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Biomedical subjects

H Schunkert

Publications and source records attributed to H Schunkert.

At least 55 records · Page 3Linked to original sources
PubMed2000

Are patients with renal failure good candidates for percutaneous coronary revascularization in the new device era?

BACKGROUND: Patients with end-stage renal disease undergoing conventional balloon angioplasty have reduced procedural success and increased complication rates. This study was designed to determine the immediate and long-term outcomes of patients with varying degrees of renal failure undergoing percutaneous coronary intervention in the current device era. METHODS AND RESULTS: We compared the immediate and long-term outcomes of 362 renal failure patients (creatinine >1.5 mg/dL) with those of 2972 patients with normal renal function who underwent percutaneous coronary intervention between 1994 and 1997. Patients with renal failure were older and had more associated comorbidities. They had reduced procedural success (89.5% versus 92.9%, P:=0.007) and greater in-hospital combined major event (death, Q-wave myocardial infarction, emergent CABG; 10.8% versus 1.8%; P:<0.0001) rates. Renal failure was an independent predictor of major adverse cardiac events (MACEs) (OR, 3.41; 95% CI, 1.84 to 6.22; P:<0.00001). Logistic regression analysis identified shock, peripheral vascular disease, balloon angioplasty strategy, and unstable angina as independent predictors of in-hospital MACEs in the renal group. Compared with 362 age- and sex-matched patients selected from the control group, patients with renal failure had a lower survival rate (27.7% versus 6.1%, P:<0.0001) and a greater MACE rate (51% versus 33%, P:<0.001) at long-term follow-up. Cox regression analysis identified age and PTCA strategy as independent predictors of long-term MACEs in the renal group. Finally, within the renal failure population, the dialysis and nondialysis patients experienced remarkably similar immediate and long-term outcomes. CONCLUSIONS: Although patients with renal failure can be treated with a high procedural success rate in the new device era, they have an increased rate of major events both in hospital and at long-term follow-up. Nevertheless, utilization of stenting and debulking techniques improves immediate and long-term outcomes.

Aged↗
PubMed2000

Localization of a small genomic region associated with elevated ACE.

Defining the relationship between multiple polymorphisms in a small genomic region and an underlying quantitative trait locus (QTL) represents a major challenge in human genetics. Pedigree analyses have shown that angiotensin I-converting enzyme (ACE) levels are influenced by a QTL located within or close to the ACE gene and most likely resides in the 3' region of this locus. We genotyped seven polymorphisms spanning 13 kb in the 3' end of ACE in 159 Afro-Caribbean subjects to evaluate the linkage disequilibrium between these sites and to narrow the genomic region associated with an elevated ACE level using a cladistic analysis. The linkage disequilibrium measurement D' and a haplotype tree revealed three distinct haplotype segments, presumably because of recombination. The value of the linkage disequilibrium parameter p(excess) was highest for site 22982, which is located in the middle segment. A series of nested, cladistic analyses confirmed that the other two regions are unlikely to be the ACE-linked QTL and that the variant resides in the middle region. Analyses of the same polymorphisms in 98 unrelated Europeans in the Monitoring Trends and Determinants in Cardiovascular Diseases (MONICA) study resulted in fewer haplotypes than were observed among the Afro-Caribbean subjects, suggesting that populations with greater genetic diversity may be especially informative for fine-scale mapping.

Black People↗
PubMed2000

Body composition and prevalence of left ventricular hypertrophy.

