 mV × ms or modified Sokolow-Lyon criteria: SV1 + RV5/RV6 >38 mV) after 14 days of placebo treatment. Follow-up echocardiography was done after 1 year of blinded treatment with either losartan or atenolol, in some cases supplemented with thiazide and calcium antagonist to reach target a BP of 140/90 mm Hg. Results Baseline systolic/diastolic BP were reduced from 174 ± 20/95 ± 11 to 151 ± 19/84 ± 11 mm Hg. LV mass was reduced from 234 ± 56 to 207 ± 51 g and relative wall thickness from 0.41 ± 0.07 to 0.38 ± 0.06 (all P < .001). Prevalence of concentric LV hypertrophy decreased from 24% to 6%, eccentric LV hypertrophy from 46% to 37%, and concentric LV remodeling from 10% to 6%; normal geometry increased from 20% to 51%. A shift toward lower LV mass and relative wall thickness was found, as approximately 73% of those with concentric LV remodeling at baseline shifted to normal geometric pattern, whereas only 7% of those with normal pattern at baseline shifted to concentric LV remodeling. Of patients with concentric LV hypertrophy at baseline, 34% shifted to eccentric LV hypertrophy, whereas only 3% with eccentric LV hypertrophy at baseline had concentric LV hypertrophy. Furthermore, multiple regression analysis showed that Doppler stroke volume reduction was a significant correlate of LV mass reduction (β = 0.108, P < .001) independent of BP, heart rate change, and assigned drug treatment. Conclusions Antihypertensive treatment reduces LV mass and decreases the prevalence of LV hypertrophy and concentric LV remodeling. Additional control of Doppler stroke volume potentiates the effect of BP reduction on LV mass regression independent of the BP reduction per se. (Am Heart J 2002;144:1057-64.)