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.     

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.     

N-terminal brain natriuretic peptide predicted cardiovascular events stronger than high-sensitivity C-reactive protein in hypertension: a LIFE substudy

BACKGROUND: N-terminal pro-brain natriuretic peptide (Nt-proBNP) and high-sensitivity C-reactive protein (hsCRP) are cardiovascular risk markers in various populations, but are not well examined in hypertension. Therefore, we wanted to investigate whether high Nt-proBNP or hsCRP predicted the composite endpoint of cardiovascular death, non-fatal stroke or non-fatal myocardial infarction independently of traditional cardiovascular risk factors and the urine albumin: creatinine ratio (UACR), which is a well established cardiovascular risk factor in hypertension. METHODS: In 945 hypertensive patients from the LIFE study with electrocardiographic left ventricular (LV) hypertrophy, we measured traditional cardiovascular risk factors including electrocardiography, morning UACR, hsCRP by immunoturbidimetry assay and Nt-proBNP by immunoassay after 2 weeks of placebo treatment. During 55 months' follow-up 80 patients suffered a composite endpoint. RESULTS: HsCRP as well as Nt-proBNP above the median values of 3.0 mg/l and 170 pg/ml, respectively, was associated with a higher incidence of composite endpoint (13.1 versus 3.8%, P < 0.01, and 11.5 versus 5.4%, P < 0.01). In Cox regression analyses, standardized log(hsCRP)/SD predicted a composite endpoint [hazard ratio (HR) 1.3 per SD = 0.47 log(mg/l), P < 0.05] after adjustment for traditional cardiovascular risk factors, but not after further adjustment for UACR. Standardized log(Nt-proBNP)/SD predicted a composite endpoint after adjustment for traditional cardiovascular risk factors [HR 1.9 per SD = 0.49 log(pg/ml), P < 0.05] as well as after further adjustment for UACR [HR 1.5 per SD = 0.49 log(pg/ml), P < 0.01]. Log(Nt-proBNP) added significantly to the Cox regression models using traditional cardiovascular risk factors with and without UACR (both P < 0.001). CONCLUSION: Nt-proBNP predicted a composite endpoint after adjustment for traditional risk factors, UACR and a history of diabetes or cardiovascular disease and added significantly to the prediction of composite endpoint, whereas hsCRP did not.     

Gender differences in regression of electrocardiographic left ventricular hypertrophy during antihypertensive therapy

Although men and women differ in the magnitude of ECG left ventricular hypertrophy, whether gender differences exist in the degree of regression of ECG left ventricular hypertrophy during antihypertensive therapy is unclear. ECG left ventricular hypertrophy defined using gender-adjusted Cornell product and Sokolow-Lyon voltage criteria was assessed serially in 9193 hypertensive patients treated with losartan- or atenolol-based regimens. Changes in ECG left ventricular hypertrophy were measured from baseline to last in-study visit, and above-average regression of hypertrophy was identified by a >or=236-mm . ms reduction in Cornell product or >or=3.5-mm reduction in Sokolow-Lyon voltage. During mean follow-up of 4.8+/-0.9 years, women had less reduction in Cornell product (-149+/-823 versus -251+/-890 mm . ms) and Sokolow-Lyon voltage (-3.0+/-6.8 versus -4.8+/-7.7 mm) than men (both P<0.001). After adjusting for baseline ECG left ventricular hypertrophy levels, baseline and change in systolic and diastolic pressures, treatment group, age, and other baseline gender differences, women had significantly less reduction in both Cornell product (adjusted means: -137 versus -276 mm . ms; P<0.001) and Sokolow-Lyon voltage (-3.6 versus -4.1 mm; P=0.005) than men and were 32% less likely to have had greater than the median level of regression of Cornell product left ventricular hypertrophy (95% CI: 24% to 39%; P<0.001) and 15% less likely to have had regression of left ventricular hypertrophy by Sokolow-Lyon criteria (95% CI: 5% to 23%; P=0.003). Thus, women have less regression of ECG left ventricular hypertrophy than men in response to antihypertensive therapy, independent of baseline gender differences in the severity of ECG left ventricular hypertrophy and after taking into account treatment effects and blood pressure changes.     

