Peripheral endothelium-dependent flow-mediated vasodilatation is associated with left ventricular mass in older persons with hypertension

Background Increased left ventricular (LV) mass is associated with greater cardiovascular disease risk. Recent studies have also shown an association of increased LV mass with attenuated endothelium-dependent coronary flow reserve. Less is known about the association between LV mass and endothelium-dependent flow-mediated dilatation (FMD) in peripheral arteries, a noninvasive measure of endothelial function. Methods Sixty-two subjects with untreated mild hypertension, aged 55 to 75 years and otherwise healthy, were examined. Resting blood pressure was obtained by the average of 4 to 5 visits, each at least 1 week apart. LV mass was determined from magnetic resonance imaging and was indexed by body surface area, height and height^2.7. Body composition was assessed with dual energy x-ray absorptiometry. FMD was measured as the percent change of brachial artery diameter during reactive hyperemia by use of high-resolution ultrasound. Results Median LV mass index was 63 g/m² (interquartile range, 58-73). In bivariate analysis, LV mass was correlated to lean body mass (r = 0.63, P < .001), diastolic blood pressure (r = 0.35, P < .01), and FMD (r = −0.27, P < .05). In multivariate analysis, 44% of the variance in log-LV mass was explained by lean body mass. An additional 6% of the variance was explained by FMD (P < .05). For each 1% point decrease in FMD, LV mass increased by 1.1%. Conclusions In addition to the expected influences of body size, impairment of brachial artery FMD was independently related to LV mass in elderly subjects with mild hypertension who did not yet have LV hypertrophy. Whether mild hypertension is the common mechanism linking LV mass and endothelial function has yet to be determined. (Am Heart J 2002;144:39-44.)     

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

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

Left ventricular remodeling in the first year after acute myocardial infarction and the predictive value of N-terminal pro brain natriuretic peptide

Background Left ventricular (LV) remodeling after myocardial infarction (MI) has received much attention because of its severe impact on morbidity and mortality rates. However, the incidence and extent of LV remodeling in a modern infarct population who were offered antiremodeling treatment in compliance with daily clinical practice is unknown. The purpose of this study was to clarify this issue and to evaluate the predictive value of N-terminal pro brain natriuretic peptide (NT-proBNP). Methods Forty-two patients with a first transmural MI were examined after 1 week, 1 month, 3 months, 6 months, and 1 year with blood samples and magnetic resonance imaging. Results In 12 patients (29%), LV end-diastolic volume index (LVEDVI) and LV end-systolic volume index (LVESVI) increased by 24% and 22% (P <.0001; P = .01). In 12 patients (29%), LVEDVI and LVESVI decreased by 19% and 23% (P <.0001; P = .0005), whereas the remaining 18 patients (43%) had stable conditions regarding these LV measures. LV ejection fraction at baseline was significantly reduced in all patient categories but was unchanged over time. Elevated NT-proBNP level at baseline was identified as an independent predictor of increase in LVEDVI during follow-up examination (P = .007). A baseline level of NT-proBNP >115 pmol/L identified patients who later had LV dilatation develop with a sensitivity and specificity of 89% and 68% (area under curve = 0.77). Conclusion In this 1-year follow-up study of patients with a first transmural MI, approximately 30% had significant increments develop in LVEDVI and LVESVI, and LV ejection fraction remained unchanged. Patients in whom LV dilatation developed could be identified early after the MI with elevated plasma levels of NT-proBNP. (Am Heart J 2002;143:696-702.)     

Cardiac dimension and function in patients with childhood onset growth hormone deficiency,before and after growth hormone retreatment in adult age

