Potential role of coenzyme Q10 in facilitating recovery from statin-induced rhabdomyolysis.

Rhabdomyolysis is a rare, but serious complication of statin therapy, and represents the most severe end of the spectrum of statin-induced myotoxicity. We report a case where coenzyme Q10 facilitated recovery from statin-induced rhabdomyolysis and acute renal failure, which had initially persisted despite statin cessation and haemodialysis. This observation is biologically plausible due to the recognised importance of coenzyme Q10 in mitochondrial bioenergetics within myocytes, and the fact that statins inhibit farnesyl pyrophosphate production, a biochemical step crucial for coenzyme Q10 synthesis. Coenzyme Q10 is generally well tolerated, and may potentially benefit patients with statin-induced rhabdomyolysis.

Take heart: bariatric surgery in obese patients with severe heart failure. Two case reports.

Bariatric surgery may be an effective treatment for obese heart failure patients, enabling access to cardiac transplantation and/or improvement of symptoms. We report the outcomes of two morbidly obese patients with end-stage heart failure, where obesity precluded cardiac transplantation and underwent laparoscopic gastric banding. A 42 year-old male with idiopathic dilated cardiomyopathy weighing 124.4 kg (BMI 42 kg/m(2)) lost 34 kg and was successfully transplanted 11 months later. A 40 year-old woman with familial dilated cardiomyopathy weighing 105 kg (BMI 40 kg/m(2)) lost 14 kg with sufficient symptomatic resolution to no longer require cardiac transplantation. In selected patients with severe heart failure and concomitant morbid obesity, bariatric surgery may be a reasonable treatment option.

Ageing, hypertension and aortic valve stenosis - Understanding the series circuit using cardiac magnetic resonance and applanation tonometry.

BACKGROUND: Aortic stenosis (AS) is no longer considered to be a disease of fixed left ventricular (LV) afterload, but rather, functions as a series circuit, with important contributions from both the valve and vasculature. Patients with AS are typically elderly, with hypertension and a markedly remodelled aorta. The arterial component is sizeable, and yet, quantifying this to-date has been difficult to determine. We compared measurement of aortic pressure, flow and global LV load using a cardiac magnetic resonance (CMR)/applanation tonometry (AT) technique to uncouple ventriculo-arterial (VA) interactions. METHODS: 20 healthy elderly patients and 20 with AS underwent a CMR/AT protocol. CMR provided LV volume and aortic flow simultaneously with AT pressure acquisition. Aortic pressure was derived by transformation of the AT waveform. Systemic vascular resistance (SVR) and global LV load were determined as the relationship of pressure to flow in the frequency domain. Values from both cohorts were compared. RESULTS: AS patients were older (p â€‹< â€‹0.01) albeit with no significant difference in brachial or central aortic pressure. SVR (14228 vs 19906 â€‹dyne â€‹s.cm-3; p â€‹= â€‹0.02) and load (740 vs 946 â€‹dyne â€‹s.cm-3; p â€‹= â€‹0.02) were higher in patients with AS, whilst aortic peak flow velocity was lower (38 vs 58 â€‹cm/s; p â€‹< â€‹0.01). CONCLUSIONS: Quantification of aortic pressure, flow velocity and global LV load using a simultaneous CMR/AT technique is able to demonstrate the progressive effects of hypertension and aortic stiffening with advanced age and valvular stenosis. This technique may help to better identify future patients at risk of VA coupling mismatch after correction of AS.

In vivo tissue reaction within the outflow conduit in patients supported by HeartWare HVAD.