A blood pressure independent association between glomerular albumin leakage and electrocardiographic left ventricular hypertrophy. The LIFE Study. Losartan Intervention For Endpoint reduction

In the Losartan Intervention For Endpoint reduction (LIFE) study left ventricular (LV) hypertrophy was associated with increased urine albumin/creatinine ratio (UACR) at baseline. To evaluate whether this association was due only to parallel blood pressure (BP)-induced changes we re-examined the patients after 1 year of antihypertensive treatment to investigate whether changes in LV hypertrophy and UACR were related independently of changes in BP. In 7,142 hypertensive patients included in the LIFE study, we measured UACR, LV hypertrophy by electrocardiography, plasma glucose and BP after 2 weeks of placebo treatment and again after 1 year of antihypertensive treatment with either an atenolol or a losartan based regime. At baseline and still after 1 year of treatment logUACR (R = 0.28, P < 0.001) was still correlated to LV hypertrophy (beta = 0.05) assessed by ECG independently of systolic BP (beta = 0.16), plasma glucose (beta = 0.19) and age (beta = 0.08). Change in logUACR (R = 0.19, P < 0.001) during treatment was correlated to change in LV hypertrophy (beta = 0.10) independently of reduction in systolic BP (beta = 0.13) and change in plasma glucose (beta = 0.06). After 1 year of antihypertensive treatment UACR was still related to LV hypertrophy independently of systolic BP, and the reduction in UACR during that first year of treatment was related to regression of LV hypertrophy independently of reduction in systolic BP. This suggests that the relationship between LV hypertrophy and glomerular albumin leakage is not just due to parallel BP-induced changes. As glomerular albumin leakage may represent generalised vascular damage we hypothesise a vascular relationship between cardiac and glomerular damage.     

Microalbuminuria in hypertensive patients with electrocardiographic left ventricular hypertrophy: the LIFE study

OBJECTIVES : Left ventricular hypertrophy and albuminuria have both been shown to predict increased cardiovascular morbidity and mortality. However, the relationship between these markers of cardiac and renal glomerular damage has not been evaluated in a large hypertensive population with target organ damage. The present study was undertaken to determine whether albuminuria is associated with persistent electrocardiographic (ECG) left ventricular hypertrophy, independent of established risk factors for cardiac hypertrophy, in a large hypertensive population with left ventricular hypertrophy who were free of overt renal failure. METHODS : Patients with stage II-III hypertension were enrolled in the study if they had left ventricular hypertrophy on a screening ECG by Cornell voltage-duration product and/or Sokolow-Lyon voltage criteria, and clinic blood pressures between 160 and 200/95-115 mmHg and plasma creatinine < 160 mmol/l. A second ECG and morning spot urine were obtained after 14 days of placebo treatment. Renal glomerular permeability was evaluated by urine albumin/creatinine (UACR, mg/mmol). Microalbuminuria was present if UACR > 3.5 mg/mmol and macroalbuminuria if UACR > 35 mg/mmol. RESULTS : The mean age of the 8029 patients was 66 years, 54% were women. Microalbuminuria was found in 23% and macroalbuminuria in 4% of patients. Microalbuminuria was more prevalent in patients of African American (35%), Hispanic (37%) and Asian (36%) ethnicity, heavy smokers (32%), diabetics (36%) and in patients with ECG left ventricular hypertrophy by both ECG-criteria (29%). Urine albumin/creatinine was positively related to Sokolow-Lyon voltage criteria and Cornell voltage-duration product criteria. In multiple regression analysis, higher UACR was independently associated with older age, diabetes, higher blood pressure, serum creatinine, smoking and left ventricular hypertrophy. Patients smoking > 20 cigarettes/day had a 1.6-fold higher prevalence of microalbuminuria and a 3.7-fold higher prevalence of macroalbuminuria than never-smokers. ECG left ventricular hypertrophy by Cornell voltage-duration product or Sokolow-Lyon criteria was associated with a 1.6-fold increased prevalence of microalbuminuria and a 2.6-fold increase risk of macroalbuminuria compared to no left ventricular hypertrophy on the second ECG. CONCLUSIONS : In patients with moderately severe hypertension, left ventricular hypertrophy on two consecutive ECGs is associated with increased prevalences of micro- and macroalbuminuria compared to patients without persistent ECG left ventricular hypertrophy. High albumin excretion was related to left ventricular hypertrophy independent of age, blood pressure, diabetes, race, serum creatinine or smoking, suggesting parallel cardiac damage and albuminuria.     