BACKGROUND: Fat-free mass (FFM) has been proposed as an optimal normalization of left ventricular (LV) mass to body size. We sought to evaluate the novel FFM-based criteria of LV hypertrophy (LVH). METHODS AND RESULTS: A population sample of 1371 men and women aged 25 to 74 years was examined by echocardiography and bioelectrical impedance analysis. Internal partition values for LVH were generated in a healthy population subgroup on the basis of LV mass divided by FFM and by the traditional indexations to body height, height(2.7), and body surface area. In contrast to the sex-specific criteria required by traditional indexations, the value of LV mass/FFM that divided individuals with and without LVH was identical for men and women (4.1 g/kg). Estimates of LVH prevalence varied significantly by type of indexation used, internally or externally derived cut points, and by population subgroups. Differences were pronounced among hypertensives and the obese. Thus, the application of LV mass/FFM more than halved the risk of LVH in obese versus nonobese women (odds ratio, 2.5; 95% confidence interval, 1.6 to 4.0) compared with criteria based on LV mass/height(2.7) (odds ratio, 5.5; 95% confidence interval, 3.6 to 8.3). Implications among hypertensives were less marked. CONCLUSIONS: Indexation of LV mass to FFM eliminates sex-specific LVH criteria. The proportion of individuals defined as having LVH using the new criteria deviate markedly from traditional indexations. Prospective investigations will be needed to identify the prognostic implications of different indexations, especially in subgroups such as the obese.

Adult↗
PubMed2000

[ACE gene polymorphism and cardiovascular diseases].

The angiotensin converting enzyme (ACE) is an integral part of enzymatic cascades leading to generation of angiotensin II as well as degradation of bradykinin. For this reason, it represents an important part for the metabolism of 2 vasoactive peptides. Early in this decade, convincing experimental evidence demonstrated the induction of this enzyme in several pathophysiological conditions including myocardial infarction and left ventricular hypertrophy. In parallel, a deletion/insertion (D/I) polymorphism of the human ACE gene was discovered that was related to 14 to 50% of the interindividual variance of serum ACE activity. More recently, this polymorphism was implicated in the pathogenesis of a variety of cardiovascular disorders including myocardial infarction, left ventricular hypertrophy, hypertension as well as nephropathy.

Chromosome Deletion↗
PubMed2000

Eleven single nucleotide polymorphisms and one triple nucleotide insertion of the human TGF-beta III receptor gene.

We found 11 single nucleotide polymorphisms and one triple nucleotide insertion in the cDNA of the human transforming growth factor beta (TGF-beta) III receptor gene (TGFBR3) located on 1p33-p32, encoding beta-glycan, a component of the TGF-beta receptor system. Inside the 5' untranslated region (UTR), a G-->A polymorphism was identified at position 311. In the open reading frame (ORF), a non-conservative T-->C polymorphism was identified at position 392, and three conservative polymorphisms were found at positions 563 (G-->A), 1548 (G-->A), and 2370 (C-->T). A triple nucleotide insertion (GCA) was identified at position 1419. Inside the 3' UTR, six polymorphisms were identified: four G-->A, at positions 2918, 3055, 3098, and 3355; one T-->A, at position 3183; and one G-->C, at position 3966. In addition to these changes, some divergences from the published sequence were observed in all 12 chromosomes tested. These included, in the ORF, an additional C after position 555, two additional G after position 563, and an additional T after position 1388. No T was found at position 1394. The alterations translate to a changed amino acid sequence. Inside the 3' UTR, additional discrepancies were identified. The discovered changes and polymorphisms may be useful for further genetic studies of TGFBR3 receptor deficiencies.

3' Untranslated Regions↗
PubMed2000

Lipoprotein lipase gene polymorphism, cholesterol subfractions and myocardial infarction in large samples of the general population.

