N-terminal pro brain natriuretic peptide in arterial hypertension--a marker for left ventricular dimensions and prognosis

In arterial hypertension risk factor evaluation, including LV mass measurements, and risk stratification using risk charts or programs, is generally recommended. In heart failure NT-proBNP has been shown to be a marker of LV dimensions and of prognosis. If the same diagnostic and prognostic value is present in arterial hypertension, risk factor evaluation would be easier. In 36 patients with arterial hypertension, electrocardiographic LV hypertrophy and preserved left ventricular function, NT-proBNP was eight-fold higher than in healthy subjects. The log NT-proBNP correlated with LV mass index (R=0.47, P=0.0002) measured by magnetic resonance imaging. In other subjects with arterial hypertension a significant but weak correlation to diastolic properties has been demonstrated. As for prognosis, a recent study in patients with hypertension, electrocardiographic left ventricular hypertrophy and preserved LV function demonstrated that NT-proBNP was a very strong prognostic marker, especially combined with a history of cardiovascular disease. Patients with high NT-proBNP and known cardiovascular disease had a seven-fold increase in CV events compared to patients with low NT-proBNP and no CV disease, while patients with either high NT-proBNP or CV disease had a three-four-fold increased risk. In conclusion NT-proBNP predicts LV mass in hypertensive patients and is a very strong prognostic marker in these patients. This could indicate a use of NT-proBNP in the future for risk stratification and perhaps monitoring of treatment in patients with arterial hypertension.     

NT-proBNP in normoalbuminuric patients with Type 2 diabetes mellitus.

OBJECTIVE: To examine levels of NT-proBNP and its relation to hypertension, as well as diastolic function in normoalbuminuric patients with Type 2 diabetes. RESEARCH DESIGN AND METHODS: The study comprised 60 Type 2 diabetic patients without albuminuria. Thirty patients were normotensive and 30 had hypertension. Exclusion criteria were cardiac symptoms and an ejection fraction < 55%. Thirty age- and sex-matched normal subjects served as controls. Diastolic dysfunction was assessed with echocardiography, by means of mitral inflow and colour M-Mode flow propagation recordings. RESULTS: Overall NT-proBNP was significantly elevated in the Type 2 diabetes group, compared with the controls [54.5 pg/ml (5-162) vs. 32.7 pg/ml (5-74.3) P = 0.02]. NT-proBNP was significantly higher among hypertensive patients compared with both normotensive patients and controls but no difference was found between the normotensive patients and the controls [58.0 pg/ml (8.5-162), P < 0.05 vs. 50.8 pg/ml (5-131) P = 0.4]. Patients with concentric and eccentric hypertrophy had significantly higher NT-proBNP levels compared with the control group [81.0 pg/ml (5-147), P < 0.001 and 66.8 pg/ml (42-128), P < 0.001], whereas patients with left ventricular remodelling (enlarged relative wall diameter but normal left ventricular mass) were comparable with the control group [42.3 pg/ml (8.3-142) P = 0.55]. Patients with left atrial enlargement also had incremental NT-proBNP values. NT-proBNP was only moderately correlated to age (r = 0.33, P < 0.05) and left ventricular diastolic diameter (r = 0.41, P < 0.05), but unrelated to diastolic function. CONCLUSIONS: NT-proBNP is significantly increased in hypertensive, normoalbuminuric patients with Type 2 diabetes. These findings were related to left ventricular hypertrophy and increased left atrial and ventricular diameters.     