Background Growth hormone (GH) replacement during childhood has been shown to increase stature; however, there is little information on its long-term effect on the heart is not yet clear. The aim of this study was to assess cardiac size and function in patients with childhood-onset GH deficiency in whom GH treatment had been stopped at the achievement of final height and the effect of a second course of GH replacement in adult age. Methods Cardiac dimensions and function, obtained with echocardiography, of 21 patients (5 women and 16 men, mean age 28 ± 8 years), all of whom were treated during childhood, were compared with 21 age- and sex-matched healthy control subjects. Eight of these patients (2 women and 6 men, mean age 28 ± 8 years) were given a second course of GH replacement therapy for 15 ± 3 months. Results The stature and all cardiac dimensions of patients with GH deficiency who were treated during childhood were significantly smaller than those of the control subjects. After the second course of GH in adulthood, the only significant change observed was an increase in left ventricular (LV) mass (93 ± 21 vs 106 ± 24 g, P = .007) and LV mass index (59 ± 12 vs 66 ± 13 g/body surface area, P = .005). Conclusion The stature and cardiac dimensions of patients with childhood-onset GH deficiency measured in adult age were smaller than those of control subjects, despite long-term GH replacement therapy during childhood. A second course of GH treatment during adulthood caused a significant increase in the estimated LV mass index in patients with both isolated and multiple pituitary hormone deficiency. (Am Heart J 2003;145:549-53.)     

Treatment of acromegaly improves myocardial abnormalities

Background Treatment for acromegaly decreases left ventricular (LV) mass, but it is not clear whether diastolic dysfunction is also reversible. With Doppler echocardiography, before and after effective therapy, we assessed the LV morphology and function of patients with acromegaly who were free of complications. Methods In 15 patients with active acromegaly (age range, 33.4 ± 9.3 years), we compared LV Doppler echocardiographic indices, before and after transsphenoidal surgery or radiotherapy or before and after both procedures, noting a significant drop in plasma levels of growth hormone (<2.0 ng/mL after oral glucose tolerance testing). Patients did not have arterial hypertension, diabetes mellitus, thyroid dysfunction, or coronary artery disease. Occasionally, in this series, patients had no symptoms of heart failure, and patients who underwent treatment with somatostatin analog drugs were not included because they did not have a significant hormonal drop. The follow-up period after hormonal control was 2.7 ± 1.7 years. We also studied 15 healthy control subjects matched for age, sex, and body surface area. Results Patients with acromegaly compared with healthy control subjects had increased LV mass index, relative wall thickness, and deteriorated diastolic function. After therapy, most of the abnormalities improved: LV mass index (104 ± 21 g/m² × 87 ± 21 g/m²; P <.01), LV relative wall thickness (0.40 ± 0.06 × 0.35 ± 0.04; P <.01), proto/telediastolic transmitral peak flow velocity ratio (1.17 ± 0.33 × 1.49 ± 0.34; P <.001), and isovolumetric relaxation period (126 ± 18 ms × 113 ± 13 ms; P <.05). Conclusion Treatment of acromegaly in patients without clinical heart failure improves both LV morphology and diastolic function. Avoidance of progression to more advanced forms of acromegalic cardiomyopathy should be possible. (Am Heart J 2002;143:873-6).     

Losartan treatment and left ventricular filling during volume loading in patients with dilated cardiomyopathy

Background Patients with mild heart failure show a reduction in preload reserve mechanism during volume expansion. At this time, the effects of volume expansion on left ventricular (LV) diastolic filling in this subset of patients have not been well characterized. Methods We evaluated the effects of acute volume loading on Doppler parameters of LV filling in 10 healthy control subjects and in 12 patients with idiopathic dilated cardiomyopathy (DCM). In patients with DCM, the effects of losartan on diastolic adaptation to volume load were also investigated. Results During volume loading, the healthy control subjects showed a decrease in isovolumic relaxation time (F = 5.3, P < .05) but an increase in the LV peak filling rate (F = 52.9, P < .001) and velocity time integral of both systolic (F = 72.8, P < .001) and diastolic (F = 4.6, P < .05) pulmonary venous flow. In patients with DCM, isovolumic relaxation time decreased more than in control subjects (F = 8.1, P < .01), and the deceleration time of the early mitral wave was reduced (F = 26.3, P < .001). Furthermore, the duration of pulmonary venous flow reversal exceeded that of mitral flow at atrial contraction (F = 28.5, P < .001). After treatment with losartan, the deceleration time of early mitral wave remained unchanged, and the duration of pulmonary venous flow reversal at atrial contraction did not exceed that of mitral flow; thus, a significant treatment effect was detectable (F = 5.6, P < .05; and F = 6.6, P <.05, respectively). Conclusions Control subjects respond to volume load with enhancement in early LV filling, whereas patients with DCM show an increase of LV filling pressure. Diastolic adaptation to volume load improves in patients with DCM after treatment with losartan. (Am Heart J 2002;143:433-40)     