OBJECTIVE: Genetic variants of the lipoprotein lipase gene have been associated with dyslipidemia and coronary artery disease. However, data have been inconsistent and are mainly based on selected predominantly male patient groups. METHODS: We evaluated the influence of the HindIII restriction fragment length polymorphism on lipid levels in the general population (1361 participants of a large population-based survey from Augsburg, Germany; 50% women) as well as the association of this polymorphism with the risk of myocardial infarction (MI; genotype frequencies in 1159 patients with documented MI under 60 years of age). RESULTS: In the population-based survey, a highly significant association between the frequent H2H2 genotype and unfavorable cholesterol subfraction levels was observed in men and in postmenopausal women whereas no significant association was observed in premenopausal women (uni- and multivariate analysis). Such unfavorable lipid levels in homozygotes for the H2 allele may be expected to be associated with a 19-25% increased risk to suffer from myocardial infarction (MI). Nevertheless, genotype and allele frequencies in the general population were not different from those in patients with previous MI (H2H2 genotype frequency 51.3% vs. 53.2%, respectively; P=0.63). CONCLUSION: This large study shows that the H2H2 genotype of the lipoprotein lipase gene polymorphism is associated with unfavorable lipid levels. Estrogen status may modulate this association in women. The effects of the genotype on lipid levels were apparently not strong enough to reveal a significant association with MI.

Adult↗
PubMed2000

Evaluation of three polymorphisms in the promoter region of the angiotensin II type I receptor gene.

BACKGROUND: Angiotensin II induces vasoconstriction and growth via stimulation of the AT1 receptor. A genetic variant (+1166A/C) in the 3' untranslated region of this gene had been found to be associated with arterial hypertension, aortic stiffness and coronary artery disease. OBJECTIVE: In order to evaluate further the potential implications of the genetic variability of the AT1 gene we explored three newly characterized single nucleotide polymorphisms (SNPs) in its promoter in a Caucasian population-based sample (n = 623). One of these (-2228G/A) is in complete linkage disequilibrium with six additional SNPs in the region such that, indirectly, potential functional implications of these sites were assessed as well. For comparison, we genotyped the previously described +1166A/C variant RESULTS: The allele frequencies of the -2228G/A, -1424C/ G and -521 C/T SNPs were 0.82/0.18, 0.963/0.037 and 0.64/0.36, respectively. Statistical analysis by one-factor ANOVA revealed no significant relationship of any allele, genotype or haplotype with age, sex, body mass index, heart rate, systolic or diastolic blood pressure, hypertension, the intake of antihypertensive medication or left ventricular mass. Likewise, renin, angiotensinogen, angiotensin-converting enzyme, aldosterone or atrial natriuretic peptide levels were not found to be associated with any of these SNPs. Surprisingly, the -2228 A allele was found to be overrepresented in subjects with diabetes mellitus (n = 25, P = 0.006). However, this result could not be confirmed when additional individuals with diabetes mellitus (n = 45) were analysed. A weak linkage disequilibrium was observed between the -2228 A allele and the +1166 C allele (chi2 1 3.1; P = 0.010). CONCLUSION: From the present data it is unlikely that any one of the nine newly characterized SNPs in the promoter region of AT1 gene is associated with arterial hypertension.

Aged↗
PubMed2000

Evaluation of brain natriuretic peptide as marker of left ventricular dysfunction and hypertrophy in the population.

OBJECTIVE: To evaluate brain natriuretic peptide (BNP) as marker of left ventricular (LV) dysfunction and hypertrophy in a population-based sample of 610 middle-aged subjects (50-67 years) who were further characterized with respect to hemodynamic and anthropometric parameters and by echocardiography. RESULTS: Left ventricular (LV) systolic function, LV mass-index, age, gender, heart rate, and medication with beta adrenergic receptor blockers were significant and independently correlated with BNP (multivariate analysis, P < 0.05 each). As compared to subjects with normal LV function and mass-index (control), subjects with LV dysfunction (LV fractional shortening < 28%) or hypertrophy (LV mass-index > 110 g/m2 in women and > 134 g/m2 in men) were characterized by increased BNP. The increase in BNP associated with LV hypertrophy (n = 69, +101% versus control, P < 0.0001) was similar in magnitude to that associated with LV dysfunction (n = 39, +98% versus control, P < 0.03). These increases were markedly exceeded in subjects with severe LV dysfunction (n = 11, LV fractional shortening < 22%, BNP +197% versus control, P < 0.01), particularly in the presence of concomitant hypertrophy (n = 7, +227%, P < 0.01). The predictive values of BNP varied considerably with the degree of LV dysfunction and the presence or absence of concomitant LV hypertrophy. With 0.81, the highest area under the receiver operator characteristic curve was obtained for the detection of severe LV dysfunction and concomitant hypertrophy and sensitivity, specificity, positive and negative predictive value for this condition were 71, 86, 7 and 99.5%, respectively, for a cut-off of 34 pg/ml. CONCLUSIONS: The current study provides new insight into regulation and diagnostic value of BNP in middle-aged subjects and demonstrates important independent effects of LV function and mass upon BNP plasma concentrations. Although measurement of BNP cannot be recommended for the detection of marginally impaired LV function in the population, it may be helpful to suggest or exclude severe LV dysfunction with concomitant hypertrophy.

