Left Ventricular Hypertrophy Changes Research Articles

Intensive Blood Pressure Lowering Improves Left Ventricular Hypertrophy in Older Patients with Hypertension: The STEP Trial.

Intensive systolic blood pressure (SBP) lowering has been increasingly used; however, its effect on cardiac remodeling remains not fully understood. This secondary analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients trial aims to determine the changes in left ventricular hypertrophy (LVH) that occur in the context of intensive SBP lowering. A total of 7141 older patients with hypertension were randomly assigned to intensive treatment (SBP target, 110-130 mm Hg) or standard treatment (130 to 150 mm Hg). LVH was defined according to the Peguero-Lo Presti criteria on a standard 12-lead ECG. At baseline, the prevalence of LVH (16.6% versus 16.5%) and the mean Peguero-Lo Presti value (1811 versus 1808 μV) were comparable between the treatment groups. During a median follow-up of 3.24 years, intensive SBP lowering was associated with a significantly lower risk of new LVH occurrence (hazard ratio, 0.76 [95% CI, 0.66-0.89]; P=0.001) and slower progression of the mean Peguero-Lo Presti index value by -23.47 μV/y (95% CI, -34.93 to -12.01; P=0.000). However, the rates of regression of baseline LVH did not differ significantly. Of note, the beneficial effect of intensive SBP lowering in terms of cardiovascular events (hazard ratio, 0.75 [95% CI, 0.59-0.97]) was not markedly attenuated after adjusting for LVH as a time-varying covariate (hazard ratio, 0.76 [95% CI, 0.59-0.97]). Intensive SBP lowering protects against LVH development in older hypertensive patients, however, this favorable effect could not explain most of the reduction in cardiovascular events associated with intensive SBP lowering.

Correlation of microalbuminuria with its clinical outcome in pre-hypertensives: a cross-sectional study from South India

Background: Prehypertension is a major public health concern. The condition is much prevalent in India and is often associated with other cardiovascular (CV) risk factors and independently increases the risk of hypertension and subsequent cardiovascular events. Several studies have shown microalbuminuria as a sensitive marker for predicting CV risk in pre-hypertensive. The objective of this study was to assess the prevalence of microalbuminuria in prehypertension and to determine its association with electrocardiogram (ECG) and echocardiographic (Echo) parameters indicative of CV risk.Methods: This cross-sectional study included a total of 75 subjects aged between 22 and 50 years, with prehypertension attending the medicine department of a tertiary care teaching hospital in Chennai, Tamil Nadu from April 2012 to November 2012. All the study subjects were evaluated with ECG and echo for cardiac changes. Statistical analysis was performed using SPSS software trial version-16 to determine the association of microalbuminuria with cardiac changes.Results: The prevalence of microalbuminuria among the included subjects was 60%. Mean value of urinary excretion of microalbuminuria was 90±2.1 µg/dl with a male preponderance in this study. Pre-hypertensive subjects with microalbuminuria had significant changes of left ventricular hypertrophy (LVH) as evident in ECG than those without microalbuminuria. Microalbuminuric prehypertensive subjects also had significant echocardiographic changes like LVH and diastolic dysfunction than those without microalbuminuria.Conclusions: The cardiovascular changes like left ventricular hypertrophy and diastolic dysfunction were evident in younger age among pre-hypertensives with microalbuminuria than those without microalbuminuria.

Study on microalbuminuria as predictor factor for target organ damage in essential hypertension in a teaching hospital, Telangana