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

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

Randomized,double-blind,placebo-controlled long-term study of isosorbide-5-mononitrate therapy in patients with left ventricular dysfunction after acute myocardial infarction

Background Nitrates are often administrated with a variety of other pharmacologic agents in the management of chronic heart failure (CHF). However, limited information is available concerning the long-term effects in patients with evidence of left ventricular (LV) dysfunction after acute myocardial infarction (AMI) already treated with standard heart failure therapy.Methods In a randomized, double-blind, placebo-controlled trial, we evaluated the effects of a 60 mg dose of isosorbide-5-mononitrate (IS-5-MN) given daily for 11 months to 47 patients with clinical or echocardiographic evidence of left ventricular dysfunction after acute myocardial infarction. Forty-five patients received a placebo.Results Invasive hemodynamic measurements did not show any difference between the treatment regimens. Overall changes in echocardiographic measurements were not significantly different between IS-5-MN therapy and the placebo groups. However, in a prespecified subgroup with left ventricular ejection fraction ≤40% at baseline, IS-5-MN therapy resulted in a lesser increase of end-diastolic volume index than the placebo (P = .047). IS-5-MN significantly reduced the serum concentration of atrial natriuretic peptide (mean 20.0 pmol/L, 95% CI 7.7-32.3, P = .002), whereas the placebo did not (P = .041 for the difference between the groups). The proportion of patients taking diuretics was significantly reduced in the IS-5-MN group, from 30 of 44 to 20 of 44 (P = .02), but not with placebo, which remained at 27 of 43 (P = 1.0, with P = .048 for the difference between the regimens).Conclusions Oral, long-term IS-5-MN therapy resulted in lower atrial natriuretic peptide levels and reduced the need for additional diuretics. Less LV dilatation was observed in patients with more severe LV dysfunction at baseline. (Am Heart J 2003;145:e1.)     

Lack of association of angiotensin-converting enzyme and angiotensinogen genes polymorphisms with left ventricular structure in young normotensive men

Left ventricular (LV) hypertrophy is a strong predictive factor for cardiovascular morbidity and mortality. LV structure and function are influenced by many variables, including genetic background. The potential role of gene polymorphisms of different components of the renin angiotensin system remains controversial. The aim of this study was to determine the influence of deletion/insertion (D/I) polymorphism of the angiotensin-converting enzyme (ACE) gene and M235-->T polymorphism of the angiotensinogen (AG) gene on left ventricular morphology and function in young normotensive men. The study included 110 normotensive healthy males (mean age 24 +/- 4 years, age range 18 to 34 years) who were assessed by echocardiography for LV structure and function. In all subjects ACE D/I polymorphism was evaluated using a polymerase chain reaction (PCR) method. M235-->T polymorphism assessment was available in 98 individuals. Significant differences between groups according to ACE I/D or AG M235-->T polymorphisms were not found for parameters of LV morphology or for parameters of systolic and diastolic function. When subjects with DD or ID genotypes were grouped, their LV mass index was higher than that in subjects with II genotypes (86 +/- 14 vs 79 +/- 15, r = 0.033, p = 0.05). There were no significant differences among other variables. In a population of young normotensive men where the influence of confounding variables such as age, gender and associated pathological conditions is minimized, the gene polymorphisms of ACE I/D and AG M235-->T are not important determinants of LV structure and function.     

Effects of sibutramine on ventricular dimensions and heart valves in obese patients during weight reduction