Arterial hypertension and cardiac arrhythmias

PURPOSE AND DATA IDENTIFICATION: One of the main clinical problems of patients with arterial hypertension is the presence of arrhythmias, especially if left ventricular hypertrophy exists. Recent results from our group and all data available via Med-Line-search have been analysed. The analysis was focused on atrial and ventricular arrhythmias and arrhythmic risk prediction, using non-invasive markers. RESULTS OF ANALYSIS AND CONCLUSION: Arterial hypertension is a major cause of non-rheumatic atrial fibrillation and other supraventricular arrhythmias. The prevalence of ventricular arrhythmias is increased in hypertensive patients without left ventricular hypertrophy, compared to normotensives. If left ventricular hypertrophy is present, the risk for ventricular tachycardias is quadrupled. The presence of left ventricular hypertrophy is associated with an increase in all-cause mortality by a factor of seven in men and nine in women. In particular, patients with hypertrophy, increased rate of ventricular extrasystoles up to non-sustained ventricular tachycardia and ST-depression in long-term ECG are threatened by sudden cardiac death. At present, it is not possible to safely identify patients with increased risk. Regression of hypertrophy exists along with a decreased rate of ventricular extrasystoles. We hypothesize that by the regression of hypertrophy, the prevalence of sustained ventricular tachycardia decreases and therefore the prognosis of those patients can be improved, although controlled studies are not yet available.     

Diagnostic accuracy of NT-proBNP compared with electrocardiography in detecting left ventricular hypertrophy of hypertensive origin

Electrocardiography (ECG) is the most widely used method for diagnosing left ventricular hypertrophy (LVH) in hypertensive patients. We assessed the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) determination compared with ECG for detecting LVH in 336 consecutive hypertensive patients with preserved systolic function. We found a significant correlation between NT-proBNP levels and left ventricular mass adjusted for body surface area (r = .41; P < .001). The area under the receiver operating characteristic curve was 0.75 (95% CI, 0.7-0.8). A cut-off of 74.2 pg/mL had a greater sensitivity than ECG (76.6% vs 25.5%; P < .001) and a higher negative predictive value (87.8% vs 76.6%; P < .001) in the identification of LVH. NT-proBNP determination may be a useful tool for LVH screening in hypertensive patients.Full English text available from: www.revespcardiol.org     

Should we perform an echocardiogram in hypertensive patients classified as having low and medium risk?

BACKGROUND: Left ventricular hypertrophy is an important predictor of cardiovascular risk and its detection contributes to risk stratification. However, echocardiography is not a routine procedure and electrocardiography (ECG) underestimates its prevalence. OBJECTIVE: To evaluate the prevalence of echocardiographic left ventricular hypertrophy in low and medium risk non-treated hypertensive subjects, in order to find out the percentage of them who would be reclassified as high risk patients. METHODS: Cross-sectional, multicenter study was performed in hospital located hypertension units. An echocardiogram was performed in 197 previously untreated hypertensive patients, > 18 years, classified as having low (61%) or medium (39%) risk, according to the OMS/ISH classification. The presence of left ventricular hypertrophy was considered if left ventricular mass index was > or = 134 or 110 g/m(2) in men and women, respectively (Devereux criteria). A logistic regression analysis was performed to identify factors associated to left ventricular hypertrophy. RESULTS: The prevalence of left ventricular hypertrophy was 23.9% (95% CI:17.9-29.9), 25.6% in men and 22.6% in women. In the low risk group its prevalence was 20.7% and in medium risk group 29.5%. Factors associated to left ventricular hypertrophy were: years since the diagnosis of hypertension, OR:1.1 (95% CI:1.003-1.227); systolic blood pressure, OR:1.08 (95% CI:1.029-1.138); diastolic blood pressure, OR:0.9 (95% CI:0.882-0.991); and family history of cardiovascular disease, OR:4.3 (95% CI:1.52-12.18). CONCLUSIONS: These findings underline the importance of performing an echocardiogram in low and high risk untreated hypertensive patients in which treatment would otherwise be delayed for even one year.     

Valor Prognóstico dos Níveis Plasmáticos de NT-proBNP em Pacientes Hospitalizados com Mais de 80 Anos de Idade em um Hospital em Pequim,China