AIM: The frequency, extent, and nature of tissue ingrowth within the continuous-flow left ventricular assist device (cf-LVAD) outflow conduit has not been systematically assessed. We sought to characterize conduit histopathology at explantation in a cohort of patients with HeartWare ventricular assist device (HVAD) and assess the effect on pump performance. METHODS: Patients undergoing routine histopathological assessment of a HeartWare HVAD removed at transplantation or autopsy were assessed. Outflow conduits were examined macroscopically, and visible tissue was sectioned for microscopic evaluation. In patients who had undergone prior contrast-enhanced computerized tomography (CT) with HVAD in situ, the outflow conduit was measured at the aortic anastomosis and 5 cm proximal to the anastomosis, in the axial and sagittal planes. All patients had their pump flow, flow pulsatility, current, and speed determined from log files examined at 1, 3, 6, 9, and 12 months after LVAD implantation. RESULTS: Twenty-five consecutive patients were assessed (24 LVAD, 1 biventricular assist device (BiVAD)). Of the 26 outflow grafts assessed, there was evidence of tissue ingrowth reaction in 24 (92%) grafts. The most common site was the distal anastomosis (18/24, 75%), with the graft body involved in 14 of 24 (58%) grafts. Microscopic evaluation revealed acute inflammatory infiltrate in 4 of 24 grafts (17%), chronic inflammatory infiltrate in 14 of 24 (58%), neointima formation in 18 of 24 (75%) and fibrosis in 18 of 24 (75%) grafts. The median depth of tissue was 1 mm (range, 0-2 mm). The mean conduit diameter was 9.5 ± 0.6 mm at the aortic anastomosis compared with 11.1 ± 0.5 mm 5 cm proximal to the anastomosis (p < 0.0001). In patients with unchanged pump speed one month after implantation, analysis of log files revealed a significant (5.8 ± 8.6%) decrease in pump flow (4.65 ± 0.86 vs 4.38 ± 0.92 L/min, p = 0.01) and flow pulsatility (5.00 ± 1.10 vs 4.16 ± 1.05 L/min, p = 0.006). CONCLUSIONS: There is evidence of tissue formation within the HVAD outflow conduit in the vast majority of patients, most commonly located at the aortic anastomosis. This is associated with significantly decreased pump flow over time.

Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease.

BACKGROUND: The increased incidence of coronary artery disease in men compared with premenopausal women suggests a detrimental role of male hormones on the cardiovascular system. However, testosterone has direct relaxing effects on coronary arteries in animals, as shown both in vitro and in vivo. The effect of testosterone on the human coronary circulation remains unknown. METHODS AND RESULTS: We studied 13 men (aged 61+/-11 years) with coronary artery disease. They underwent measurement of coronary artery diameter and blood flow after a 3-minute intracoronary infusion of vehicle control (ethanol) followed by 2-minute intracoronary infusions of acetylcholine (10(-7) to 10(-5) mol/L) until peak velocity response. A dose-response curve to 3-minute infusions of testosterone (10(-10) to 10(-7) mol/L) was then determined, and the acetylcholine infusions were repeated. Finally, an intracoronary bolus of isosorbide dinitrate (1000 microgram) was given. Coronary blood flow was calculated from measurements of blood flow velocity using intracoronary Doppler and coronary artery diameter using quantitative coronary angiography. Testosterone significantly increased coronary artery diameter compared with baseline (2.78+/-0. 74 mm versus 2.86+/-0.72 mm [P=0.05], 2.87+/-0.71 mm [P=0.038], and 2.90+/-0.75 mm [P=0.005] for baseline versus testosterone 10(-9) to 10(-7) mol/L, respectively). A significant increase in coronary blood flow occurred at all concentrations of testosterone compared with baseline (geometric mean [95% CI]: 32 [25, 42] versus 36.3 [27, 48] (P=0.006), 35.3 [26, 47] (P=0.029), 36.8 [28, 49] (P=0.002), and 37 [28, 48] (P=0.002), mL/min for baseline versus testosterone 10(-10) to 10(-7) mol/L, respectively). No differences existed in coronary diameter or blood flow responses to acetylcholine before versus after testosterone. CONCLUSIONS: Short-term intracoronary administration of testosterone, at physiological concentrations, induces coronary artery dilatation and increases coronary blood flow in men with established coronary artery disease.

Gender-related differences in the central arterial pressure waveform.