Background Obesity enhances hemodynamic alterations that predispose to a subsequent increase in left ventricular (LV) wall stress leading to LV hypertrophy. In obese subjects, weight reduction regresses LV mass (LVM), regardless of blood pressure. Sibutramine can increase blood pressure and heart rate, which may attenuate the reductions in LVM associated with weight loss. Methods Outpatients (n = 184, age 18-65 y, body mass index ≥30 to <40 kg/m²) were randomly assigned to 6 months of once daily double-blind treatment with sibutramine 10 mg or 20 mg, or placebo. LV dimensions, status and function of the valves, weight loss, blood pressure, heart rate, and electrocardiogram were assessed. Results For end point data sets, the mean ± SD LVM index (LVM/height) changes were −3.0 ± 11.9 g/m for placebo (n = 56), −4.4 ± 10.7 g/m for sibutramine 10 mg (n = 61), and −4.3 ± 10.9 g/m for sibutramine 20 mg (n = 56). The reductions observed in the sibutramine groups were statistically significant compared with baseline (P < .01), but pairwise comparison results with placebo were not statistically significant. There was no difference in overall status of the cardiac valves. A statistically significant greater weight loss was found in patients on both doses of sibutramine compared with placebo (P < .001). No statistically significant differences between the groups were observed in respect to blood pressure and electrocardiographic intervals, but a statistically significant increase in pulse rate (7 beats/min) was noted for patients with sibutramine treatment. Conclusion A 6-month treatment with sibutramine does not affect ventricular dimensions, heart valves, and electrocardiogram variables. (Am Heart J 2002;144:508-15.)     

Prognostic value of QT interval and QT dispersion in patients with left ventricular systolic dysfunction: results from a cohort of 2265 patients with an ejection fraction of < or =40%

Background Increased QT interval and QT dispersion have been associated with higher mortality in population-based studies and in patients with myocardial infarction. However, the prognostic significance of these measurements in patients with left ventricular (LV) systolic dysfunction is not clear.Methods and Results Rate corrected QT interval (QTc) and QT dispersion (QTd) were measured by means of an automated method from digitized echocardiograms in 2265 patients with an LV ejection fraction ≤40% and were related to survival. Increased QTc was strongly related to mortality in the whole group and in subsets on the basis of age and the level of LV systolic dysfunction. There was a graded increase in mortality rate with an increase in QTc. The effect of QTc on mortality was incremental to the effects of age and ejection fraction. QT interval was measurable in ≥6 leads in 1193 patients in whom QTd was computed. QTd higher than the mean value of 35 ms was associated with an increase in all cause mortality (P = .04). Its mortality impact was most pronounced in the older patients, patients with more severe LV dysfunction, and patients with increased QTc.Conclusions Both QTc prolongation and increased QTd are associated with higher mortality rate in patients with moderate and severe LV dysfunction. (Am Heart J 2003;145:132-8.)     

Association between angiotensin I-converting enzyme gene insertion/deletion polymorphism and mitral valve prolapse syndrome

Background Some studies have reported that patients with mitral valve prolapse syndrome (MVPS) also have a disorder in the autonomic or neuroendocrine function, which can cause a host of related symptoms. A potential role of the renin-angiotensin system in the pathogenesis of MVPS has been addressed. However, the role of angiotensin I-converting enzyme (ACE) genetic variant in MVPS has not been studied. We therefore performed a case-control study investigating the possible relation between ACE gene polymorphisms and MVPS in Taiwan Chinese.Methods We studied 100 patients with MVPS diagnosed by echocardiography and 100 age- and sex-matched normal control patients. ACE gene insertion/deletion (I/D), A-240T, and G2350A polymorphisms were identified by polymerase chain reaction-based restriction analysis.Results There was a significant difference in the distribution of ACE I/D genotypes (P = .003) and allelic frequencies (P = .001) between MVPS cases and control patients. An odds ratio for the risk of MVPS associated with the ACE II genotype was 2.14 (95% CI 1.20-3.80 ). An odds ratio for the risk of MVPS associated with ACE I allele was 1.96 (95% CI 1.30-2.97). The A-240T and G2350A polymorphisms of the ACE gene showed no association with MVPS (P = .20, P = .13, respectively).Conclusions This study showed that patients with MVPS have a higher frequency of ACE II genotype, which supports a role of the ACE I/D gene polymorphism in determining the risk of MVPS among the Chinese population in Taiwan. (Am Heart J 2003;145:169-73.)     

