Single-drug therapy and reduction of left ventricular mass in hypertension

Echocardiography has provided most of what is understood today about the relationships between human hypertension, cardiac anatomic and functional responses. It has proven its value in determining the effects of antihypertensive therapy on cardiac structure and function. A growing body of research supports initial concerns that not all drugs effective for blood pressure reduction are effective for reduction of left ventricular mass and regression of LVH. It has been of interest that agents initially believed to be ineffective for left ventricular mass reduction (principally diuretics and beta blockers) on the basis of pathophysiological theory and inadequate clinical trials, may in fact be quite effective for LVH regression, as well as improved cardiac outcomes. Hence, supposed inefficacy of these agents for this purpose should no longer be used as a reason to disregard long-standing recommendations of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of Hypertension supporting the use of diuretics and beta blockers for the initial pharmacotherapy of hypertension.     

QT dispersion as a marker of left ventricular mass in essential hypertension

Resting L1210 cells were treated with nimustine (ACNU), a bifunctional alkylating anticancer agent, for 2 h in a nutrient-depleted medium. The cells were then transferred to a fresh medium and incubated for a further 48 h. Functions of the cells thus prepared were examined in terms of the dye-exclusion of the membrane, 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl] -2H-tetrazolium hydroxide, inner salt, sodium salt (XTT)-reducing ability of the mitochondria, and heat generation due to vital metabolism as the measure of cell viability. The cells treated with ACNU were functioning normally in all the cell functions examined but were completely devoid of proliferating capacity. These results suggest the possibility that ACNU might impair the proliferative capacity of the resting cell population inside a solid tumor without causing such impairment to the cells of normal organs and tissues composed of intrinsically non-proliferative cells.     

Effects of losartan on hypertension and left ventricular mass: a long-term study

Trinucleotide repeat expansions are involved in an increasing number of neurodegenerative disorders. Eight disorders are caused by translated CAG expansions with sizes usually below 100-200 repeats. Expansions are observed in unrelated genes, and the threshold above which the disease becomes manifest varies according to the locus. There is a strong negative correlation between age at onset and the number of repeats. Direct molecular diagnosis, which is now possible, allows classification according to genotype, thereby multiplying the number of related disorders. Molecular analysis is also useful to diagnose disorders with variable and overlapping clinical features. Recent findings suggest that intranuclear inclusions are a characteristic of disorders with translated CAG expansions. Their formation might constitute an important step in the pathological process. Friedreich ataxia is the first disorder caused by a trinucleotide repeat expansion located within an intron. The clinical spectrum of the disease and its diagnostic criteria have been recently reevaluated in a large series of patients. Interestingly, Friedreich's ataxia is now thought to be associated with intramitochondrial iron accumulation. Frataxin, the protein that is mutated, might normally be responsible for mitochondrial iron homeostasis in tissues that are affected by the disease.     

Determinants of the pulmonary artery pressure rise in left ventricular dysfunction

Pulmonary artery hypertension in patients with left ventricular dysfunction is related to poor outcome but the role of cardiac functional abnormalities in the genesis of pulmonary hypertension remains unknown. The aim of this prospective study was to identify the determinants of pulmonary hypertension in 102 consecutive patients with primary left ventricular dysfunction (ejection fraction < 50%). Systolic pulmonary artery pressure was measured by continuous wave Doppler. Left ventricular systolic and diastolic function, severity of functional mitral regurgitation, cardiac output, and left atrial volume were assessed using Doppler echocardiography. In patients with left ventricular dysfunction, systolic pulmonary artery pressure was increased (51 +/- 14 mmHg, range 23 to 87 mmHg). Mitral deceleration time (r = -0.61; p = 0.0001) and mitral effective regurgitant orifice (r = 0.50; p = 0.0001) were the strongest parameters related to systolic pulmonary artery pressure. Multivariate analysis identified these two variables as the strongest predictors of systolic pulmonary artery pressure in association with the mitral E/A ratio (p = 0.006) and age (p = 0.005). In conclusion, pulmonary hypertension is common and variable in patients with left ventricular dysfunction. It is closely related to diastolic dysfunction and severity of functional mitral regurgitation but not independently to the degree of left ventricular systolic dysfunction. These findings underline the importance of assessing diastolic function and quantifying mitral regurgitation in patients with left ventricular dysfunction.     