OBJECTIVES: This study investigated the effect of age and gender on central arterial hemodynamic variables derived from noninvasive tonometric carotid pressure waveforms. BACKGROUND: Women have a greater age-related increase in left ventricular (LV) mass than do men and are more likely to experience symptomatic heart failure after infarction despite their higher ejection fraction. In studies of these changes, ventricular afterload is incompletely defined by brachial blood pressure (BP) measurements. We hypothesized that there exist gender differences in pulsatile vascular load, as revealed by pressure waveform analysis, which may produce suboptimal afterload conditions in women. METHODS: Data from 350 healthy normotensive subjects (187 female) aged 2 to 81 years were analyzed in decade groups. Augmentation index (AIx, the difference between early and late pressure peaks divided by pulse pressure) was used as an index of pulsatile afterload, and the ratio of diastolic to systolic pressure-time integral gave a subendocardial viability index. Heart rate, BP, ejection duration and maximal rate of pressure rise (dP/dt(max)) were also determined. RESULTS: Male subjects had a slightly higher systolic pressure until age 50. Female subjects had higher systolic pressure augmentation after the 1st decade, a difference that was significant after age 30 (p < 0.005 for each decade). In both males and females there was a strong age dependence for AIx (r = 0.77, p < 0.001 for females, r = 0.66, p < 0.001 for males). Although males had a larger body size and higher systolic pressure, systolic pressure-time integral was similar in males and females across all age groups. Diastolic pressure-time integral was consistently lower in females because of their shorter diastolic period. Subendocardial viability index was lower in females across the entire group. Differences in stature and heart rate may contribute to these findings. CONCLUSIONS: These new data may help to explain previous findings in women of an age-related increase in LV mass and excess symptomatic heart failure that are not explained by differences in brachial BP.

Effect of inhaled nitric oxide on normal human left ventricular function.

OBJECTIVES: This study determined the effects of inhaled nitric oxide (NO) on load-independent indexes of normal human left ventricular (LV) function. BACKGROUND: Inhaled NO is a potent and selective pulmonary vasodilator. However, when it is used in patients with congestive heart failure, the decrease in pulmonary vascular resistance (PVR) is often associated with an increase in pulmonary capillary wedge pressure. NO has been shown to have a negative inotropic action, but it is not known whether it affects LV chamber function when delivered by inhalation. METHODS: Eleven subjects (51 to 69 years old) with normal LV function (mean ejection fraction 72% [range 60% to 80%]) were studied. Four patients had concomitant coronary artery disease. Pressure-volume loop recordings were used to determine end-systolic and end-diastolic pressure-volume and preload recruitable stroke work relations. NO was delivered at 20 ppm for 10 min. In an additional group of patients with normal LV function, PVR (n = 5) and NO metabolites (n = 9) were measured. RESULTS: There was no effect of inhaled NO on steady state LV pressures, volumes, contractility, contraction duration, active relaxation (time constant of relaxation, peak negative first derivative of left ventricular pressure), diastolic compliance or PVR. NO metabolites (methemoglobin and nitrate) were present in the LV cavity at the same concentration as right atrial venous blood, suggesting inactivation of free NO before arrival in the LV chamber. This study had a power of 0.995 to detect a 5% change in contractility (slope of preload recruitable stroke work relation) for alpha = 0.05, based on the multiple linear regression model used. CONCLUSIONS: These results indicate that 20 ppm of inhaled NO does not have significant effects on normal LV function. This lack of effect may be due in part to rapid inactivation of free NO in transit to the heart.

Effects of postmenopausal hormone replacement therapy on central abdominal fat, glycemic control, lipid metabolism, and vascular factors in type 2 diabetes: a prospective study.