Deceleration time of early filling in patients with left ventricular systolic dysfunction: functional and prognostic independent value

Background Although diastolic function parameters have been mentioned as significant predictors of functional capacity and prognosis in patients with left ventricular (LV) systolic dysfunction, it has not been fully elucidated whether they keep an independent predictive value when multiple parameters from a wide variety of examinations are considered. Methods We prospectively studied 60 patients with New York Heart Association (NYHA) class II-IV chronic heart failure symptoms and LV ejection fraction <0.4. At the time of entry into the study, demographic data and functional class were obtained, and usual Doppler echocardiographic, radionuclide ventriculographic, cardiopulmonary exercise testing and hemodynamic variables were determined. Deceleration time of early filling (DT) and NYHA functional class were the only independent predictors of functional capacity as assessed by means of peak oxygen uptake (peak Vo₂). Mean follow-up was 21 ± 6 months, and event-free survival was defined as the absence of cardiac death, urgent cardiac transplantation, or hospital admission requiring inotropic or mechanical support. Results Multivariate Cox analysis showed that DT (P = .008), peak Vo₂ (P = .01), and NYHA class (P = .02) were independent predictors of event-free survival at 1 year. Patients in the lowest tertile of DT (<130 ms) had a significantly lower event-free survival than patients in the intermediate (44% vs 80%, P = .03) and in the highest tertile (44% vs 83%, P = .02). Patients with both a DT <130 milliseconds and a peak Vo₂ <14 mL/kg/min had the highest rate of events at 1 year (83% vs 22% for the remaining patients, relative risk 3.75, P < .001). Conclusions In patients with LV systolic dysfunction, DT is a powerful independent predictor of functional capacity and prognosis among a wide variety of variables. A shortened DT (<130 ms) identifies a subgroup of patients with a worse outcome, especially when combined with a reduced peak Vo₂ (<14 mL/kg/min). (Am Heart J 2002;143:1101-6.)     

Efficacy and time-efficiency of a "sonographer-driven" contrast echocardiography protocol in a high-volume echocardiography laboratory

Background Contrast echocardiography (CE) has not gained widespread use despite numerous studies demonstrating its efficacy in the assessment of left ventricular (LV) function. Methods We sought to determine whether CE could be used in a high-volume echocardiography laboratory in a clinically effective and time efficient manner. We implemented a protocol with a feasibility phase and an established phase. Cost-benefit analyses were done on the basis of time use. Results During the feasibility and established phases, data on 119 and 672 patients, respectively, were obtained. After a “sonographer-driven” protocol, contrast studies represented 7% to 8% of the total number of routine transthoracic and stress studies. Stress studies accounted for only 15% of the total number of contrast studies. Obesity was the most common indication for contrast use. LV visualization indices and wall thickening assessment, as evaluated by 2 blinded readers, were significantly improved with CE compared with second harmonic imaging alone. The time to make the decision to use CE and the time taken to administer contrast decreased significantly from the feasibility phase to the established phase (8.3 ± 5 vs 7.6 ± 5 min, P < .01, and 13.4 ± 10 vs 10.2 ± 5 min, P < .001, respectively). On the basis of time use only, a cost analysis indicated that savings were obtained at a 10-minute reduction in study time. Conclusions A “sonographer-driven” CE protocol for LV assessment is feasible in high-volume echocardiography laboratories. It is clinically effective because it significantly improves LV global and regional wall motion visualization. A “sonographer-driven” CE protocol can reduce decision and administration times substantially, thus making CE time-efficient. (Am Heart J 2003;145:535-41.)     

Association of the ScaI atrial natriuretic peptide gene polymorphism with nonfatal myocardial infarction and extent of coronary artery disease

Background There is growing evidence from recent studies that atrial natriuretic peptide (ANP) plays an important part in coronary blood flow regulation and in atherosclerosis. Transition T2238→C in the atrial natriuretic peptide (ANP) precursor gene, which leads potentially to the translation of ANP with 2 additional arginines, has been suggested to be associated with salt-sensitive hypertension. According to our knowledge, this study is the first to look for the potential association of the ScaI ANP gene polymorphism with the history of nonfatal myocardial infarction and the extent of coronary artery disease (CAD).Methods The study was performed in 847 consecutive, white patients (719 men and 128 women) with significant coronary artery stenosis confirmed by means of elective coronary angiography (at least 1 coronary artery with ≥50% lumen narrowing). Screening for the T2238→C substitution was performed by means of polymerase chain reaction of genomic DNA, followed by ScaI digestion and agarose gel electrophoresis.Results We found a significant association of the A2A2 ScaI ANP genotype with a higher incidence of positive history of nonfatal myocardial infarction (odds ratio 1.85, 95% CI 1.33-2.58) and multiple-vessel CAD (odds ratio 1.45, 95% CI 1.02-2.06). The ScaI ANP genotype distribution did not differ with age, sex, body mass index, plasma lipids, hypertension, diabetes mellitus, and family history of CAD in studied groups.Conclusions Our results suggest that the ScaI ANP polymorphism may be associated with nonfatal myocardial infarction and the extent of CAD. However, the precise mechanism of this association remains to be determined. (Am Heart J 2003;145:125-31.)     