Analysis of Variance↗
PubMed2000

Haematocrit profoundly affects left ventricular diastolic filling as assessed by Doppler echocardiography.

BACKGROUND: The main determinants of diastolic function--pre- and afterload of the heart--are affected by the haematocrit, but the relation between haematocrit and diastolic function is unclear. OBJECTIVE: To study the association between interindividual haematocrit values and diastolic function, by echocardiography. DESIGN: In a cross-sectional survey, blood pressure, haematocrit values, and high-quality Doppler indexes of left ventricular filling were obtained in 1297 individuals, 25-74 years of age, and analysed by regression analyses. RESULTS: Haematocrit and systolic blood pressure were strongly correlated (r = 0.23; P < 0.0001). Moreover, haematocrit was inversely correlated with the peak velocity of early left ventricular filling and with the peak velocity of early filling divided by late filling (E/A ratio; both P< 0.005). Left ventricular isovolumic relaxation time (IVRT) was positively associated with haematocrit (r= 0.18, P< 0.001). In individuals with an abnormal Doppler filling pattern (E/A(< 50 years) < 1, E/A(> 50 years) < 0.5, or IVRT(< 30 years) > 92 ms, IVRT30-50 years > 100 ms or IVRT> 50 years > 1 05 ms; n = 119), greater haematocrit values were observed than in those with normal diastolic parameters (P< 0.001). Conversely, individuals with an increased haematocrit (> 50% in men, > 45% in women; n = 16) had a greater risk of presenting with abnormal left ventricular filling (31.3%) compared with individuals with normal (12.1%; n = 898;) or low (< 40% in men, < 35% in women: 10.5%, n = 38; P = 0.07) haematocrit. Strong and significant associations between haematocrit and Doppler indexes of left ventricular filling were confirmed after adjustment for multiple potential confounders including blood pressure, antihypertensive medication and body mass index. Similarly, blood pressure and parameters of diastolic filling were strongly associated correlations that were not affected by inclusion of haematocrit values into the regression model. CONCLUSION: The data point to substantial adaptations of diastolic filling in response to both blood pressure and the characteristics of the medium that is propelled by the heart Therefore, in addition to blood pressure values, the variability of haematocrit values should be considered when diastolic function is being evaluated by Doppler echocardiography.

Adult↗
PubMed2000

Effects of indapamide in rats with pressure overload left ventricular hypertrophy.