Increased left ventricular mass in salt-sensitive hypertensive patients

Clinical, biochemical and echocardiographic characteristics were evaluated from 50 essential hypertensive patients classified asccording to their salt-sensitivity status. Salt-sensitive hypertension was diagnosed by means of ambulatory blood pressure monitoring (ABPM) in 22 (44%) patients showing a significant increase in mean BP (P < 0.05) from a 7-day period of low salt (20 mmol NaCl/day) intake, to a 7-day period of high salt (260 mmol NaCl/day) intake. The remaining 28 (56%) patients were considered as having salt-resistant hypertension. Compared with salt-resistant patients, salt-sensitive ones showed an increased left ventricular mass index (P = 0.0118), septal (P = 0.0021) and posterior wall thickness (P = 0.0026), without differences in the internal diastolic diameter. Decreased values of HDL-cholesterol (P = 0.0475) and increased total cholesterol/HDL-cholesterol ratio (P = 0.0098) were also observed in the salt-sensitive, compared with the salt-resistant hypertensive patients. Age, gender, body mass index, systolic and diastolic BP, fasting plasma glucose, creatinine and uric acid did not differ between salt-sensitive and salt-resistant patients. We conclude that, at the same level of BP, salt-sensitive patients exhibit an increased prevalence of left ventricular hypertrophy and a worse lipid profile. These two aspects may confer to salt-sensitive patients an increased risk in terms of cardiovascular morbidity and mortality.     

The importance of left ventricular hypertrophy in human hypertension

Hemodynamic and non-hemodynamic factors contribute to the development of left ventricular hypertrophy (LVH). The presence of LVH is an important independent risk factor for total mortality and for cardiovascular morbidity and mortality. Direct cardiac effects of LVH include an increased risk of developing of congestive heart failure, an increased risk of arrhythmic events, and a reduced coronary flow reserve, promoting myocardial ischemic episodes. In addition, hypertension may promote the development of coronary artery atherosclerosis. The prognostic implications of LVH underscore the importance of diagnostic procedures. The electrocardiogram has a high specificity to identify patients with LVH but the sensitivity is fairly low. Echocardiography provides higher sensitivity and also gives important information, such as the pattern of left ventricular geometry, which is of prognostic importance, and the presence of diastolic dysfunction, which is an early abnormality in the evolution of hypertensive LVH. Reversal of LVH appears to improve prognosis. Reduction of blood pressure is one important component in the regression of LVH. Important quantitative differences exist between drug classes in the reversal of cardiac hypertrophy despite similar antihypertensive effects, suggesting other factors to be of importance in the regression of left ventricular mass. LVH is reduced more by angiotensin-converting enzyme inhibitors than by other antihypertensive drug classes, suggesting an effect on structural myocardial changes beyond that provided by the reduction of blood pressure. Recent data suggest that angiotensin II receptor antagonists (AIIRAs) have quantitatively similar effects on left ventricular mass as do angiotensin-converting enzyme inhibitors. A comparative trial of the AIIRA irbesartan and the beta-blocker atenolol demonstrated that despite similar reductions in blood pressure, the reductions attained in left ventricular mass with irbesartan were progressive and numerically greater than those attained with atenolol. Taken together, these findings provide circumstantial evidence for an important role of angiotensin II acting on angiotensin type 1 (AT1) receptors in the development or maintenance of cardiac hypertrophy. Confirmation of the favorable effects of angiotensin-converting enzyme inhibitors and AIIRAs on left ventricular mass in larger trials, including those assessing cardiovascular morbidity and mortality, will be of major importance in the future treatment of hypertension.     