OBJECTIVE: To examine the effects of hormone replacement therapy (HRT) on lipid metabolism, glycemic control, total body and central abdominal fat, blood pressure (BP), and arterial pulse wave velocity (APWV) in overweight postmenopausal females with type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a 12-month prospective study of 14 subjects (mean +/- SD age 57.5+/-5.6 years, BMI 29.5+/-4.8 kg/m2) randomized to 6 months of observation or HRT before crossover. HRT consisted of 2 months of conjugated equine estrogen (CEE) 0.625 mg daily, followed by 4 months CEE and medroxyprogesterone 5 mg daily. Measures included anthropometry, fasting glucose, insulin, HbA1c, total and HDL cholesterol, triglycerides, apolipoprotein B, LDL particle size, nonesterified fatty acids (NEFA), sex hormone-binding globulin, resting energy expenditure (REE), total and central abdominal fat (by dual-energy X-ray absorptiometry), resting BP, APWV (by applanation tonometry), physical activity, well-being, and sexual function. RESULTS: Six months of HRT resulted in significant reductions in waist-to-hip ratio (-0.03+/-0.01 vs. 0.01+/-0.009, P = 0.007), HbA1c (-0.34+/-0.24 vs. 0.6+/-0.4%, P = 0.04), total cholesterol (-0.6+/-0.1 vs. 0.2+/-0.2 mmol/l, P = 0.001), central abdominal fat (-175+/-51 vs. -24+/-56 g, P = 0.05), and improved physical functioning (P = 0.05), compared with observation. There was a minor increase in REE with HRT (33+/-23 vs. -38+/-23 kJ/day, P = 0.04). Total fat mass, fasting glucose, insulin, triglyceride, apolipoprotein B, NEFA, resting BP, APWV, and physical activity were unchanged. CONCLUSIONS: Postmenopausal HRT in these overweight women with type 2 diabetes was associated with a reduction in central adiposity and improvement in lipid metabolism and glycemic control without deterioration in weight status or cardiovascular parameters measured. Whether HRT-induced improvements in these cardiovascular risk factors result in lower long-term cardiovascular morbidity and mortality, as observed in nondiabetic women, awaits further study.

Gender-related differences in left ventricular chamber function.

OBJECTIVES: While women have lower rates of atherosclerotic disease than men, they are more likely to suffer cardiac failure following infarction or cardiac surgery, despite typically having a greater left ventricular (LV) ejection fraction. We hypothesised that gender differences in systolic chamber function and ventriculo-vascular coupling may contribute to these clinical findings. METHODS: LV chamber function was determined in a cohort of 30 patients (16 women) aged 48-75 years with normal LV function using pressure-volume loops obtained by simultaneous conductance catheter volumetry and micromanometer pressure. End-systolic and end-diastolic pressure volume (ESPVR, EDPVR) and preload recruitable stroke work relations (PRSWR) were derived. Results were analysed according to gender, and the effects of body size and chamber dimensions were examined. RESULTS: The groups were closely matched for age (60+/-6 vs. 60+/-8 years) and co-morbid conditions. Women had higher end-systolic blood pressure (139.7+/-21.1 vs. 123.6+/-12.6 mmHg, P=0.001), and smaller LV cavity volume (end-diastolic volume 96.4+/-30.6 vs. 139+/-30.7 ml, P=0.001). Women had significantly higher LV end-systolic elastance (Ees, 2.65+/-0.10 vs. 1.96+/-0.09 mmHg ml(-1), P<0.002), arterial elastance (2.41+/-1.13 vs. 1.54+/-0.55 mmHg ml(-1), P=0.01) and lower passive LV diastolic compliance (slope EDPVR, 6.12+/-0.37 vs. 10.0+/-0.50 ml mmHg(-1), P<0.001). While there was a strong relationship between end-systolic elastance and chamber volume (r=0.69, P<0.001), gender differences in chamber function all persisted after indexing to body size. Higher LV systolic function in women was also shown in PRSWR analysis (slope, M(SW); 101.4+/-3.8 vs. 90.4+/-2.8 mmHg, P<0.05), which is independent of chamber size. After normalising volumes to resting diastolic volume, the greater systolic and diastolic elastance in women was accounted for. The ratio of end-systolic to arterial elastance, a measure of ventriculo-vascular coupling, was similar in women and men (1.19+/-0.40 vs. 1.54+/-0.30, respectively, P=0.23). CONCLUSIONS: This study demonstrates greater systolic chamber function and lower diastolic compliance in women. Within the range of chamber dimensions seen in patients with normal LV function, a strong relationship was found between cardiac size and end-systolic elastance. While these differences were not accounted for by indexing to body size, the greater ventricular elastance in women was removed after normalising to chamber size. Despite differences in resting ventricular elastance, appropriate ventriculo-vascular coupling was maintained in both genders as the greater end-systolic elastance in women was matched by similarly elevated arterial elastance.

Inhaled nitric oxide in cardiology practice.