We studied the in vivo effects of the antihypertensive diuretic agent indapamide on left ventricular (LV) morphology in chronically pressure-overloaded rat hearts. LV pressure and subsequently LV mass were increased by banding the ascending aorta over a period of 6 weeks. Thereafter, animals were treated with low-dose (1 mg/kg/day, n = 9) or high-dose (10 mg/kg/day, n = 9) indapamide for another 6 weeks. Low-dose indapamide treatment reduced LV weights as compared with vehicle-treated controls (n = 9; -12%; p = 0.008). Furthermore, low-dose indapamide treatment resulted in a decrease of myocyte volume (59.0 +/- 10.6 vs. 79.0 +/- 9.8 m3 x 10(-27); p < 0.05) and an improvement of molecular markers of hypertrophy: a reduction of LV atrial natriuretic factor mRNA expression (-37%; p < 0.05), and an increase of the V1/V3 myosin ratio (+121%; p < 0.05). Low-dose indapamide also reduced significantly plasma (-65%) and LV angiotensin-converting enzyme (ACE) activities (-74%) as well as LV mRNA levels (-24%). These changes were observed despite continued pressure overload of the LV and despite a lack of significant changes in sodium excretion with the prolonged administration of low-dose indapamide. High-dose indapamide treatment showed no significant effects on LV mass, structure, and gene expression. Furthermore, high-dose indapamide increased plasma renin activity substantially, whereas low-dose treatment was without effect on circulating renin. In conclusion, in rats with continuous LV pressure-overload low-dose treatment with indapamide leads to mild regression of cardiac hypertrophy, accompanied by a downregulation of components of the cardiac renin-angiotensin system. These effects may be mediated by mechanisms apart from the known diuretic and antihypertensive actions of indapamide, because sodium excretion and blood pressure were stable with long-term treatment and are unlikely to be related to LVH regression in this model.

Animals↗
PubMed2000

Comparative coronary anatomy in six twin pairs with coronary artery disease.

OBJECTIVE: To compare the coronary anatomy and the location of coronary lesions in monozygotic and dizygotic twin pairs affected with coronary artery disease. DESIGN: Coronary angiographic findings were compared with respect to the distribution of coronary blood supply and the location of coronary lesions. MAIN OUTCOME MEASURES: Distribution of coronary blood supply, diameters and length of proximal coronary arteries. RESULTS: The lumen diameters of the left main coronary artery, the left anterior descending coronary artery, the circumflex artery, and the right coronary artery, as well as the lengths of the left main coronary artery, showed similar variability within monozygotic and dizygotic twin pairs. With respect to the dominance pattern of coronary blood supply, two of three monozygotic twin pairs differed, while all dizygotic twin pairs were concordant. Concordant and discordant locations of stenoses were found with similar frequency in monozygotic and dizygotic twin pairs. CONCLUSIONS: The dominance pattern of coronary blood supply and the location of coronary lesions are not strictly hereditary. The high concordance of premature coronary artery disease found in monozygotic twin pairs may largely be related to factors that are independent of the macroanatomic distribution of the coronary blood supply.

Adult↗
PubMed2000

Evaluation of the aldosterone synthase (CYP11B2) gene polymorphism in patients with myocardial infarction.

Left ventricular remodeling after myocardial infarction involves activation of the renin-angiotensin-aldosterone system. Recently, the biallelic -344T/C polymorphism of the aldosterone synthase gene was associated with increased aldosterone levels, arterial hypertension, diastolic dysfunction, and left ventricular dilatation. We hypothesized that this polymorphism may also affect left ventricular geometry and function after myocardial infarction. By using a standardized questionnaire, as well as anthropometric and echocardiographic measurements, we thus studied 606 patients (533 men and 73 women) who had a myocardial infarction before the age of 60 years. The aldosterone synthase gene polymorphism was analyzed after polymerase chain reaction amplification and restriction enzyme digestion. The results demonstrated that there was no association of the aldosterone synthase gene polymorphism with echocardiographically determined left ventricular dimensions, wall thicknesses, or indexes of systolic or diastolic function. Furthermore, anthropometric data, including blood pressure levels, were balanced between the different genotypes. Finally, the allele frequency was similar for patients with myocardial infarction and a sample group from the normal population (n=1675). The data indicate that the allele status of the aldosterone synthase gene polymorphism is not useful for the identification of patients with myocardial infarction who have impaired left ventricular function or unfavorable remodeling.

Alleles↗
PubMed2000

Hormone replacement therapy and interrelation between serum interleukin-6 and body mass index in postmenopausal women: a population-based study.

