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H Schunkert

Publications and source records attributed to H Schunkert.

At least 73 records · Page 4Linked to original sources
PubMed1999

Evidence for a vasopressin system in the rat heart.

Traditionally, a hypothalamo-neurohypophysial system is thought to be the exclusive source of arginine vasopressin (AVP), a potent antidiuretic, vasoconstricting, and growth-stimulating neuropeptide. We have identified de novo synthesis of AVP in the heart as well as release of the hormone into the cardiac effluents. Specifically, molecular cloning of sequence tags amplified from isolated, buffer-perfused, and pressure-overloaded rat hearts allowed the detection of cardiac AVP mRNA. Subsequent experiments revealed a prominent induction of AVP mRNA (peak at 120 minutes, 59-fold, P<0. 01 versus baseline) and peptide (peak at 120 minutes, 11-fold, P<0. 01 versus baseline) in these isolated hearts. Newly induced vasopressin peptide was localized most prominently to endothelial cells and vascular smooth muscle cells of arterioles and perivascular tissue using immunohistochemistry. In addition to pressure overload, nitric oxide (NO) participated in these alterations, because inhibition of NO synthase by Nomega-nitro-L-arginine methyl ester markedly depressed cardiac AVP mRNA and peptide induction. Immediate cardiac effects related to cardiac AVP induction in isolated, perfused, pressure-overloaded hearts appeared to be coronary vasoconstriction and impaired relaxation. These functional changes were observed in parallel with AVP induction and largely prevented by addition of a V1 receptor blocker (10(-8) mol/L [deamino-Pen1, O-Me-Tyr2, Arg8]-vasopressin) to the perfusion buffer. Even more interesting, pressure-overloaded, isolated hearts released the peptide into the coronary effluents, offering the potential for systemic actions of AVP from cardiac origin. We conclude that the heart, stressed by acute pressure overload or NO, expresses vasopressin in concentrations sufficient to cause local and potentially systemic effects.

Animals↗
PubMed1999

Risk predictors in patients scheduled for percutaneous coronary revascularization.

Traditionally, procedural risks associated with conventional balloon coronary angioplasty have been largely attributed to unfavorable lesion morphology. However, factors predicting adverse events in the current practice of percutaneous coronary revascularization are unclear. The present study was undertaken to determine factors predicting major adverse events (death or Q-wave myocardial infarction or emergency bypass surgery) in 3,335 consecutive patients undergoing percutaneous coronary revascularization in the current practice of percutaneous coronary revascularization. During the period of observation, the rate of lesions treated successfully increased from 91% to 95% (P < 0.0001), whereas the rate of major adverse events (MACE) decreased from 3.6% to 1.6% (odds ratio [OR], 0.70 per year). Using multiple stepwise logistic regression analysis, cardiogenic shock (OR, 8.59; confidence interval [CI], 4.27-17.27), renal disease (OR, 3.33; CI, 1.95-5.69), evolving myocardial infarction (OR, 2.80; CI, 1.47-5.31), congestive heart failure (OR, 2.18; CI, 1.23-3.86), total number of lesions treated (OR, 1.28; CI, 1.03-1.59), age (OR, 1.03; CI, 1.01-1.06), and history of prior coronary intervention (OR, 0.51; CI 0.26-0.99) were identified as independent predictors of MACE. In addition, vascular disease (OR, 2. 48; CI 1.37-4.50) and unstable angina pectoris (OR, 0.44; CI 0.25-0. 79) were related to adverse events when patients in cardiogenic shock were excluded from the model. With the exception of most unfavorable lesion morphology (AHA/ACC lesion type C; OR, 2.05; CI, 1.19-3.52), anatomic parameters added no further information. In the present era of device technology, success rates of percutaneous coronary revascularization procedures have increased and remain to be determined by lesion morphology. In contrast, the rate of MACE is declining and best predicted by easily identified patient characteristics.