Baseline characteristics in relation to electrocardiographic left ventricular hypertrophy in hypertensive patients: the Losartan intervention for endpoint reduction (LIFE) in hypertension study. The Life Study Investigators

The Losartan Intervention For Endpoint (LIFE) reduction in hypertension study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of atenolol on the reduction of cardiovascular morbidity and mortality. A total of 9194 patients with hypertension and ECG left ventricular hypertrophy (LVH) by Cornell voltage-duration product and/or Sokolow-Lyon voltage criteria were enrolled in the study, with baseline clinical and ECG data available in 8785 patients (54% women; mean age, 67+/-7 years). ECG LVH by Cornell voltage-duration product criteria was present in 5791 patients (65.9%) and by Sokolow-Lyon voltage in 2025 patients (23.1%). Compared with patients without ECG LVH by Cornell voltage-duration product criteria, patients with ECG LVH by this method were older; more obese; more likely to be female, white, and to have never smoked; more likely to be diabetic and have angina; and had slightly higher systolic, diastolic, and pulse blood pressures. In contrast, patients with ECG LVH by Sokolow-Lyon criteria were slightly younger; less obese; more likely to be male, black, and current smokers; less likely to have diabetes; more likely to have angina and a history of cerebrovascular disease; and had higher systolic and pulse blood pressure but slightly lower diastolic blood pressure than patients without ECG LVH by this method. By use of multivariate logistic regression analyses, presence of ECG LVH by Cornell voltage-duration product criteria was predominantly associated with higher body mass index, increased age, and female gender, whereas presence of ECG LVH by Sokolow-Lyon voltage criteria was predominantly related to lower body mass index, male gender, and black race. Thus, hypertensive patients who meet Cornell product and Sokolow-Lyon voltage criteria are associated with different, but potentially equally adverse, risk factor profiles.     

Electrocardiographic characteristics and metabolic risk factors associated with inappropriately high left ventricular mass in patients with electrocardiographic left ventricular hypertrophy: the LIFE Study

BACKGROUND: To investigate electrocardiographic (ECG) and metabolic abnormalities associated with left ventricular (LV) mass inappropriately high for workload and body size (termed 'inappropriate left ventricular mass'; ILVM) in hypertensive patients with ECG left ventricular hypertrophy (LVH). METHODS: In patients enrolled in the Losartan Intervention for Endpoint Reduction (LIFE) Echocardiographic Substudy, LV structure and functions were assessed by echocardiography; Sokolow-Lyon and Cornell voltage, QRS duration, Cornell voltage-duration product and ST strain pattern in leads V5-V6 were evaluated on standard ECG tracings. ILVM was defined as observed LV mass greater than 128% of that predicted by sex, body size and stroke work. RESULTS: In univariate analysis, compared with subjects with appropriate LV mass (n = 593), ILVM (n = 348) was associated with older age, diabetes, higher body mass index, lower systolic blood pressure, higher serum creatinine and urinary albumin/creatinine levels, higher LV mass index and greater prevalence of wall motion abnormalities (all P < 0.05). ILVM was associated with higher Cornell voltage and voltage-duration product but not higher Sokolow-Lyon voltage, with longer QRS and higher prevalences of ECG ST strain and echocardiographic wall motion abnormalities, independent of covariates including echocardiographically defined LVH or LV geometry. In separate logistic models, the likelihood of ILVM was significantly related to prolonged QRS duration, higher Cornell voltage, and greater Cornell voltage-duration independently (all P < 0.01). CONCLUSION: In hypertensive patients with ECG LVH, ILVM was associated with prolonged QRS duration and higher Cornell voltage, with ECG ST strain pattern, and with echocardiographic wall motion abnormalities independent of traditionally defined LVH.     

N-terminal pro-brain natriuretic peptide, but not high sensitivity C-reactive protein, improves cardiovascular risk prediction in the general population.