Inhaled nitric oxide allows selective pulmonary vasodilatation with rapidity of action. It is effective in the acute post-operative management of pulmonary hypertension in cardiac surgical patients and is also valuable in assessing the pulmonary vasodilator capacity in patients with chronic pulmonary hypertension. This review examines the current role of inhaled nitric oxide in cardiac medicine, discussing issues concerning its administration and toxicity, as well as a summary of clinical studies in cardiac patients. New roles, as a modifier of platelet and leukocyte function, post-thrombolysis and following lung transplantation are described. New agents and alternative therapies, which prolong pulmonary activity, are also discussed.

Tamoxifen is not detrimental to endothelial function in postmenopausal women with breast cancer.

BACKGROUND: Tamoxifen has mixed estrogen agonist and antagonist properties in estrogen-regulated tissues. Its effect on the cardiovascular system is not well defined. We carried out a study to investigate the effect of tamoxifen on peripheral vascular endothelial function. METHODS: Three groups of postmenopausal women (median age, 56 years; range, 39 to 69 years) with breast cancer were studied. Patients in group 1 (n = 10) were newly diagnosed with breast cancer and studied before and after 4 weeks treatment with tamoxifen. Group 2 women (n = 6) had been receiving long-term tamoxifen (3 to 5 years) and were studied while taking tamoxifen and 4 weeks after stopping it. The final group of 6 subjects were in remission from primary breast cancer and were not receiving or had previously received tamoxifen. Ultrasound assessments of endothelial function were done before and 4 weeks after the initiation or discontinuation of tamoxifen with the nontreatment group acting as control. All ultrasound imaging was made by a single investigator blinded to the therapeutic status of the subject. Brachial artery diameter was measured by ultrasound at baseline and 1 minute after reactive hyperemia. Flow-mediated reactivity (FMR) was defined as percent change in artery diameter from baseline 1 minute after reactive hyperemia. RESULTS: There was no change in FMR in patients before compared with 4 weeks after starting tamoxifen (4.06% +/- 1.44% vs 3.97% +/- 1.20%, respectively, mean +/- standard error of the mean [SEM], P =.97). There was no significant change in FMR on withdrawal from tamoxifen (1.84% +/- 1.98% vs -0.42% +/- 1.44% on tamoxifen vs off tamoxifen, mean +/- SEM, P =.36). FMR in subjects taking tamoxifen was no different from the control group (3.17% +/- 1.05% vs 3.16% +/- 0.91%, respectively, mean +/- SEM, P =.995). CONCLUSIONS: Tamoxifen does not appear to affect endothelial function in the short term in postmenopausal women with breast cancer.

Effect of hormone replacement therapy on non-invasive cardiovascular haemodynamics.

OBJECTIVE: To determine the detailed effects of hormone replacement therapy (HRT) on non-invasive haemodynamics, including an assessment of the effect on the pulsatile afterload assessed in terms of the augmentation index and pulse-wave velocity. DESIGN: A cross-sectional study of healthy postmenopausal women using carotid and radial tonometry and pulse-wave velocity measurements. SETTING: Community-based ambulatory women attending the menopause centre at a tertiary hospital. PATIENTS: Seventy postmenopausal women divided into those not currently being administered HRT (n = 38, aged 46-72 years) and those who were being administered a variety of HRT (n = 32, aged 49-67 years). METHODS: Central arterial pressure waveforms were measured using carotid applanation tonometry to derive the augmentation index and ejection duration. The arterial pulse-wave velocity was assessed using paired carotid, radial and dorsalis tonometry waveforms. RESULTS: Women being administered HRT had a significantly lower augmentation index (20.4 +/- 8.6 versus 27.0 +/- 10.2%, P = 0.005) and shorter ejection times (320 +/- 17 versus 329 +/- 18 ms, P = 0.037). There was no significant difference in brachial blood pressure (131/76 versus 129/77 mmHg). Women being administered HRT exhibited a greater reversal in the age-related loss of amplification which occurs owing to arterial stiffening. This amplification between central and peripheral systolic blood pressures was greater among women being administered HRT (5.3 +/- 6.2 versus 2.2 +/- 4.0 mmHg, P = 0.014). There was no difference in pulse-wave velocity between the two groups. CONCLUSIONS: HRT appears to improve the pulsatile vascular afterload by decreasing the augmentation of the late systolic blood pressure. This effect is not apparent from routine brachial cuff measurements, which, as a result, may underestimate haemodynamic benefits. Such effects may help to explain a portion of the improvement in cardiovascular morbidity found in other trials.