Background: Microalbuminuria in hypertensives is related to future development of cardiovascular morbidity. It is a simple test which is easily available. In the present study we attempted to look at the prevalence of microalbuminuria in cases of essential hypertension and also to determine its association with left ventricular hypertrophy and carotid intima-media thickness and retinopathy. Aim of the study: To study microalbuminuria as a predictor factor for target organ damage in essential hypertension. Materials and Methods: Hospital based prospective observational study done on 45 cases for duration of one year. Cases of essential hypertension were studied for microalbuminuria, for changes of left ventricular hypertrophy, left ventricular mass index distribution and for retinopathy. Results: There was a slight male predominance and the M:F ratio was 2.7:1. Majority of cases were among 40-50 years age group ie, 62.2% cases. Microalbuminuria was present in 77.7% cases. ECG changes of left ventricular hypertrophy were present in 77.7% cases. Obesity and over weight were present in 15 (33.3%) subjects. Among 35 cases with microalbuminuria, 19 patients had hypertensive retinopathy changes. Among these 19 patients, Grade II retinopathy was most common and was diagnosed in 68.4% cases. Conclusion: Microalbuminuria is common in patients with essential hypertension. Microalbuminuria can predict cardiovascular and ocular morbidity in the form of left ventricular hypertrophy, increased carotid intima-media thickness; and ocular morbidity respectively. Screening of all patients with essential hypertension will help to predict the future risk for target organ damage. Keywords: Microalbuminuria, Essential Hypertension, Left ventricular hypertrophy.

High FGF23 Levels Failed to Predict Cardiac Hypertrophy in Animal Models of Hyperphosphatemia and Chronic Renal Failure.

Increased fibroblast growth factor 23 (FGF23) levels are an independent predictor for adverse cardiac events suggesting a role as a link that drives cardiomyopathic changes in cardiorenal syndrome. The search for the underlying mechanism driving this interaction has led to the hypothesis that FGF23 causes pathogenic changes in the heart. Increased serum FGF23 has been independently shown to cause increased cardiac morbidity, mortality, and hypertrophy by signalling through FGF receptor 4. This mechanistic concept was based on preclinical studies demonstrating inhibition of FGF23 signaling through FGF4, which led to suppression of left ventricular hypertrophy and fibrosis in a 2-week rat 5/6 nephrectomy study and a 12-week (2%) high-phosphate diet mouse model in which FGF23 levels were markedly elevated. In this report, renal dysfunction was observed in the 5/6 nephrectomy model, and FGF23 levels were significantly elevated, whereas no changes in left ventricular hypertrophy were observed at 2 or 4 weeks postnephrectomy. Mice placed on a high-phosphate diet that did not cause significant renal dysfunction resulted in significantly elevated FGF23 but no changes in left ventricular hypertrophy. The in vivo studies reported here, which were performed to recapitulate the observations of FGF23 as a driver of cardiac hypertrophy, did not lend support to the FGF23-driven cardiac remodelling hypothesis.

SCREENING AND ASSESSMENT OF CARDIAC AUTONOMIC NEUROPATHY IN LONG STANDING TYPE 2 DIABETIC WOMEN

Patients with long-standing diabetes mellitus undergoing surgical interventions are under considerable risk, hence posing a surgical challenge, as they may have cardiovascular and/or cardiac autonomic neuropathy (CAN). CAN is serious, often overlooked and underdiagnosed, with possible arrhythmias and silent ischemia that may be life threatening. The aim of this study was to screen for one of the underdiagnosed high-risk problems by assessment of CAN in long-standing type 2 diabetic women undergoing stressful situations. Cross-sectional study. Hundred type 2 diabetic women scheduled for major surgery were assessed by autonomic function tests. CAN was assessed by analyzing heart rate variations during three standard tests (deep breathing, lying to standing, and the valsalva maneuver). Sympathetic functions were assessed by checking orthostatic hypotension. The CAN score of each patient was analyzed. Continuous 24 h ECG monitoring was performed to evaluate arrhythmia, corrected QT (QTc), and QT dispersion (QTd). Transthoracic Doppler echocardiography, with a focus on left ventricular hypertrophy, diastolic, and systolic dysfunctions, was carried out. Patients were classified as having mild (with only one abnormal test) or severe CAN when two or more abnormal function tests were present. Exclusion criteria included any systemic illness that could affect the results of the study or the autonomic functions, smoking, hypertension, and patients with evident ischemia. CAN was detected in 70% of the patients studied, and 70% of them had a severe case of CAN. Postural hypotension was detected in 34% of the patients studied. QTc prolongation and QTd were frequent. ECG and Doppler echocardiography changes of left ventricular hypertrophy were more prevalent among patients with CAN. Diabetics with CAN were significantly older, had a longer duration of diabetes mellitus, and higher HbA1-c, higher pulse pressure, triglyceride, uric acid, and urinary albumin excretion rate. They also had a significantly increased left ventricular mass index and diastolic dysfunction. Middle-aged women with long-standing diabetes are vulnerable to CAN with postural hypotension and prolonged QTc intervals, QTd, and increased left ventricular mass index. Identification of CAN is crucial to prevent the hazards of cardiovascular insults during stressful situations, and cases with severe CAN may require coronary artery disease screening preoperatively.