AIM: Serum N-terminal pro-brain natriuretic peptide (Nt-proBNP), high sensitivity (hs)-C-reactive protein, and urine albumin/creatinine ratio (UACR) are cardiovascular (CV) risk markers in the general population. The aim of this study was to determine whether they predicted CV events independently of established CV risk factors and whether they did so in an additive fashion. METHODS AND RESULTS: In a population-based sample of 2656 individuals, 41, 51, 61, and 71 years old, we measured UACR, serum Nt-proBNP, hs-C-reactive protein, insulin, lipids and plasma glucose, clinic blood pressures, body composition, left ventricular (LV) mass index, and ejection fraction (EF) by echocardiography and pulse wave velocity. During the following 9.4 years, the combined CV endpoint (CEP) of CV death (136), non-fatal stroke, or non-fatal myocardial infarction occurred in 219 subjects. After adjustment for established CV risk factors using Cox-regression analyses, CEP and CV death were predicted by log(Nt-proBNP)/SD [hazard ratio (HR) = 1.58 and HR = 1.80, both P < 0.001] and by log(UACR)/SD (HR = 1.44 and HR = 1.52, both P < 0.001) in an additive fashion, but not by log(hs-C-reactive protein)/SD (HR = 1.17, P = 0.06 and HR = 1.13, NS). CV risk functions were constructed on the basis of Cox-regression analyses. Inclusion of Nt-proBNP and UACR did not increase the area under the receiver-operating characteristic plots. CONCLUSION: Serum Nt-proBNP and UACR, but not hs-C-reactive protein, predicted CV events after adjustment for established CV risk factors including LV EF and relative wall thickness. However, more studies in relevant subgroups are needed before Nt-proBNP and UACR can be recommended for risk prediction in the general population to select subjects for primary prevention.     

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.     

Prognostic Value of a New Electrocardiographic Method for Diagnosis of Left Ventricular Hypertrophy in Essential Hypertension

Objectives. We tested the prognostic value of a new electrocardiographic (ECG) method (Perugia score) for diagnosis of left ventricular hypertrophy (LVH) in essential hypertension and compared it with five standard methods (Cornell voltage, Framingham criterion, Romhilt-Estes point score, left ventricular strain, Sokolow-Lyon voltage).Background. Several standard ECG methods for assessment of LVH are used in the clinical setting, but a comparative prognostic assessment is lacking.Methods. A total of 1,717 white hypertensive subjects (mean age 52 years; 51% men) were prospectively followed up for up to 10 years (mean 3.3).Results. At entry, the prevalence of LVH was 17.8% (Perugia score), 9.1% (Cornell), 3.9% (Framingham), 5.2% (Romhilt-Estes), 6.4% (strain) and 13.1% (Sokolow-Lyon). During follow-up there were 159 major cardiovascular morbid events (33 fatal). The event rate was higher in the subjects with than in those without LVH (all p < 0.001) according to all methods except the Sokolow-Lyon method. By multivariate analysis, an independent association between LVH and cardiovascular disease risk was maintained by the Perugia score (hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.5 to 2.8) and the Framingham (HR 1.91, 95% CI 1.1 to 3.2), Romhilt-Estes (HR 2.63, 95% CI 1.7 to 4.1) and strain methods (HR 2.11, 95% CI 1.4 to 3.2). The Perugia score showed the highest population-attributable risk for cardiovascular events, accounting for 15.6% of all cases, whereas the Framingham, Romhilt-Estes and strain methods accounted for 3.0%, 7.4% and 6.8% of all events, respectively. LVH diagnosed by the Perugia score was also associated with an increased risk of cardiovascular mortality (HR 4.21, 95% CI 2.1 to 8.7), with a population-attributable risk of 37.0%.Conclusions. The Perugia score carried the highest population-attributable risk for cardiovascular morbidity and mortality compared with classic methods for detection of LVH. Traditional interpretation of standard electrocardiography maintains an important role for cardiovascular risk stratification in essential hypertension.     

Regression of electrocardiographic left ventricular hypertrophy or strain is associated with lower incidence of cardiovascular morbidity and mortality in hypertensive patients independent of blood pressure reduction – A LIFE review