Postmenopausal women are at increased risk to develop osteoporosis, coronary artery disease, heart failure, and hypertension. Interleukin-6 (IL-6) may be a pathogenetic element in these disorders. Serum IL-6 levels increase during aging and seem to be related to increased body fat mass. In the present retrospective study we aimed to investigate the role of hormone replacement therapy (HRT) on serum IL-6 levels and the interrelation of IL-6 and body fat mass. Parameters were assessed in a population-based sample of postmenopausal women (n = 302) and, for comparison, 245 men of the same age. Women with HRT (n = 92) had significantly lower serum IL-6 levels compared to subjects without HRT, which was independent of age, antihypertensive therapy, smoking habits, and blood pressure (1.5 +/- 0.1 vs. 2.9 +/- 0.6 pg/mL; P = 0.017). In women without HRT, the body mass index (BMI) was correlated with serum IL-6 levels (P < 0.001). Multivariate analysis controlling simultaneously for the effects of blood pressure and heart rate confirmed the positive correlation (P = 0.001). However, in subjects with HRT no such correlation between IL-6 and BMI was demonstrated, which was confirmed after controlling covariates. In male subjects, BMI correlated with serum IL-6 (P = 0.009), which was, however, blunted after controlling for blood pressure and heart rate, probably indicating an influence of the sympathetic nervous system on this interrelation. In conclusion, women receiving HRT display lower serum IL-6 levels and a blunted interrelation of IL-6 and BMI. As IL-6 may be a pathogenetic factor in age-related diseases, HRT-related inhibition of IL-6 secretion could be an important element for the favorable effects of HRT in postmenopausal women.

Aged↗
PubMed2000

The importance of early intervention in CHF--signs and symptom relief.

Effective treatments of congestive heart failure (CHF) must not only reduce mortality, but should also reduce the severity of the signs and symptoms of the syndrome, as these can have a major impact on quality of life. Early intervention can help to make everyday activities easier for patients with CHF and may slow disease progression. This review provides an overview of the efficacies of various therapies in improving the signs and symptoms of CHF, with particular reference to recent data from randomised, double-blind studies of patients receiving the AT(1)-receptor blocker, candesartan cilexetil.

Angiotensin Receptor Antagonists↗
PubMed1999

Lack of association between a polymorphism of the aldosterone synthase gene and left ventricular structure.

BACKGROUND: Cardiac growth and function may be modulated in part by trophic effects of neurohormones. Specifically, aldosterone has been shown to stimulate the growth of cardiac myocytes and the accumulation of cardiac extracellular matrix proteins. Moreover, a variant of the aldosterone synthase gene (a cytosine/thymidine exchange at position -344 in the transcriptional regulatory region) has been associated with enlargement and disturbed filling of the left ventricle (LV) in a small sample of young white adults. The aim of the present study was to reinvestigate the implications of aldosterone synthase -344C/T allele status for serum aldosterone levels, blood pressure, and LV structure and function in large population-based samples. METHODS AND RESULTS: Individuals who participated in the echocardiographic substudy of the third MONICA (MONitoring trends and determinants in CArdiovascular disease) survey (n=1445) or in the second follow-up of the first MONICA survey (n=562) were studied by standardized anthropometric, echocardiographic, and biochemical measurements as well as genotyping for aldosterone synthase -344C/T allele status. In both surveys, the distribution of sex, age, arterial blood pressure, and body mass index was homogeneous in the aldosterone synthase genotype groups. Echocardiographic LV wall thicknesses, dimensions, and mass indexes were not significantly associated with a specific aldosterone synthase genotype. Likewise, no association was detectable with echocardiographic measures of LV systolic or diastolic function. Data were consistent in both samples and not materially different in subgroups defined by age, sex, or intake of antihypertensive medication. Finally, no significant association was observed for aldosterone synthase allele status and serum aldosterone levels in the group of 562 individuals. CONCLUSIONS: The data are not in favor of a significant contribution of the C/T exchange at position -344 in the aldosterone synthase transcriptional regulatory region to the variability of serum aldosterone levels, blood pressure, or cardiac size or function as found in 2 white population-based samples.

Adult↗