Gender specific differences in left ventricular adaptation to obesity and hypertension

We studied the correlation between retinal nerve fiber layer thickness and visual field loss in 117 eyes of 62 patients with open angle glaucoma using the Aulhorn Classification as modified by Greve. We divided the peripapillary area into four quadrants [superior (S), inferior (I), temporal (T), nasal (N)] and the total (T0), and measured the peripapillary retinal nerve fiber layer thickness (NFLT) with a confocal scanning laser polarimeter (Nerve Fiber Analyzer). We also obtained the relative ratios (mean ratios) of the total circumference to the nasal quadrant (T0/N), the superior to the nasal quadrant (S/N), the temporal to the nasal quadrant (T/N), the inferior to the nasal quadrant (I/N), the total to the temporal quadrant (T0/T), the superior to the temporal quadrant (S/T), the nasal to the temporal quadrant (N/T), and the inferior to the temporal quadrant (I/T). Significant decreases were observed in the mean ratios to the temporal quadrant, i.e., T0/T, S/T, and I/T, in stages I to VI when compared with stage 0. However, no significant differences were observed among stages I to VI. These results suggest that these parameters may not precisely reflect the progression of the disease, but may aid differential diagnosis of the early stage (stage 0) from the middle and late stages (stages I to VI).     

Relationships between left ventricular mass, left ventricular work and coronary artery size in aortic regurgitation--possible mechanism of myocardial ischemia

To investigate the relationships between coronary artery size, left ventricular (LV) mass, and LV stroke work in aortic regurgitation (AR), these values were measured in 19 patients with severe AR. Twenty normal subjects and 15 patients with mitral regurgitation (MR) were used as control groups. The coronary area index, i.e., the coronary cross-sectional area divided by body surface area (BSA), was larger in the AR group than in the control groups in all measured sites except for the peripheral left anterior descending coronary artery (LAD) and right coronary artery (RCA). However, the coronary area index divided by the LV mass was significantly smaller in AR and MR patients than in normal subjects. Furthermore, the coronary area index divided by LV stroke work was smaller in AR patients than in MR patients and normal subjects. These results suggest that the coronary blood flow associated with the increased LV mass and stroke work caused by regurgitation was insufficient in patients with severe AR, especially in the area of the LAD. Therefore, the occurrence of myocardial ischemia in patients with severe AR may involve inadequate enlargement of the coronary artery which perfuses the LV, in addition to factors such as decreased coronary perfusion pressure, increased coronary artery resistance and decreased coronary flow reserve.     

Glucose intolerance exaggerates left ventricular hypertrophy and dysfunction in essential hypertension

The influence of glucose intolerance, the preclinical stage of diabetes mellitus, on the progression of left ventricular hypertrophy and left ventricular dysfunction in essential hypertension, was assessed with two-dimensional M-mode echocardiography in age- and sex-matched essential hypertensive patients with (n = 28) or without (n = 44) glucose intolerance, and normotensive control subjects (n = 29). Left ventricular mass index in hypertensive patients with glucose intolerance was significantly higher than that in hypertensive patients without glucose intolerance (mean +/- SD, 115.6 +/- 28.2 v 102.1 +/- 22.1 g/m2; P < .05). Left ventricular diastolic function as reflected by peak lengthening rate was reduced in glucose-intolerant hypertensive patients than in hypertensive patients without glucose intolerance (2.68 +/- 0.71 v 3.16 +/- 0.82/sec; P < .05). End-systolic wall stress/left ventricular end-systolic volume index, an index of left ventricular contractility, was reduced more in glucose-intolerant hypertensive patients than in hypertensive patients without glucose intolerance (2.75 +/- 0.55 v 3.13 +/- 0.55 10(3) dyn.m2/cm2.mL-1; P < .01). These findings suggest that glucose intolerance accelerates progression of left ventricular hypertrophy and deteriorates left ventricular diastolic function and contractility in essential hypertension.     