Aged↗
PubMed1999

The cardiac endothelin system in established pressure overload left ventricular hypertrophy.

In normal hearts, endothelin-1 (ET-1) has been shown to initiate myocyte growth and to modulate cardiac function. However, regulation of the various components of the system and the functional effects of ET-1 in established left ventricular hypertrophy (LVH) are less clear. We thus studied ET-1, ET(A) receptor, and endothelin converting enzyme (ECE-1) mRNA regulation as well as the effects of ET-1 on coronary resistance, LV contractility and relaxation in hypertrophied rat hearts. Cardiac pressure overload, secondary to banding of the ascending aorta, resulted in a transient increase of cardiac ET-1 and ET(A) receptor mRNAs that reached a maximum at 2 days (+75% and +40%, respectively, P<0.05, each). ET-1 mRNA levels reached a second peak at 84 days of pressure overload (+60%, P<0.05), at the later time point in conjunction with elevated ECE-1 mRNA levels (+20%, P<0.05). The functional implications of ET-1 were examined in a study of isolated perfused hearts. Both hearts with established LVH and sham control hearts responded to ET-1 perfusion (10(-1)] to 10(-9) M) with an increase of coronary perfusion pressure (CPP; +85+/-15 and +75+/-8 mm Hg; P<0.001 each) and a slight decrease of LV systolic pressure (LVP; -12+/-9 and -9+/-7 mm Hg; P = NS). In contrast, ET-1 increased LV end-diastolic pressure (LVEDP) only in LVH hearts (+22+/-7 mm Hg, P<0.05 versus baseline and +20+/-7 mm Hg, P<0.05 versus sham). Direct stimulation of protein kinase C mimicked the effects of ET-1, whereas inhibition of this kinase or the Na+ -H+ exchanger blunted the effects of ET-1 on CPP, LVP, and LVEDP. Interestingly, coadministration of the vasodilator and the nitric oxide (NO) donor nitroglycerin not only prevented the increase of CPP and LVEDP, but also uncovered a slight positive inotropic effect of ET-1 in LVH hearts. Thus, the cardiac expression of ET-1, ET(A), and ECE-1 mRNAs displays a distinct pattern during early and advanced cardiac pressure overload. Furthermore, ET-1 mediates a slight depression of systolic, and a profound depression of diastolic, functional parameters in hearts with established LVH, effects that appear to be secondary to ET-1-related coronary vasoconstriction. The data suggest a functional role of the endothelin system in hearts with established pressure overload hypertrophy.

Amiloride↗
PubMed1999

Familial predisposition of left ventricular hypertrophy.

OBJECTIVES: The study evaluated the contribution of familial predisposition to the risk of left ventricular hypertrophy (LVH). BACKGROUND: Left ventricular hypertrophy is a multifactorial condition that serves as an important predictor of cardiovascular mortality. At present it is unclear whether familial predisposition contributes to the manifestation of LVH. Thus, we determined whether siblings of subjects with LVH are at increased risk to present with an elevation of LV mass or an abnormal LV geometry. METHODS: Echocardiographic and anthropometric measurements were performed in 2,293 individuals who participated in the echocardiographic substudies of population-based MONICA Augsburg surveys. In addition, a total of 319 siblings of survey participants with echocardiographic evidence of LVH were evaluated. The risk of these siblings to present with LVH or abnormal LV geometry was estimated by comparison with 636 subjects matched for gender and age that were selected from the entire echocardiography study base. RESULTS: Blood pressure, body mass index, age, and gender (i.e., known determinants of LV mass) were comparable in LVH-siblings and the matched comparison group. However, septal and posterior wall thicknesses, relative wall thickness as well as LV mass index were significantly elevated in LVH-siblings (p < 0.001, each) whereas LV dimensions did not differ. Likewise, the prevalence of LVH was raised in LVH-siblings, as was the relative risk of LVH after adjustment for confounders (p < 0.05). More specifically, LVH-siblings displayed increased prevalences of concentric remodeling and concentric LVH (p < 0.05) but not of eccentric LVH. CONCLUSIONS: Familial predisposition appears to contribute to increased LV wall thickness, to the development of LV hypertrophy and abnormal LV geometry.