Testosterone enhances flow-mediated brachial artery reactivity in men with coronary artery disease.

Acute administration of high-dose testosterone in men with coronary artery disease improves endothelial function.

Inhaled nitric oxide in cardiology.

Inhaled nitric oxide (INO) allows selective pulmonary vasodilatation with rapidity of action. It is effective in the acute management of reversible pulmonary hypertension in cardiac medical and surgical patients and is also useful in assessing the pulmonary vasodilator capacity in patients with chronic pulmonary hypertension. This review will examine the role of INO in the management of cardiac patients, compared to alternatives where available. The use of INO in cardiac failure, post-operative cardiac patients, patients with congestive cardiac failure or congenital heart disease will also be reviewed. Newer alternatives with prolonged pulmonary activity and simpler administration are also discussed.

Effect of combination hormone replacement therapy on ambulatory blood pressure and arterial stiffness in diabetic postmenopausal women.

BACKGROUND: Diabetes mellitus negates the premenopausal gender benefit with respect to coronary artery disease. Whether hormone replacement therapy (HRT) offers any cardiovascular advantage to diabetic postmenopausal women is not known. Diabetic subjects have increased vascular load and abnormal 24-h blood pressure (BP) profiles. Hormone replacement therapy has been shown to improve indexes of arterial load in nondiabetic postmenopausal women as well as to restore circadian variation in BP. This aim of this study, therefore, was to determine prospectively whether HRT improved arterial stiffness and 24-h ambulatory BP profile in diabetic postmenopausal women. METHODS: Twelve diabetic postmenopausal women were studied. Six subjects were also hypertensive. Vascular load was characterized by carotid arterial pulse waveform analysis to calculate central augmentation index. All subjects also underwent 24-h BP monitoring. Subjects were studied before commencement of HRT and were then randomized to two groups. The first group was observed for 6 months and then given 2 months of estrogen alone, followed by 4 months of combination estrogen with progestin. The second group received the HRT regimen first, then were restudied after 6 months off HRT. RESULTS: The HRT did not affect either clinic or ambulatory BP. There were no changes in indexes of vascular load or pulse pressure, an indirect measure of arterial stiffness. There was a low rate of circadian variation in 24-h BP at baseline (55%), which was unaltered by HRT. CONCLUSIONS: The HRT was well tolerated. Despite evidence for a beneficial effect of HRT on indexes of arterial load and ambulatory BP previously reported in normal subjects, we found no change in this cohort of diabetic postmenopausal women.

Hereditary and environmental influences on arterial function.

1. With the ageing population and increasing heart failure, arterial function has been shown to contribute to cardiovascular risk because of its adverse effects on ventriculovascular coupling. Population studies have confirmed independent prognostic information of arterial stiffening on cardiovascular survival. 2. The term 'arterial function' encompasses a range of phenotypes, including measures of arterial structure/remodelling, measures of arterial wall mechanics, surrogate measures of stiffness and of wave reflection. There exists significant interaction between these measures and none is truly independent of the others. Added to this complexity is the recognition that, although arterial function has a strong genetic component, quantification requires a range of techniques from twin to family and population studies. 3. The contribution of heritability is often derived from statistical models with input from genomic scanning and candidate gene studies. Studies to date confirm a significant heritable component for the majority of phenotypes examined. However, it has also been recognized that the factors involved in blood pressure maintenance are likely to be separate to those in arterial structural degeneration with ageing. Candidate genes for arterial function go beyond those of the sympathetic and renin-angiotensin systems and include genes involved in signalling pathways and extracellular matrix modulation. 4. The present review examines the evidence for heritability of the major arterial function phenotypes with environmental and ageing modulation. A brief overview of the impact of atherosclerotic risk factors on arterial function is included.