Prevention of Obesity‐Associated Coronary and Cardiac Diastolic Dysfunction by Deletion of Smooth Muscle Cell Mineralocorticoid Receptor in Females

Coronary microvascular dysfunction is independently predictive of cardiac diastolic dysfunction and both conditions are common in obesity and associated metabolic syndrome. Recent work by us and others indicates that mineralocorticoid receptor (MR) antagonism treats obesity‐associated coronary and cardiac diastolic dysfunction. Vascular cell‐specific MR involvement in these obesity‐related defects remains unclear. Thus, we evaluated the hypothesis that deletion of smooth muscle cell (SMC) MR would prevent obesity‐associated coronary and cardiac diastolic dysfunction in females. Female wild‐type (WT) and SMC MR knockout (KO) mice were fed a standard chow or western diet (WD) to induce obesity for 16 weeks. WD feeding induced obesity, hyperinsulinemia, hypercholesterolemia, and visceral adipose inflammation in both WT and SMC MR KO mice. Assessment of coronary vascular function via wire myography revealed WD‐induced impairment of endothelium‐dependent vasodilation and enhanced vasoconstriction to the thromboxane A2 analog U46619 in WT but not SMC MR KO mice. Vasodilation to the nitric‐oxide donor sodium nitroprusside was unchanged by WD feeding. Global quantitative proteomics of aortas from each group revealed a number of differentially expressed proteins following WD feeding including upregulation of the oxidative stress‐related small GTPase Rac‐1 in WT but not SMC MR KO aortas. Accordingly, pretreatment of coronary arteries with the superoxide dismutase mimetic Tempol restored endothelium‐dependent vasodilation in WD‐fed WT mice with no effect in SMC MR KO vessels. Furthermore, WD feeding induced cardiac diastolic dysfunction assessed by echocardiography (i.e., increased E/E′, reduced E′/A′, increased diastolic stiffness). Coincident with prevention of WD‐induced coronary dysfunction, SMC MR deletion prevented WD‐induced cardiac diastolic dysfunction. Importantly, this cardioprotective effect of SMC MR deletion occurred independent of changes in left ventricular hypertrophy, blood pressure, aortic stiffening, and proteinuria. Taken together, our data demonstrate a central role of SMC MR signaling underlying WD‐induced coronary and cardiac diastolic dysfunction in females. Importantly, this study adds to an emerging body of evidence suggesting a vascular origin of cardiac dysfunction in obesity.Support or Funding InformationSupported by NIH (HL136386 to SBB, HL119290 to IZJ) and the Department of Veterans Affairs BLR&D (CDA‐2 IK2 BX002030). BC is supported by Department of Veterans Affairs (IK6 BX004016 and I01 BX002255).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The prevalence of electrocardiographic abnormalities in the Russian population in the early 21st century (the ESSE-RF study)

Electrocardiography (ECG) takes the lead in assessing the prevalence of coronary artery disease (CAD) in the population. ECG disorders, grouped in the Major (certain) and Minor (possible) categories, are prognostic markers of a high risk of cardiovascular diseases and sudden cardiac death. Unified assessing methods of ECG disorders prevalence and their associations with socio-demographic parameters have not previously been made in Russia.Aim. To study the prevalence of ECG parameters of certain and possible coronary artery disease among population of Russia, depending on the socio-demographic characteristics — age, sex, education and place of residence (city or country).Material and methods. We used 17504 ECGs from representative samples of population (25-64 years old), who participated in the epidemiological study “Epidemiology of cardiovascular diseases and their risk factors in the Russian Federation”. The analysis using Minnesota code was carried out among men and women of four age groups, two educational levels, among citizens and countrymen.Results. The highest prevalence was observed in the “Certain” (5,7%) and “Possible signs of CAD” (7,1%) categories, in the “Certain” (3,8%) and “Possible myocardial ischemia” groups (4,9%), the smallest is in the “Rhythm and conduction disorder” (0,7%) and “STT changes in left ventricular hypertrophy” (0,4%) groups. It was shown that the frequency of ECG disorders increases with age, has an sharp increase after 55 years, regardless of sex. In the age dynamics of categories, STT changes and atrial fibrillation have a decrease of gender differences. All groups of ECG disorders are detected more often among men than women, except for STT changes. With an increase in the level of education, the frequency of ECG pathologies decreases, with the exception of the groups of “major” and “minor Q (QS)”, “major rhythm and conduction disorders”. The prevalence of most ECG disorders does not depend on the place of residence. However, signs of major myocardial ischemia in men are more common in country than in the city (3,9% vs. 2,7%, p<0,05).Conclusion. The results confirm the patterns identified earlier. There is a steady association of ECG data with socio-demographic characteristics.