Adult↗
PubMed1999

Implications of small reference vessel diameter in patients undergoing percutaneous coronary revascularization.

OBJECTIVES: The purpose of this study was to determine whether small reference diameter of the culprit coronary artery influences the outcome of an attempted percutaneous revascularization procedure in the current era of interventional cardiology. BACKGROUND: Although the interventional strategy is largely determined by the size of the culprit coronary artery, earlier quantitative studies have not shown a worse acute outcome for small reference vessel diameter (< or =2.5 mm). METHODS: A total of 2,306 patients undergoing percutaneous coronary revascularization was divided in groups with reference diameters < or =2.5 mm (n = 813) or >2.5 mm (n = 1,493). Success and in-hospital major adverse cardiac event (death, Q-wave myocardial infarction and emergency coronary artery bypass graft) rates between both groups were compared. RESULTS: Patients with lesions in small vessels were older and presented more frequently with female gender, diabetes mellitus, heart failure, peripheral vascular, multivessel coronary disease and American Heart Association/American College of Cardiology (AHA/ACC) lesion type C (p < or = 0.01, each). Further, utilization of interventional devices differed markedly. In contrast to stents (18.5% vs. 41.9%) and directional atherectomy (3.7% vs. 13.5%), conventional balloon angioplasty (73% vs. 50%) and rotational atherectomy (16.1% vs. 8.3%) were used more often in smaller vessels (p < or = 0.0001, each). Success rate was lower in the small vessel group (92% vs. 95%; p = 0.006). Major adverse cardiac events occurred more frequently in small than large vessels (univariate 3.4% vs. 2.0%, p = 0.03; multivariate odds ratio 2.1, p = 0.02), particularly when proximal coronary segments were compared. CONCLUSIONS: Lesions in vessels with small reference diameter represent a distinct group with respect to clinical and morphologic characteristics as well as device utilization. These lesions have lower chances of successful percutaneous intervention and carry relatively higher risks, specifically when located in proximal coronary segments.

Aged↗
PubMed1999

Central vasopressin is modulated by chronic blockade of the renin-angiotensin system in experimental left ventricular hypertrophy.

We studied the interaction of the central renin-angiotensin system (RAS) and vasopressin system in rats with left ventricular hypertrophy (LVH) due to aortic banding. In these animals plasma vasopressin is elevated and vasopressin content is increased in specific brain areas. Chronic blockade of the RAS by angiotensin-converting enzyme (ACE) inhibition (ramipril) and AT1 receptor antagonism (losartan) significantly attenuated circulating and central vasopressin in rats with LVH. Given the antidiuretic, vasoconstrictive, and growth-promoting effects, vasopressin may participate in the cardiovascular alterations in LVH. Blockade of the RAS strongly ameliorates central and peripheral-vasopressin. Therefore, central modulatory effects on vasopressin might contribute to the therapeutic efficacy of ACE inhibitors and AT1 antagonists.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Relation between dehydroepiandrosterone sulfate and blood pressure levels in a population-based sample.