Cornell product criteria, Sokolow–Lyon voltage criteria and electrocardiographic (ECG) strain (secondary ST-T abnormalities) are markers for left ventricular hypertrophy (LVH) and adverse prognosis in population studies. However, the relationship of regression of ECG LVH and strain during antihypertensive therapy to cardiovascular (CV) risk was unclear before the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study. We reviewed findings on ECG LVH regression and strain over time in 9193 hypertensive patients with ECG LVH at baseline enrolled in the LIFE study.The composite endpoint of CV death, nonfatal MI, or stroke occurred in 1096 patients during 4.8 ± 0.9 years follow-up. In Cox multivariable models adjusting for randomized treatment, known risk factors including in-treatment blood pressure, and for severity ECG LVH by Cornell product and Sokolow–Lyon voltage, baseline ECG strain was associated with a 33% higher risk of the LIFE composite endpoint (HR. 1.33, 95% CI [1.11–1.59]). Development of new ECG strain between baseline and year-1 was associated with a 2-fold increased risk of the composite endpoint (HR. 2.05, 95% CI [1.51–2.78]), whereas the risk associated with regression or persistence of ECG strain was attenuated and no longer statistically significant (both p > 0.05). After controlling for treatment with losartan or atenolol, for baseline Framingham risk score, Cornell product, and Sokolow–Lyon voltage, and for baseline and in-treatment systolic and diastolic blood pressure, 1 standard deviation (SD) lower in-treatment Cornell product was associated with a 14.5% decrease in the composite endpoint (HR. 0.86, 95% CI [0.82–0.90]). In a parallel analysis, 1 SD lower in-treatment Sokolow–Lyon voltage was associated with a 16.6% decrease in the composite endpoint (HR. 0.83, 95% CI [0.78–0.88]).The LIFE study shows that evaluation of both baseline and in-study ECG LVH defined by Cornell product criteria, Sokolow–Lyon voltage criteria or ECG strain improves prediction of CV events and that regression of ECG LVH during antihypertensive treatment is associated with better outcome, independent of blood pressure reduction.     

Ethnic differences in electrocardiographic criteria for left ventricular hypertrophy: the LIFE study. Losartan Intervention For Endpoint

BACKGROUND: African Americans have greater precordial QRS voltages than whites, with concomitant higher prevalences of electrocardiographic (ECG) left ventricular hypertrophy (LVH) and lower specificity of ECG LVH criteria for the identification of anatomic hypertrophy. However, the high mortality associated with LVH in African American patients makes more accurate ECG detection of LVH in these patients a clinical priority. METHODS: Electrocardiograms and echocardiograms were obtained at study baseline in 120 African American and 751 white hypertensive patients enrolled in the Losartan Intervention For Endpoint (LIFE) echocardiographic substudy. The ECG LVH was determined using Sokolow-Lyon, 12-lead sum, and Cornell voltage criteria. Echocardiographic LVH was defined by LV mass indexed to height(2.7) >46.7 g/m(2.7) in women and >49.1 g/m(2.7) in men. RESULTS: After adjusting for ethnic differences in LV mass, body mass index, sex, and prevalence of diabetes, mean Sokolow-Lyon and 12-lead sum of voltage were significantly higher, but Cornell voltage was lower, in African Americans than in whites. As a consequence of these differences, when identical partition values were used in both ethnic groups, Sokolow-Lyon and 12-lead voltage criteria had lower specificity in African Americans than whites (44% v 69%, P = .007 and 44% v 59%, P = .10) but had greater sensitivity in African Americans (51% v 27%, P < .001 and 62% v 45%, P = .003). In contrast, Cornell voltage specificity was higher (78% v 62%, P = .09) but sensitivity was slightly lower (49% v 57%, P = 0.16) in African Americans. However, when overall test performance was compared using receiver operating curve analyses that were independent of partition value selection, ethnic differences in test performance disappeared, with no differences in accuracy of any of the ECG voltage criteria for the identification of LVH between African American and white hypertensive individuals. CONCLUSIONS: When standard, non-ethnicity-specific thresholds for the identification of LVH are used, Sokolow-Lyon and 12-lead voltage overestimate and Cornell voltage underestimates the presence and severity of LVH in African American relative to white individuals. However, these apparent ethnic differences in test performance disappear when ethnic differences in the distribution of ECG LVH criteria are taken into account. These findings demonstrate that ethnicity-specific ECG criteria can equalize detection of anatomic LVH in African American and white patients.     