Acute effects of 17beta-estradiol on ventricular and vascular hemodynamics in postmenopausal women.

Because premenopausal women have lower cardiovascular morbidity than postmenopausal women, it has been proposed that estrogen may have a protective role. Estrogen is involved in smooth muscle relaxation both through its specific receptor as well as through calcium channel blockade. This study examined the acute effect of estradiol on invasive cardiovascular hemodynamics in 18 postmenopausal women (age 62.6 +/- 7.6 years, means +/- SD). The effect of estradiol on left ventricular chamber performance was studied in 9 women using simultaneous left ventricular pressure-volume recordings. In a further group of 9 women, the acute effect of estradiol on arterial function was assessed using input impedance (derived from simultaneous aortic pressure and flow recordings), pressure waveform analysis, and pulse wave velocity. After 2 mg micronized 17beta-estradiol was administered, serum estradiol levels increased from 50.9 +/- 21.9 to 3,190 +/- 2,216 pmol/l, P < 0.0001. There was no effect of estradiol on either left ventricular inotropic or lusitropic function. There was no acute effect of estradiol on arterial impedance, reflection coefficient, augmentation index, or pulse wave velocity. There was a trend to decreased heart rate and cardiac output in both groups of 9 women. Because heart rate and cardiac output were common to both hemodynamic data sets, results for these parameters were pooled. Across all 18 women, there was a small but significant decrease in heart rate (69.2 +/- 10.4 vs. 67.2 +/- 9.9 beats/min, P = 0.02), as well as a significant decrease in cardiac output (4.82 +/- 1.77 vs. 4.17 +/- 1.56 l/min, P = 0.002). Despite achieving supraphysiological serum levels, this study found no significant effect of acute 17beta-estradiol on ventricular or large artery function.

Effect of sex hormones on cardiac mass.

Increased left-ventricular mass is an important cardiovascular risk factor for morbidity and mortality. Apart from obvious differences in cardiac size, the changes in left-ventricular mass in response to age and hypertrophic stimuli are very different in men and women. Whereas left-ventricular mass increases with age in apparently healthy women, it remains constant in men. Under increased cardiac loading conditions, such as hypertension or aortic stenosis, this disparity between sexes is even more striking. Findings are especially pronounced in people aged 50 years or older, in whom reproductive hormone concentrations have fallen. Whether the differences in left-ventricular mass changes are related to endogenous sex-hormone concentrations has never been shown. Androgens have anabolic effects on cardiac cells, and oestrogens have antiproliferative properties, we therefore postulate that the normal decline in endogenous sex hormones with age has contrary effects on ventricular mass in men and women in normal and pathological states.

Heritability of central systolic pressure augmentation: a twin study.

Less than 50% of the variance in left ventricular mass is explained by conventional factors such as age, blood pressure, and body size. Genetic influences may account for part of the unexplained variance. The central (aortic) pressure augmentation index has been suggested as a noninvasive measure of pulsatile load, which is a likely determinant of left ventricular mass. We quantified the genetic influence on augmentation index and determined the extent to which this influence is dependent on the effects of age, height, heart rate, and blood pressure. We performed a classical twin study composed of 225 monozygotic and 594 dizygotic female white twin pairs aged 18 to 73 years. Augmentation index and mean arterial pressure were based on the central pressure wave derived from the radial waveform as measured by applanation tonometry. Quantitative genetic modeling techniques were used to analyze the data. The heritability of augmentation index was 37%, whereas heritabilities for blood pressure traits varied between 13% and 25%. Most of the variance in augmentation index could be explained by genetic and environmental factors specifically influencing augmentation index. Only a relatively small part of the total variance in augmentation index could be attributed to genes in common with height (3.1%), heart rate (4.6%), and mean arterial pressure (5.6%). Age explained 19% of the total variation in augmentation index. In conclusion, augmentation index has a significant heritable component, which is largely independent of the influence of blood pressure, heart rate, height, and age. Finding genes for the augmentation index could help to unravel pathophysiological mechanisms causing left ventricular hypertrophy and lead to improvements in prevention, diagnosis, and treatment of at-risk populations.