Endogenous dehydroepiandrosterone sulfate (DHEAS) levels have been reported to be positively related to blood pressure levels. To further analyze this association, we quantified DHEAS in middle-aged subjects (mean age +/-SEM: 57.8+/-0.1 years) of a population-based sample (n = 646). DHEAS levels were higher in hypertensive as compared with normotensive individuals (1.26+/-0.04 v. 1.09+/-0.03 microg/mL, P = .01). After adjustment for age, gender, and body mass index, DHEAS levels were significantly related to systolic blood pressure (P = .01). In addition, in a subgroup of individuals without antihypertensive medication adjusted DHEAS levels were significantly related to systolic and diastolic blood pressure (n = 461; P<.05, both). DHEAS levels were also related to aldosterone (r = 0.15; P = .002) and androstenedione (its main metabolite; r = 0.66; P<.001) but not to renin levels. Like DHEAS, aldosterone, but not androstenedione, was significantly related to blood pressure levels and hypertension status. In a regression analysis that accounted for aldosterone and renin levels, both DHEAS and aldosterone kept their significant relationships with systolic blood pressure levels. Taken together, we observed a consistent positive association between endogenous DHEAS and systolic blood pressure levels that was independent of other, similarly regulated, adrenal steroids.

Aged↗
PubMed1999

Association of arginine vasopressin and arterial blood pressure in a population-based sample.

BACKGROUND: The role of arginine vasopressin (AVP) in the development and maintenance of arterial hypertension is controversial. Furthermore, it remains unclear whether chronic treatment with antihypertensive agents modulates levels of AVP, with potential secondary effects on vascular tone and fluid homeostasis. OBJECTIVE: To investigate the relation between plasma AVP and arterial blood pressure in a population-based sample of 534 middle-aged subjects. RESULTS: Overall, levels of AVP were higher in hypertensive subjects (2.15 +/- 0.26 pg/ml; n = 289) than in normotensive subjects (1.45 +/- 0.15 pg/ml; n = 245; P < 0.05). (Hypertension was defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg, or receiving antihypertensive medication.) In untreated individuals, plasma levels of AVP were found to be correlated with both systolic (r = 0.15, P = 0.002) and diastolic (r = 0.14, P = 0.005) blood pressure. The differences between the lowest and highest quartile of AVP levels were 5.1 mmHg (P = 0.03) and 2.6 mmHg (NS) for systolic and diastolic blood pressure, respectively, after adjustment for age and sex. Moreover, it appeared that the relation between AVP and blood pressure was particularly strong in subjects with low levels of renin (< 10 mU/l; n = 118; systolic blood pressure r = 0.24, P = 0.007; diastolic blood pressure r = 0.19, P = 0.03). Specifically, patients receiving monotherapy with diuretics (n = 39) or beta-blockers (n = 54) displayed elevated plasma levels of AVP (2.93 +/- 0.98 pg/ml and 2.74 +/- 0.74 pg/ml respectively); however, only in patients taking diuretics was this finding apparently independent of confounding variables. Other monotherapies with angiotensin-converting enzyme inhibitors (n = 9) or Ca(2+)-antagonists (n = 19) were not associated with levels of AVP. CONCLUSION: The data suggest that plasma levels of AVP display a discernible relationship with arterial blood pressure and hypertension, particularly when renin levels are low. In addition, with the exception of diuretics, no modulation of AVP levels is attributable to the intake of antihypertensive agents as it occurs in a population-based sample.

Aged↗
PubMed1998

Changes in left ventricular structure and function in patients with white coat hypertension: cross sectional survey.