Relation of echocardiographic left ventricular mass and hypertrophy to persistent electrocardiographic left ventricular hypertropy in hypertensive patients: the LIFE study

Background: The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) trial used left ventricular hypertrophy (LVH) on a screening ECG to identify patients at high risk for morbid events. Because of regression to the mean, not all patients who met screening criteria had persistent ECG LVH on the ECG performed at study baseline.Methods: The relationship of echocardiographic LV mass and LVH to persistence or loss of ECG LVH between screening and baseline evaluation was examined in 906 hypertensive patients in the LIFE study, who had echocardiograms and additional ECG performed at study baseline. Patients were categorized according to the presence or absence of ECG LVH by Cornell voltage-duration product criteria or Sokolow-Lyon voltage criteria; echocardiographic LVH was defined by LV mass index (LVMI) > 104 g/m² in women and > 116 g/m² in men.Results: A total of 678 patients (75%) had persistent ECG LVH at baseline evaluation. Compared with the 228 patients without ECG LVH on the second ECG by either criterion, the 106 patients with LVH by both Cornell product and Sokolow-Lyon criteria had significantly higher LVMI (140 ± 31 v 114 ± 21 g/m², P < .001) and a higher prevalence of echocardiographic LVH (86% v 55%, P < .001). Patients with ECG LVH on the baseline ECG by either Cornell product criteria (n = 410) or Sokolow-Lyon voltage criteria (n = 162) had intermediate values of LVMI (125 ± 25 and 121 ± 21 g/m²) and prevalences of echocardiographic LVH (78% and 62%). After controlling for possible effects of age, sex, ethnicity, systolic blood pressure, and body mass index, persistence of ECG LVH on the baseline ECG was associated with an increased risk of echocardiographic LVH: compared with patients with neither ECG criteria for LVH, patients with only Sokolow-Lyon voltage criteria had a 1.2-fold increased risk of echocardiographic LVH, those with only Cornell product criteria had a 2.7-fold increased risk, and patients with both ECG criteria had a 4.1-fold increased risk of echocardiographic LVH (P < .001).Conclusions: Persistent ECG LVH between screening and LIFE study baseline identified patients with greater LV mass and a higher prevalence of echocardiographic LVH, suggesting that these patients may be at higher risk for subsequent morbid and mortal events.     

Cardiovascular risk prediction by N-terminal pro brain natriuretic peptide and high sensitivity C-reactive protein is affected by age and sex

BACKGROUND: Previous studies have shown that the urine albumin/creatinine ratio (UACR), high sensitivity C-reactive protein (hsCRP) and N-terminal pro brain natriuretic peptide (Nt-proBNP) predict cardiovascular events in a general population aged 41, 51, 61 or 71 years. This study investigated the impact of age and sex on their prognostic performance in a subgroup of 1994 apparently healthy individuals without diabetes, previous stroke or myocardial infarction, who did not receive any cardiovascular, antidiabetic or lipid-lowering medication. METHODS: In 1993-1994 we recorded cardiovascular risk factors, UACR, hsCRP and Nt-proBNP. The composite cardiovascular endpoint (CEP) of cardiovascular death and non-fatal stroke or myocardial infarction was assessed after 9.5 years. RESULTS: In Cox regression analyses predicting CEP, the effects of log(hsCRP) and log(Nt-proBNP) were modulated by sex (P < 0.05) and age (P < 0.05), respectively. The effect of logUACR was not significantly modulated by age or sex. Log(hsCRP)/SD did not predict CEP in women, but did predict CEP in 41 plus 51-year-old men [hazard ratio (HR) 1.71; 95% confidence interval, 1.1-2.6; P < 0.05] and 61 plus 71-year-old men (HR 1.64; 1.3-2.2; P < 0.001). Log(Nt-proBNP)/SD predicted CEP in 61 plus 71-year-old women (HR 1.74; 1.2-2.5; P < 0.01) and in 61 plus 71-year-old men (HR 1.58; 1.3-2.0; P < 0.001). CONCLUSION: Elevated hsCRP, reflecting early atherosclerosis, predicted CEP even in 41 plus 51-year-old men. Elevated Nt-proBNP, reflecting subclinical cardiovascular damage, predicted CEP in 61 plus 71-year-old subjects. Elevated UACR, reflecting endothelial dysfunction as well as microvascular damage, predicted events independently of age and sex, but primarily in 61 plus 71-year-old subjects.     

单纯夜间高血压与左室肥厚的关系

目的 探讨单纯夜间高血压与左室肥厚的关系.方法 在浙江省景宁县14个村的居民中,记录24 h血压和12导联心电图.结果 647例受检者中单纯夜间高血压[平均血压≥120/70mm Hg(1 mm Hg=0.133 kPa)]有72例(11.1%).夜间和白天的收缩压或舒张压都是左室肥厚的独立影响因素(P<0.01).但单纯夜间高血压患者左室肥厚的患病率(23.6%)与正常血压者(17.4%)相比,差异无统计学意义(P=0.24).结论 在本横断面研究中,单纯夜间高血压与用心电图诊断的左室肥厚没有显著独立关联.     