BackgroundDespite growing evidence that N-terminal pro-brain natriuretic peptide (NT-proBNP) has an important prognostic value in older adults, there is limited data on its prognostic predictive value.ObjectivesThe aim of this study is to evaluate the clinical significance of NT-proBNP in hospitalized patients older than 80 years of age in Beijing, China.MethodsThis prospective, observational study was conducted in 724 very elderly patients in a geriatric ward (age ≥80 years, range, 80100 years, mean, 86.6 3.0 years). Multivariate linear regression analysis was used to screen for factors independently associated with NT-proBNP, and the Cox proportional hazard regression model was used to screen for relationships between NT-proBNP levels and major endpoints. The major endpoints assessed were all-cause death and MACEs. P values < 0.05 were considered statistically significant.ResultsThe prevalence rates of coronary heart disease, hypertension, and diabetes mellitus were 81.4%, 75.1%, and 41.2%, respectively. The mean NT-proBNP level was 770 ± 818 pg/mL. Using multivariate linear regression analyses, correlations were found between plasma NT-proBNP and body mass index, atrial fibrillation, estimated glomerular filtration rate, left atrial diameter, left ventricular ejection fraction, use of betablocker, levels of hemoglobin, plasma albumin, triglycerides, serum creatinine, and blood urea nitrogen. The risk of all-cause death (HR, 1.63; 95% CI, 1.0052.642; P = 0.04) and major adverse cardiovascular events (MACE; HR, 1.77; 95% CI, 1.2893.531; P = 0.04) in the group with the highest NT-proBNP level was significantly higher than that in the group with the lowest level, according to Cox regression models after adjusting for multiple factors. As expected, echocardiography parameters adjusted the prognostic value of NT-proBNP in the model.ConclusionsNT-proBNP was identified as an independent predictor of all-cause death and MACE in hospitalized patients older than 80 years of age.     

The effect of coronary angioplasty on plasma NT-proBNP level in patients with and without arterial hypertension

AIMS: The purpose of the study was to assess the effect of percutaneous transluminal coronary angioplasty (PTCA) on plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level in hypertensive and normotensive subjects with and without systolic left ventricular dysfunction. METHODS AND RESULTS: Forty patients affected by ischemic heart disease and submitted to PTCA were studied. The patients were divided into four groups: group I - 10 patients with essential arterial hypertension (HT) and normal left ventricular ejection fraction (EF); group II - 10 patients with HT and EF < 55%; group III - 10 patients without HT and with normal EF; group IV - 10 patients without HT and with EF < 55%. Blood samples were collected twice: 24 h before and after PTCA. The plasma NT-proBNP concentrations increased significantly in group I (368+/-103 pg/ml vs 488 +/- 182 pg/ml; p < 0.05), in group III (257 +/- 107 pg/ml vs 447 +/- 198 pg/ml; p < 0.05), and in group IV (419 +/- 99 pg/ml vs 826 +/- 432 pg/ml; p < 0.05) 24 h after PTCA. There were significant differences in the relative change in plasma NT-proBNP concentrations between groups I and II, and between groups III and IV. CONCLUSIONS: Successful coronary angioplasty results in a rise in plasma NT-proBNP concentration. The increase is less expressive in patients with systolic left ventricular dysfunction. The presence of hypertension does not affect NT-proBNP concentration after PTCA.     

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.     

Cardiovascular morbidity and mortality in hypertensive patients with a history of atrial fibrillation: The Losartan Intervention For End Point Reduction in Hypertension (LIFE) study

OBJECTIVES: We assessed the impact of antihypertensive treatment in hypertensive patients with electrocardiographic (ECG) left ventricular (LV) hypertrophy and a history of atrial fibrillation (AF). BACKGROUND: Optimal treatment of hypertensive patients with AF to reduce the risk of cardiovascular morbidity and mortality remains unclear. METHODS: As part of the Losartan Intervention For End point reduction in hypertension (LIFE) study, 342 hypertensive patients with AF and LV hypertrophy were assigned to losartan- or atenolol-based therapy for 1,471 patient-years of follow-up. RESULTS: The primary composite end point (cardiovascular mortality, stroke, and myocardial infarction) occurred in 36 patients in the losartan group versus 67 in the atenolol group (hazard ratio [HR] = 0.58, 95% confidence interval [CI] 0.39 to 0.88, p = 0.009). Cardiovascular deaths occurred in 20 versus 38 patients in the losartan and atenolol groups, respectively (HR = 0.58, 95% CI 0.33 to 0.99, p = 0.048). Stroke occurred in 18 versus 38 patients (HR = 0.55, 95% CI 0.31 to 0.97, p = 0.039), and myocardial infarction in 11 versus 8 patients (p = NS). Losartan-based treatment led to trends toward lower all-cause mortality (30 vs. 49, HR = 0.67, 95% CI 0.42 to 1.06, p = 0.090) and fewer pacemaker implantations (5 vs. 15, p = 0.065), whereas hospitalization for heart failure took place in 15 versus 26 patients and sudden cardiac death in 9 versus 17, respectively (both p = NS). The benefit of losartan was greater in patients with AF than those with sinus rhythm for the primary composite end point (p = 0.019) and cardiovascular mortality (p = 0.039). CONCLUSIONS: Losartan is more effective than atenolol-based therapy in reducing the risk of the primary composite end point of cardiovascular morbidity and mortality as well as stroke and cardiovascular death in hypertensive patients with ECG LV hypertrophy and AF.     