OBJECTIVES: To assess the relation between white coat hypertension and alterations of left ventricular structure and function. DESIGN: Cross sectional survey. SETTING: Augsburg, Germany. SUBJECTS: 1677 subjects, aged 25 to 74 years, who participated in an echocardiographic substudy of the monitoring of trends and determinants in cardiovascular disease Augsburg study during 1994-5. OUTCOME MEASURES: Blood pressure measurements and M mode, two dimensional, and Doppler echocardiography. After at least 30 minutes' rest blood pressure was measured three times by a technician, and once by a physician after echocardiography. Subjects were classified as normotensive (technician <140/90 mm Hg, physician <160/95 mm Hg; n=849), white coat hypertensive (technician <140/90 mm Hg, physician >=160/95 mm Hg; n=160), mildly hypertensive (technician >=140/90 mm Hg, physician <160/95 mm Hg; n=129), and sustained hypertensive (taking antihypertensive drugs or blood pressure measured by a technician >=140/90 mm Hg, and physician >=160/95 mm Hg; n=538). RESULTS: White coat hypertension was more common in men than women (10.9% versus 8.2% respectively) and positively related to age and body mass index. After adjustment for these variables, white coat hypertension was associated with an increase in left ventricular mass and an increased prevalence of left ventricular hypertrophy (odds ratio 1.9, 95% confidence interval 1.2 to 3.2; P=0.009) compared with normotensive patients. The increase in left ventricular mass was secondary to significantly increased septal and posterior wall thicknesses whereas end diastolic diameters were similar in both groups with white coat hypertension or normotension. Additionally, the systolic white coat effect (difference between blood pressures recorded by a technician and physician) was associated with increased left ventricular mass and increased prevalence of left ventricular hypertrophy (P<0.05 each). Values for systolic left ventricular function (M mode fractional shortening) were above normal in subjects with white coat hypertension whereas diastolic filling and left atrial size were similar to those in normotension. CONCLUSION: About 10% of the general population show exaggerated inotropic and blood pressure responses when mildly stressed. This is associated with an increased risk of left ventricular hypertrophy.

Adult↗
PubMed1998

[A case of Carney complex].

HISTORY AND CLINICAL FINDINGS: For some months a 57-year-old woman had noted increasing shortness of breath, associated in the last few weeks with undirected vertigo and several brief periods of lost consciousness. She was finally admitted because of additional central facial paresis. On auscultation a high-frequency systolic murmur was heard over the apex and a discrete diastolic murmur over Erb's point. There were numerous facial freckles and three cutaneous myxomas. INVESTIGATIONS: Echocardiography revealed irregular tumours throughout the left atrium and a large broad-based one prolapsing through the mitrale valve in diastole. Computed tomography demonstrated a 6 x 6 cm tumour in the left lower abdomen, probably arising from the left ovary, and a second 3 x 3 cm presacral tumour. TREATMENT AND COURSE: At cardiac surgery four tumours were found in the left atrium and resected: histologically they were benign myxomas. Removal required extensive resection in the area of the interatrial septum and the atrial wall, resulting in 2 degrees AV block for which a VDD pacemaker was implanted. CONCLUSION: Atrial myxomas may be the cardinal sign of the Carney Complex, an autosomal dominant syndrome with cutaneous myxomas, myxoid abdominal tumours, hormone-producing tumours in the testicles, adrenal cortex or hypophysis, schwannoma as well as lentigines. For this reason, further tumours should be looked for if freckles and/or cutaneous tumours are found in association with an atrial myxoma. The patient and family should be informed about the genetic aspects.

Dyspnea↗
PubMed1998

Neurohormonal activity and left ventricular geometry in patients with essential arterial hypertension.