Serial evaluation of electrocardiographic left ventricular hypertrophy for prediction of risk in hypertensive patients

Background

Although the presence and severity of electrocardiographic (ECG) left ventricular hypertrophy (LVH) have been associated with an increased risk of cardiovascular (CV) morbidity and mortality, the relationship of regression of ECG LVH during antihypertensive therapy to CV risk has only recently been examined.

Methods

Electrocardiographic LVH was evaluated over time in 9193 hypertensive patients enrolled in the Losartan Intervention for Endpoint Reduction in Hypertension study. Patients were treated with losartan- or atenolol-based regimens and followed with serial ECGs at 6 months and then yearly until death or study end. Electrocardiographic LVH was measured using gender-adjusted Cornell product (RaVL + SV3 [+6 mm in women]) ? QRS duration) and Sokolow-Lyon voltage (SV1 + RV5/6).

Results

After mean (SD) follow-up of 4.8 (0.9) years, the Losartan Intervention for Endpoint Reduction in Hypertension study composite end point of CV death, nonfatal myocardial infarction, or stroke occurred in 1096 patients. In Cox regression models controlling for treatment type, baseline Framingham risk score, baseline, and in-treatment blood pressure and for severity of baseline ECG LVH by Cornell product and Sokolow-Lyon voltage, lower in-treatment ECG LVH by Cornell product and Sokolow-Lyon voltage were associated with 14% and 17% lower rates, respectively, of the composite CV end point: adjusted hazard ratios (HRs) of 0.86 (95% confidence interval [CI], 0.82-0.90; P < .001) for every 1050 mm · ms (1 SD) decrease in Cornell product and 0.83 (95% CI, 0.78-0.88; P < .001) for every 10.5 mm (1 SD) decrease in Sokolow-Lyon voltage. In parallel analyses, lower Cornell product and Sokolow- Lyon voltage were each independently associated with lower risks of CV mortality (HR, 0.78; 95% CI, 0.73-0.83; P < .001; HR, 0.80; 95% CI, 0.73-0.87; P < .001), of myocardial infarction (HR, 0.90; 95% CI, 0.82-0.98; P = .011; HR, 0.90; 95% CI, 0.81-1.00; P = .043), and of stroke (HR, 0.90; 95% CI, 0.84-0.96; P = .002; HR, 0.81; 95% CI, 0.75-0.89; P < .001). Regression of ECG LVH was also associated with significantly reduced risks of sudden cardiac death, new-onset atrial fibrillation, hospitalization for heart failure, and new-onset diabetes mellitus.

Conclusions

Regression of ECG LVH by Cornell product and/or Sokolow-Lyon voltage criteria during antihypertensive therapy is associated with lower likelihoods of CV morbidity and mortality, all-cause mortality, and new-onset diabetes, independent of blood pressure lowering and treatment modality in essential hypertension. These findings suggest that antihypertensive therapy targeted at regression or prevention of ECG LVH may improve prognosis.     

老年男性心电图Cornell电压标准及其应用价值

目的 探讨老年男性心电图Comell电压标准及其诊断老年男性左室肥厚的价值.方法 回顾性分析北京医院自1990年来进行尸体解剖的老年男性患者资料,排除心电图ORS波时限≥0.12 s及起搏心电图的患者.测量死亡前3个月内标准12导联心电图QRS波振幅,分析老年男性Comell、Sokolow-Lyon电压值与左室前壁厚度的相关性.计算老年男性无器质性心脏病组Comell电压值的均数及其97.5%的上限值,分析老年男性心电图Comell电压标准诊断老年男性左室肥厚的敏感性、准确性.结果 老年男性心电图Comell、Sokolow-Lyon电压值与左室前壁厚度相关.老年男性无器质性心脏病组心电图Sv3+RaVL平均值为(1.32±0.79)mV,以其97.5%的上限值2.9 mV为Comell标准诊断老年男性左室肥厚的敏感性、准确性分别为34.3%、77.5%,高于Sokolow-Lyon标准.结论 心电图Comell电压标准诊断中国老年男性左室肥厚的界值可采用2.9 mV,其诊断老年男性左室肥厚的敏感性、准确性高于Sokolow-Lyon标准.     