Usefulness of NT-proBNP level for diagnosing left ventricular hypertrophy in hypertensive patients. A cardiac magnetic resonance study

The presence of left ventricular hypertrophy (LVH) is associated with an increase in cardiovascular morbidity and mortality in hypertensive patients. We investigated the diagnostic value of the N-terminal probrain natriuretic peptide (NT-proBNP) level for detecting LVH in hypertensive patients with a conserved left ventricular ejection fraction. The study involved 27 consecutive patients. Cardiac magnetic resonance imaging was performed to determine left ventricular mass and the plasma NT-proBNP level was measured. A significant correlation was found between the NT-proBNP level and left ventricular mass (r=0.598; P=.001). Use of a cut-off point of 35 pg/mL enabled the presence of LVH to be identified with a sensitivity of 100% (95% confidence interval [CI], 69%-100%) and a specificity of 70.6% (95% CI, 44.1%-89.6%). The area under the receiver operating characteristic (ROC) curve was 0.867 (95% CI, 0.73-1; P< .05). The plasma NT-proBNP level may be useful for identifying patients with LVH.     

The value of NT-proBNP in early risk stratification of acute coronary syndromes.

INTRODUCTION: The N-terminal portion of brain natriuretic peptide (NT-proBNP) has been identified as an indicator of prognosis in different cardiovascular diseases. Its role in risk stratification in patients with acute coronary syndromes (ACS) is still under evaluation. OBJECTIVE: We aimed to evaluate the prognostic value of NT-proBNP measured in the first 48 hours after admission due to an acute coronary syndrome. METHODS: Our study included 142 patients (aged 62.7 +/- 12.0 years, 70.4% males) admitted to a cardiology unit with an ACS. All laboratory evaluations were performed in the first 48 hours after admission. The mean follow-up was 200 days. Death from any cause or hospitalization because of a major acute cardiovascular event (whichever occurred first) was defined as the end-point. RESULTS: Cardiovascular risk factors were found in a significant proportion of our sample (hypertension in 56.3%, diabetes mellitus in 38.0%, current or previous smoking in 51.4%, dyslipidemia in 67.6%). Fifty-eight patients had left ventricular systolic dysfunction (LVSD). Serum levels of NT-proBNP were 2174 +/- 4801 pg/ml. Variables associated with event-free survival in univariate analysis were: NT-proBNP (HR 1.007, 95% CI 1.003-1.011, for each 100 pg/ml increment), serum glucose (hazard ratio [HR] 1.007, 95% CI 1.001-1.012, for each 1 mg/dl increment) and maximum cardiac troponin I (cTnI) level (HR 1.005, 95% CI 1.001-1.009, for each 1 ng/ml increment). The white blood count (WBC) was marginally associated with a poor prognosis (HR 1.152, 95% CI 0.994-1.335, for each 1000/mm3 increment). After adjustment for the above variables, age, sex, left ventricular systolic dysfunction, diabetes, coronary anatomy and coronary revascularization using a forward likelihood ratio Cox regression model, NT-proBNP remained the only variable with significant prognostic value (HR 1.007, 95% CI 1.003-1.011, for each 100 pg/ml increment). CONCLUSIONS: These data suggest that NT-proBNP is a strong clinical predictor of prognosis in acute coronary syndromes. Its early measurement should be included in the risk stratification strategy in this setting.     