Association of the human minK gene 38G allele with atrial fibrillation: evidence of possible genetic control on the pathogenesis of atrial fibrillation

Background Human minK protein is the β-subunit of I_Ks potassium channel and plays an important role in cardiac cellular electrophysiology. We investigated the association between human atrial fibrillation and the polymorphism of minK gene (38G or 38S) with a case-control study. Methods We included 108 patients with atrial fibrillation and 108 control subjects. The case patients and control subjects were matched regarding age, sex, presence of valvular heart disease, and presence of left ventricular dysfunction. The genotype of minK was determined with polymerase chain reaction and restriction fragment analysis. Results The results showed an association between the minK 38G allele and atrial fibrillation. The odds ratios for atrial fibrillation in patients with 1 and 2 minK 38G alleles were 2.16 (95% CI 0.81-5.74) and 3.58 (95% CI 1.38-9.27), respectively, when compared with patients without minK 38G allele. In a logistic regression model, the odds ratio for atrial fibrillation was 1.80 (95% CI 1.20-2.71, P < .0046) for patients with 1 more minK 38G allele. Conclusion We report the association between the minK 38G allele and clinical atrial fibrillation. Our findings suggest possible genetic control on the pathogenesis of atrial fibrillation. (Am Heart J 2002;144:485-90.)     

Angiotensinogen gene polymorphism is associated with insulin resistance in nondiabetic men with or without coronary heart disease

Background Variants of the angiotensinogen gene may increase the risk of having arterial hypertension and coronary heart disease (CHD), but their effect on insulin resistance remains unknown.Methods We determined M235 and T174 allele status and fasting plasma glucose, insulin, and lipids values in nondiabetic men with CHD documented on angiography (n = 102) and in a control group (n = 145). Plasma glucose and insulin responses to 75 gm oral glucose tolerant test and insulin resistance as measured by an insulin suppression test were also carried out in 46 (45%) patients with CHD and in 73 (50%) members of a control group.Results We found no association between M235T status and blood pressure, fasting plasma glucose, insulin, most of the lipids values, and insulin resistance in patients with CHD and normal subjects. Nevertheless, compared with individuals with homozygotes T174, subjects with heterozygotes T174M were associated with greater glucose and insulin response to the oral glucose tolerance test and insulin resistance indicated by higher steady state plasma glucose concentrations in patients with CHD (14.7 ± 0.9 vs 11.3 ± 0.7 mmol/L, p < 0.04). Similar findings were found in the control group, with higher steady-state plasma glucose values in individuals with heterozygotes T174M than in those with homozygotes T174 (10.1 ± 1.4 vs 7.7 ± 0.4 mmol/L, p < 0.05).Conclusion We suggest that the angiotensinogen T174M allele might be associated with insulin resistance in nondiabetic men with and without CHD. (Am Heart J 1998;136:125-31.)     

Effect of beta2-adrenergic receptor functioning and increased norepinephrine on the hypercoagulable state with mental stress

Background Procoagulant stress responses may contribute to atherosclerosis development and acute coronary thrombosis. In the present study, we examined the role of β₂-adrenergic receptor function and plasma catecholamines in the stress-induced increase in the 2 hypercoagulability markers thrombin-antithrombin III (TAT) complex and fibrin D-dimer (DD). Methods Lymphocyte β₂-adrenoreceptor sensitivity and density were assessed at rest, and plasma levels of TAT, DD, epinephrine, and norepinephrine were measured at rest and in response to a standardized mental stress task in 19 normotensive and mildly hypertensive nonmedicated subjects (mean age 38 years, age range 29 to 48 years). Results The stressor elicited a significant increase in TAT (P = .024), DD (P = .026), and norepinephrine (P = .005). Resting β₂-adrenoreceptor sensitivity (isoproterenol-stimulated cyclic adenosine monophosphate production) plus the norepinephrine change scores (stress minus rest) accounted for 59% of the variance in the absolute TAT increase in response to stress (P = .001). Hypertension status and demographic variables such as sex did not influence the results. Conclusions Acute mental stress may trigger a hypercoagulable state evidenced by increased thrombin activity and increased fibrin turnover. β₂-Adrenergic receptor sensitivity and plasma catecholamine activity may mediate the procoagulant response to acute stressors. These mechanisms may help explain the adverse impact of mental stress on the cardiovascular system. (Am Heart J 2002;144:68-72.)     