Differences in cardiovascular risk profile between electrocardiographic hypertrophy versus strain in asymptomatic patients with aortic stenosis (from SEAS data)

Electrocardiograms are routinely obtained in clinical follow-up of patients with asymptomatic aortic stenosis (AS). The association with aortic valve, left ventricular (LV) response to long-term pressure load, and clinical covariates is unclear and the clinical value is thus uncertain. Data from clinical examination, electrocardiogram, and echocardiogram in 1,563 patients in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study were used. Electrocardiograms were Minnesota coded for arrhythmias and atrioventricular and intraventricular blocks; LV hypertrophy was assessed by Sokolow-Lyon voltage and Cornell voltage-duration criteria; and strain by T-wave inversion and ST-segment depression. Degree of AS severity was evaluated by echocardiography as peak aortic jet velocity and LV mass was indexed by body surface area. After adjustment for age, gender, LV mass index, heart rate, systolic and diastolic blood pressures, blood glucose, digoxin, antiarrhythmic drugs, drugs acting on the renin-angiotensin system, diuretics, β blockers and calcium receptor blockers; peak aortic jet velocity was significantly greater in patients with electrocardiographic strain (mean difference 0.13 m/s, p <0.001) and LV hypertrophy by Sokolow-Lyon voltage criteria (mean difference 0.12 m/s, p = 0.004). After similar adjustment, LV mass index was significantly greater in patients with electrocardiographic strain (mean difference 14.8 g/cm(2), p <0.001) and LV hypertrophy by Sokolow-Lyon voltage criteria and Cornell voltage-duration criteria (mean differences 8.8 and 17.8 g/cm(2), respectively, p <0.001 for the 2 comparisons). In multiple comparisons patients with electrocardiographic strain had increased peak aortic jet velocity, blood glucose, and uric acid, whereas patients with LV hypertrophy by Sokolow-Lyon voltage criteria were younger and patients with LV hypertrophy by Cornell voltage-duration criteria more often were women. In conclusion, electrocardiographic criteria for LV hypertrophy and strain are independently associated with peak aortic jet velocity and LV mass index. Moreover, clinical covariates differ significantly between patients with electrocardiographic strain and those with LV hypertrophy by Sokolow-Lyon voltage criteria and Cornell voltage-duration criteria.     

Long-term effects of chlorthalidone versus hydrochlorothiazide on electrocardiographic left ventricular hypertrophy in the multiple risk factor intervention trial

Chlorthalidone (CTD) reduces 24-hour blood pressure more effectively than hydrochlorothiazide (HCTZ), but whether this influences electrocardiographic left ventricular hypertrophy is uncertain. One source of comparative data is the Multiple Risk Factor Intervention Trial, which randomly assigned 8012 hypertensive men to special intervention (SI) or usual care. SI participants could use CTD or HCTZ initially; previous analyses have grouped clinics by their main diuretic used (C-clinics: CTD; H-clinics: HCTZ). After 48 months, SI participants receiving HCTZ were recommended to switch to CTD, in part because higher mortality was observed for SI compared with usual care participants in H-clinics, whereas the opposite was found in C-clinics. In this analysis, we examined change in continuous measures of electrocardiographic left ventricular hypertrophy using both an ecological analysis by previously reported C- or H-clinic groupings and an individual participant analysis where use of CTD or HCTZ by SI participants was considered and updated annually. Through 48 months, differences between SI and usual care in left ventricular hypertrophy were larger for C-clinics compared with H-clinics (Sokolow-Lyon: -93.9 versus -54.9 μV, P=0.049; Cornell voltage: -68.1 versus -35.9 μV, P=0.019; Cornell voltage product: -4.6 versus -2.2 μV/ms, P=0.071; left ventricular mass: -4.4 versus -2.8 g, P=0.002). At the individual participant level, Sokolow-Lyon and left ventricular mass were significantly lower for SI men receiving CTD compared with HCTZ through 48 months and 84 months of follow-up. Our findings on left ventricular hypertrophy support the idea that greater blood pressure reduction with CTD than HCTZ may have led to differences in mortality observed in the Multiple Risk Factor Intervention Trial.