Plasma NT-proBNP concentration is related to ambulatory pulse pressure in peripheral arterial disease

BACKGROUND: Increased levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP) are associated with left ventricular dysfunction (LVD) and left ventricular hypertrophy (LVH), but the relation of NT-proBNP to ambulatory blood pressure (ABP) and hypertensive target organ damage in high-risk patients with peripheral arterial disease (PAD) has not been studied. We hypothesized that NT-proBNP levels were increased in patients with PAD in comparison to a matched control group and that levels of NT-proBNP were related to ABP. METHODS: Blood samples were analysed for NT-proBNP in 103 males with PAD and 96 age- and sex-matched controls. Ninety-eight PAD patients performed ABP monitoring and 99 underwent Tc-99m Sestamibi myocardial perfusion SPECT. RESULTS: NT-proBNP was significantly increased in PAD patients compared with controls [median (interquartiles)] 167(76, 418) vs 68(38, 142) pg/ml, p<0.001. Plasma levels of NT-proBNP correlated positively to systolic blood pressure (SBP), pulse pressure (PP), night-day ratio of SBP and showed the strongest correlation to average night PP (r=0.42, p<0.001). In multiple regression analysis, night PP remained independently related to NT-proBNP. CONCLUSION: NT-proBNP levels are markedly increased in PAD patients compared to age-matched controls. Night PP is related to NT-proBNP levels independently of other variables highlighting the importance of ambulatory PP as a cardiovascular risk factor. Measurement of NT-proBNP could be indicated in PAD patients for further risk stratification.     

Tissue Doppler imaging provides incremental prognostic value in patients with systemic hypertension and left ventricular hypertrophy

OBJECTIVES: We sought to determine the prognostic value of left ventricular (LV) mitral annular velocities measured by tissue Doppler imaging (TDI) in hypertensive patients with echocardiographic evidence of LV hypertrophy. BACKGROUND: Echo LV hypertrophy and LV geometry provide additional predictive value of all-cause mortality beyond traditional cardiovascular risk factors. Limited data exist regarding the predictive value of TDI velocities for cardiovascular risk stratification in treated hypertensive patients. METHODS: Two-dimensional and Doppler echocardiograms were obtained in 252 consecutive subjects, including 174 subjects with systemic hypertension and 78 age-matched normal subjects. The end point was cardiac death in subsequent median follow-up of 19 months. RESULTS: Nineteen patients (7.54%) died of cardiac causes. The TDI mitral annulus systolic velocity and the early diastolic mitral annular velocity (Em) were significantly lower in the non-survivors (all P < 0.001). The pseudonormal (PN) or restrictive filling pattern (RFP) was associated with cardiac mortality. The other parameters associated with cardiac mortality were LV ejection fraction, LV mass index, inter-ventricular septal wall thickness in diastole and the ratio of early mitral inflow to early myocardial velocity. In multivariate analysis, Em, inter-ventricular septal wall thickness in diastole and either PN or RFP were the strongest predictors. The addition of Em < 3.5 cm/s significantly improved the outcome of a model that contained clinical risk factors, inter-ventricular septal wall thickness in diastole > 1.4 cm and either PN or RFP (P = 0.043). CONCLUSIONS: Early diastolic mitral annulus velocity measured by TDI provides prognostic information, incremental to clinical data and standard echocardiographic variables, for risk stratification of hypertensive patients under treatment.     