Screening and assessment of cardiac autonomic neuropathy in long-standing type 2 diabetic women

Abstract Background Patients with long-standing diabetes mellitus undergoing surgical interventions are under considerable risk, hence posing a surgical challenge, as they may have cardiovascular and/or cardiac autonomic neuropathy (CAN). CAN is serious, often overlooked and underdiagnosed, with possible arrhythmias and silent ischemia that may be life threatening. Objectives The aim of this study was to screen for one of the underdiagnosed high-risk problems by assessment of CAN in long-standing type 2 diabetic women undergoing stressful situations. Study design Cross-sectional study. Patients and methods Hundred type 2 diabetic women scheduled for major surgery were assessed by autonomic function tests. CAN was assessed by analyzing heart rate variations during three standard tests (deep breathing, lying to standing, and the valsalva maneuver). Sympathetic functions were assessed by checking orthostatic hypotension. The CAN score of each patient was analyzed. Continuous 24 h ECG monitoring was performed to evaluate arrhythmia, corrected QT (QTc), and QT dispersion (QTd). Transthoracic Doppler echocardiography, with a focus on left ventricular hypertrophy, diastolic, and systolic dysfunctions, was carried out. Patients were classified as having mild (with only one abnormal test) or severe CAN when two or more abnormal function tests were present. Exclusion criteria included any systemic illness that could affect the results of the study or the autonomic functions, smoking, hypertension, and patients with evident ischemia. Results CAN was detected in 70% of the patients studied, and 70% of them had a severe case of CAN. Postural hypotension was detected in 34% of the patients studied. QTc prolongation and QTd were frequent. ECG and Doppler echocardiography changes of left ventricular hypertrophy were more prevalent among patients with CAN. Diabetics with CAN were significantly older, had a longer duration of diabetes mellitus, and higher HbA1-c, higher pulse pressure, triglyceride, uric acid, and urinary albumin excretion rate. They also had a significantly increased left ventricular mass index and diastolic dysfunction. Conclusion Middle-aged women with long-standing diabetes are vulnerable to CAN with postural hypotension and prolonged QTc intervals, QTd, and increased left ventricular mass index. Identification of CAN is crucial to prevent the hazards of cardiovascular insults during stressful situations, and cases with severe CAN may require coronary artery disease screening preoperatively.

The Effects of Simvastatin on Left Ventricular Hypertrophy and Left Ventricular Function in Patients with Essential Hypertension