Relationship between coronary angioplasty laboratory volume and outcomes after hospital discharge

Background Although an inverse association has been established between short-term complications of percutaneous coronary interventions (PCIs) and the volume of angioplasty procedures performed by catheterization laboratories, no data are available on the association between laboratory volume and long-term outcomes. Methods A cohort study of 25,222 patients undergoing PCI in 43 laboratories in Pennsylvania from October 1994 to December 1995 was performed by use of the Pennsylvania Health Care Cost Containment Council database. The association of laboratory volume with inhospital, 1-month, and 6-month events was estimated by use of multivariable analyses adjusting for patient and procedural characteristics. Results Although a higher volume of procedures was associated with reduced inhospital coronary bypass ([CABG] 0.6 odds ratio [OR] for ≥400 vs <400 PCIs/year; 95% CI 0.4, 0.8), it was not associated with CABG occurring within 1 month after discharge (P = .71; OR 1.0, 95% CI 0.6, 1.7). Laboratory volume was also not significantly associated with postdischarge revascularization (PCI or CABG) at 1 month (P = .58; OR 1.1, 95% CI 0.8, 1.4) or 6 months (P = .47; OR 1.04, 95% CI 0.91, 1.19). In addition, laboratory volume was not associated with rates of myocardial infarction (P = .14), death (P = .28), or the combined outcome of PCI, CABG, myocardial infarction, or death (P = .90) at 1 month after hospital discharge. Conclusions Although our study confirmed the volume/complication relationship for inhospital CABG, it did not reveal an association between volume and postdischarge events. These results suggest that inhospital complications will remain the standard for assessing laboratory volume and that selective use of higher-volume laboratories may not improve long-term outcomes. (Am Heart J 2002;143:833-40.)     

The cardiac component of cardiac cachexia

Background Recent evidence suggests the importance of noncardiac mechanisms in the genesis of the syndrome of cardiac cachexia. This raises the question of the relative role of the heart itself in this syndrome. This study sought to assess the cardiac dimensions, mass, and function and changes in these parameters over time in patients with chronic heart failure with and without cachexia. Methods Doppler echocardiography was performed in 28 patients with nonedematous weight loss (>7.5% over a period of >6 months) compared with 56 matched patients without weight loss in a ratio of 1:2 (age 71 ± 13 vs 67 ± 8 years, P = .07; New York Heart Association class 2.9 ± 0.7 vs 2.6 ± 0.6, P = .08). In 18 cachectic and 35 noncachectic patients with previous echocardiographic recordings, we analyzed the changes in left ventricular (LV) dimensions and mass over time. Results Cardiac dimensions including LV diastolic (69 ± 9 mm vs 67 ± 13 mm) and systolic cavity diameter (58 ± 11 mm vs 55 ± 15 mm), LV mass (480 ± 180 g vs 495 ± 190 g), and LV systolic and diastolic function including fractional shortening (16% ± 10% vs 18% ± 10%), isovolumic relaxation time (29 ± 22 ms vs 36 ± 27 ms), and E/A ratio (2.7 ± 1.6 vs 3.3 ± 2.9) did not differ between cachectic and noncachectic patients (all P > .1). By analyzing changes in LV mass over time, we found an increase (>20%) in 2 (11%) cachectic and 14 (40%) noncachectic patients and a decrease in LV mass (>20%) in 9 (50%) cachectic and 8 (23%) noncachectic patients (χ² test, P < .05). Conclusions Although no specific cardiac abnormality could be detected echocardiographically in cachectic patients compared with patients with noncachectic chronic heart failure in a cross-sectional study, over time a significant loss of LV mass (>20%) occurs more frequently in patients with cardiac cachexia. (Am Heart J 2002;144:45-50.)