Blood pressure and left ventricular mass in children with different maternal histories of hypertension: the Hypertension in Pregnancy Offspring Study

The treatment of chronic, nonhealing wounds is discussed. The authors have successfully utilized locally acting growth factors as an adjunct to aggressive, comprehensive management in a clinical setting. At the Holmes Regional Wound Care Center, wounds with an average duration of 75 weeks at presentation were 100% epithelialized in an average of 10 weeks of therapy. The use of topical PROCUREN, or autologous platelet-derived wound healing factors (PDWHF) is introduced to the podiatric literature.     

Variants of renin-angiotensin system genes and echocardiographic left ventricular mass

AIMS: Variants of renin-angiotensin system genes are shown to be associated with cardiovascular pathology. The association between renin-angiotensin system genes and left ventricular mass was investigated in a population-based case-control study. METHODS AND RESULTS: The association between echocardiographic left ventricular mass and both insertion/deletion polymorphism of the angiotensin-converting enzyme gene and the methionine-threonine variant at position 235 of the angiotensinogen gene was studied in a random cohort of 430 hypertensive and 426 control subjects. No differences in the adjusted left ventricular mass values between the different genotypes were seen among either the hypertensive or the control subjects, whether men or women, or in the subgroups of normotensive or physically active subjects. Gene variation had no statistically significant synergistic effect on left ventricular mass values. In control women, the deletion allele of the angiotensin-converting enzyme gene was associated with an increased risk of left ventricular hypertrophy. However, this finding was based on a small number of women with left ventricular hypertrophy and should be interpreted with caution. CONCLUSION: Variations in renin-angiotensin system genes had no major effect on left ventricular mass in this middle-aged population-based cohort of hypertensives and control subjects.     

Right ventricular diastolic disfunction and its relation to left ventricular performance in patients with hypertension

The potential effects of propofol emulsion (Diprivan) on the neuromuscular transmission and muscular contraction were studied using in vitro and in vivo nerve-muscle preparations of rats. The contractions of the isolated rat diaphragm elicited by either indirect or direct electrical stimulation were inhibited by propofol emulsion at threshold concentrations of 42 and 112 mumol l-1, respectively. Similarly, the gastrocnemius muscle contractions induced by either indirect or direct electrical stimulation in vivo were inhibited by propofol emulsion administration as a bolus injection of 2.5 mg kg-1 intravenously, followed by intravenous infusion of 150 micrograms kg-1 min-1 for 1 h into rats. The inhibitory effects of propofol in both preparations were greater with indirect rather than direct stimulation. Propofol emulsion was found to be capable of enhancing the paralysis of the indirectly stimulated rat diaphragm in vitro and gastrocnemius muscle in vivo induced by either pipecuronium or succinylcholine. The combination of propofol and pipecuronium led to a synergistic inhibition of the neuromuscular transmission, while the combination of propofol and succinylcholine led to additive inhibition. Pretreatment with propofol emulsion at these threshold concentrations markedly inhibited the stimulant effects of aminophylline and digoxin on the indirectly and directly induced diaphragmatic contractions. Also, the enhancement effects of aminophylline on the indirectly and directly and of digoxin on indirectly induced rat gastrocnemius muscle contractions were markedly inhibited by propofol emulsion administration to rats. Pretreatment with propofol emulsion at the threshold concentrations enhanced the inhibitory effects of verapamil on diaphragmatic contractions elicited either indirectly or directly and enhanced the inhibitory effect of adenosine on the contractions elicited indirectly. Similarly, the inhibitory effects of verapamil on the indirectly and directly and of adenosine on indirectly induced rat gastrocnemius muscle contractions were markedly potentiated by propofol emulsion administration to rats. In addition, doubling the concentration of calcium in the bathing fluid produced no change in the inhibitory effects of propofol emulsion on either indirectly or directly elicited diaphragmatic contractions, while doubling the concentration of external magnesium potentiated the propofol effects. Pretreatment with 4-aminopyridine suppressed the inhibitory effects of propofol emulsion on diaphragmatic contractions elicited either indirectly or directly. These results suggest that propofol acts presynaptically to inhibit the neuromuscular transmission and acts at the muscle membrane to inhibit the muscular contraction.     