Prognostic significance of isolated, non-specific left ventricular repolarization abnormalities in hypertension

OBJECTIVE: Clinicians are often confronted with the incidental finding of isolated minor, non-specific repolarization changes on the electrocardiogram (ECG) in hypertensive patients. The aim of this study was to investigate the prognostic significance of such changes. DESIGN: Prospective, observational study. METHODS: A total of 1970 hypertensive patients without prevalent cardiovascular disease were followed for up to 9.1 years (mean 4.7 years). Patients with ECG abnormalities including ischaemia, previous infarction, bundle branch block, atrial fibrillation and ventricular pre-excitation were excluded. Patients were divided into three groups: normal left ventricular (LV) repolarization (n = 1355); minor repolarization changes (n = 504); and typical LV strain (n = 111). RESULTS: During follow-up, 78 patients developed new-onset ischaemic heart disease. The event rates were 0.50, 1.28 and 3.08 per 100 patient-years in the groups with normal repolarization, minor changes, and typical LV strain, respectively (P < 0.001). After adjustment for the effect of age, sex, diabetes, serum cholesterol, smoking, LV hypertrophy and 24-h pulse pressure, the risk for developing coronary events was higher in patients with minor repolarization changes (hazard ratio 2.07, 95% confidence interval 1.23-3.47; P < 0.01) or LV strain (hazard ratio 4.00, 95% confidence interval 2.09-7.65; P < 0.001) than in patients with normal repolarization (reference category). Population-attributable risks were 21 and 14%, respectively. Minor ST-T changes also retained an adverse prognostic value among patients without LV hypertrophy (hazard ratio 1.90, 95% confidence interval 1.08-3.33; P = 0.026). CONCLUSION: We have identified minor, non-specific LV repolarization changes as a novel, independent risk factor for ischaemic heart disease in patients with uncomplicated hypertension.     

QRS duration and QT interval predict mortality in hypertensive patients with left ventricular hypertrophy: the Losartan Intervention for Endpoint Reduction in Hypertension Study

Left ventricular hypertrophy is a risk factor for cardiovascular mortality, including sudden cardiac death. Experimentally, left ventricular hypertrophy delays ventricular conduction and prolongs action potential duration. Electrocardiographic QRS duration and QT interval measures reflect these changes, but whether these measures can further stratify risk in patients with electrocardiographic left ventricular hypertrophy is unknown. We measured the QRS duration and QT intervals from the baseline 12-lead electrocardiograms in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study, which included hypertensive patients with electrocardiographic evidence of left ventricular hypertrophy randomized to either losartan-based or atenolol-based treatment to lower blood pressure. In the present study, we related study baseline electrocardiographic measures to cardiovascular and all-cause mortality. There were 5429 patients (male 45.8%; mean age 66+/-7 years) included in the present analyses. After a mean follow-up of 4.9+/-0.8 years, there were 417 deaths from all causes, including 214 cardiovascular deaths. In separate univariate Cox regression analyses, QRS duration and several QT measures were significant predictors of cardiovascular mortality and all-cause mortality. However, in multivariate Cox analyses including all electrocardiographic measures and adjusting for other risk factors as well as treatment strategy, only QRS duration and maximum rate-adjusted QT(apex) interval remained as significant independent predictors of cardiovascular (P=0.022 and P=0.037, respectively) and all-cause mortality (P=0.038 and P=0.002, respectively). In conclusion, in a hypertensive risk population identified by electrocardiographic left ventricular hypertrophy, increased QRS duration and maximum QT(apex) interval can further stratify mortality risk even in the setting of effective blood pressure-lowering treatment.     

Markers of electrical instability in hypertensive patients with and without ventricular arrhythmias. Are they useful in identifying patients with different risk profiles?