This study is to evaluate the effects of Simvastatin on left ventricular hypertrophy and left ventricular function in patients with essential hypertension. Untreated or noncompliance with drug treatment patients with simple essential hypertension were treated with a therapy on the basis of using Telmisartan to decrease blood pressure (BP). There were 237 patients who had essential hypertension combined with left ventricular hypertrophy as diagnosed by echocardiography, taken after their BPs were decreased to meet the values of the standard normal. Among them, there were only 41 out of the original 237 patients, 17.3%, who had simple essential hypertension combined with left ventricular hypertrophy without any other co-existing disease. They were the patients selected for this study. All patients were randomly, indiscriminately divided into two groups: one was the control group (Group T), treated with the Telmisartan-based monotherapy; the other was the target group (Group TS), treated with the Telmisartan-based plus simvastatin therapy. The changes of left ventricular hypertrophy and left ventricular function were rediagnosed by echocardiography after 1 year. The results we obtained from this study were as follows: (i) The average BPs at the beginning of the study, of simple essential hypertension combined with left ventricular hypertrophy, were high levels (systolic blood pressure (SBP) 189.21 ± 19.91 mm Hg, diastolic blood pressure 101.40 ± 16.92 mm Hg). (ii) The Telmisartan-based plus simvastatin therapy was significantly effective in lowering the SBP (128.26 ± 9.33 mm Hg vs. 139.22 ± 16.34 mm Hg). (iii) After the 1-year treatment, the parameters of left ventricular hypertrophy in both groups were improved. Compared to group T, there were no differences in the characteristics of the subjects, including interventricular septum, left ventricular mass, left ventricular mass index, ejection fraction, left atrium inner diameter at baseline. The patients’ interventricular septum (Group TS 10.30 ± 1.80 mm vs. Group T 10.99 ± 1.68 mm, P < .05), LVM (Group TS 177.43 ± 65.40 g vs. Group T 181.28 ± 65.09 g, P < .05), and LVMI (Group TS 100.97 ± 37.33 g/m2 vs. Group T 106.54 ± 27.95 g/m2, P < .05), all dropped more prominently (P < .05) in group TS; the ejection fraction rose more remarkably in group TS (Group TS: 57.50 ± 16.41% to 65.43 ± 11.60%, P < .01 while showing no change in Group T); the left ventricular hypertrophy reversed more significantly and the left ventricular systolic function improved more. (iv) The left atrium inner diameter of Group TS decreased (P < .01), the ratio of E/A, which indicates the left ventricular diastolic function, continued to drop further, showing no change to the trend of left ventricular diastolic function declination. Patients who have hypertension with left ventricular hypertrophy usually suffer other accompanying diseases at the same time. Telmisartan-based plus Simvastatin treatment can significantly reduce SBP, reverse left ventricular hypertrophy, improve the left ventricular systolic function, but it has no effect on reversing the left ventricular diastolic function. This experiment indicated that Simvastatin can reverse left ventricular hypertrophy and improve left systolic function.

Relationship between the change in left ventricular hypertrophy and asleep blood pressure after sodium restriction and/or diuretic treatment

Salt restriction and/or diuretic treatment convert nondippers to dippers; however, few reports have compared the relationships among the changes in asleep ambulatory blood pressure, left ventricular mass index(LVMI), and relative wall thickness between nondippers and dippers. We treated 30 never-treated hypertensive outpatients [office blood pressure (OBP) > 140/90 mmHg]with salt restriction (NaCl < 6 g/day) and/or indapamide(1 or 2 mg/day) to control both OBP (< 140/90 mmHg) and home BP (< 135/85 mmHg) for 4 months. OBP and home BP (measured monthly), ambulatory blood pressure, and echocardiogram (measured at the baseline and at the end of the treatment period) were evaluated. There were 12 nondippers [asleep/awake systolic BP (SBP) ratio > 0.90] and 18 dippers. Asleep SBP/diastolic BP decreased in both nondippers(149 ± 19/81 ± 16 – 126 ± 22/74 ± 13 mmHg) and dippers(129 ± 9/81 ± 8 – 121 ± 9/74 ± 10 mmHg; P between groups =0.005/0.11). LVMI significantly decreased in nondippers (116 ± 17.3 – 82 ± 27.8 kg/m2; P = 0.02), but not in dippers (P = 0.31; P between groups =0.11).The change in RWT was significantly different between nondippers (0.50 ± 0.07 – 0.47 ± 0.10) and dippers(0.43 ± 0.07 – 0.45 ± 0.07; P between groups = 0.036).