The purpose of this study was to investigate whether the basal activity of the renin-angiotensin-aldosterone system or the basal levels of the atrial natriuretic peptide (ANP) are related to distinct patterns of left ventricular (LV) geometry in patients with essential hypertension. The left ventricle of patients with arterial hypertension may be exposed to a variety of growth-regulating mechanisms, including pressure overload and humoral activation. The interaction of such growth stimuli may be involved in the modulation of LV geometry. LV geometry was determined echocardiographically in 104 patients with mild to moderate essential hypertension. The same number of age- and sex-matched normotensive subjects served as controls. Plasma renin activity (PRA) and serum concentrations of aldosterone and ANP were measured by radioimmunoassay. Correlation analyses revealed that PRA was significantly associated with septal wall thickness and LV mass index (r = 0.25; p < 0.005 each). In addition, as compared with normal subjects (1.0 +/- 0.7 ng/ml/hr), PRA was significantly increased in patients with concentric LV hypertrophy (LVH) (3.4 +/- 6.6 ng/ml/hr, p < 0.01). Aldosterone displayed a close correlation with septal, posterior, and relative wall thickness (r > 0.27, p < 0.005 each). Compared with normal subjects (74 +/- 27 pg/ml), patients with hypertension and pathologic patterns of LV geometry were characterized by elevations of aldosterone (LV remodeling 203 +/- 93 pg/ml, concentric LVH 123 +/- 67 pg/ml; eccentric LVH 199 +/- 89 pg/ml; p < 0.05 each). ANP was significantly associated with septal wall thickness, left ventricular dimension, and LV mass index (r > 0.22, p < 0.005 each). Furthermore, compared with normal subjects (50 +/- 17 pg/ml), ANP values were significantly increased in patients with hypertension and concentric LVH (80 +/- 44 pg/ml, p < 0.005) and eccentric LVH (88 +/- 24 pg/ml, p < 0.001). Multivariate analysis adjusting for systolic blood pressure, body mass index, and age revealed that renin and ANP were independently associated with LV mass index (p < 0.05 each). Interestingly, adjusted PRA levels were not related to any specific pattern of LV geometry. In contrast, adjusted ANP levels were associated with concentric and eccentric LVH, whereas adjusted aldosterone levels were significantly elevated in subjects with LV remodeling and eccentric LVH (p < 0.005). Thus elevated levels of renin and ANP may be found in patients with hypertension and elevated LV mass index. In addition, ANP and aldosterone are related to specific geometric patterns of the left ventricle. The data may further stimulate the discussion on the mechanisms that account for alterations of LV geometry in hypertension.

Aldosterone↗
PubMed1998

Development of heart failure following isoproterenol administration in the rat: role of the renin-angiotensin system.

OBJECTIVE: High dosages of catecholamines induce cardiomyocyte necrosis and interstitial fibrosis in rats. We investigated whether this initial damage is followed by the development of heart failure and assessed the particular role of the renin-angiotensin system using ramipril. METHODS AND RESULTS: Following the administration of 0 mg or 150 mg isoproterenol/kg 6 groups of Wistar rats were followed for 2 or 16 weeks: Sham, isoproterenol, isoproterenol + ramipril. Isoproterenol induced significant increases of echocardiographically measured left ventricular end-diastolic posterior wall thickness and dimension, whereas ramipril treatment significantly attenuated these changes. Left ventricular end-diastolic pressure was markedly increased in isoproterenol-treated rats and normalized following ramipril. Isoproterenol rats were further characterized by hormonal activations including transient elevations of plasma renin activity, aldosterone and cardiac angiotensin converting enzyme activity. Histomorphological characterization of isoproterenol-treated hearts demonstrated cardiomyocyte necrosis and reparative fibrosis. Ramipril treatment only slightly reduced the amount of necrosis as well as the expression of extracellular matrix proteins. CONCLUSIONS: In rats, a toxic dosage of isoproterenol caused characteristic myocardial damage that subsequently resulted in mild heart failure. Ramipril administration following isoproterenol was highly effective to attenuate hemodynamic and hormonal alterations as well as the development of left ventricular hypertrophy, but had only little influence on the expression of extracellular matrix proteins. Since angiotensin converting enzyme inhibition had no impact on the initial myocardial injury, the development of heart failure in this model seems to require functional integrity of the renin-angiotensin system.

Adrenergic beta-Agonists↗
PubMed1998

Reciprocal regulation of pulmonary and cardiac angiotensin-converting enzyme in rats with severe left ventricular hypertrophy.