Left ventricular geometry and severe left ventricular hypertrophy in children and adolescents with essential hypertension

BACKGROUND: Left ventricular (LV) hypertrophy has been established as an independent risk factor for cardiovascular disease in adults. Recent research has refined this relationship by determining a cutpoint of 51 g/m(2.7) for LV mass index indicative of increased risk and defining LV geometric patterns that are associated with increased risk. The purpose of this study was to evaluate severe LV hypertrophy and LV geometry in children and adolescents with essential hypertension. METHODS AND RESULTS: A cross-sectional study of young patients (n=130) with persistent blood pressure elevation above the 90th percentile was conducted. Nineteen patients (14%) had LV mass greater than the 99th percentile; 11 of these were also above the adult cutpoint of 51 g/m(2.7). Males, subjects with greater body mass index, and those who had lower heart rate at maximum exercise were at significantly (P<.05) higher risk of severe LV hypertrophy. In addition, 22 patients (17%) had concentric LV hypertrophy, a geometric pattern that is associated with increased risk of cardiovascular disease in adults. Seven patients had LV mass index above the cutpoint and concentric hypertrophy. No consistent significant determinants of LV geometry were identified in these children and adolescents with hypertension. CONCLUSIONS: Severe LV hypertrophy and abnormal LV geometry are relatively prevalent in young patients with essential hypertension. These findings suggest that these patients may be at risk for future cardiovascular disease and underscore the importance of recognition and treatment of blood pressure elevation in children and adolescents. Weight loss is an important component of therapy in young patients with essential hypertension who are overweight.     

Increased left ventricular muscle mass after long-term altitude training in athletes

STUDY OBJECTIVES: To compare the costs and effectiveness of directly observed therapy (DOT) vs self-administered therapy (SAT) for the treatment of active tuberculosis. DESIGN: Decision analysis. SETTING: We used published rates for failure of therapy, relapse, and acquired multidrug resistance during the initial treatment of drug-susceptible tuberculosis cases using DOT or SAT. We estimated costs of tuberculosis treatment at an urban tuberculosis control program, a municipal hospital, and a hospital specializing in treating drug-resistant tuberculosis. OUTCOME MEASURES: The average cost per patient to cure drug-susceptible tuberculosis, including the cost of treating failures of initial treatment. RESULTS: The direct costs of initial therapy with DOT and SAT were similar ($1,206 vs $1,221 per patient, respectively), although DOT was more expensive when patient time costs were included. When the costs of relapse and failure were included in the model, DOT was less expensive than SAT, whether considering outpatient costs only ($1,405 vs $2,314 per patient treated), outpatient plus inpatient costs ($2,785 vs $10,529 per patient treated), or outpatient, inpatient, and patients' time costs ($3,999 vs $12,167 per patient treated). Threshold analysis demonstrated that DOT was less expensive than SAT through a wide range of cost estimates and clinical event rates. CONCLUSION: Despite its greater initial cost, DOT is a more cost-effective strategy than SAT because it achieves a higher cure rate after initial therapy, and thereby decreases treatment costs associated with failure of therapy and acquired drug resistance. This cost-effectiveness analysis supports the widespread implementation of DOT.     

Determinants of perceived health in patients with left ventricular dysfunction: a structural modeling analysis

The species composition, abundance, and distribution of mosquito larvae in tires were determined on 3 dates at a relatively large rural tire dump (about 300,000 tires) in southeastern IL (Jasper County). Several observations at this site differed from those in previous reports about mosquitoes in tireyards, including 1) a relatively high percentage of tires positive for Aedes triseriatus larvae in an open-field area, 2) a greater abundance of Culex pipiens than Cx. restuans in late-season collections, 3) a seasonal change in the distribution of Aedes atropalpus larvae in tires from open field and edge of woods areas, and 4) the presence of Ae. albopictus as a major late-season species. Ae. albopictus adults were captured in sod-baited gravid traps along the edge of a wooded riparian area 200 m from the tire pile.     