Primary and secondary repolarization changes in left ventricular hypertrophy: a model study

Primary and secondary repolarization changes in left ventricular hypertrophy: a model study

Secondary and primary repolarization changes in left ventricular hypertrophy: a model study

The contributions of reduced conduction velocity (CV) and prolonged action potential duration (APD) to QT interval prolongation and T wave and T vector loop morphology in left ventricular hypertrophy (LVH) were studied using an analytical computer model. Three types of anatomic LVH were simulated: concentric and eccentric hypertrophy, and left ventricular dilatation. In each LVH type, depolarization changes were simulated by CV slowing and primary repolarization changes by APD prolongation. Both CV slowing and APD prolongation prolonged the QT interval; however, the secondary and primary repolarization changes differed in additional electrocardiogram (ECG) characteristics creating specific vectorcardiographic/ECG patterns. The secondary repolarization changes were characterized by prolonged QT interval, accompanied by pronounced QRS changes, including increased maximum spatial QRS vector magnitude, prolonged QRS duration, QRS morphology consistent with intraventricular conduction delay, lower values of the T/QRS duration ratio, increased maximum spatial T vector magnitude, narrow and prolonged discordant T vector loops, and discordant tall T waves creating a pattern of ST strain in the precordial ECG leads. QT prolongation in primary repolarization changes was accompanied with inconsiderable changes of QRS amplitude and duration, higher values of the T/QRS duration ratio, widened rounded T loops, and notched or bifid T waves in left precordial leads of the 12-lead ECG. These simulation data are consistent with the accumulated evidence suggesting that LVH induces changes in CV and APD. Our results emphasize the need for simultaneous consideration of morphologic QRS and T wave patterns together with QT prolongation in clinical evaluation of LVH.

A novel mechanism of heart failure with normal ejection fraction

Background:Patients with heart failure and a normal left ventricular ejection fraction have significantly reduced left ventricular long-axis function. This paper proposes an explanation for this apparent paradox and suggests a...

Anemia and the Heart in Chronic Kidney Disease

Cardiovascular disease is highly prevalent at all stages of chronic kidney disease (CKD) and is the leading cause of morbidity and mortality. Individuals with CKD commonly have multiple risk factors for the development of cardiovascular disease, including both traditional and nontraditional risk factors. Anemia is a nontraditional cardiovascular risk factor found in CKD that contributes to the development and progression of structural abnormalities of the heart, namely left ventricular hypertrophy and dilation. In addition, a deficiency of erythropoietin per se also may have important pathophysiologic consequences. In this review we summarize the evidence from observational studies showing an association between anemia and adverse cardiac outcomes at all stages of CKD. In addition, we provide an overview of the evidence accumulating from randomized controlled trials conducted in both nondialysis and dialysis CKD populations evaluating the effect of anemia correction on cardiac outcomes such as changes in left ventricular hypertrophy.

Progression of left ventricular hypertrophy and the angiotensin-converting enzyme gene polymorphism in hypertrophic cardiomyopathy

Background Hypertrophic cardiomyopathy is an inherited primary disorder of the myocardium characterised by clinical heterogeneity. The severity and rate of progression of hypertrophy is an important factor in prognosis, and is likely to be dependent on factors including age, the disease-causing gene mutation, environmental influences and genetic modifiers. Methods To study the influence of age on progression of hypertrophy, 62 patients with hypertrophic cardiomyopathy followed up for a minimum of 2 years were studied to determine the changes in left ventricular hypertrophy based on transthoracic M-mode and 2D echocardiography. DNA studies were performed to determine the role of the angiotensin-converting enzyme (ACE) gene deletion polymorphism in modulating progression of left ventricular hypertrophy. Results Sixty-two patients were followed-up over a period of 6.0±3.2 years (range 2–16 years). Patient data were analysed in two age groups: group 1 (patients aged ≤30 years at first echocardiogram) had an increase in left ventricular septal wall thickness from 23.8±8.9 to 28.8±8.7 mm ( p<0.001), while group 2 (patients aged >30 years) had a smaller but significant increase from 17.8±4.2 to 19.5±6.2 mm ( p<0.05). DNA analysis of the ACE gene deletion polymorphism showed those with the deletion/deletion (D/D) genotype had a greater progression of left ventricular hypertrophy compared to those carrying the other ACE genotypes (increase in hypertrophy: 6.2±3.3 vs. 1.7±4.2 mm; p<0.01, D/D vs. I/D genotype; 2.8±5.8 mm; p=ns, D/D vs. I/I genotype). This association was independent of age, body mass and resting blood pressure. Conclusions Progression of left ventricular hypertrophy is most evident in the first 3 decades of life, but is also observed in older age groups. Presence of the ACE gene D/D polymorphism may be an important marker to identify those individuals with hypertrophic cardiomyopathy who are likely to have more progressive disease, and therefore at higher risk of adverse clinical outcomes.