OBJECTIVE: Numerous studies support the concept that cardiac angiotensin-converting enzyme (ACE) is involved in the pathophysiology of left ventricular hypertrophy. However, the pulmonary vasculature is considered to be the most prominent site of ACE expression. We thus examined the tissue specificity of ACE regulation in rats with severe cardiac pressure overload hypertrophy in transition to cardiac failure with secondary pulmonary hypertension. METHODS AND RESULTS: Rats were studied 12 weeks after banding of the ascending aorta (LVH, n = 20) that resulted in a 1.7-fold increase in left ventricular (LV) to body weight ratio. In addition, as compared to sham-operated rats (n = 20), we observed in LVH rats a 1.6-fold increase in right ventricular (RV) to body weight ratio, the development of pulmonary hypertension, and elevated plasma renin activities. Moreover, ACE mRNA and activity levels were more than 2-fold higher in both hypertrophied ventricles (P < 0.01, each). In contrast, pulmonary ACE mRNA and activity levels were markedly decreased in animals with LVH (more than 30%, respectively, P < 0.05 vs. sham), Interestingly, LV and RV ACE activity, as well as systolic pulmonary artery pressure and plasma renin activity, were all inversely related to pulmonary ACE activity. In order to differentiate the potential role of elevated renin in the down-regulation of pulmonary ACE, additional rats (n = 12) were treated with furosemide that resulted in a 8-fold rise in plasma renin activity, but only in a marginal decrease of pulmonary ACE mRNA levels and activity (-10% vs. sham (n = 8), P-value n.s.). CONCLUSIONS: The data indicate tissue specific reciprocal regulation of pulmonary and cardiac ACE in rats with cardiac pressure overload hypertrophy and pulmonary hypertension, a phenomenon that may potentially result in a partial shift of angiotensin II formation from the pulmonary to the cardiac circulation.

Animals↗
PubMed1998

The associations of body size and body composition with left ventricular mass: impacts for indexation in adults.

OBJECTIVES: We investigated the relationship between body size, body composition and left ventricular mass (LVM) in adults, and assessed the impact of different indexations of LVM on its associations with gender, adiposity and blood pressure. BACKGROUND: The best way to normalize LVM for body size to appropriately distinguish physiologic adaptation from morbid heart morphology was discussed. METHODS: We undertook a community survey of 653 men and 718 women, aged 25 to 74 years. Lean body mass (LBM) was determined by bioelectric impedance analyses and LVM was assessed by two-dimensional guided M-mode echocardiography. RESULTS: After traditional indexations to body height, body height2.7, or body surface area, men had higher LVM than women (p < 0.001). These gender differences disappeared (p > 0.05) when LVM was indexed to LBM. The type of indexation also modified the strength of the association between adiposity and LVM. The estimated impact of body fat on LVM indexed to LBM was less than half that obtained with traditional indexations. In contrast, the magnitude of the associations of blood pressure with LVM was entirely independent of the type of indexation. CONCLUSIONS: This study showed the prominent influence of body composition on adult heart size. Indexation for LBM removed gender differences for LVM and reduced the impact of adiposity, but left the effects of blood pressure unchanged. We suggest that this approach be used for clinical and research applications.

Adaptation, Physiological↗
PubMed1998

Augmentation of the cardiac natriuretic peptides by beta-receptor antagonism: evidence from a population-based study.

OBJECTIVES: The present retrospective analysis of data derived from a population-based study examined the relationship between intake of beta-receptor antagonists and plasma concentrations of the cardiac natriuretic peptides and their second messenger. BACKGROUND: Beta-receptor antagonists are widely used for treatment of cardiovascular disease. In addition to direct effects on heart rate and cardiac contractility, recent evidence suggests that beta-receptor antagonists may also modulate the cross talk between the sympathetic nervous system and the cardiac natriuretic peptide system. METHODS: Plasma concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and their second messenger cyclic guanosine monophosphate (cGMP) were assessed in addition to anthropometric, hemodynamic and echocardiographic parameters in a population-based sample (n = 672), of which 80 subjects used beta-receptor antagonists. RESULTS: Compared to subjects without medication, subjects receiving beta-receptor antagonists were characterized by substantially elevated ANP, BNP and cGMP plasma concentrations (plus 32%, 89% and 18%, respectively, p < 0.01 each). Analysis of subgroups revealed that this effect was highly consistent and present even in the absence of hypertension, left atrial enlargement, left ventricular hypertrophy or left ventricular dysfunction. The most prominent increase was observed in a subgroup with increased left ventricular mass index. By multivariate analysis, a statistically significant and independent association between beta-receptor antagonism and ANP, BNP and cGMP concentrations was confirmed. Such an association could not be demonstrated for other antihypertensive agents such as angiotensin-converting enzyme inhibitors or diuretics. CONCLUSIONS: Beta-receptor antagonists appear to augment plasma ANP, BNP and cGMP concentrations. The current observation suggests an important contribution of the cardiac natriuretic peptide system to the therapeutic mechanism of beta-receptor antagonists.