Latent impairment of left ventricular filling in hypertension without left ventricular hypertrophy and improvement by dipyridamole treatment: pulsed Doppler echocardiography study

Left ventricular (LV) filling impairment in patients with hypertension (HT) not necessarily associated with LV hypertrophy has not been sufficiently investigated. Therefore, we examined the response of LV filling to isometric exercise in patients with HT without LV hypertrophy and LV filling abnormality at rest. We studied 25 patients (aged 40 to 66 years, mean 51 +/- 7 years) and 13 age-matched normal subjects. The HT patients were selected by the following criteria: 1) systolic blood pressure (sBP) over 160 mmHg and/or diastolic BP over 90 mmHg was observed at least three times during the last 6 months, 2) LV wall thickness was under 11 mm, and 3) the ratio of peak atrial LV inflow velocity (A) to peak early diastolic LV inflow velocity (E) was within the mean +/- SD of normal subjects. LV inflow was measured by pulsed Doppler flowmetry before and during handgrip exercise (50% maximal effort for one minute and a half) in the patients before [HT-D (-)] and after [HT-D (+)] dipyridamole (D) administration (0.28 mg/kg/4 min) and in the normal subjects (N). Doppler-derived indices were A, E, A/E, DR (the deceleration rate from peak to half of the early diastolic inflow velocity), % delta A/E (% change in A/E from baseline), and % delta DR (% change in DR from baseline). There was no significant difference in LV wall thickness between the HT and N groups. There was also no significant difference in A/E at rest between the three groups. Increase of sBP and heart rate were similar in all groups during handgrip exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term effects of delapril hydrochloride on procollagen type III amino-terminal peptide, left ventricular mass and left ventricular function in hypertensive patients

The long-term effect of delapril hydrochloride, a non-sulfhydryl angiotensin converting enzyme inhibitor, on serum concentrations of procollagen type III amino-terminal peptide (PIIIP) and left ventricular mass (LVM) and function were investigated in 15 hypertensive patients. Patients were treated with delapril hydrochloride 30 mg/day po for 12 months. Blood samples and an echocardiogram were obtained before treatment and after 6 and 12 months of treatment. Blood pressure, PIIIP, and LVM significantly decreased associated with an increase in left ventricular fractional shortening and mean systolic and diastolic posterior wall velocity at 6 and 12 months of treatment. Positive correlations between PIIIP and LVM (r=0.49, p<0.005) and negative correlations between PIIIP and left ventricular fractional shortening (r=-0.31, p<0.05) were found. Delapril hydrochloride reduced PIIIP and LVM and improved cardiac function in hypertensive patients.     

Regression of left ventricular hypertrophy in hypertension: changing patterns with successive meta-analyses

Left ventricular hypertrophy (LVH) may be an important target for therapy in hypertension, although definitive data in humans are not available. An important question is whether antihypertensive drugs vary in their ability to cause the regression of LVH. Without adequately powered controlled comparisons, meta-analysis provides the best method of assessing the overall results of the numerous smaller published studies. A succession of meta-analyses have indicated a strong relationship between changes in blood pressure and LVH regression. We have reviewed studies conducted for 5 years since the first major meta-analysis. Methodology was found to have improved, and the overall ranking of drug classes according to their effects on LVH regression were: calcium antagonists, angiotensin converting enzyme inhibitors, diuretics, alpha-blockers, beta-blockers, and lifestyle changes. Changes from earlier reports may reflect the use of new preparations within some classes of drugs and large studies are required to define whether this will be reflected in clinical outcomes.