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.

Chronic vasopressin V1A but not V2 receptor antagonism prevents heart failure in chronically infarcted rats

Evidence is increasing that therapeutic modulation of neurohormonal activation with vasopressin receptor antagonists via V1A and V2 receptors may favourably affect prognosis of heart failure. This study was designed to compare in vivo hemodynamic effects of early treatment (1–21 days after infarction) with a V1A (SR-49059 or ((2S)1-[(2R3S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzene-sulfonyl)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2-carboxamide); 0.3 mg/kg/day) and a V2 (SR-121463B or (1-[4-(N-tert-Butylcarbamoyl)-2-methoxybenzene sulfonyl]-5-ethoxy-3-spiro-[4-(2-morpholinoethyoxy)-cyclo-hexane]indol-2one,furmate; 0.5 mg/kg/day) receptor antagonist in myocardial infarcted rats, chronically instrumented for hemodynamic measurements. Left ventricular dysfunction in conscious myocardial infarcted rats, which was evidenced by a significantly decreased cardiac output (myocardial infarction: 70±3 vs. sham: 81±3 ml/min) and stroke volume (myocardial infarction: 190±10 vs. sham: 221±7 μl), was restored by the vasopressin V1A (81±2 ml and 224±5 μl, respectively) but not V2 receptor antagonist. Improved cardiac output with the vasopressin V1A receptor antagonist resulted from an increased stroke volume at a reduced myocardial infarction induced tachycardia. In addition to the hemodynamic measurements, left ventricular hypertrophy and capillary density were determined, histologically measured as the cross-sectional area of Gomori-stained myocytes and Lectin-stained capillaries per tissue area, respectively. The observed left ventricular concentric hypertrophy (myocardial infarction: 525±38 vs. sham: 347±28 μm2; P<0.05) and reduced capillary density (myocardial infarction: 2068±162 vs. sham: 2800±250 number/mm2; P<0.05) in the spared myocardium of myocardial infarcted rats, remained unaffected by the vasopressin V1A or V2 receptor antagonist. Thus, chronic vasopressin V1A but not V2 receptor blockade prevents heart failure in 3-week-old infarcted rats. Moreover, the improved cardiac function could not attributed to changes in left ventricular hypertrophy and/or capillary density.

Relationship between home blood pressure and longitudinal changes in target organ damage in treated hypertensive patients.

Cross-sectional studies have shown that home blood pressure (BP) correlates with hypertensive target organ damage better than clinic BP. However, there have been few longitudinal studies regarding the predictive value of home BP on the changes in organ damage in treated hypertensive patients. Clinic and home BP over a 12-month period, antihypertensive medication use, echocardiographic and electrocardiographic results, and serum creatinine and urinary protein levels were examined in 209 treated hypertensive patients in 1993. These patients were prospectively followed for 5 years. The patients were divided into 4 subgroups according to hypertension control as follows: good control (<140/90 mmHg for clinic BP, <135/85 mmHg for home BP), improved, worsened, and poor control. The average clinic BP was 147.0+/-14.9/87.0+/-7.6 mmHg (mean+/-SD) in 1993 and 146.0+/-13.7/84.1+/-7.5 mmHg in 1998. The average home BP was 136.8+/-10.4/84.3+/-7.6 mmHg in 1993 and 136.1+/-9.7/81.2+/-7.7 mmHg in 1998. The left ventricular mass index (LVMI) positively correlated with both home systolic BP and clinic systolic BP in 1998 but not in 1993. The correlation tended to be closer for home BP than for clinic BP. LVMI did not change in patients with good or improved home systolic BP, while it increased in those with poor or worsened home systolic BP. The relationship between changes in LVMI and clinic BP was not significant. In conclusion, Home BP was more effective than clinic BP as a predictor of changes in left ventricular hypertrophy in treated hypertensive patients. Home BP should be controlled to below 135/85 mmHg to prevent cardiac hypertrophy.