BACKGROUND: Markers of electrical instability of the ventricular myocardium, namely abnormal repolarization and late potentials, are frequently observed in patients with hypertension when both ventricular arrhythmias and left ventricular hypertrophy are present. This information cannot be extrapolated to the population of hypertensive patients with ventricular arrhythmias but without left ventricular hypertrophy. OBJECTIVE: To evaluate QT duration, QT dispersion and the incidence of ventricular late potentials in patients with essential hypertension, already on anti-hypertensive therapy, both with and without non-sustained ventricular arrhythmia. DESIGN: The study population consisted of 49 patients with essential hypertension who were compared to 89 control normotensive subjects both with and without frequent (> 30 per h) ventricular ectopic beats (VPBs). Patients were divided into four groups: (1) hypertensive patients without VPBs (H, n = 19), (2) hypertensive patients with VPBs (HA, n = 30), (3) normotensive subjects without VPBs (C, n = 28), and (4) normotensive subjects with VPBs (CA, n=61). METHODS: Echocardiographic parameters, QT interval, QT dispersion and signal-averaged ECG were evaluated without withdrawing anti-hypertensive drugs. RESULTS: In no case was left ventricular hypertrophy documented. The number of VPBs during 24 h Holter recording (median 11 343 versus 7617) and the incidence of repetitive VPBs (37 versus 46% of patients) were similar in the two groups of patients (HA versus CA). Signal-averaged ECG parameters were normal and not different between the four groups. QT interval was longer in hypertensive patients compared to controls irrespective of the presence of VPBs. QT dispersion was slightly greater in subjects with VPBs, both hypertensive and normotensive, compared to subjects without arrhythmias. CONCLUSIONS: In patients with hypertension well-controlled by drug therapy and without left ventricular hypertrophy, frequent VPBs are not associated with markers indicating an electrophysiological substrate for re-entrant arrhythmias. However, QT prolongation suggests the persistence of a higher risk of cardiovascular mortality that is independent of the presence of VPBs.     

Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension

OBJECTIVE: To assess the prognostic significance of left ventricular mass and geometry in initially healthy persons with essential hypertension. DESIGN: An observational study of a prospectively identified cohort. SETTING: University medical center. PATIENTS: Two hundred and eighty patients with essential hypertension and no pre-existing cardiac disease were evaluated using echocardiography between 1976 and 1981. Two hundred and fifty-three subjects or their family members (90%) were contacted for a follow-up interview an average of 10.2 years after the initial echocardiogram was obtained; the survival status of 27 patients lost to follow-up was ascertained using National Death Index data. MEASUREMENTS AND MAIN RESULTS: Left ventricular mass exceeded 125 g/m2 in 69 of 253 patients (27%). Cardiovascular events occurred in a higher proportion of patients with than without left ventricular hypertrophy (26% compared with 12%; P = 0.006). Patients with increased ventricular mass were also at higher risk for cardiovascular death (14% compared with 0.5%; P less than 0.001) and all-cause mortality (16% compared with 2%; P = 0.001). Electrocardiographic left ventricular hypertrophy did not predict risk. Patients with normal left ventricular geometry had the fewest adverse outcomes (no cardiac deaths; morbid events in 11%), and those with concentric hypertrophy had the most (death in 21%; morbid events in 31%). In a multivariate analysis, only age and left ventricular mass--but not gender, blood pressure, or serum cholesterol level--independently predicted all three outcome measures. CONCLUSIONS: Echocardiographically determined left ventricular mass and geometry stratify risk in patients with essential hypertension independently of and more strongly than blood pressure or other potentially reversible risk factors and may help to stratify the need for intensive treatment.     

Plasma N-terminal pro-brain natriuretic peptide: a marker of left ventricular hypertrophy in hypertrophic cardiomyopathy.