Adrenergic beta-Antagonists↗
PubMed1998

Gender specific differences in left ventricular adaptation to obesity and hypertension.

Recent reports indicate that the prognostic implications of left ventricular hypertrophy (LVH) are more profound in women than in men. The prognosis of LVH is also related to the underlying geometric pattern. We therefore assessed the relation of separate and concurrent influences of obesity and hypertension on gender-specific patterns of LV adaptation. Five hundred and twenty participants of a community-based study (aged 52 to 67 years) were examined by M-mode echocardiography. Study subjects were divided into four groups: normals, obese, hypertensives, and subjects presenting with both obesity and hypertension. The groups were compared for various measures of left ventricular mass (LVM) and geometry. Relative to normal subjects, the increments in wall thickness, ventricle diameters, and LVM were all significant and of similar magnitude for obese men and women. Likewise, hypertensive men and women showed similar relative increments of LVM and wall thickness but no changes in end-diastolic internal diameters. Accordingly, obesity was predominantly associated with eccentric hypertrophy (men +/- 14%, women +17%, P<0.05 vs normals) and hypertension with concentric hypertrophy (men +16%, women +30%, P<0.01 vs normals). Women with concurrent obesity and hypertension presented with a further increase of LVM and wall thickness above values in the merely obese or hypertensive (P<0.001) and they displayed LVH more frequently than only obese or hypertensive women (P<0.05). We conclude that the hearts of postmenopausal women respond more susceptibly to the concurrence of hypertension and obesity. In particular the prognostically less favourable concentric LVH is a common finding. Our study may help to explain the higher risk associated with LVH in women.

Adaptation, Physiological↗
PubMed1998

Effects of hormone replacement therapies on fibrinogen and plasma viscosity in postmenopausal women.

In women, cardiovascular morbidity and mortality sharply increase after the onset of menopause. There is substantial evidence that hormone replacement therapy (HRT) may decrease the risk of coronary heart disease (CHD); however, the mechanisms of this preventive effect are unclear. We investigated the association between HRT and plasma viscosity as well as fibrinogen levels in postmenopausal women of a population-based sample (n=300, age 52-65 years). A total of 94 women used HRT; of these, 50 took oestrogen monotherapy and 44 used oestrogen-progesterone combinations. HRT was associated with significantly lower fibrinogen concentrations (2.32 v 2.68 g/l, P<0.001) and decreased plasma viscosity (1.147 v 1.176 mPa/s, P=0.01). Multivariate analyses controlling simultaneously for the effects of age, smoking, body mass index, and use of diuretics confirmed decreased fibrinogen and plasma viscosity values in women using HRT. A trend towards lower plasma viscosity (1.139 v 1.160 mPa/s) and plasma fibrinogen (2.28 v 2.44 g/l) was observed in women on oestrogen-progesterone combinations as compared with oestrogen monotherapy users: however, after controlling for the above-mentioned variables these differences were not statistically significant. This study demonstrates decreased plasma viscosity in women on HRT. Improved rheology offers a mechanism by which HRT lowers the risk of CHD in postmenopausal women.

Aged↗