Postoperative changes in diastolic function of the left ventricle in patients with aortic valve stenosis

Diastolic dysfunction in valvular aortic stenosis frequently precedes systolic dysfunction. The purpose of this study was to examine the changes in left ventricular diastolic function after aortic valve replacement. Seventy eight patients with significant isolated valvular aortic stenosis were enrolled in the study. The echocardiographic examination was performed with ACUSON-XP 10 imaging system. Complete M-mode, 2-dimensional and Doppler echocardiographic results were obtained. In 48 patients right and left heart catheterisation was performed. Left ventricular diastolic function was evaluated by pulse Doppler recording of inflow velocity on the tips of the mitral valve leaflets. Forty two underwent aortic valve replacement. They were followed up 6-12 months postoperatively. Abnormal patterns of left ventricular diastolic filling were noticed in almost all patients (Table 1). Most prominent changes were found in subjects with marked and diffuse hypertrophy (Table 2). After aortic valve replacement decrease in left ventricular size, mass, pressures and improvement in systolic Function (Table 3). Twelve months after the operation late diastolic filling velocity was lower (A = 64 +/- 15 cm/s, Avti = 7.1 +/- 1.8 cm), early diastolic filling velocity was higher (E = 83 +/- 14 cm/s, Evti = 10.3 +/- 1.4 cm), deceleration time (DT = 123 +/- 14 ms) and isovolumetric relaxation time (IRT = 66 +/- 6 ms) were longer in patients with preoperative moderate hypertrophy (Table 4). In patients with severe left ventricular hypertrophy changes in diastolic function were slower. We found decrease in early diastolic filling velocity (A = 44 +/- 6 cm/s, Avti = 4.6 +/- 04 cm), increase in late diastolic filling velocity (E = 67 +/- 14 cm/s, Evti = 9.4 +/- 1.7 cm), with prolongation of deceleration (DT = 131 +/- 18 ms) and isovolumetric relaxation time (IRT = 94 +/- 23 ms) (Table 5). In adults with significant sympthomatic aortic valve stenosis, aortic valve replacement is therapy of choice. Replacement of the diseased aortic valve with a prosthetic valve yields relief of left ventricular outflow obstruction. Myocardial remodeling with regression of mass transpires as the heart adapts to the new level of afterload. In patients with moderate left ventricular hypertrophy improvement in diastolic function during the first year after aortic valve replacement is visible, while in patients with extreme myocardial hypertrophic changes it was slower.

Improvement in fatty acid utilization in relation to a change in left ventricular hypertrophy in spontaneously hypertensive rats.

Although fatty acid metabolism is reportedly impaired in myocardial hypertrophy, it is unclear whether the antihypertensive drugs are associated with improved fatty acid metabolism. In order to evaluate the effects of antihypertensive drugs on fatty acid metabolism and myocardial perfusion, the simultaneous uptake of iodine-125(125I)-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and thallium-201 (Tl) were measured in 3 groups of rats: (1) spontaneously hypertensive rats (SHR) without treatment (SHR-N), (2) SHR chronically treated with captopril (SHR-C), and (3) SHR chronically treated with hydralazine (SHR-H). Captopril and hydralazine were administered to their respective groups for 3 weeks from 12 weeks of age. The hearts were removed 10 min after simultaneous intravenous injections of BMIPP and Tl and the 125I and 201Tl counts were measured to calculate the uptake ratio. The systolic blood pressure (SBP) in SHR-N was 222+/-10 mm Hg, whereas the SHR-C and SHR-H groups showed significant SBP reduction (156+/-11, and 158+/-10 mm Hg, respectively) (p<0.01 each). The heart/bodyweight ratio was significantly lower in SHR-C (2.48+/-0.09) than in SHR-N (2.74+/-0.11) (p<0.05). However, there was no significant difference in the heart/bodyweight ratio between SHR-N and SHR-H (2.65+/-0.09). The ratio of BMIPP uptake to Tl uptake (BMIPP/Tl) was significantly higher in SHR-C (0.71+/-0.13) than in SHR-N (0.50+/-0.09) (p<0.05). However, BMIPP/Tl in SHR-H (0.53+/-0.09) was similar to that in SHR-N. These results suggest that captopril improves fatty acid metabolism in the hypertrophied ventricle in SHR. The metabolic alterations may improve with left ventricular hypertrophy regression but are not effected by the reduction of blood pressure only.