BACKGROUND: B-type natriuretic peptide is secreted mainly in the left ventricle in response to elevated wall tension. Plasma levels of the peptide correlate positively with cardiac filling pressures, making it an excellent marker for the presence of left ventricular dysfunction. In hypertrophic cardiomyopathy, enhanced production of B-type natriuretic peptide is observed. However, the relationship of the various structural and functional features present in the disease with the high plasma levels described is not yet fully clarified. In the present study, we prospectively assessed in hypertrophic cardiomyopathy the relationship of plasma NT-proBNP levels with the extent of left ventricular hypertrophy, presence of left ventricular outflow obstruction and echocardiographic parameters of left ventricular diastolic function. METHODS: The study population included 190 individuals: 53 patients with hypertrophic cardiomyopathy and well-preserved left ventricular systolic function (group A), 92 healthy relatives with no disease expression (group B), and an additional group of 46 healthy volunteers (group C) as controls for NT-proBNP levels. Groups A and B were characterized clinically and by echocardiography and compared with each other. Plasma NT-proBNP levels were measured (ECLIA-Elecsys proBNP) and compared in the 3 groups of individuals included in the study. In hypertrophic cardiomyopathy patients, correlation was sought between NT-proBNP levels, NYHA functional class and echocardiographic data. RESULTS: Groups A and B differed (p < 0.001) in septal thickness, maximal wall thickness, left ventricular hypertrophy score, left atrial size, left atrial fractional shortening, derived transmitral filling indices and plasma NT-proBNP levels (group A: 909.9 +/- 1554.2 pg/ml; group B: 40.7 +/- 45.1 pg/ml). Left ventricular diastolic size and pulmonary venous flow velocity-derived indices were similar in the 2 groups. NT-proBNP levels in group B and C (39.4 +/- 34.5 pg/ml) were similar (p = NS). In hypertrophic cardiomyopathy patients, NT-proBNP levels correlate directly with NYHA functional class (r = 0.56, p < 0.001), septal thickness (r = 0.53, p < 0.001), maximal wall thickness (r = 0.59, p < 0.001), left ventricular hypertrophy score (r = 0.63, p < 0.001), left atrial size (r = 0.32, p = 0.023) and mitral deceleration time (r = 0.46, p = 0.001) and inversely with left atrial fractional shortening (r = -0.41, p = 0.005). Functional class also correlates directly with left ventricular hypertrophy score (r = 0.39, p = 0.006), with the most symptomatic patients having the highest scores. CONCLUSIONS: In hypertrophic cardiomyopathy, plasma NT-proBNP levels depend mainly on the severity of left ventricular hypertrophy rather than on the presence of obstruction. Measurement of the peptide may help in the clinical characterization and follow-up of patients with this disease.     

Usefulness of QT-interval parameters for cardiovascular risk stratification in type 2 diabetic patients with arterial hypertension

QT-interval parameters are potential indicators of increased cardiovascular risk. We evaluated prospectively their prognostic value, in relation to other risk markers, for cardiovascular fatal and nonfatal events in a cohort of 271 hypertensive type 2 diabetic outpatients. QT intervals were measured from 12-lead standard ECGs obtained on admission and maximum rate-corrected QT-interval duration and QT-interval dispersion (QTd) calculated. Clinical and laboratory data and 2-D echocardiograms (available in 126 patients) were recorded. Survival analyses included Kaplan-Meier survival curves, uni and multivariate Cox proportional-hazards models. After a median follow-up of 55 months (range 2-84), 68 total fatal or nonfatal cardiovascular events and 34 cardiovascular deaths (24 of them from cardiac causes) were observed. In multivariate Cox analysis, QTd was an independent predictor for total cardiovascular events (HR: 1.16, 95% CI: 1.01-1.34, for each 10 ms increments) and for cardiac deaths (HR: 1.28, 95% CI: 1.01-1.60). Other independent risk indicators for cardiovascular morbidity and mortality were echocardiographic left ventricular hypertrophy (Echo-LVH), serum triglycerides, presence of pre-existing cardiac and peripheral arterial disease, age, diabetes duration, heart rate and the presence of frequent ventricular premature contractions on ECG. The combination of QTd and Echo-LVH improved cardiovascular risk stratification compared with either alone, the presence of both prolonged QTd (>65 ms) and Echo-LVH was associated with a 3.2-fold (95% CI: 1.7-6.1) increased risk of a first cardiovascular event and a 5.9-fold (95% CI: 2.1-16.4) increased risk of cardiovascular death. Thus, QT provided additive prognostic information for cardiovascular morbidity and mortality beyond that obtained from conventional risk markers, including Echo-LVH, in type 2 diabetic patients with arterial hypertension.     

A review of the role of electrocardiography in the diagnosis of left ventricular hypertrophy in hypertension

ECG remains the first line method for detection of left ventricular hypertrophy (LVH) in patients with hypertension. ECG diagnosis of LVH predicts a several-fold increase in age- and risk factor-adjusted cardiovascular morbidity and mortality in asymptomatic patients with essential hypertension. When compared with traditional ECG methods, Cornell voltage product and multifactorial criteria such as the Perugia criterion allow detection of LVH in a higher proportion of subjects while carrying a high attributable risk for cardiovascular morbidity and mortality. Hence, traditional interpretation of standard ECG maintains an important role for cardiovascular risk stratification in hypertension.